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Simulation and analysis of the jet flow patterns from supersonic nozzles of laser cutting using OpenFOAM | Request PDF Request PDF | Simulation and analysis of the jet flow patterns from supersonic nozzles of laser cutting using OpenFOAM | The operating pressure of gas-assisted laser cutting and the resulting exit jet pattern is one of the most important process parameters in... | Find, read and cite all the research you need on ResearchGate June 2019 The International Journal of Advanced Manufacturing Technology 102(1) DOI: 10.1007/s00170-019-03346-5 Authors: Mohamed Darwish Università degli Studi di Modena e Reggio Emilia Leonardo Orazi Università degli Studi di Modena e Reggio Emilia Diego Angeli Università degli Studi di Modena e Reggio Emilia Read publisher preview Request full-text Download citation Copy link Link copied Request full-text Download citation Copy link Link copied To read the full-text of this research, you can request a copy directly from the authors. Citations (16) References (22) Abstract The operating pressure of gas-assisted laser cutting and the resulting exit jet pattern is one of the most important process parameters in high-pressure laser cutting. Many studies have been done to illustrate the effect of this parameter on both laser cutting quality and laser cutting capability. However, most of these studies have been done using conical nozzles. In this paper, the exit jet from supersonic nozzle has been studied, analyzed, and simulated under three different operating conditions, namely desired design, under-expansion, and over-expansion to illustrate the effect of these operating conditions on the dynamic characteristics of the exit jet. Quasi 1-D gas dynamics theory has been used to calculate the desired design operating condition, and then an axisymmetric 2-D model has been created using the OpenFOAMⓇ Computational Fluid Dynamics (CFD) toolbox to simulate the gas-assisted laser cutting flow through the modeled supersonic nozzle. Finally, the proposed simulations have been validated by comparing the results with experimental observations reported in previous literature. The effect of the turbulent viscosity has been considered through the proposed model to better simulate real conditions. Moreover, the model has been optimized to be effectively used for engineering purposes. The simulation results are qualitatively consistent with the reported experimental measurements and they demonstrate that in the case of supersonic nozzles, the exit jet pattern is characterized by high uniformity, absence of Mach disks, and bounded shape for a long distance especially under the desired design operating conditions. Discover the world's research 25+ million members 160+ million publication pages 2.3+ billion citations Join for free Publisher Preview 1 A preview of this full-text is provided by Springer Nature. Learn more Preview content only Content available from The International Journal of Advanced Manufacturing Technology This content is subject to copyright. Terms and conditions apply. The International Journal of Advanced Manufacturing Technology (2019) 102:3229–3242 https://doi.org/10.1007/s00170-019-03346-5 ORIGINAL ARTICLE Simulation and analysis of the jet flow patterns from supersonic nozzles of laser cutting using OpenFOAM Mohamed Darwish 1 · Leonardo Orazi 1 · Diego Angeli 1 Received: 8 August 2018 / Accepted: 17 January 2019 / Published online: 13 February 2019 © Springer-Verlag London Ltd., part of Springer Nature 2019 Abstract The operating pressure of gas-assisted laser cutting and the resulting exit jet pattern is one of the most important process parameters in high-pressure laser cutting. Many studies have been done to illustrate the effect of this parameter on both laser cutting quality and laser cutting capability. Ho wever , most of these studies have been done using conical nozzles. In this paper, the exit jet from supersonic nozzle has been studied, analyzed, and simulated under three different operating conditions, namely desired design, under-expansion, and over -expansion to illustrate the effect of these operating conditions on the dynamic characteristics of the exit jet. Quasi 1-D gas dynamics theory has been used to calculate the desired design operating condition, and then an axisymmetric 2-D model has been created using the OpenFOAM  Computational Fluid Dynamics (CFD) toolbox to simulate the gas-assisted laser cutting flow through the modeled supersonic nozzle. Finally , the proposed simulations have been validated by comparing the results with e xperimental observations reported in previous literature. The effect of the turbulent viscosity has been considered through the proposed model to better simulate real conditions. Moreover, the model has been optimized to be effecti vely used for engineering purposes. The simulation results are qualitatively consistent with the reported experimental measurements and they demonstrate that in the case of supersonic nozzles, the exit jet pattern is characterized by high uniformity, absence of Mach disks, and bounded shape for a long distance especially under the desired design operating conditions. Keywords OpenFOAM  · Compressible flow · Gas-assisted laser cutting · Supersonic nozzle · Laser cutting · Over-expansion · Under-e xpansion 1 Introduction Laser can be used for several material processing applica- tions such as cutting, welding, and heat treatments. Cur- rently, laser cutting is the most common industrial applica- tion since laser has the ability to cut faster and with a higher quality than the other competing processes [ 1 , 2 ]. During the cutting process, the laser beam passes through a nozzle from which a coaxial gas jet flows. This gas-assisted laser cutting is needed both to aid the cutting operation by providing a mechanical force to eject the melt and to protect the optics from spatter. The stand-off tolerance which represents the  Mohamed Darwish [email protected] 1 DISMI - Department of Sciences and Methods for Engineeering, University of Modena and Reggio Emilia, Modena, Italy allowable distance between the nozzle tip and work-piece is mainly determined by the pattern and uniformity of the exit jet. Thus, an uniform, bounded exit jet allows operators to utilize the advantage of long stand-off tolerance during laser cutting process [ 1 ]. In industry, conical (subsonic) nozzles are commonly employed to direct the gas jet into the cutting kerf on the work-piece. The exit jet from subsonic (conical) nozzles is usually associated with the formation of Mach disks when the operating stagnation pressure exceeds 1.89 bar which is a typical condition in most laser cutting operations. Therefore, the exit jet from subsonic nozzle is characterized by poor dynamic characteristics and hence low stand- off distance [ 3 , 4 ]. Numerous studies have been done to investigate the effect of both nozzle types and nozzle designs (dimensions) on the dynamic characteristics of the exit jet and hence the stand-off distance. Moreover , many numerical simulations and experimental observations hav e been done to illustrate how the stand-off distance is affected by the dynamic characteristics of the exit jet within the cut Content courtesy of Springer Nature, terms of use apply. Rights reserved. Citations (16) References (22) ... During the thermal cutting process, the kinetic energy of the high-speed gas from the nozzle provides a mechanical force that ejects the melt and protects the nozzle from spatter [12] . The quality of the cutting can be evaluated from the kerf width, kerf angle, deposition of dross, bevel profile, and so on. ... ... The standoff distance, which represents the allowable distance between the nozzle tip and workpiece, is mainly determined by the pattern and uniformity of the gas flow through the nozzle exit. Nevertheless, these parameters are still empirically determined [12] . ... Investigation of Gas Flow Dynamics inside Kerf during Thermal Cutting Process using CFD and Schlieren Method Thesis Full-text available Feb 2023 Upendra Tuladhar This study investigates and discusses the performance of the thermal cutting process through the assessment of gas flow dynamics inside the kerf geometry. The flow dynamics of the highspeed gas passing through a nozzle during the process of thermal cutting play an important role in affecting the cutting performance. However, the gas flow dynamics are greatly influenced by the shape of the cut kerf, and the cut kerf geometry is affected by the varying operating conditions. This study is focused on understanding the effects of thermal cutting process parameters on the kerf geometry and the study of gas flow dynamics inside various kerf geometries through computational fluid dynamics (CFD) and the Schlieren method. Plasma arc cutting experiments were designed based on a multivariable factorial design. The effects of varying current input and cutting speed on the shaping of kerf geometry were investigated. A quadratic polynomial regression model was was proposed to establish relationship between process parameters and the response variables. An analysis of variance (ANOVA) was performed to analyze the significance of independent variables influencing the kerf geometry. The analysis results revealed that the selected variables had a significant influence on the kerf geometry, and the proposed regression models fit the experimental data fairly well. For the investigation of the gas flow dynamics inside the thermal cut kerf, various geometrical features of the kerf were considered, such as the kerf length difference on the top and bottom surfaces and the kerf taper. A plasma-cut sample was used to model the kerf geometry for this study. A prototype kerf was assembled using a pair of clear glasses and an inclined substrate. The inclined substrate prepared using a 3D printer was sandwiched between the glasses. The glasses acted as the walls and the inclined substrate represented cut front of the kerf. The Schlieren technique was used to examine gas flow from inside the assembled kerf. Image processing was carried out on the Schlieren images captured before and after the injection of gas. The image processing results were used for the validation of the numerical models. The effect of turbulent viscosity was investigated in several turbulence models using computational fluid dynamics analyses. The results of the CFD analyses confirmed that the k–ω turbulence model was the most suitable turbulence model for the kerf geometry used in this study. The simulation results for this model were in good agreement with the experimental measurements. The thermal cutting process relies on gas flow behavior that remains consistent over a wide range of operating conditions in order to get consistent results. The gas flow characteristics inside the thermal cut kerf with various kerf geometry and the nozzle exit diameter were studied. The nozzles studied in this research were of the converging–straight type, and the exit diameters (ϕ_exit) were 1.5 mm, 2.0 mm, and 2.5 mm. The numerical simulation results and the Schlieren experiment results were compared for the verification. The results from numerical and experimental studies confirm that a 2.0 mm nozzle shows a higher degree of consistency in flow behavior at variable operating conditions for the kerf geometries investigated. View Show abstract ... The spectral radiative properties of major participating gases such as (CO 2 ), (H 2 O) are calculated from HITEMP-2010 database. A small CD nozzle which is designed for the perfect expansion of air by 1D calculation with nozzle throat diameter 1.98 mm and area ratio 1.5942, is considered as the design of nozzle for present study [1] . All three plumes are in the under-expanded state for this CD nozzle and hence expands rapidly at supersonic speed as the plumes exit from the nozzle and forms a series of expansion and compression waves. ... ... Darwish et al. [1] have designed a convergent divergent (C-D) nozzle using one dimensional flow isentropic relations for perfect expansion conditions for air. The designed C-D nozzle has an exit diameter of 2.5 mm and throat diameter of 1.98 mm, thus the area ratio A r = 1.5942. ... Estimation of thermal load on the nozzle base plate from small plumes at high temperature Preprint Full-text available Jan 2023 Kamal Khemani Pradeep Kumar Ganesh Natarajan A numerical study is performed to estimate thermal load on the nozzle base plate, which is in the upstream direction to the flow, from three hot plumes of pure (CO 2), (H 2 O) and 50-50 (%) composition of (CO 2) and (H 2 O) expanding through a convergent-divergent (CD) nozzle in a quiescent medium at 1.1 bar pressure and 298K temperature. The base plate of the nozzle heats up due to thermal radiation, emitting from the hot gases in the form of plumes. The spectral radiative properties of major participating gases such as (CO 2), (H 2 O) are calculated from HITEMP-2010 database. A small CD nozzle which is designed for the perfect expansion of air by 1D calculation with nozzle throat diameter 1.98 mm and area ratio 1.5942, is considered as the design of nozzle for present study [1]. All three plumes are in the under-expanded state for this CD nozzle and hence expands rapidly at supersonic speed as the plumes exit from the nozzle and forms a series of expansion and compression waves. The hot plumes emanating from the nozzle develop very high temperature in a small vicinity around the base plate, due to diffusion and develop very high temperature on the base plate. Barring this region, the maximum amount of radiative flux on base plate for these three plumes, i.e., CO 2 plume, mixture plume and H 2 O plume are 4000 W/m 2 , 2300 W/m 2 and 1300 W/m 2 , respectively and the maximum temperature developed due to these corresponding fluxes are 323 K, 312 K and 308 K, respectively. View Show abstract ... During the thermal cutting process, the kinetic energy of the high-speed gas from the nozzle provides a mechanical force that ejects the melt and protects the nozzle from spatter [6] . The quality of the cutting can be evaluated from the kerf width, kerf angle, deposition of dross, bevel profile, and so on. ... ... The stand-off distance, which represents the allowable distance between the nozzle tip and workpiece, is mainly determined by the pattern and uniformity of the gas flow through the nozzle exit. Nevertheless, these parameters are still empirically determined [6] . ... Numerical Modeling of an Impinging Jet Flow inside a Thermal Cut Kerf Using CFD and Schlieren Method Article Full-text available Sep 2022 Upendra Tuladhar Sang-Hyun Ahn Dae-Won Cho Tae-Kook Park View ... During the thermal cutting process, the kinetic energy of the high-speed gas from the nozzle provides a mechanical force that ejects the melt and protects the nozzle from spatter [6] . The quality of the cutting can be evaluated from the kerf width, kerf angle, deposition of dross, bevel profile, and so on. ... ... The stand-off distance, which represents the allowable distance between the nozzle tip and workpiece, is mainly determined by the pattern and uniformity of the gas flow through the nozzle exit. Nevertheless, these parameters are still empirically determined [6] . ... Numerical Modeling of an Impinging Jet Flow inside a Thermal Cut Kerf Using CFD and Schlieren Method Article Full-text available Sep 2022 Upendra Tuladhar Seokyoung Ahn The dynamics of high-pressure gas flow injected through a nozzle during a thermal cutting process has an important effect on cutting performance. In this study, an actual gas flow condition inside a cut kerf of a plasma cut sample was simulated by considering various geometric features of the cut kerf, such as kerf width difference and cutting length difference between the top and bottom surfaces. A prototype cut kerf shape was fabricated using a transparent material. A gas flow shadowgraph from inside the fabricated cut kerf was observed using the Schlieren method. In addition, image processing was performed on images obtained with the Schlieren method before and after gas injection, which were used to validate the numerical simulation models. The effect of turbulent viscosity in various turbulent models was studied using computational fluid dynamics analyses. The results confirmed that the k–ω turbulent model was the most suitable turbulent model for the geometry used in this study. The simulation results for this model were qualitatively consistent with the reported experimental measurements. View Show abstract ... Otto et al. have shown the potential of this tool for simulating laser processing applications [43,44]. Darwish et al. [45] recently used the CFD solvers of OpenFOAM to simulate supersonic flow through a nozzle designed for laser cutting. The model they proposed was then used to predict the behavior of different nozzle designs [46]. ... Analysis of the oscillations induced by a supersonic jet applied to produce nanofibers Article Full-text available Oct 2022 INT J MECH SCI Felix Quintero Ángel F. Doval A. Goitia Juan Pou High-performance fibers are key components for enhancing the mechanical properties of composite materials. The development of high strength nanofibers augurs the production of new nano-composites with outstanding features. However, the robust production of continuous glass nanofibers that can be feasible processed for efficiently manufacturing nanocomposites is still challenging. Recently, Cofiblas (Continuous Fiberizing by Laser melting and Supersonic dragging) was demonstrated as a technique capable of producing continuous glass nanofibers with unlimited length. Cofiblas process has some similarities with the widely known melt blowing technique for the production of polymeric fibers. In both techniques, the design of the gas nozzle is key to ensure the feasibility of the process since the turbulences of the gas jet may induce strong whipping of the filament. This paper gives novel experimental evidences on the correlation of the supersonic gas jet instabilities with the oscillation of the filament in the melt-blowing and Cofiblas processes, relating these oscillations with the presence of shock waves and unsteadiness in the flow, and gives valuable insight into the use of supersonic jets in the melt blowing process as an effective approach for the formation of nanofibers. A thin 3D-axisymmetric model in OpenFOAM® was put to test by comparing the performance of different solvers which were validated by flow visualization of the exit jet using digital holography (DH). In order to perform a realistic and thorough validation, we simulated the optical measurements of the flow from the CFD simulations of the mass density by Abel transform and numerical differentiation. The application of digital holography as the flow visualization technique makes possible both a precise validation of the density maps obtained from the Abel transformation of the 2D-alike results, and the analysis of the shockwave pattern in the air jet. Conversely, the numerical reconstruction of time-averaged holograms is employed to detect unsteadiness in the flow and to analyze the fiber oscillation, which is essential to assess the stability of the process. Lastly, the analysis and comparison of the vibration of the filament using the basic design and the optimized nozzle demonstrates a clear influence of the shock waves and flow unsteadiness in the stability of the filament. View Show abstract ... The authors in [15][16][17] investigated the interaction of gas flows within the cut kerf to study the dynamic characteristics of the exit jet at various stand-off distances during the laser cutting process. Darwish et al. [18] investigated the effect of inlet stagnation pressure and nozzle geometry on the behavior of the gas flow. They used a quasi-1-D gas dynamics theory to calculate the exact-design operating conditions for three different supersonic nozzles. ... Analysis of Gas Flow Dynamics in Thermal Cut Kerf Using a Numerical and Experimental Approach for Nozzle Selection Article Full-text available Sep 2022 Upendra Tuladhar Sang-Hyun Ahn Dae-Won Cho Tae-Kook Park View ... The authors in [15][16][17] investigated the interaction of gas flows within the cut kerf to study the dynamic characteristics of the exit jet at various stand-off distances during the laser cutting process. Darwish et al. [18] investigated the effect of inlet stagnation pressure and nozzle geometry on the behavior of the gas flow. They used a quasi-1-D gas dynamics theory to calculate the exact-design operating conditions for three different supersonic nozzles. ... Analysis of Gas Flow Dynamics in Thermal Cut Kerf Using a Numerical and Experimental Approach for Nozzle Selection Article Full-text available Sep 2022 Upendra Tuladhar Seokyoung Ahn Consistency in gas flow behavior under various operating conditions is expected for uni- form cutting performance in the thermal cutting process. The slope of the cut front in the kerf slot of a sample cutting material varies with the operating condition which affects the gas flow pattern. Therefore, how the nozzle exit diameter and the slope of the cut front effects gas flow behavior has been studied using the Reynolds averaged Navier–Stokes (RANS) based k–ω turbulence model. Convergent–straight-type nozzles with exit diameters φexit of 1.5 mm, 2 mm and 2.5 mm were used to study the flow patterns through the kerf slots of variable cut front slopes. The numerical simula- tion results were then compared with the results obtained from the Schlieren experiments. In addi- tion, image processing was performed in the Schlieren images for clear visualization and precise comparison of the numerical and experimental data. The results confirm that a nozzle with an exit diameter of 2 mm shows a higher consistency in flow behavior in variable operating conditions. View Show abstract ... A small scale problem as reported in [15] has been considered for the estimation of thermal load on the base plate. This makes transmissivity of the gas very small, therefore, optical thin approximation holds good for the current problem. ... Estimation of Thermal Load on Rocket Base Plate from Water Vapour Plume Conference Paper Dec 2021 Kamal Khemani Pradeep Kumar Ganesh Natarajan A numerical study is performed to estimate thermal load on rocket base plate from a pure water vapour plume expanding through a convergent-divergent (CD) nozzle. Radiation is the only mode for heat load as the base plate is in the upstream direction to the flow, thus in order to estimate heat load accurately we need to calculate radiative properties accurately. The radiative properties of water vapour (H 2 O) such as the spectral absorption coefficient is calculated from HITEMP-2010 database. Employing an optically thin approximation, the Planck mean absorption coefficient is calculated from the spectral absorption coefficient and assembled at different pressures, temperatures and mole-fractions into a Planck mean look-up table. The existing sonicFoam application is then modified to incorporate species conservation, viscous work and Planck mean absorption-emission model with the radiation transfer equation (RTE) to develop a new application named as sonicRadFoam. Numerical investigations are conducted for a plume expanding from 7.11 bar and 2000 K to ground atmospheric conditions using sonicRadFoam. It is observed that the plume expands rapidly as it exits from the nozzle. The hot gases emanating from the nozzle diffuses and develops very high temperature in a very small region around the nozzle on the base plate. This in turn produces very high heat flux. Barring this region, the maximum amount of radiative flux on the base plate from H 2 O plume is 1300 W/m 2 and the maximum temperature developed due to radiative flux is 308 K. View Show abstract CFD Modeling of Adsorption Rate Prediction for Granular Activated Carbon Packed Bed Article Feb 2023 Yuma Kasai Yoshinori Jinbo Hideya Kamikawa Toshiyuki Sanada View A COMPUTATIONAL FRAMEWORK FOR RADIATIVE TRANSFER WITH COMPRESSIBLE FLOWS -APPLICATION TO THERMAL LOAD ESTIMATION BY ROCKET PLUMES Thesis Oct 2021 Kamal Khemani Pradeep Kumar The exhaust plume from the rocket is a product of high temperature, high pressure gases exiting from the combustion chamber. These gases expands rapidly in the convergent divergent (CD) nozzle at supersonic velocities due to the conversion of thermal energy into kinetic energy, which generates the thrust to lift off the rocket. The structure of the plume is non uniform, containing different flow regimes and supersonic shock patterns. It appears as bright luminous flame which emits radiation in the visible, ultraviolet (UV) and infrared (IR) parts of the electromagnetic spectrum. The major part of plume radiation comes from participating gases like CO2 and H2O which shows strong emission of thermal radiation in the infrared region of the spectrum. This heats up the base plate of the rocket and becomes the source of tracking by enemies in the case of missiles, fighter jets and combat aircraft(s). The radiative properties of participating gases are calculated using the high temperature spectroscopic absorption parameter (HITEMP) with LBL method for a single thermodynamic state. The absorption coefficient obtained from HITEMP is highly erratic in nature containing millions of spectral lines which attains same value multiple times. This unnecessarily increases the computational cost required to solve the radiative transfer equation (RTE) for a single thermodynamic state and is therefore used only for benchmarking purposes. The general heat transfer application like combustion, rocket propulsion, gasification contains thousands of thermodynamic states. In order to deal with this difficulty, the full spectrum k-distribution method (FSK) was implemented, which reorders the oscillatory absorption coefficient obtained from HITEMP into smooth monotonically increasing function. This drastically reduces the computational time required to solve RTE, i.e., around a million times and is exact for homogeneous and isothermal medium. The FSK was applied to non-homogeneous and non-isothermal medium by generating the k-distribution look-up table for different thermodynamic states of temperature, pressure and mole-fraction. The look-up table can directly be used to extract properties for the thermodynamic states of plume. Further, the k-distribution for unavailable thermodynamic states can easily be calculated by using multidimensional linear interpolation technique. The k-distribution for mixture of participating gases was calculated from different gas mixing models for homogeneous isothermal and non-homogeneous non-isothermal medium. The RTE is solved using finite volume discrete ordinate method (FVDOM) with other modes of heat transfer and fluid flow using OpenFOAM - an open source CFD package. The flow, temperature and species fields are obtained using a pressure based compressible flow application - sonicFoam. The application is tested for a convergent divergent nozzle designed by one dimensional isentropic calculations for air at perfect expansion conditions. The nozzle is attached with a buffer section in which air expands from 7.11 bar pressure to 1 atm and achieves a maximum Mach number 2.1. The sonicFoam application is modified to incorporate work done due to viscous forces, species transport equation and radiation transfer equation and named as sonicRadFoam. The same CD nozzle is used to expand hot gases at stagnation pressure and temperature 7.11 bar and 2000 K, respectively to calculate heat load on rocket base plate for three different plumes viz, pure H2O plume, pure CO2 plume and mixture plume containing 50% mixture of CO2 and H2O. This becomes the case of underexpanded plume which exits with the maximum Mach number of 2.25. The Planck mean absorption coefficient has been calculated based on the thermodynamic state of the gases in the plume and used with the radiation model. The hot gases emanating from the nozzle get diffused and develops a very high temperature in a very small region around the nozzle on the base plate which in turn produces high heat flux. Barring this region, the maximum amount of radiative flux on base plate for these three plumes, i.e., CO2 plume, mixture plume and H2O plume are 4000W=m2, 2300W=m2 and 1300W=m2, respectively and the maximum temperature developed due to these fluxes are 323 K, 312 K and 308 K, respectively. View Show abstract Show more Design and evaluation of high-pressure nozzle assembly for laser cutting of thick carbon steel Article Full-text available Sep 2017 INT J ADV MANUF TECH Sundar Marimuthu Ashish Nath Pinkulal Dey S. P. Chaudhuri Laser cutting of carbon steel is extensively used across a range of industries, due to its advantage of high speed, low kerf and high quality. Currently, a 1-kW carbon dioxide (CO2) laser with its subsonic nozzle assembly can be used only to cut steel plates up to around 10 mm. This paper aims to design and evaluate a high-pressure supersonic laser cutting nozzle assembly, which can enable a 1-kW CO2 laser to cut steel of up to 50 mm thickness. Basic gas dynamic and compressible flow equations were used to design the supersonic nozzle assembly. The flow of the high-pressure gas jet inside the nozzle assembly was investigated using computational fluid dynamics (CFD), and the structural integrity of the high-pressure nozzle assembly was ensured using finite element analysis (FEA). The gas flow pattern at the exit of the nozzle assembly was computed and compared with the experimental observation made through a shadowgraph technique. Laser cutting experiments were performed with the developed supersonic nozzle assembly to demonstrate cutting of 50-mm-thick low carbon steel with 1-kW CO2 laser. View Show abstract Study on the Role of Supersonic Nozzle in Fiber Laser Cutting of Stainless Steel Article Full-text available Jan 2017 MSA Yijun Zhou Jilan Kong Jin Zhang Striation-free laser cutting, especially for thick section steel, is hard to obtain due to several factors. The inside shape of the gas nozzle is considered to be one of the most vital factors in striation-free fiber laser cutting. 0.8 mm normal nozzle and a supersonic nozzle are used to cut 0.8 mm AISI316L stainless steel (022Cr17Ni12Mo2) separately. The orthogonal experiment takes nozzle standoff distance, cutting speed, Laser power and gas pressure as its impacting factors. The same orthogonal table is adopted in different condition, using normal nozzle and using supersonic nozzle. In the mean time, Ar gas is used as assisted cutting gas in the experiment. The data from this experiment show that supersonic nozzle seems to be a strong helper for fiber laser cutting. Feed rate’s effect seems stable and inconspicuous under the condition of using supersonic nozzle. View Show abstract RANS Modelling for Compressible Turbulent Flows Involving Shock Wave Boundary Layer Interactions Thesis Full-text available Jul 2014 Ioannis Asproulias The main objective of the thesis is to provide a detailed assessment of the performance of four types of Low Reynolds Number (LRN) Eddy Viscosity Models (EVM), widely used for industrial purposes, on flows featuring SWBLI, using experimental and direct numerical simulation data. Within this framework the two-equation linear k-ε of Launder and Sharma (1974) (LS), the two-equation linear k-ω SST, the four-equation linear φ-f of Laurence et al. (2004) (PHIF) and the non-linear k-ε scheme of Craft et al. (1996b,1999) (CLSa,b) have been selected for testing. As initial test cases supersonic 2D compression ramps and impinging shocks of different angles and Reynolds numbers of the incoming boundary layer have been selected. Additional test cases are then considered, including normal shock/isotropic turbulence interaction and an axisymmetric transonic bump, in order to examine the predictions of the selected models on a range of Mach numbers and shock structures. For the purposes of this study the PHIF and CLSa,b models have been implemented in the open source CFD package OpenFOAM. Some results from validation studies of these models are presented, and some explorations are reported of certain modelled source terms in the ε-equation of the PHIF and CLSb models in compressible flows. Finally, before considering the main applications of the study, an examination is made of the performance of different solvers and numerical methods available in OpenFOAM for handling compressible flows with shocks.The performance of the above models, is analysed with comparisons of wall-quantities (skin-friction and wall-pressure), velocity profiles and profiles of turbulent quantities (turbulent kinetic energy and Reynolds stresses) in locations throughout the SWBLI zones. All the selected models demonstrate a broadly consistent performance over the considered flow configurations, with the CLSb scheme generally giving some improvements in predictions over the other models. The role of Reynolds stress anisotropy in giving a better representation of the evolution of the boundary layer in these flows is discussed through the performance of the CLSb model. It is concluded that some of the main deficiencies of the selected models is the overestimation of the dissipation rate levels in the non-equilibrium regions of the flow and the underestimation of the amplification of Reynolds stress anisotropy, especially within the recirculation bubble of the flows. Additionally, the analysis of the performance of the considered EVM's in a normal shock/isotropic turbulence interaction illustrates some drawbacks of the EVM formulation similar to the ones observed in normally-strained incompressible flows. Finally, a hybrid Detached Eddy Simulation (DES) approach is incorporated for the prediction of the transonic buffet around a wing. View Show abstract Analysis of De-Laval nozzle designs employed for plasma figuring of surfaces Article Full-text available Oct 2016 INT J ADV MANUF TECH Nan Yu Renaud Jourdain Mustapha Gourma Paul Shore Plasma figuring is a dwell time fabrication process that uses a locally delivered chemical reaction through means of an inductively coupled plasma (ICP) torch to correct surface figure errors. This paper presents two investigations for a high temperature jet (5000 K) that is used in the context of the plasma figuring process. Firstly, an investigation focuses on the aerodynamic properties of this jet that streamed through the plasma torch De-Laval nozzle and impinged optical surfaces. Secondly, the work highlights quantitatively the effects of changing the distance between the processed surface and nozzle outlet. In both investigations, results of numerical models and experiments were correlated. The authors’ modelling approach is based on computational fluid dynamics (CFD). The model is specifically created for this harsh environment. Designated areas of interests in the model domain are the nozzle convergent-divergent and the impinged substrate regions. Strong correlations are highlighted between the gas flow velocity near the surface and material removal footprint profiles. In conclusion, the CFD model supports the optimization of an ICP torch design to fulfil the demand for the correction of ultra-precision surfaces. View Show abstract Evaluation and optimal design of supersonic nozzle for laser-assisted oxygen cutting of thick steel sections Article Full-text available Sep 2016 INT J ADV MANUF TECH Chi Zhang Peng Wen Yueming Yuan Xuejun Fan With the full use of combustion heat from Fe-O reaction, laser-assisted oxygen cutting (LASOX) is able to cut thick mild steel plates by a defocused laser of medium power (approximately 1 kW). The dynamic behavior of oxygen gas flow, determined by nozzle structure and cutting parameters, is the key factor affecting cut ability and quality. It is significant to understand the method to design a suitable supersonic nozzle and to evaluate its performance. A supersonic minimum length nozzle (MLN) was designed and made specially for LASOX. The configuration (D exit/D critical) of the designed nozzle was chosen based on two-dimensional isentropic calculation of dynamic gas pressure. The divergent section of the MLN was designed in accordance with the method of characteristics (MOC). Numerical simulation and Schlieren visualization were used to observe and compare the flow behavior of the free jet from the designed MLN nozzle and a commercial supersonic nozzle. The MLN nozzle generates a highly uniform and stable supersonic jet extending a longer distance along the axis of nozzle, which is around 1.4 times longer than that from the commercial supersonic nozzle. Mild steel plates in 20 mm thickness were cut to investigate the effect of cutting parameters on LASOX cut quality of two nozzles. The MLN significantly improved cutting quality due to the better performance of gas flow. The optimal cut quality is related to both oxygen pressure and cutting speed. The oxygen content was measured along the cut surface to explain the difference in cut quality. View Show abstract Laser material processing: Fourth edition Book Jan 2010 W. M. Steen Jyoti Mazumder Lasers play a major part in the processing of the disparate materials used in engineering and manufacturing. The range of procedures in which they are involved is ever increasing. The informal style of Laser Material Processing (4th Edition) will guide you smoothly from the basics of laser physics to the detailed treatment of all the major materials processing techniques for which lasers are now essential. Helps you to understand how the laser works and to decide which laser is best for your purposes. New chapters on laser physics, drilling, micro- and nanomanufacturing and biomedical laser processing reflect the changes in the field since the last edition, updating and completing the range of practical knowledge about the processes possible with lasers already familiar to established users of this well-known text. Provides a firm grounding in the safety aspects of laser use. Now with end-of-chapter exercises to help students assimilate information as they learn. The authors' lively presentation is supported by a number of original cartoons by Patrick Wright and Noel Ford which will bring a smile to your face and ease the learning process. Laser Material Processing (4th Edition) will be of use as university or industrial course material for senior undergraduate, graduate and non-degree technical training in optoelectronics, laser processing and advanced manufacturing. Practising engineers and technicians in these areas will also find the book an authoritative source of information on the ever- expanding use of industrial lasers in material processing. Praise for the third edition: "It is the great merit of this book to offer a compact survey on laser material processing. A useful and fascinating book, pleasant to read with many useful figures and examples of industrial applications. It is a textbook for advanced students in this field, but also a reference book for engineers." H. Weber, Technische Universität Berlin "Laser Material Processing is a clear and instructive textbook for students who will become the next generation of laser specialists, and it is a good source of updated knowledge for practicing engineers and technicians in optoelectronics, laser processing, materials treatment, and advanced manufacturing. The book also will be helpful as a reference source. The chapters are largely independent of one another, and a reader interested in only one topic may be satisfied by reading all of parts of the relevant chapter without going to other chapters. Well written, with many useful diagrams and examples of industrial applications, Steen's book is a good guide in the field." The Industrial Physicist "Material processing is one of the most important applications of lasers... Laser Material Processing gives a compact survey and can be used as university or industrial course material... The book will guide the reader smoothly from the basics of laser physics to the detailed treatment of all major material processing techniques for which lasers are essential... I can recommend this book as an authoritative source of information on the rapidly expanding use of industrial lasers in material processing. " View Show abstract A visual observation of the air flow pattern for the high speed nozzle applicable to high power laser cutting and welding Article Dec 2013 INT COMMUN HEAT MASS Chi-Shan Tseng Chun-Ming Chen Chi-Chuan Wang In this study, the flow pattern and pressure variation of the nozzles applicable to high power laser cutting and welding were studied. A total of five nozzles are made and tested with nozzle diameter ranging from 0.8 to 4 mm. The depth of focus and the width of focus are measured based on the flow visualization. It is found that the depth of focus is increased with the rise of exit Mach number while the width of focus is increased with the nozzle diameter. The visual results indicate that the supersonic nozzle reveals a more concentrated jet flow pattern even the flow has passed through the depth of focus. On the other hand, appreciate deviation of the flow pattern is observed for the subsonic nozzle after the depth of focus. As far as more concentrated air flow pattern is concerned, a supersonic nozzle with an exit diameter less than 3.0 mm is recommended. The total pressure decreasing tremendously with the exit Mach number is encountered while moderate decline of the static and dynamic pressure for supersonic nozzles is seen. However, its corresponding dynamic pressure is still higher than that of the subsonic nozzle. View Show abstract The Theory of Laser Materials Processing Book Jan 2009 John Dowden In this chapter some aspects of the interaction of femtosecond laser pulses with metals has been considered and compared with the effects of longer pulses. The most important point is, perhaps, that metals exposed to femtosecond laser pulses are no longer in local thermal equilibrium. On short time scales the electron and phonon subsystem are decoupled and may have very different temperatures. Moreover, the electrons are governed by a nonequilibrium distribution and not by the Fermi-Dirac distribution even for low intensities. In many cases, depending on the value of the electron temperature relaxation time, the parabolic heat conduc-tion (TTM) is no longer suitable for the determination of the electron temperature distribution and should be replaced by the ETTM. View Show abstract Gas Dynamic Effects on Laser Cut Quality Article Dec 2001 J Manuf Process Kai Chen Y. Lawrence Yao Vijay Modi The presence of a gas jet plays an important role in laser cutting. Both the cutting efficiency and cut quality are very sensitive to gas pressure and nozzle standoff distance because of the complex nature of shock fronts and associated phenomena in a supersonic gas jet impinging on a workpiece. An idealized case is considered first, where the cut is assumed to be a circular hole directly underneath and concentric with the gas jet nozzle. A more realistic case of an axisymmetric nozzle impinging on a plate with a linear cut is considered next. Unlike the idealized case, the problem now is three-dimensional. Simple experiments to measure the through-kerf mass flow rate were carried out for both geometries. The two important forces exerted by the gas jet for melt ejection, namely, shear force and pressure gradient, show the same trend as that of the mass flow rate with varying gas pressure and standoff. The mass flow rate for the three-dimensional case shows the same behavior as that of the axisymmetric case, indicating the basic shock structures of the axisymmetric case are applicable to the real cutting cases. Laser cutting of mild steels under the corresponding conditions was performed, and the cut quality characterized by roughness, dross attachment, and recast layer thickness was analyzed. The deterioration of cut quality with the gas pressure and standoff is found to closely match reductions in through-kerf mass flow rate. It is thus verified that the shock structure of the gas jet and the associated mass flow rate have a direct impact on laser cutting as predicted. View Show abstract Numerical analysis of supersonic gas-dynamic characteristic in laser cutting Article Jan 2009 OPT LASER ENG Shaogang Guo Hu jun Jun Luo Lei Zhenqiang Yao The influence of the processing parameters on the dynamic characteristic of supersonic impinging jet in laser cutting is studied numerically. The numerical modeling of a supersonic jet impinging on a plate with a hole is presented to analyze the gas jet–workpiece interaction. The model is able to make quantitative predictions of the effect of the standoff distance and exit Mach number on the mass flow rate and the axial thrust. The numerical results show that the suitable cutting range is slightly different for different exit Mach number, but the optimal cutting parameter for certain exit total pressure is nearly changeless. So the better cut quality and capacity can be obtained mainly by setting the suitable standoff distance for a certain nozzle pressure. View Show abstract Show more Recommendations Discover more Article A case study of a pool and weir fishway modeled with OpenFOAM and FLOW-3D June 2017 · Ecological Engineering Jason Duguay Jay Lacey J. Gaucher OpenFOAM's interFoam solver is validated for modeling the complex three dimensional flow field of a large pool and weir fishway. Numerical results from OpenFOAM and the commercial solver FLOW-3D are compared and validated with in situ experimental velocity, turbulence and water surface profiles. OpenFOAM and FLOW-3D produced similar flow fields. The models accurately predicted velocity magnitudes ... [Show full abstract] throughout the pool and the barrier velocity immediately downstream of the notch. The models over-predicted the width and depth of the jet issuing from the notch and significantly under-predicted turbulent kinetic energy levels within it. In both models a large roller occupies a generous volume of the sampled pool, the presence of which is not supported by experimental measurements. The findings demonstrate that interFoam coupled with the standard k ? ? turbulence model is able to estimate barrier velocities, flow rates, turbulence magnitudes and depths to accuracies acceptable for fishway design evaluation. Read more Article Full-text available Experimental and Modeling Study of a Low NOx Combustor for Aero-Engine Turbofan February 2009 · Combustion Science and Technology Alessio Frassoldati Alberto Cuoci Tiziano Faravelli [...] G. Cinque An advanced low-NOx combustor is studied experimentally in the frame of the recent European Program EEFAE (Efficient and Environmentally Friendly Aero-Engine) for the CLEAN (Component vaLidator for Environmentally-friendly Aero-eNgine) demonstrator.The experimental measurements are compared with model predictions obtained using a 3-D computational fluid dynamics (CFD) proprietary code properly ... [Show full abstract] coupled with a numerical tool called Kinetic Post-Processor (KPP). One of the aims of this paper is also to describe a methodology for computing steady turbulent reacting flows in complex shape combustors: the thermo-fluid dynamics results of the CFD code are processed by the KPP with the use of detailed kinetics for predicting pollutant emissions, with special emphasis to nitrogen oxides. The comparisons between experimental measurements and model predictions indicate the current limitations of the procedure but also the possibilities of this powerful tool. From the kinetics point of view, the need for accurate high-pressure experimental data on NOx formation is also highlighted. View full-text Article Full-text available Dispersion of carbon dioxide from vertical vent and horizontal releases—A numerical study May 2013 · ARCHIVE Proceedings of the Institution of Mechanical Engineers Part E Journal of Process Mechanical Engineering 1989-1996 (vols Jennifer Wen Ali Heidari Baopeng Xu Hongen Jie Numerical simulations of far-field carbon dioxide dispersion were conducted for a vertical vent release and a horizontal release from a shock tube. These scenarios had also been studied experimentally at field scale commissioned by National Grid. This work and the experiments both form part of the National Grid dense phase CO2 pipeLine TRANSportation (COOLTRANS) research programme. All tests ... [Show full abstract] involved releases of dense phase CO2 into an atmospheric flow. The dispersing plumes were subjected to transient wind conditions where both the direction and magnitude of the wind fluctuated with time. As part of the COOLTRANS research programme, the far-field dispersion simulations started from source terms derived from the near-field simulations conducted by the University of Leeds and outflow simulations conducted by University College London. The numerical model used for the far-field simulations is based on OPENFOAM, which is an object-oriented open source computational fluid dynamics toolbox. A dedicated solver CO2FOAM has been developed within the framework of OPENFOAM for simulating dispersion from dense phase CO2 releases. This has included the implementation of the homogeneous equilibrium method for fully compressible two-phase flow, treatment of the transient atmospheric boundary conditions and the time-varying inlet boundary conditions. The experimental measurements were supplied to the authors after the predictions were completed and submitted to National Grid. Hence, the validation reported here is indeed “blind.” While further fine tuning of the model and validation is still underway, the relatively good agreement between the predictions and measurements in the present study has demonstrated the potential of CO2FOAM as an effective predictive tool for far-field CO2 dispersion in the context of pipeline transportation for carbon capture and storage. View full-text Article Development of a new OpenFOAM solver using regularized gas dynamic equations February 2018 · Computers & Fluids Matvey Kraposhin Elena V Smirnova T.G. G. Elizarova Maria Alexandrovna Kiryushina The paper introduces the development of a new OpenFOAM solver QGDFoam for the numerical simulation of viscous compressible flows within a wide range of Mach numbers in the framework of the OpenFOAM formalism. The new solver is based on the implementation of regularized, or quasi-gas dynamic (QGD) equations. The mixed finite-volume and finite-difference approximation is constructed on unstructured ... [Show full abstract] space grids with co-located variables storage and explicit time scheme for convection approximation. The solver has been tested for a range of 1D Riemann problems and 2D cases, comparing results with analytic solutions and OpenFOAM's implementation of the Kurganov–Tadmor scheme known as rhoCentralFoam. Read more Last Updated: 12 Jun 2023 Discover the world's research Join ResearchGate to find the people and research you need to help your work. Join for free ResearchGate iOS App Get it from the App Store now. 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https://www.researchgate.net/publication/331072958_Simulation_and_analysis_of_the_jet_flow_patterns_from_supersonic_nozzles_of_laser_cutting_using_OpenFOAM
Press Release: Foreign Ministers in Havana Call for Democratization of United Nations, Enlargement of Security Council Global Policy Forum is a policy watchdog that follows the work of the United Nations. We promote accountability and citizen participation in decisions on peace and security, social justice and international law. Press Release: Foreign Ministers in Havana Call for Democratization of United Nations, Enlargement of Security Council The "democratization" and modernization of the United Nations were urged yesterday by some 40 Ministers from developing countries meeting here informally to discuss the role of the UN in the 21st century. "The only way to improve our lot as developing countries is to ask for a fair share in the UN's decision-making process", they said. The Ministers, most of whom are Ministers of Foreign Affairs and who represent all regions of the developing world, from the Caribbean and Latin America to Africa, the Middle East and Asia, are here to attend the South Summit of the "Group of 77", the largest third world coalition in the United Nations. Yesterday's off-the-record exchange among Ministers preceded meetings of Heads of State and Government, which began today and continue through Friday. On Friday, the leaders are expected to adopt a declaration and programme of action charting a new course for the third world in the years to come. Permanent membership in the Security Council for developing countries, the elimination of the veto, and "transparency" in the Council's work were called for, along with an "early warning system" to prevent the emergence or development of conflicts, an increasing number of which are erupting in the South. The UN and its specialized agencies must be committed to international peace and security and at the same time to development and the eradication of poverty, which are "two sides of the same coin", the officials said. The original vision of the United Nations, as contained in the Charter, does not need to be redefined, the Ministers said. However, many of them expressed reservations about the principle of "humanitarian intervention" that has been much discussed in recent months as a solution to the dilemma posed by internal conflicts and massive human rights violations. "That principle is now being defined as the power of the international community to intervene against governments on the basis of criteria defined by the few", deplored one speaker. He and others called for reaffirming the Charter's provisions on respect for sovereignty, sovereign equality, non-intervention in internal affairs and self-determination. No "one-size-fits-all" The UN should play a greater role in socioeconomic development and investment in human beings, said a number of Ministers, adding that, while debates on democratization and good governance were appropriate, there was "no one-size-fits-all" model of what constitutes a democratic government; the form of government chosen should address the particularities of each country. Good governance also required capacity-building, as many developing countries lacked the necessary institutions and machineries. "Ethics for governance need to be looked at" noted one Minister, "but not in the absence of those institutions". The Ministers called for restoring the primacy of the UN General Assembly and said the Bretton Woods institutions should be reformed as well, to allow developing countries to participate in the decision-making process, given the major impact of their policies on those nations' economies. The World Bank should provide support to investment in infrastructure and social capital but without demanding "unachievable" conditions of its beneficiary nations, said one leader, who also proposed a role for the IMF in stabilizing volatile international capital flows and cancelling developing countries' debt. The need for new sources of financing for development as a result of declining ODA was stressed by almost all participants in the ministerial debate. Decreasing aid, and the growing income and technology gaps between North and South which were due in large part to economic globalization and liberalization, made it urgent for the developing nations to cooperate more closely, both with the industrialized countries and among themselves. While the relationship between the North and South was cooperative in many areas, in others – particularly in such economic areas as trade – was based on fierce competition. Developing countries would have to work together to defend their economic interests and ensure their equitable participation in the international economic system. "Liberalization, transparency and good governance are being demanded of developing countries", said one Minister, "and the same standards should be applied to developed countries". Another argued that "we are asked to trade on equal terms with the North, when we don't even have the goods to trade; we must not become a dumping ground for theirs". On knowledge and technology – one of the four main topics on the agenda of the South Summit, along with globalization, North-South relations, and South-South cooperation -- the Ministers noted that 80 per cent of digital knowledge was to be found in the developed world. That gap would have to be closed, they said, "but not by leaving it up to the private sector; rather, by involving the United Nations". They urged increased investment in education and training as well as energy and social infrastructure to enable the South to catch up with the North and develop its full potential in those areas. On the UN's role in the new century, the Ministers also advocated: Finding ways to encourage the implementation and enforcement of humanitarian and human rights law; Creating a capacity-building fund to support developing countries' work in such fields as remote sensing, information technology and biotechnology; and Forging a partnership between North and South that extends not just to economic and social questions but also to cross-border terrorism; illegal trafficking in drugs, arms and people; and money laundering. For the international community in general, the Ministers defined a number of key challenges, including improved living standards, reversing the brain drain and the "privatization" of knowledge, and effective realization of the right to development. The faith of developing countries in multilateral negotiations should be reinvigorated, and the developed world should make good on the "broken promise" of allocating 0.7% of GDP to aid, they insisted. For more information, contact the Executive Secretary of the South Summit, Mr. Mourad Ahmia, Havana International Conference Center, Room 1105, tel: +537/282.786, fax: +537/288.655; or http://www.g77.org or http://www.cumbresur.cu
https://archive.globalpolicy.org/security-council/security-council-reform/41263.html?tmpl=component&print=1&page=.html
Water Area Data for Alabama and Tennessee - Area on the Open Data Network The water area of Alabama was 1,775 in 2010. The water area of Tennessee was 909 in 2010.API Land Area API Water Area API Land area is a measurement providing the size, in square miles, of the land portions of geographic entities for which the Census Bureau tabulates and disseminates data. Area is calculated from the specific boundary recorded for each entity in the Census Bureau's geographic database. Land area is based on current information in the TIGER® data base, calculated for use with Census 2010. Water Area figures include inland, coastal, Great Lakes, and territorial sea water. Inland water consists of any lake, reservoir, pond, or similar body of water that is recorded in the Census Bureau's geographic database. It also includes any river, creek, canal, stream, or similar feature that is recorded in that database as a two- dimensional feature (rather than as a single line). The portions of the oceans and related large embayments (such as Chesapeake Bay and Puget Sound), the Gulf of Mexico, and the Caribbean Sea that belong to the United States and its territories are classified as coastal and territorial waters; the Great Lakes are treated as a separate water entity. Rivers and bays that empty into these bodies of water are treated as inland water from the point beyond which they are narrower than 1 nautical mile across. Identification of land and inland, coastal, territorial, and Great Lakes waters is for data presentation purposes only and does not necessarily reflect their legal definitions. Above charts are based on data from theU.S. Census American Community Survey|ODN Dataset|API- Notes:1. ODN datasets and APIs are subject to change and may differ in format from the original source data in order to provide a user-friendly experience on this site.2. To build your own apps using this data, see the ODN Dataset and API links.3. If you use this derived data in an app, we ask that you provide a link somewhere in your applications to the Open Data Network with a citation that states: "Data for this application was provided by the Open Data Network" where "Open Data Network" links to http://opendatanetwork.com. Where an application has a region specific module, we ask that you add an additional line that states: "Data about REGIONX was provided by the Open Data Network." where REGIONX is an HREF with a name for a geographical region like "Seattle, WA" and the link points to this page URL, e.g. http://opendatanetwork.com/region/1600000US5363000/Seattle_WA Geographic and Area Datasets Involving Alabama or Tennessee API Hamilton County Health Department COVID-19 Data TN Counties COVID-19 Vaccinations Four State Census Block Groups Existing Hydro Non-powered Damms in Colorado This data set contains a list of U.S. Existing Non-powered Dams (NPD) with hydropower potential greater than 1MW. This data set consists of geo-referenced digital data and associated attributes created in Hadjerioua B. Y. Wei S.-C. Kao and B. T. Smith (2012) An Assessment of Energy Potential at Non-powered Dams in the United States Technical Manual 2011/251 Oak Ridge National Laboratory Oak Ridge TN.. OLAS Population-based Water Stress and Risk Dataset for Latin America and the Caribbean LAC is the most water-rich region in the world by most metrics; however, water resource distribution throughout the region does not correspond demand. To understand water risk throughout the region, this dataset provides population and land area estimates for factors related to water risk, allowing users to explore vulnerability throughout the region to multiple dimensions of water risk. This dataset contains estimates of populations living in areas of water stress and risk in 27 countries in Latin America and the Caribbean (LAC) at the municipal level. The dataset contains categories of 18 factors related to water risk and 39 indices of water risk and population estimates within each with aggregations possible at the basin, state, country, and regional level. The population data used to generate this dataset were obtained from the WorldPop project 2020 UN-adjusted population projections, while estimates of water stress and risk come from WRI’s Aqueduct 3.0 Water Risk Framework. Municipal administrative boundaries are from the Database of Global Administrative Areas (GADM). For more information on the methodology users are invited to read IADB Technical Note IDB-TN-2411: “Scarcity in the Land of Plenty”, and WRIs “Aqueduct 3.0: Updated Decision-relevant Global Water Risk Indicators”. | https://www.wri.org/data/aqueduct-global-maps-30-data | | https://www.worldpop.org/ | | https://gadm.org/ | hubNashville (311) Service Requests Details of service requests to hubNashville, Metro Nashville government's comprehensive customer service system. Residents or visitors can connect with a Metro representative to request services, share feedback, or ask questions by calling 311 (615-862-5000 if out of county when making the call) or by visiting https://hub.nashville.gov. TN Child Care This map shows child care agencies operating in the Greater Chattanooga area. This map focuses on the location of the agency, program certification status for the facility, and children age acceptance. Streets – Active and Retired data.sfgov.org Street Centerlines, active and retired. Note: The Class Code field is used for symbolization: 1 = Freeway 2 = Major street/Highway 3 = Arterial street 4 = Collector Street 5 = Residential Street 6 = Freeway Ramp 0 = Other (private streets, paper street, etc.) Final Disadvantaged Communities (DAC) 2023 data.ny.gov The Climate Leadership and Community Protection Act (CLCPA) directs the Climate Justice Working Group (CJWG) to establish criteria for defining disadvantaged communities. This dataset identifies areas throughout the State that meet the final disadvantaged community definition as voted on by the Climate Justice Working Group. The New York State Energy Research and Development Authority (NYSERDA) offers objective information and analysis, innovative programs, technical expertise, and support to help New Yorkers increase energy efficiency, save money, use renewable energy, accelerate economic growth, and reduce reliance on fossil fuels. To learn more about NYSERDA’s programs, visit nyserda.ny.gov or follow us on Twitter, Facebook, YouTube, or Instagram. SLR Passive Flooding - 0.5 Ft. Scenario highways.hidot.hawaii.gov Passive flooding was modeled by the University of Hawaii Coastal Geology Group using a modified "bathtub" approach following methods described in Cooper et al. 2013. The passive flooding model provides an initial assessment of low-lying areas susceptible to flooding by sea level rise. Passive flooding includes areas that are hydrologically connected to the ocean (marine flooding) and low-lying areas that are not hydrologically connected to the ocean (groundwater). Data used in modeling passive flooding include global sea level rise projections, digital elevation models (DEM), and the mean higher high water (MHHW) datum from local tide gauges. DEMs used in this study are freely available from NOAA and the U.S. Army Corps of Engineers (USACE). DEMs are derived from aerial light detection and ranging (LiDAR) data. The horizontal and vertical positional accuracies of the DEMs conform to flood hazard mapping standards of the Federal Emergency Management Agency (FEMA 2012). The IPCC AR5 RCP8.5 sea level rise scenario was used in modeling exposure to passive flooding from sea level rise at 0.5, 1.1, 2.0, and 3.2 feet. This particular layer depicts passive flooding using the 0.5-ft (0.1660-m) sea level rise scenario. While the RCP8.5 predicts that this scenario would be reached by the year 2030, questions remain around the exact timing of sea level rise and recent observations and projections suggest a sooner arrival. Passive flooding was modeled using the DEMs in geographic information systems software to identify areas below a certain sea level height (flooded by sea level rise) when raising water levels above current Mean Higher High Water (MHHW) tidal datum. In other words, water levels are shown as they would appear during MHHW, or the average higher high water height of each tidal day. The area flooded was derived by subtracting a tidal surface model from the DEM. Assumptions and Limitations: In many areas around the State, representing sea level rise from passive marine flooding will likely produce an underestimate of the area inundated or permanently submerged because the model does not account for waves and coastal erosion, important processes along Hawaii's highly dynamic coasts. For this reason, coastal erosion and annual high wave flooding (provided separately) are also modeled to provide a more comprehensive picture of the extent of hazard exposure. The passive flooding model does not explicitly include flooding through storm drain systems and other underground infrastructure, which would contribute to flooding in many low-lying areas identified in the model. The DEMs used in the modeling depict a smoothed topographic surface and do not identify basements, parking garages, and other development below ground that would be affected by marine and groundwater flooding with sea level rise. The passive flooding model is intended to provide an initial screening tool for sea level rise vulnerability. More detailed hydrologic and engineering modeling may be necessary to fully assess passive marine flooding hazards at the scale of individual properties. Data compiled by the Pacific Islands Ocean Observing System (PacIOOS) for the Hawaii Sea Level Rise Viewer hosted at https://pacioos.org/shoreline/slr-hawaii/. For further information, please see the Hawaii Sea Level Rise Vulnerability and Adaptation Report: https://climateadaptation.hawaii.gov/wp-content/uploads/2017/12/SLR-Report_Dec2017.pdf
https://opendatanetwork.herokuapp.com/entity/0400000US01-0400000US47/Alabama-Tennessee/geographic.area.water_area?ref=related-peer&year=2010
Mesa View Regional Hospital Diagnosis Related Group (DRG) - Readmission Quality Outcomes - Jan 2014 to Dec 2018 Research Diagnosis Related Groups (DRG) level Readmission quality outcomes for Mesa View Regional Hospital located at 1299 Bertha Howe Ave, Mesquite, NV, 89027 Mesa View Regional Hospital Diagnosis Related Group (DRG) - Readmission Quality Outcomes - Jan 2014 to Dec 2018 Research Diagnosis Related Groups (DRG) level Readmission quality outcomes for Mesa View Regional Hospital located at 1299 Bertha Howe Ave, Mesquite, NV, 89027 & includes data from NPIs 1275588782 Readmission Rate (%) Mesa View Regional Hospital Top DRG's Readmission Outcomes Mesa View Regional Hospital Nevada United States MountainView Hospital Sunrise Hospital and Medical Center St. Rose Dominican Hospitals - Sien… DRG 194 Readmission Rate (%) All Inpatient Readmission Outcomes Readmission Rate Mesa View Regional Hospital Nevada United States <table><tr><th></th><th> Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Total Hospitalizations After Exclusion</th><th> Total Users</th><th> Readmission Rate(%)</th><th> Nevada Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Nevada Total Hospitalizations After Exclusion</th><th> Nevada Total Users</th><th> Nevada Readmission Rate(%)</th><th> National Total Hospitalizations ( Jan 2014 to Dec 2018)</th><th> National Total Hospitalizations After Exclusion</th><th> National Total Users</th><th> National Readmission Rate(%)</th></tr><tbody><tr><td> All Inpatient</td><td> 1,790</td><td> 1,609</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Surgical</td><td> 363</td><td> 354</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Non Surgical</td><td> 1,427</td><td> 1,255</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Pulmonology</td><td> 412</td><td> 365</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Orthopedics</td><td> 356</td><td> 343</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> General Medicine</td><td> 269</td><td> 231</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Cardiovascular</td><td> 235</td><td> 199</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Gastroenterology & Endocrinology</td><td> 212</td><td> 189</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Urology</td><td> 162</td><td> 152</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Neurology</td><td> 42</td><td> 37</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> General Surgery</td><td> 29</td><td> 27</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Obstetrics & Gynecology</td><td> 23</td><td> 22</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Oncology & Hematology</td><td> 20</td><td> 17</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Colorectal</td><td> 14</td><td> 13</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table> Readmission Rate (%) Pulmonology Readmission Outcomes Readmission Rate Mesa View Regional Hospital Nevada United States <table><tr><th></th><th> Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Total Hospitalizations After Exclusion</th><th> Total Users</th><th> Readmission Rate(%)</th><th> Nevada Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Nevada Total Hospitalizations After Exclusion</th><th> Nevada Total Users</th><th> Nevada Readmission Rate(%)</th><th> National Total Hospitalizations ( Jan 2014 to Dec 2018)</th><th> National Total Hospitalizations After Exclusion</th><th> National Total Users</th><th> National Readmission Rate(%)</th></tr><tbody><tr><td> Simple Pneumonia And Pleurisy</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 194:SIMPLE PNEUMONIA AND PLEURISY WITH COMPLICATION OR COMORBIDITY (CC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 195:SIMPLE PNEUMONIA AND PLEURISY WITHOUT COMPLICATION OR COMORBIDITY (CC)/MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 193:SIMPLE PNEUMONIA AND PLEURISY WITH MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Chronic Obstructive Pulmonary Disease</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 190:CHRONIC OBSTRUCTIVE PULMONARY DISEASE WITH MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 191:CHRONIC OBSTRUCTIVE PULMONARY DISEASE WITH COMPLICATION OR COMORBIDITY (CC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 192:CHRONIC OBSTRUCTIVE PULMONARY DISEASE WITHOUT COMPLICATION OR COMORBIDITY (CC)/MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Pulmonary Edema And Respiratory Failure</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 189:PULMONARY EDEMA AND RESPIRATORY FAILURE</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Respiratory Infections And Inflammations</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Pulmonary Embolism</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table> Readmission Rate (%) Orthopedics Readmission Outcomes Readmission Rate Mesa View Regional Hospital Nevada United States <table><tr><th></th><th> Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Total Hospitalizations After Exclusion</th><th> Total Users</th><th> Readmission Rate(%)</th><th> Nevada Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Nevada Total Hospitalizations After Exclusion</th><th> Nevada Total Users</th><th> Nevada Readmission Rate(%)</th><th> National Total Hospitalizations ( Jan 2014 to Dec 2018)</th><th> National Total Hospitalizations After Exclusion</th><th> National Total Users</th><th> National Readmission Rate(%)</th></tr><tbody><tr><td> Major Hip And Knee Joint Replacement Or Reattachment Of Lower Extremity</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 470:MAJOR JOINT REPLACEMENT OR REATTACHMENT OF LOWER EXTREMITY WITHOUT MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Hip And Femur Procedures Except Major Joint</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 481:HIP AND FEMUR PROCEDURES EXCEPT MAJOR JOINT WITH COMPLICATION OR COMORBIDITY (CC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 482:HIP AND FEMUR PROCEDURES EXCEPT MAJOR JOINT WITHOUT COMPLICATION OR COMORBIDITY (CC)/MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Fractures Of Hip And Pelvis</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 536:FRACTURES OF HIP AND PELVIS WITHOUT MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Lower Extremity And Humerus Procedures Except Hip,Foot,Femur</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Major Joint And Limb Reattachment Procedures Of Upper Extremity</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 483:MAJOR JOINT/LIMB REATTACHMENT PROCEDURE OF UPPER EXTREMITIES</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Fracture, Sprain, Strain And Dislocation Except Femur, Hip, Pelvis And Thigh</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table> General Medicine   | Back to Top Readmission Rate (%) General Medicine Readmission Outcomes Readmission Rate Mesa View Regional Hospital Nevada United States <table><tr><th></th><th> Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Total Hospitalizations After Exclusion</th><th> Total Users</th><th> Readmission Rate(%)</th><th> Nevada Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Nevada Total Hospitalizations After Exclusion</th><th> Nevada Total Users</th><th> Nevada Readmission Rate(%)</th><th> National Total Hospitalizations ( Jan 2014 to Dec 2018)</th><th> National Total Hospitalizations After Exclusion</th><th> National Total Users</th><th> National Readmission Rate(%)</th></tr><tbody><tr><td> Septicemia Or Severe Sepsis</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 871:SEPTICEMIA OR SEVERE SEPSIS WITHOUT MV >96 HOURS WITH MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 872:SEPTICEMIA OR SEVERE SEPSIS WITHOUT MV >96 HOURS WITHOUT MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Cellulitis</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 603:CELLULITIS WITHOUT MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Nutritional And Miscellaneous Metabolic Disorders</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 641:MISCELLANEOUS DISORDERS OF NUTRITION, METABOLISM , FLUIDS AND ELECTROLYTES WITHOUT MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Signs And Symptoms</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 948:SIGNS AND SYMPTOMS WITHOUT MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Poisoning And Toxic Effects Of Drugs</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 918:POISONING AND TOXIC EFFECTS OF DRUGS WITHOUT MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table> Readmission Rate (%) Cardiovascular Readmission Outcomes Readmission Rate Mesa View Regional Hospital Nevada United States <table><tr><th></th><th> Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Total Hospitalizations After Exclusion</th><th> Total Users</th><th> Readmission Rate(%)</th><th> Nevada Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Nevada Total Hospitalizations After Exclusion</th><th> Nevada Total Users</th><th> Nevada Readmission Rate(%)</th><th> National Total Hospitalizations ( Jan 2014 to Dec 2018)</th><th> National Total Hospitalizations After Exclusion</th><th> National Total Users</th><th> National Readmission Rate(%)</th></tr><tbody><tr><td> Heart Failure And Shock</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 291:HEART FAILURE AND SHOCK WITH MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 292:HEART FAILURE AND SHOCK WITH COMPLICATION OR COMORBIDITY (CC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 293:HEART FAILURE AND SHOCK WITHOUT COMPLICATION OR COMORBIDITY (CC)/MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Cardiac Arrhythmia And Conduction Disorders</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 310:CARDIAC ARRHYTHMIA AND CONDUCTION DISORDERS WITHOUT COMPLICATION OR COMORBIDITY (CC)/MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 309:CARDIAC ARRHYTHMIA AND CONDUCTION DISORDERS WITH COMPLICATION OR COMORBIDITY (CC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Acute Myocardial Infarction</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 280:ACUTE MYOCARDIAL INFARCTION, DISCHARGED ALIVE WITH MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Peripheral Vascular Disorders</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table> Readmission Rate (%) Gastroenterology & Endocrinology Readmission Outcomes Readmission Rate Mesa View Regional Hospital Nevada United States <table><tr><th></th><th> Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Total Hospitalizations After Exclusion</th><th> Total Users</th><th> Readmission Rate(%)</th><th> Nevada Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Nevada Total Hospitalizations After Exclusion</th><th> Nevada Total Users</th><th> Nevada Readmission Rate(%)</th><th> National Total Hospitalizations ( Jan 2014 to Dec 2018)</th><th> National Total Hospitalizations After Exclusion</th><th> National Total Users</th><th> National Readmission Rate(%)</th></tr><tbody><tr><td> G.I. Obstruction</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 390:G.I. OBSTRUCTION WITHOUT COMPLICATION OR COMORBIDITY (CC)/MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 389:G.I. OBSTRUCTION WITH COMPLICATION OR COMORBIDITY (CC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Esophagitis, Gastroenteritis And Miscellaneous Digestive Disorders</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 392:ESOPHAGITIS, GASTROENTERITIS AND MISCELLANEOUS DIGESTIVE DISORDERS WITHOUT MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Disorders Of Pancreas Except Malignancy</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 439:DISORDERS OF PANCREAS EXCEPT MALIGNANCY WITH COMPLICATION OR COMORBIDITY (CC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 440:DISORDERS OF PANCREAS EXCEPT MALIGNANCY WITHOUT COMPLICATION OR COMORBIDITY (CC)/MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> G.I.Hemorrhage</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 378:G.I. HEMORRHAGE WITH COMPLICATION OR COMORBIDITY (CC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 379:G.I. HEMORRHAGE WITHOUT COMPLICATION OR COMORBIDITY (CC)/MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Diabetes</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table> Readmission Rate (%) Urology Readmission Outcomes Readmission Rate Mesa View Regional Hospital Nevada United States <table><tr><th></th><th> Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Total Hospitalizations After Exclusion</th><th> Total Users</th><th> Readmission Rate(%)</th><th> Nevada Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Nevada Total Hospitalizations After Exclusion</th><th> Nevada Total Users</th><th> Nevada Readmission Rate(%)</th><th> National Total Hospitalizations ( Jan 2014 to Dec 2018)</th><th> National Total Hospitalizations After Exclusion</th><th> National Total Users</th><th> National Readmission Rate(%)</th></tr><tbody><tr><td> Kidney And Urinary Tract Infections</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 690:KIDNEY AND URINARY TRACT INFECTIONS WITHOUT MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 689:KIDNEY AND URINARY TRACT INFECTIONS WITH MAJOR COMPLICATION OR COMORBIDITY (MCC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> Renal Failure</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 683:RENAL FAILURE WITH COMPLICATION OR COMORBIDITY (CC)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table> <table><tr><th></th><th> Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Total Hospitalizations After Exclusion</th><th> Total Users</th><th> Readmission Rate(%)</th><th> Nevada Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Nevada Total Hospitalizations After Exclusion</th><th> Nevada Total Users</th><th> Nevada Readmission Rate(%)</th><th> National Total Hospitalizations ( Jan 2014 to Dec 2018)</th><th> National Total Hospitalizations After Exclusion</th><th> National Total Users</th><th> National Readmission Rate(%)</th></tr><tbody><tr><td> Intracranial Hemorrhage Or Cerebral Infarction</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td> DRG 065:INTRACRANIAL HEMORRHAGE OR CEREBRAL INFARCTION WITH COMPLICATION OR COMORBIDITY (CC) OR TPA IN 24 HOURS</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table> Obstetrics & Gynecology   | Back to Top <table><tr><th></th><th> Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Total Hospitalizations After Exclusion</th><th> Total Users</th><th> Readmission Rate(%)</th><th> Nevada Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Nevada Total Hospitalizations After Exclusion</th><th> Nevada Total Users</th><th> Nevada Readmission Rate(%)</th><th> National Total Hospitalizations ( Jan 2014 to Dec 2018)</th><th> National Total Hospitalizations After Exclusion</th><th> National Total Users</th><th> National Readmission Rate(%)</th></tr><tbody><tr><td> Uterine And Adnexal Procedures For Non-Malignancy</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table> <table><tr><th></th><th> Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Total Hospitalizations After Exclusion</th><th> Total Users</th><th> Readmission Rate(%)</th><th> Nevada Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Nevada Total Hospitalizations After Exclusion</th><th> Nevada Total Users</th><th> Nevada Readmission Rate(%)</th><th> National Total Hospitalizations ( Jan 2014 to Dec 2018)</th><th> National Total Hospitalizations After Exclusion</th><th> National Total Users</th><th> National Readmission Rate(%)</th></tr><tbody><tr><td> Red Blood Cell Disorders</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table> <table><tr><th></th><th> Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Total Hospitalizations After Exclusion</th><th> Total Users</th><th> Readmission Rate(%)</th><th> Nevada Total Hospitalizations (Jan 2014 to Dec 2018)</th><th> Nevada Total Hospitalizations After Exclusion</th><th> Nevada Total Users</th><th> Nevada Readmission Rate(%)</th><th> National Total Hospitalizations ( Jan 2014 to Dec 2018)</th><th> National Total Hospitalizations After Exclusion</th><th> National Total Users</th><th> National Readmission Rate(%)</th></tr><tbody><tr><td> Major Small And Large Bowel Procedures</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table>
https://dexur.com/hospital/3015267/r/drg/201401-201812/
(PDF) Chikungunya-Wolbachia interplay in Aedes albopictus PDF | A severe Chikungunya (CHIK) outbreak recently hit several countries of the Indian Ocean. On La Réunion Island, Aedes albopictus was incriminated... | Find, read and cite all the research you need on ResearchGate Chikungunya-Wolbachia interplay in Aedes albopictus December 2008 Insect Molecular Biology 17(6):677-8 DOI: 10.1111/j.1365-2583.2008.00842.x Abstract and Figures A severe Chikungunya (CHIK) outbreak recently hit several countries of the Indian Ocean. On La Réunion Island, Aedes albopictus was incriminated as the major vector. This mosquito species is naturally co-infected with two distinct strains of the endosymbiont Wolbachia, namely wAlbA and wAlbB, which are increasingly attracting interest as potential tools for vector control. A PCR quantitative assay was developed to investigate Wolbachia/mosquito host interactions. We show that Wolbachia densities are slightly decreased in CHIK virus (CHIKV)-infected females. We measured the impact of CHIKV replication on a lysogenic virus: WO bacteriophage. Our data indicate that WO is sheltered by wAlbB, likely at a single copy per bacteria, and that CHIKV replication is not a physiological stress triggering WO entrance into the lytic cycle Variation of virus load across the experiment. Each cross depicts a CHIKV load for one particular mosquito. Ordinal axis is a logarithmic scale. … Co-variation of Wolbachia and WO across the experiment. The co-variation of WO (circle symbols and full lines linking means per days), wAlbA (squares and dashed lines) and wAlbB (triangles and dot-dashed lines) densities for CHIKV infected (A), or uninfected (B) mosquitoes. Stars label raw data that have been excluded in statistical modelling. … Blackwell Publishing Ltd Chikunguny a- W olbachia interplay in Aedes albopictus P . T ortosa*†, A. Courtiol*†, S. Moutailler‡, A.-B. Failloux‡ and M. Weill*† * Université Montpellierz 2; † CNRS, Institut des Sciences de l’Evolution, Equipe Génétique de l’Adaptation, C.C . 065, Place Eugène Bataillon 34095 Montpellier cedex 05, France; and ‡ Institut Pasteur , Unité de Génétique moléculaire des Bunyavirus, 25-28 rue du Docteur Roux, 75724 Paris, F rance Abstract A severe Chikungunya (CHIK) outbreak recently hit several countries of the Indian Ocean. On La Réunion Island, was incriminated as the major vector. This mosquito species is naturally co-infected with two distinct strains of the endosymbiont Wolbachia , namely w AlbA and w AlbB, which are increasingly attracting interest as potential tools for vector control. A PCR quantitative assay was developed to investigate Wolbachia /mosquito host interactions. We show that Wolbachia densities are slightly decreased in CHIK virus (CHIKV)-infected females. We measured the impact of CHIKV replication on a lysogenic virus: WO bacteriophage. Our data indicate that WO is sheltered by w AlbB, likely at a single copy per bacteria, and that CHIKV replication is not a physiological stress triggering WO entrance into the lytic cycle. Keywords: Aedes albopictus , Chikunguny a, Wolbachia , WO, quantitative PCR. Introduction Aedes albopictus is considered as a mosquito species of major concern since its worldwide expansion over the past 25 years (Gratz, 2004). The species has been shown to be a vector for more than 20 arboviruses and was determined to be the main vector for the Chikunguny a (CHIK) outbreak on La Réunion Island in 2005–2006 (Delatte et al ., 2008). The epidemic spread throughout the other islands of the Indian Ocean, and later jumped to India and Italy , where a growing number of cases has been reported (Charrel et al ., 2008). It is interesting to note that A. albopictus native from South-East Asia has succeeded in colonizing at least 12 European countries (Scholte & Schaffner, 2007). It has become established in Italy since 1990 (Sabatini et al ., 1990) where it caused the first CHIK outbreak in Europe in 2007 (Rezza et al ., 2007). Several CHIK virus (CHIKV) isolated from patients in La Réunion Island during the 2005–2006 outbreak were sequenced (Schuffenecker et al ., 2006). Ph ylogenetic studies demonstrated the emergence of a point mutation in a viral glycoprotein encoding gene. This mutation, which was not detected at the beginning of the outbreak, was present in more than 90% of the clinical isolates during the epidemics peak, denoting evolutionary success (Schuffenecker et al ., 2006). V ectorial competence exper- iments showed that this substitution fav oured a better transmissibility of the virus by the mosquito A. albopictus (Vaz eille et al ., 2007). A. albopictus is naturally co-infected with two distinct Wolbachia endosymbiotic bacteria, w AlbA and w AlbB (Sinkins et al ., 1995b; Kittay apong et al ., 2000, 2002; Armbruster et al ., 2003). These endosymbionts are mater- nally inherited reproductive parasites that have developed distinct host manipulations which all increase the fitness of infected females. So far , the only described phenotype conferred by Wolbachia to mosquitoes is Cytoplasmic Incompatibility (CI) (Sinkins, 2004). In the simplest CI configuration, infected males sterilize uninfected f emales by provoking a premature arrest of egg de velopment. Wolbachia -infected females hav e thus a reproductive advantage over uninf ected ones. CI w as extensively studied in Culex pipiens mosquitoes, which exhibit complex incompatibility patterns (Laven, 1959; Duron et al ., 2006a,b, 2007). CI penetrance is particularly high in mosquitoes and is typically associated with a 90 to 100 percent failure of egg hatching (Dutton & Sinkins, 2005), making Wolbachia a promising candidate for vector control programs . Although the genetic determinants of CI are still unknown, a bacterial mobile element, WO bacteriophage, has been particularly studied as it is suspected to control CI directly or indirectly . In response to e xternal stress signals, bacteriophages are known to shift from a dormant state Received 5 June 2008; accepted after re vision 18 August 2008. Cor- respondence: M. W eill, CNRS, Institut des Sciences de l’Evolution, Equipe Génétique de l’Adaptation, C.C. 065, Place Eugène Bataillon 34095 Montpellier cedex 05, France. T el.: +33 4 67 14 32 62; F ax: +33 4 67 14 36 22; E-mail: m [email protected] 678 P . T ortosa et al. Journal compilation © 2008 The Royal Entomological Society , 17 , 677–684 No claims to original government works integrated in the chromosome to an extra chromosomal replicative cycle (Herskowitz & Hagen, 1980). The multiplica- tion step culminates with bacterial lysing and the subsequent liberation of numerous phage particles. WO has been proposed to bear the genetic determinants of CI in Culex pipiens mosquitoes (Sinkins et al ., 2005; W alker et al ., 2007). Quantification of Wolbachia and WO densities together with the measure of CI penetrance in the parasitoid wasp Nasonia vitripennis led to the proposal of an alternative mechanism. Both Wolbachia and WO densities were negatively correlated, validating a lytic scenario where newly assembled viruses leave lysed bacteria (Bordenstein et al ., 2006). CI and WO densities were shown to be negatively correlated which strongly suggests that WO entrance in lytic cycle indirectly lowers CI penetrance by decreasing Wolbachia density (Bordenstein et al ., 2006). Other quantitative approaches have contributed to the study of the interactions of Wolbachia with their hosts. It was shown that the presence of insecticide resistance genes was associated with increased Wolbachia densities in C. pipiens natural and laboratory populations (Berticat et al ., 2002; Duron et al ., 2006c). The high physiological cost of insecticide resistance genes might interfere with the efficient control of Wolbachia by the host. In addition, it was established that in highly infected resistant strains, Wolbachia represent an additive cost for mosquitoes (Duron et al ., 2006c). Quantitative (Dutton & Sinkins, 2004; Chauvatcharin et al ., 2006) or semi quantitative (Sinkins et al ., 1995a; Ruang-areerate et al ., 2004) methods have already been developed to e valuate Wolbachia densities in A. albopictus . However , none of these methods have been used to study the impact of a replicating parasite such as CHIKV on host/ since a few days after artificial infection, CHIKV localiz es in the eggs of A. albopictus females (V azeille et al ., 2007) where it may interact directly with Wolbachia . Se ve ra l relevant questions are still pending. For example , it is not known whether the expected fitness cost conferred b y CHIKV active replication, as previously shown f or another arbovirus/mosquito couple (Mahmood et al ., 2004), may affect Wolbachia densities. Moreo ver, little is known about WO phage and the signals controlling replicative cycles of temperate phages sheltered by endosymbiotic bacteria. We therefore tested the possibility of a ph ysiological stress such as CHIKV infection affecting the WO cycle. quantitative PCR tool that allowed us to study the WO- Wolbachia /CHIKV/mosquito multipartite relationships. A. albopictus females were fed with uninf ected or CHIKV- infected blood. RNA and DNA were prepared from each individual mosquito and used to measure CHIKV , w AlbA, w AlbB and WO phage densities. Raw data were then submitted to a statistical analysis to find all of the variables that significantly affected endosymbiont densities. Our data demonstrates that w AlbB, not w AlbA, harbours the WO phage, which contrasts with previously published data. In our experimental conditions, CHIKV infection did not trigger WO entrance into the lytic cycle. This analysis re vealed that CHIKV infection slightly lowers and WO densities. Results w AlbA, w AlbB, and WO are aff ected by CHIKV infection Samples consisting of 64 female mosquitoes fed with uninfected (N = 30) or CHIKV-inf ected blood (N = 34) were frozen at different days after the b lood meal. The RNA fraction was used to quantify CHIKV loads in each mosquito. The viral load reached a maximum 3 days after infection and then slightly decreased (Fig. 1). F or each mosquito, the Wolbachia number was normalized by the nuclear actin reference gene, and the Wolbachia load is given as Wolbachia genome per actin copy number . As shown in Fig. 2, densities do not vary substantially though the experiment and roughly show a slight increase with aging. The effect of CHIKV infection on Wolbachia densities was investigated by considering viral loads as well as infection status (infected vs . uninfected) v ariables. Based on raw data for inf ected mosquitoes, the viral load was non-significantly correlated with w AlbA density (Spearman correlation test: ρ = 0.23, P = 0.17) and with w AlbB density ( ρ = 0.31, P = 0.071), and marginally cor- related with WO ( ρ = 0.34, P = 0.046). Howe ver, the use of linear regression model was required to exclude indirect correlations possibly induced by confounding eff ects such as the number of days after the blood meal. These Figure 1. Variation of virus load across the experiment. Each cross depicts a CHIKV load for one particular mosquito. Ordinal axis is a logarithmic scale. Chikungunya-Wolbachia interplay in A. albopictus 679 Journal compilation © 2008 The Royal Entomological Society , 17 , 677–684 No claims to original government works statistical models simultaneously explore the effects of different variables (called cov ariates, WO , w AlbA, w AlbB, but also CHIKV infection status and load, the number of days after blood meal and some interactions) on one variable of interest (called the ‘response’, here w AlbA, w AlbB, or WO , successively analyzed using three separate linear models). Regression models sho wed no effect of viral load on w AlbA ( F 1,58 = 2.86, P = 0.096), w AlbB ( F 1,55 = 3.28, P = 0.075) or WO ( F 1,59 = 0.35, P = 0.56). We then analyzed the effect of CHIKV inf ection status on endosymbiont densities (Fig. 2). Inf ection had a negative impact on raw w AlbA, w AlbB, and WO density a verages (means for uninfected: 1.53, 2.76, and 2.23 respectively; means for infected: 1.20, 2.15, and 1.42), but these dif- ferences were not significant (Wilcoxon rank test: W = 414, P = 0.15; W = 440, P = 0.27; and W = 380, P = 0.057, respectively). However , all three linear regression models (models for w AlbA, w AlbB and WO) revealed a significant effect of infection status ( F 1,59 = 4.51, P = 0.038; F 3,56 = 5.42, P < 0.01 and F 2,60 = 13.49, P < 0.0001 respectively). This showed that, once the variations in the other c ov- ariates were taken into account, CHIKV infection status affects all three densities. In addition, as for the raw data, regression models show that infection decreases w AlbA, w AlbB and WO densities which are respectiv ely lowered by 29.7, 12.6 and 33.8% (when other covariates set at their mean values for their respective inf ection status). The proportion of variance explained by CHIKV infection status was relatively low with 2.7% of variance e xplained in the w AlbA model, 11.6% in the w AlbB model and 2.9% in the WO model. Our analysis showed that CHIKV loads were not correlated with endosymbiont densities, while Wolbachia and W O densities were significantly decreased in CHIKV infected vs. uninfected mosquitoes. w AlbB, not w AlbA, harbors the W O phage Direct correlation tests between WO and Wolbachia densities revealed that both w AlbA and w AlbB were strongly correlated with phage densities (Spearman’s rank correlation test: ρ = 0.75, P < 0.0001 and ρ = 0.95, P < 0.0001 respectiv ely). with each other (Spearman’s rank correlation test: ρ = 0.77, P < 0.0001), there was a possibility that the correlation between the density of one Wolbachia strain and WO was indirect. More generally , this kind of association could be spuriously induced by any variable correlated with WO and Wolbachia at the same time. Multiple linear regression Figure 2. Influence of viral infection on Wolbachia and WO densities across the experiment. Density variations of w AlbA (Fig. 2A), w AlbB (Fig. 2B) and WO (Fig. 2C) across the experiment are presented for infected (full symbols) and uninfected (empty symbols) mosquitoes. Blac k lines link mean density for infected mosquitoes and grey lines link mean density f or uninfected ones. Stars label raw data that have been excluded in statistical modelling. 680 P . T ortosa et al. Journal compilation © 2008 The Royal Entomological Society , 17 , 677–684 No claims to original government works models were used to avoid such conf ounding effects. Here, the model reduction resulted in the identification of three significant covariates: CHIKV inf ection status, w AlbB density , and their interaction. In the minimal adequate model, these three variables explained 93.6% of phage v ariance, while all other dependent variables, including w AlbA, were not significant (for w AlbA: F 1,59 = 0.67, P = 0.41). w AlbB alone density ( F 1,60 = 820, P < 0.0001). From this analysis, one sample was excluded because its consideration led to a violation of the homoscedasticity assumption, which was required to interpret results from these linear regression models (with this data point, the homoscedasticity assumption is rejected: Breusch-P agan test, Bp = 24.06, P < 0.0001; without it, the homoscedasticity assumption is not rejected: Breusch-Pagan test, Bp = 4.36, P = 0.23). Interestingly, this sample corresponded to an atypical uninfected individual, and clearly illustrates that w AlbB and not w AlbA harbors WO (Fig. 3B for day 7). Hence, removing this point could not overestimate the effect of w AlbB on WO in the model. We therefore conclude that WO is sheltered by w AlbB and not by w AlbA (Fig. 3). CHIKV does not induce the WO phage lytic cycle T emperate bacteriophages have been studied for a long time. Substantial w ork has led to a good understanding of the Escherichia coli lambda paradigm replicative cycle at the mechanistic level (Hersko witz & Hagen, 1980). Entrance into the lytic cycle is under the control of external stress signals, most of which induce host cell death (Panet et al ., 2005). Although lytic cycles ha ve been established Gavotte et al ., 2004; Bordenstein et al ., 2006; Chauvatcharin et al ., 2006), signals controlling replicative cycles of WO or any other temperate phage of endosymbiotic bacteria are not known. In order to study the eff ect of CHIKV active replication in inducing the WO lytic cycle, w e investigated the relation between the intensity of CHIKV replication and the density of Wolbachia and phages. As shown in Fig. 1, CHIKV infection of A. albopictus is followed by a quick viral replication: a ~500 fold increase in vir al load is observed only 3 days after the infected blood meal. We measured the effect of such an active replication, which surely aff ects mosquito physiology , on endosymbiont densities. Induction of the lytic cycle is expected to lead to an increase in WO and a decrease in w AlbB copy numbers as ne wly assembled WO particles leave lysed Wolbachia . The comparison of WO/ w AlbB ratios in CHIKV infected vs. uninfected mosquitoes is thus particularly informative and is expected to increase in a lytic scenario. However , the WO/ w AlbB ratio in CHIKV - infected mosquitoes appears slightly lower than in uninf ected individuals (0.61 ± 0.03 and 0.78 ± 0.04 respectively). This can be observed in Figure 4 where W O phage numbers are plotted against w AlbB in CHIKV -infected or uninfected infection, although affecting WO density , does not induce its entrance into the lytic cycle. Discussion Our results show that CHIKV infection is associated with a slight reduction in Wolbachia density . This decrease might result from competition for resources between W olbachia and replicating CHIKV inside mosquito cells. Indeed, the CHIKV replication rate is massive, yielding a ~500-fold increase in viral copy numbers 3 days after artificial infection. On the other hand, this result might provide some insights Figure 3. Co-variation of Wolbachia and W O across the experiment. The co-variation of WO (circle symbols and full lines linking means per days), w AlbA (squares and dashed lines) and w AlbB (triangles and dot-dashed lines) densities for CHIKV infected (Fig. 3A), or uninfected (Fig. 3B) mosquitoes. Stars label raw data that ha ve been excluded in statistical modelling. Chikungunya-Wolbachia interplay in A. albopictus 681 Journal compilation © 2008 The Royal Entomological Society , 17 , 677–684 No claims to original government works into the nature of Wolbachia /host interactions in A. albopictus . A previous work compared Wolbachia densities in insecticide- resistant vs. -susceptib le C. pipiens mosquitoes that shared the same genetic background. This study rev ealed that resistant mosquitoes were more heavily infected by Wolbachia than susceptible mosquitoes (Berticat et al ., 2002). Since some insecticide resistance genes are known to carry a heavy genetic cost (Lenormand et al ., 1999), Ber ticat et al ., concluded that mosquitoes might control Wolbachia levels less efficiently when they suff er from a physiological resistance cost (Berticat et al ., 2002). In our experiments, CHIKV artificial infection is followed b y a robust replication phase. Such a burst of replication could legitimately be associated with a heavy physiological cost to the host. How ever , we do not observe any increase in Wolbachia density , but rather a significant, although slight, reduction in bacterial loads. Wolbachia interactions with their hosts range from strict parasitism to mutualism (Min & Benzer, 1997; Vavre et al ., 1999; Dedeine et al ., 2001; Dobson et al ., 2002). Our data suggest that endosymbiont/ host relations are less parasitic in A. albopictus than they are in C. pipiens, which is in agreement with a previous work showing a selective advantage conf erred by Wolbachia infection to A. albopictus adult females (Dobson et al ., 2004). Interestingly , CHIKV infection status, but not viral load, statistically affected Wolbachia and phage densities. This may be interpreted as a global response of the mosquito to viral infection, similar to an immune response, rather than a physiological tuning of mosquito ph ysiology to the level of CHIKV infection. Quantification of the four genes using a single standard curve yielded a clear correlation between WO bacteriophage numbers and w AlbB, but not w AlbA densities. We carried out similar quantitative experiments on sev eral natural populations collected on La Réunion Island and found similar results (data not shown), suggesting that, in A. albopictus natural populations from La Réunion Island, WO is sheltered by w AlbB. However, considering the indirect nature of the data, the construction of mono infected lines from La Réunion is required to address this question. Indeed, w AlbB and WO linkage contrasts with pre viously published results showing that a w AlbA mono-inf ected line harboured the WO phage (Chauv atcharin et al ., 2006). We cannot exclude that the W O phage may be integrated at different loci among the distinct mosquito populations worldwide. It must be reiter ated, however , that the mono- infected line used in the previous study is atypical. This line was isolated pre-1970 in Koh Samui Island, Thailand, and maintained in laboratory facilities until now . It was suggested that this mono-infected line might represent an ancestral mono-infection or , alternatively , result from the loss of w AlbB during the long period of laboratory maintenance (Armbruster et al ., 2003). In any case , studies carried out on such a peculiar line require cautious interpretations. The possibility of CHIKV infection as a stressful stimulus that induces WO entrance into the lytic cycle w as also examined. Our data showed that CHIKV infection, although followed by an e xtensive viral replication phase, does not induce the phage lytic cycle. In contr ast with what would be expected in a lytic cycle where W O phage particles intensively replicate prior to leaving lysed bacteria, the WO/ w AlbB ratio is slightly reduced in CHIKV positive mosquitoes. The average value of this r atio is consistently less than one (Mean 0.72 ± 0.13). Mosquitoes could be therefore infected with two types of w AlbB symbionts, some harbouring a phage and others not. This inference implies a selective advantage of the simultaneous presence of W O+ and WO– w AlbB inside a single mosquito, prev enting the loss of one Wolbachia type by drift. We also cannot exclude a limitation of qPCR technology for comparisons of different genes, as PCR efficiencies are not strictly identical, although WO and w AlbB amplification efficiencies were very similar and close to the optimum in our experimental conditions. Thus, our data suppor t the presence of one phage copy per w AlbB bacteria. This is in accordance with published data showing one unique W O orf7 sequence per A. albopictus specimen (Chauv atcharin et al ., 2006). T o our knowledge, this is the first report monitor ing the effect of a replicating parasite on W olbachia and WO phage densities. Our data sho wed that w AlbB and not w AlbA shelters WO prophage, lik ely at a single copy number , and that CHIKV infection did not induce the W O lytic cycle. Figure 4. Raw correlation between WO and w AlbB. WO and w AlbB densities are reported for CHIKV infected (filled symbols) or uninfected (empty symbols). The full line represents the linear adjustment for infected mosquitoes (Spearman’s correlation coefficient: ρ = 0.94) and the dashed line represents the linear adjustment for uninfected mosquitoes (Spearman’s correlation coefficient: ρ = 0.96). 682 P . T ortosa et al. Journal compilation © 2008 The Royal Entomological Society , 17 , 677–684 No claims to original government works Because of the lack of comparable data in the literature, w e could not conclude whether the Wolbachia decrease in CHIKV-inf ected mosquitoes results from a competition for mutualistic relationship. Similar quantitative experiments on other biological systems will surely be published in the near future. In addition to the present w ork, such quantitative data will be of great help for understanding complex multipartite relationships. Experimental procedures Artificial infection of A. albopictus females with CHIKV All artificial infection experiments were carried out with the CHIKV variant harbouring a point mutation A226V in the E1 gene. This variant, termed CHIKV 06.21, was provided by the National Reference Centre for arboviruses at the Institut P asteur. It was originally isolated in November 2005 on La Réunion Island from the serum of a newborn presenting meningo-encephalitis symptoms. The vir us was maintained at 28 ° C in C6/36 A. albopictus cells grown in L-15 medium supplemented with 10% foetal calf serum, penicillin 1000 units/ml, streptomycin 1 mg/ml, and 1X tryptose phosphate medium. Cell infection w as determined by indirect immunofluorescence as previously described (Schuffeneck er et al ., 2006). Supernatant was collected when 80% of cells were infected and viral titres were determined on plates. Titre is given as lysis plaque forming units (pfu) per ml. The mosquitoes used in these experiments were the F4 generation of a population originally collected in March 2006 in Saint-Denis de La Réunion. Containers of fertilised females were placed under glass feeders loaded with 3 ml of blood and sealed with chicken skin as previously described (V azeille et al ., 2007). Five to 7 da ys-old females were starved for 24 h before a 20 min long blood meal. Mosquitoes were then placed at 4 ° C to immobilize them and fully fed females were put in containers placed in a BSL-3 insectarium at 28 ° C with 80% humidity and a 12 h/12 h light period. Females were f ed with a 10% sugar solution. From day 0 to da y 14 after blood meal, three individual mosquitoes were frozen every day . Mosquitoes found dead in the cage were discarded from the study . Nucleic acids purification and quantitative PCRs T otal nucleic acids were prepared from each mosquito with a commercial purification kit as previously described (Vazeille et al ., 2007) except that DNA and RNA fractions were sequentially eluted from the column with low salt buffer and water , respectively. Thus, each mosquito specimen could provide RNA used for CHIKV load determination by quantitative Reverse Transcriptase (qRT)-PCR as well as DNA suitable for Wolbachia and WO density measure- ments by quantitative (q)PCR. The standard curve and qRT -PCRs were carried following previ- ously described conditions (Vazeille et al ., 2007). Reactions were performed in triplicate for each mosquito and signals were normalized to the standard curve using serial dilutions of RNA synthetic transcripts. Normalized data were used to measure the number of RNA copies in infected mosquitoes according to the Δ C t analysis. Quantitative PCR required the preliminary cloning of each locus on a single vector in order to obtain comparable data between the different Wolbachia and mosquito quantified genes. We therefore constructed pQuantAlb plasmid bearing each of the four loci: w AlbA- wsp , w AlbB- wsp , WO- orf7 and A. albopictus actin gene as a nuclear reference. For this, two to four pairs of PCR primers targeting each locus were tested by qPCR on A. albopictus DNA template. The presence of specific amplification products was verified with melting curves. Standard curves were constructed f or each primer pair and their linearity and PCR efficiency were measured by qPCR at three different annealing temperatures (60 ° C, 65 ° C, and 70 ° C). One pair was selected at the optimal 65 ° C annealing temperature for each locus and used for the pQuantAlb construction (see below). The plasmid was then serially diluted to build a standard curve with all four loci present at an equimolar concentration. Each mosquito was analysed in triplicate for the four loci with Alborf7Qrev (CTG GCA TCT TTG AT A CAT T AC) and WHOcapalbABdir1 (GAG AAA GCA GT A GAA AT A GG), actAlb-dir (GCA AAC GTG GT A TCC TGA C) and actAlb-rev (GTC A GG AGA ACT GGG TGC T), QAdir1 (GGG TTG ATG TTG AAG GAG) and QArev2 (CAC CAG CTT TTA CTT GAC C), 183F(AA G GAA CCG AAG TTC A TG) and QBrev2 (AGT TGT GAG T AA AGT CCC) primer pairs for WO- orf7 , actin , w AlbA- wsp and w AlbB- wsp loci, respectively . About 2 ng of genomic DNA was mixed with 0.5 μ M of each primer, 1 μ l of anti- Ta q -containing master mix and com- pleted to 5 μ l with water (master mix and anti- T aq antibody were used according to Roche LightCycler instructions for SYBR technology , (Wittwer et al ., 1997)). PCR was run for 45 cycles (94 ° C for 4 s, 65 ° C for 14 s, and 72 ° C f or 19 s). A new standard curve was performed for each qPCR run, so that signals could be standardized with the nuclear actin reference. The mean genome number of WO , w AlbA, and w AlbB was obtained per actin copy number. Construction of the pQuantAlb plasmid All PCR reactions used in these cloning procedures were per- formed on the Aedes albopictus total DNA template. An actin fragment of 139 bp was first amplified with actAlb-dir and actAlb-rev primers and cloned directly into the pCR II T opo vector (Invitrogen, San Diego, CA, USA), producing pCRactAlb. Similarly, a wsp gene fragment of 264 bp from w AlbA was amplified with QAdir1 and QARev2 primers, and cloned into the pCR II T opo vector. The resulting pCRAlbA plasmid was digested with Eco RI enzyme and the w AlbA-containing DNA fragment was gel purified. This fragment was blunt ended with T4 DNA P olymerase and cloned into pCRactAlb at the Eco RV restriction site giving pCRact-AlbA. A w AlbB wsp fragment of 112 bp was amplified with Xho -183F (A TC TCG AGA AGG AAC CGA AGT TCA TG) and Xba -QBrev (TTC T AG AGT TGT GA G T AA AGT CCC) primers, digested with Xho I/ Xba I restriction enzymes and subsequently cloned into pCRact-AlbA at the Xho I/ Xba I sites, yielding pCRact-AlbAB. Finally , pQuantAlb was constructed by the insertion at the Bam HI/ Hind III sites of a PCR fragment containing 160 bp of the phage orf7 gene, obtained with WOalbABdir1-Bam (AA G GA T CCG AGA AAG CAG T AG AAA T AG G) and Alborf7Qrev -Hind (CCA AGC TTC TGG CA T CTT TGA T AC ATT A C) primers. The resulting pQuantAlb plasmid, containing a single copy of DNA from w AlbA, w AlbB , WO, and actin A. albopictus nuclear DNA, was checked by sequencing. Statistical analysis In order to study whether CHIKV is linked to WO phage and both Wolbachia ( w AlbA and w AlbB), we first used simple Spearman’ s rank correlation tests, and then constructed linear regression Chikungunya-Wolbachia interplay in A. albopictus 683 Journal compilation © 2008 The Royal Entomological Society , 17 , 677–684 No claims to original government works models. Three different linear models were constructed as follows: w AlbA ~ Days * Status * w AlbB + Days * Status * WO + Days * CHIKV w AlbB ~ Days * Status * w AlbA + Days * Status * WO + Days * CHIKV WO ~ Days * Status * w AlbA + Days * Status * w AlbB + Days * CHIKV Alternatively WO, w AlbA or w AlbB are the variable ‘response’. The covariates are variables present on the right side of the tilde. The symbol ‘+’ means that the two ter ms surrounding the symbols are considered only as two single effects. The symbol ‘*’ means that the two terms surrounding the symbol are considered as two single effects and their interaction. Days represents days after blood meal . Status represents the CHIKV infection status , and CHIKV the CHIKV loads . The model considering WO as the variable ‘response’ allows also to study whether the WO phage is linked to one or both Wolbachia ( w AlbA and w AlbB). All full models were sequentially reduced in order to remove all non-significant terms. At each reduction step, the normality of residuals was evaluated b y the Shapiro-Wilk test, and the absence of heteroscedasticity and autocorrelation in residuals were checked using the Breusch- Pagan and Durbin-Watson tests , respectively . In cases of assump- tions violability , if the violation due to a few outliers, the corresponding data were excluded (excluded points are star labelled in the figures); otherwise Box-Cox (Box & Co x, 1964) transformations were performed. The significance of covariates was assessed by F test on type II ANOVA tables. All data analyses w ere performed under R 2.6.0 (http://www.R-project.org) using lmtest (Zeileis & Hothorn, 2002) and the M ASS package (V enables & Ripley , 2002). Acknowledgments We would like to thank Georges Lutf alla and Nicole Pasteur for their support during the study, Sylv ain Charlat and Olivier Duron for critical reading of the manuscript. This work was financed by the ANR CHIKVENDOM Santé- Environnement ( Ministère délégué à la Recherche ), b y the Conseil Régional de La Réunion and by the Région Languedoc Roussillon (Montpellier, F rance). Contribution 2008.095 of Institut des Sciences de l’Evolution de Montpellier (UMR CNRS-UM2 5554). References Armbruster, P ., Damsky, W.E. Jr., Giordano, R., Birungi, J., Munstermann, L.E. and Conn, J.E. 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In Emerging P ests V ector-bor ne Dis Europe (T akken, W. and Knols, B ., eds). pp. 241–2607. W ageningen Academic Publishers, Wageningen. Schuffenecker, I., Iteman, I., Michault, A., Murri, S., F rangeul, L., Vaney, M.C . et al . (2006) Genome microev olution of chikun- gunya viruses causing the Indian Ocean outbreak. PLoS Med 3 : e263. Sinkins, S.P . (2004) Wolbachia and cytoplasmic incompatibility in mosquitoes. Insect Biochem Mol Biol 34 : 723–729. Sinkins, S.P ., Braig, H.R. and O’Neill, S.L. (1995a) W olbachia pipientis: bacterial density and unidirectional cytoplasmic incompatibility between infected populations of Aedes albopictus. Exp Parasitol 81 : 284–291. Sinkins, S.P ., Braig, H.R. and O’Neill, S.L. (1995b) Wolbachia superinfections and the expression of cytoplasmic incompati- bility. Proc Biol Sci 261 : 325–330. Sinkins, S.P ., Walker, T ., Lynd, A.R., Steven, A.R., Makepeace, B.L., Godfray, H.C. et al . (2005) Wolbachia variability and host effects on crossing type in Culex mosquitoes. Nature 436 : 257– 260. Vavre, F ., Girin, C. and Bouletreau, M. (1999) Phylogenetic status of a fecundity-enhancing W olbachia that does not induce thelytoky in T richogramma. Insect Mol Biol 8 : 67–72. Vazeille, M., Moutailler, S ., Coudrier, D., Rousseaux, C., Khun, H., Huerre, M. et al . (2007) T wo Chikungunya Isolates from the Outbreak of La Reunion (Indian Ocean) Exhibit Different Patterns of Infection in the Mosquito, Aedes albopictus. PLoS ONE 2 : e1168. Venab les, WN and Ripley, BD (2002) Modern Appl Statistics with S , 4th edn. Springer, New York. Walker, T ., Klasson, L., Sebaihia, M., Sanders, M.J., Thomson, N.R., Parkhill, J. et al . (2007) Ankyrin repeat domain-encoding genes in the wPip strain of Wolbachia from the Cule x pipiens group. BMC Biol 5 : 39. Wittwer, C.T ., Herrmann, M.G., Moss, A.A. and Rasmussen, R.P . (1997) Continuous fluorescence monitoring of rapid cycle DNA amplification. Biotechniques 22 : 130–131, 134–138. Zeileis, A. and Hothorn, T . (2002) Diagnostic checking in regression relationships. In Book Diagnostic Checking in Regression Relationships, R News 2(3), 7–10. URL http:// ... Studies showed resistance genes were associated with Wolbachia population density increase in insect organisms and infection stability ensures interference of viral replication. This phenomenon still requires deeper studies (Tortosa et al. 2008; Hoffmann et al. 2014;Yeap et al. 2011). ... ... Aedes albopictus is a mosquito with great spreading potential and is an important arbovirus vector with high biological flexibility capable of growing in many environments and climates. Aedes albopictus, different from Aedes aegypti, is a natural Wolbachia host, specifically WAlb (Tortosa et al. 2008; Yeap et al. 2011;Das et al. 2014;Hughes et al. 2012;Calvitti et al. 2015). ... Control of arboviruses vectors using biological control by Wolbachia pipientis: a short review Article Full-text available ARCH MICROBIOL Nara Juliana Santos Araújo Márcia Jordana Ferreira Macêdo Luis Pereira de Morais Henrique Coutinho The number of arbovirus cases has increased in recent years, demonstrating a need for investing in effective control actions. Among these actions, are strategies using biological control vectors, a field where Wolbachia pipientis has shown itself as useful. Wolbachia pipientis, an obligatory intracellular Gram-negative bacteria, which parasites arthropods naturally or through laboratory-induced infections, is capable of manipulating the reproduction of its host. A systematic literature review gathering studies on this bacteria over last 10 years (2007–2021) was performed given its important role in the reduction of insect disease vectors. 111 articles were found, from which 78 were used in this study. Information on the Wolbachia biology, mechanism of action and potential for the biological control of insect disease vectors was gathered. The present study may contribute to the knowledge surrounding the bacterium, as well as stimulate the production of other studies with the same theme. ... In the somatic cells of male Drosophila, the autophagic response reduces Wolbachia density, but the opposite occurs in germ cells of females [49]. In multiple studies, infection with another bacterium [50] or virus [51, 52] that triggers the innate Toll and immune deficiency (IMD) pathways appears to also cause reductions in Wolbachia density. We know from transcriptional studies that the activity of these pathways varies across mosquito tissues, including the midgut, carcass and salivary gland, when induced by infection [53], but their basal expression can also vary as per an examination of the control data for these same studies [54,55]. ... Cross-tissue and generation predictability of relative Wolbachia densities in the mosquito Aedes aegypti Austin J. Mejia Heverton Leandro Carneiro Dutra M. J. Jones Elizabeth A McGraw Background The insect endosymbiotic bacterium Wolbachia is being deployed in field populations of the mosquito Aedes aegypti for biological control. This microbe prevents the replication of human disease-causing viruses inside the vector, including dengue, Zika and chikungunya. Relative Wolbachia densities may in part predict the strength of this ‘viral blocking’ effect. Additionally, Wolbachia densities may affect the strength of the reproductive manipulations it induces, including cytoplasmic incompatibility (CI), maternal inheritance rates or induced fitness effects in the insect host. High rates of CI and maternal inheritance and low rates of fitness effects are also key to the successful spreading of Wolbachia through vector populations and its successful use in biocontrol. The factors that control Wolbachia densities are not completely understood. Methods We used quantitative PCR-based methods to estimate relative density of the Wolbachia w AlbB strain in both the somatic and reproductive tissues of adult male and female mosquitoes, as well as in eggs. Using correlation analyses, we assessed whether densities in one tissue predict those in others within the same individual, but also across generations. Results We found little relationship among the relative Wolbachia densities of different tissues in the same host. The results also show that there was very little relationship between Wolbachia densities in parents and those in offspring, both in the same and different tissues. The one exception was with ovary–egg relationships, where there was a strong positive association. Relative Wolbachia densities in reproductive tissues were always greater than those in the somatic tissues. Additionally, the densities were consistent in females over their lifetime regardless of tissue, whereas they were generally higher and more variable in males, particularly in the testes. Conclusions Our results indicate that either stochastic processes or local tissue-based physiologies are more likely factors dictating Wolbachia densities in Ae. aegypti individuals, rather than shared embryonic environments or heritable genetic effects of the mosquito genome. These findings have implications for understanding how relative Wolbachia densities may evolve and/or be maintained over the long term in Ae. aegypti . Graphical Abstract ... The specific PCR products generated by each set of primers were cloned into the pMD-18T vector (Takara) to generate standard curves. Primers for rps6 (Zheng et al. 2019) and wsp of wPip (Liang et al. 2020), wAlbA (Tortosa et al. 2008) , and wAlbB (Zheng et al. 2019) have been previously reported. ... Quality control of long-term mass-reared Aedes albopictus for population suppression Sep 2021 J PEST SCI Yongjun Li Meichun Zhang Xiaohua Wang Zhiyong Xi The endosymbiotic bacterium Wolbachia is being developed as a tool to suppress mosquito populations and their transmitted pathogens, with successful field trials in multiple countries having resulted in efforts to scale up the capacity to mass-produce mosquitoes for release. However, major challenges exist to achieving this goal, including concerns that mass-reared mosquitoes will adapt to laboratory conditions during long-term maintenance and experience inbreeding depression, resulting in poor performance of the released mosquitoes in the field. Here, we assessed the performance of the Aedes albopictus HC line infected with a triple-strain Wolbachia after mass-rearing at scaled-up densities of up to 15 million mosquitoes per week for over 50 generations. In comparison with the wild-type GUA line, the HC mosquitoes had desirable characteristics for mass-rearing and release, including robust male mating competitiveness, high female reproductive capacity, reduced vector competence for dengue virus, and increased Wolbachia density. Although the larval survival rate of the HC and GUA lines was similar, the HC larvae developed significantly faster, possibly because of up-regulation of the molting hormone 20-hydroxyecdysone-related gene E75 in the HC larvae. Our results indicate that over many generations mass-reared mosquito lines can retain their quality if large effective population sizes with sufficient genetic heterogeneity are maintained under optimized rearing conditions and demonstrate the long-term feasibility of deploying Wolbachia -based approaches for area-wide management of mosquito vectors for disease control. ... p < .0001; Figure 1k and Table 2d) Table 3d). In different arthropod host species, Wolbachia may either protect (e.g., Braquart-Varnier et al., 2015;Hughes, Koga, Xue, Fukatsu, & Rasgon, 2011;Kambris, Cook, Phuc, & Sinkins, 2009;Moreira et al., 2009;Panteleev et al., 2007;Teixeira, Ferreira, & Ashburner, 2008), have no effect (e.g., Tortosa, Courtiol, Moutailler, Failloux, & Weill, 2008; Wong, Hedges, Brownlie, & Johnson, 2011;Zouache, Michelland, Failloux, Grundmann, & Mavingui, 2012), or even increase the susceptibility (e.g., Graham et al., 2012;Hughes et al., 2014) of its arthropod hosts to infection depending on the pathogens tested, the Wolbachia strain (e.g., Chrostek et al., 2013;Martinez et al., 2017;Osborne, Leong, O'Neill, & Johnson, 2009), but also the host genetic background (although to a lesser extent; e.g. Martinez et al., 2017). ... Population-specific effect of Wolbachia on the cost of fungal infection in spider mites Article Full-text available Flore Zélé Mustafa Altintas Inês Santos Sara Magalhaes Many studies have revealed the ability of the endosymbiotic bacterium Wolbachia to protect its arthropod hosts against diverse pathogens. However, as Wolbachia may also increase the susceptibility of its host to infection, predicting the outcome of a particular Wolbachia‐host–pathogen interaction remains elusive. Yet, understanding such interactions and their eco‐evolutionary consequences is crucial for disease and pest control strategies. Moreover, how natural Wolbachia infections affect artificially introduced pathogens for biocontrol has never been studied. Tetranychus urticae spider mites are herbivorous crop pests, causing severe damage on numerous economically important crops. Due to the rapid evolution of pesticide resistance, biological control strategies using entomopathogenic fungi are being developed. However, although spider mites are infected with various Wolbachia strains worldwide, whether this endosymbiont protects them from fungi is as yet unknown. Here, we compared the survival of two populations, treated with antibiotics or naturally harboring different Wolbachia strains, after exposure to the fungal biocontrol agents Metarhizium brunneum and Beauveria bassiana. To control for potential effects of the bacterial community of spider mites, we also compared the susceptibility of two populations naturally uninfected by Wolbachia, treated with antibiotics or not. In one population, Wolbachia‐infected mites had a better survival than uninfected ones in absence of fungi but not in their presence, whereas in the other population Wolbachia increased the mortality induced by B. bassiana. In one naturally Wolbachia‐uninfected population, the antibiotic treatment increased the susceptibility of spider mites to M. brunneum, but it had no effect in the other treatments. These results suggest that natural Wolbachia infections may not hamper and may even improve the success of biological control using entomopathogenic fungi. However, they also draw caution on the generalization of such effects, given the complexity of within‐host–pathogens interaction and the potential eco‐evolutionary consequences of the use of biocontrol agents for Wolbachia‐host associations. ... Twenty-eight mosquitoes from regions with local dengue cases (Guangzhou and Jinghong), with only imported cases (Xiamen and Haikou) and without dengue cases (Wenchang and Fuzhou) were amplified individually by quantitative PCR using strain-specific primers qAF/qAR [27] and qBF/qBR ( We used a serial dilution of pEASY ® -T5 Zero Cloning vectors containing one copy each of RPS6 [28], wAlbAq-wsp and wAlbBq-wsp gene fragments, and used their primers set up in each PCR to plot standard curves, in case any binding efficiency difference appeared. Every mosquito DNA template was quantified three times for each of the RPS6, wAlbAq-wsp and wAlbBq-wsp genes. ... Identification and molecular characterization of Wolbachia strains in natural populations of Aedes albopictus in China Article Full-text available Jan 2020 Yaping Hu Zhiyong Xi Xiao-Bo Liu Qi-Yong Liu Background: Aedes albopictus is naturally infected with Wolbachia spp., maternally transmitted bacteria that influence the reproduction of hosts. However, little is known regarding the prevalence of infection, multiple infection status, and the relationship between Wolbachia density and dengue outbreaks in different regions. Here, we assessed Wolbachia infection in natural populations of Ae. albopictus in China and compared Wolbachia density between regions with similar climates, without dengue and with either imported or local dengue. Results: To explore the prevalence of Wolbachia infection, Wolbachia DNA was detected in mosquito samples via PCR amplification of the 16S rRNA gene and the surface protein gene wsp. We found that 93.36% of Ae. albopictus in China were positive for Wolbachia. After sequencing gatB, coxA, hcpA, ftsZ, fbpA and wsp genes of Wolbachia strains, we identified a new sequence type (ST) of wAlbB (464/465). Phylogenetic analysis indicated that wAlbA and wAlbB strains formed a cluster with strains from other mosquitoes in a wsp-based maximum likelihood (ML) tree. However, in a ML tree based on multilocus sequence typing (MLST), wAlbB STs (464/465) did not form a cluster with Wolbachia strains from other mosquitoes. To better understand the association between Wolbachia spp. and dengue infection, the prevalence of Wolbachia in Ae. albopictus from different regions (containing local dengue cases, imported dengue cases and no dengue cases) was determined. We found that the prevalence of Wolbachia was lower in regions with only imported dengue cases. Conclusions: The natural prevalence of Wolbachia infections in China was much lower than in other countries or regions. The phylogenetic relationships among Wolbachia spp. isolated from field-collected Ae. albopictus reflected the presence of dominant and stable strains. However, wAlbB (464/465) and Wolbachia strains did not form a clade with Wolbachia strains from other mosquitoes. Moreover, lower densities of Wolbachia in regions with only imported dengue cases suggest a relationship between fluctuations in Wolbachia density in field-collected Ae. albopictus and the potential for dengue invasion into these regions. ... Braquart-Varnier et al. 2015;Cattel et al. 2016;Hughes et al. 2011;Kambris et al. 2009;Moreira et al. 2009;Panteleev et al. 2007;Teixeira et al. 2008;Ye et al. 2013), have no effect (e.g. Tortosa et al. 2008; Wong et al. 2011;Zouache et al. 2012), or even increase the susceptibility (e.g. Fytrou et al. 2006;Graham et al. 2012;reviewed in Hughes et al. 2014) of its arthropod hosts to infection depending on the pathogens tested, the Wolbachia strain (Chrostek et al. 2013;Martinez et al. 2017;Osborne et al. 2009), but also on the host genetic background, although to a lesser extend (Martinez et al. 2017). ... Population-specific effect of Wolbachia on the cost of fungal infection in spider mites Preprint Full-text available Apr 2019 Flore Zélé Mustafa Altintas Inês Santos Sara Magalhaes Many studies have revealed the ability of the endosymbiotic bacteria Wolbachia to protect its arthropod hosts against diverse pathogens. However, as Wolbachia may also increase the susceptibility of its host to infection, predicting the outcome of a particular Wolbachia -host-pathogen interaction remains elusive. Yet, understanding such interactions is crucial for disease and pest control strategies. Tetranychus urticae spider mites are herbivorous crop pests, causing severe damage on numerous economically important crops. Due to the rapid evolution of pesticide resistance, biological control strategies using generalist entomopathogenic are being developed. However, although spider mites are infected with various Wolbachia strains worldwide, whether this endosymbiont protects them from fungi is as yet unknown. Here, we compared the survival of two populations, treated with antibiotics or harbouring different Wolbachia strains, after exposure to the fungal biocontrol agents Metarhizium brunneum and Beauveria bassiana . In one population, Wolbachia affected survival in absence of fungi but not in their presence, whereas in the other population Wolbachia increased the mortality induced by B. bassiana . To control for potential effects of the bacterial community of spider mites, we also compared the susceptibility of two populations naturally uninfected by Wolbachia , treated with antibiotics or not. The antibiotic treatment increased the susceptibility of spider mites to M. brunneum in one naturally Wolbachia -uninfected population, but it had no effect in the other treatments. These results highlight the complexity of within-host pathogens interactions, and the importance of considering the whole bacterial community of arthropods when assessing the effect of Wolbachia in a particular system. View Show abstract ... Ae. albopictus actin gene was amplified with the forward primer actAlb-dir (GCA AAC GTG GTA TCC TGA C) and reverse primer actAlb-rev (GTC AGG AGA ACT GGG TGCT). A standard curve mentioned by Tortosa et al. [38] was used as the reference. q-PCR reactions were performed in a 20 µl total volume containing 2 ng of genomic DNA, 0.5 µM of each primer and 3 µl of FastStart Universal SYBR Green Master (Roche). ... Wolbachia Population in Vectors and Non-vectors: A Sustainable Approach Towards Dengue Control Article Full-text available Feb 2019 CURR MICROBIOL Ipsita Mohanty Animesha Rath Swayam Prava Swain Rupenangshu Kumar Hazra Wolbachia is gram negative obligate endosymbiont known for reproductive manipulation in the host. It is important to study the presence of natural Wolbachia in mosquitoes which can later help in understanding the effect of transfected strain on indigenous strain. With this view, the present study is undertaken to focus on the prevalence, diversity, infection frequencies, phylogeny and density of indigenous Wolbachia strains in wild mosquito species of Odisha. Our study confirms Wolbachia presence in Ae. albopictus, Cx. quinquefasciatus, Cx. vishnui, Cx. gelidus, Ar. subalbatus, Mn. uniformis, and Mn. indiana. Wolbachia in the above mosquitoes were separated into two supergroups (A and B). Ae. albopictus, the major vector of dengue and chikungungunya had both super-infection and mono-infection. The ovaries of Ae. albopictus were highest in density of Wolbachia as compared to midguts or salivary glands. wAlBA and wAlbB density were variable in mosquitoes of F1 generation for both the sex and at different age. We also found that Wolbachia super-infection in females tends to increase whereas wAlbA density reduced completely as compared to wAlbB in males when they grew old. Giemsa stained squashed ovaries revealed pink pleomorphic Wolbachia cells with different shapes and forms. This study is unique in its kind covering the major aspects of the endosymbiont Wolbachia and focusing on its potential as a biocontrol agent in arboviral outbreaks. Knowledge on potential of the indigenous strain and interactions between Wolbachia and viruses can be utilized further to reduce the global burden of vector borne diseases. ... The relative abundance of gut bacteria was monitored by qPCR using the hypervariable V5-V6 regions of the16S rRNA gene and the actin gene for the host. Standard curves were plotted on 10fold serial dilutions from 1 × 10 8 to 1 × 10 1 copies/μL of a purified PCR product from the targeting 16S rRNA gene region of Acinetobacter and a DNA plasmid (pQuantAlb) (Tortosa et al. 2008) containing the actin gene fragment. The 20 µL reaction contained 5 ng DNA of template, 1X LightCycler DNA Master SYBR Green I (Roche Applied Science, Switzerland) and the primers 784F (5'-AGGATTAGATACCCTGGTA-3') and 1061R (5'-CRRCACGAGCTGACGAC-3') at 300 nM for the16S rRNA gene or ActAlbdir (5'-GCAAACGTGGTATCCTGAC-3') and ActAlbrev (5'-GTCAGGAGAACTGGGTGCT-3') at 200 nM for the actin gene. ... Short-term impacts of anthropogenic stressors on Aedes albopictus mosquito vector microbiota Article Sep 2018 Morgane Guégan Guillaume Minard Florence Hélène Tran Claire Valiente Moro Recent studies have highlighted the potential role of microbiota in the biology of the Aedes albopictus mosquito vector. This species is highly anthropogenic and exhibits marked ecological plasticity, with a resulting high potential to colonize a wide range of habitats—including anthropized areas—under various climatic conditions. We put forward the hypothesis that climate and anthropogenic activities, such as the use of antibiotics in agriculture and human medicine, might affect the mosquito-associated bacterial community. We thus studied the additive impact of a temperature decrease and antibiotic ingestion on the temporal dynamics of Ae. albopictus survival and its associated bacterial communities. The results showed no effects of disturbances on mosquito survival. However, short-term temperature impacts on bacterial diversity were observed, while both the community structure and bacterial diversity were affected by early antibiotic ingestion. The genera Elizabethkingia, Chryseobacterium and Wolbachia, as well as an unclassified member of the Bacteroidales order were particularly affected. Antibiotics negatively impacted Elizabethkingia abundance, while Chryseobacterium was completely eliminated following both disturbances, to the benefit of Wolbachia and the unclassified Bacteroidales species. These results generated fresh insight into the effects of climate and anthropogenic activities such as the use of antibiotics on mosquito microbiota. Wolbachia Inhibits Binding of Dengue and Zika Viruses to Mosquito Cells Article Full-text available Aug 2020 Peng Lu Qiang Sun Ping Fu Zhiyong Xi As traditional approaches to the control of dengue and Zika are insufficient, significant efforts have been made to develop utilization of the endosymbiotic bacterium Wolbachia to reduce the ability of mosquitoes to transmit pathogens. Although Wolbachia is known to inhibit flaviviruses in mosquitoes, including dengue virus (DENV) and Zika virus (ZIKV), it remains unclear how the endosymbiont interferes with viral replication cycle. In this study, we have carried out viral binding assays to investigate the impact of the Wolbachia strain wAlbB on the attachment of DENV serotype 2 (DENV-2) and ZIKV to Aedes aegypti Aag-2 cells. RNA interference (RNAi) was used to silence a variety of putative mosquito receptors of DENV that were differentially regulated by wAlbB in Aag-2 cells, in order to identify host factors involved in the inhibition of viral binding. Our results showed that, in addition to suppression of viral replication, Wolbachia strongly inhibited binding of both DENV-2 and ZIKV to Aag-2 cells. Moreover, the expression of two putative mosquito DENV receptors – dystroglycan and tubulin – was downregulated by wAlbB, and their knock-down resulted in the inhibition of DENV-2 binding to Aag-2 cells. These results will aid in understanding the Wolbachia-DENV interactions in mosquito and the development of novel control strategies for mosquito-borne diseases. Wolbachia strain wAu efficiently blocks arbovirus transmission in Aedes albopictus Preprint Full-text available Nov 2019 Maria Vittoria Mancini Christie Herd Thomas Ant
https://www.researchgate.net/publication/224745191_Chikungunya-Wolbachia_interplay_in_Aedes_albopictus
Browsing Knowledge Repository by Subject "LAND USE" Browsing Knowledge Repository by Subject "LAND USE" Sustainability of Biogas and Solid Biomass Value Chains in Ethiopia: Results and Recommendations from Implementation of the Global Bioenergy Partnership Indicators - Summary  United Nations Environment Programme ; Food and Agriculture Organization of the United Nations ( 2019 ) The Global Bioenergy Partnership (GBEP) project provides technical assistance to government officials and experts in Ethiopia and Kenya to assess the sustainability of their bioenergy sectors and to build their capacity ... Sustainable Urban Infrastructure Transitions in the ASEAN Region: A Resource Perspective  United Nations Environment Programme ; International Resource Panel ( 2018 ) Drawing from the conclusions in the forthcoming global report of the International Resource Panel “The Weight of Cities: Resource Requirements of Future Urbanization” this regional report aims to support policy makers by ... 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Towards Zero-Pollution Cities: Making Mega Cities Resource Efficient, Inclusive, and Low Polluting - Delhi, India Case Study  United Nations Environment Programme ; International Resource Panel ( 2017 ) Delhi, India is typical of many megacities in Asia and Africa, with large populations, swift economic growth that spurs in-migration, and an already stressed built environment with significant underserved populations lacking ... Training in Land and Coastal Use Planning: Case Study Venezuela - CEP Technical Report 13  United Nations Environment Programme ; Caribbean Environment Programme ( 1992 ) This project was originally designed to strengthen the capabilities of governments of the region to undertake environmentally sound development and to manage the marine and coastal resources by providing training in land ... 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World Atlas of Desertification: Second Edition  United Nations Environment Programme ( 1997 ) World atlas of desertification World Environment Day 2020 - A Practical Guide for Individuals, Faith Groups, Businesses, Cities, Governments, Schools & Universities, Youth Groups and Civil Society  United Nations Environment Programme ; ( 2020 )
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EudraCT Number 2012-005340-24 - Clinical trial results - EU Clinical Trials Register Clinical trials The European Union Clinical Trials Register allows you to search for protocol and results information on: interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the Clinical Trials Information System (CTIS). The EU Clinical Trials Register currently displays 43628 clinical trials with a EudraCT protocol, of which 7211 are clinical trials conducted with subjects less than 18 years old.   The register also displays information on 18700 older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006). Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ). Clinical Trial Results: An international, multicentre, randomised, open-label, no-treatment controlled, parallel group, dose-response study to investigate the effect of once daily nitisinone on 24-hour urinary homogentisic acid excretion in patients with alkaptonuria after 4-weeks treatment. Summary EudraCT number 2012-005340-24 Trial protocol GB Global end of trial date 13 Dec 2013 Results information Results version number v1(current) This version publication date 16 Jul 2022 First version publication date 16 Jul 2022 Other versions Summary report(s) SONIA 1 Main & Supplementary paper Trial Information Subject Disposition Baseline Characteristics End Points Adverse Events More Information Trial information Top of page Trial identification Sponsor protocol code SONIA1 Additional study identifiers ISRCTN number - US NCT number NCT01828463 WHO universal trial number (UTN) - Sponsors Sponsor organisation name University of Liverpool & Royal Liverpool University Hospital dom Sponsor organisation address Prescot St, Liverpool, United Kingdom, L7 8XP Public contact Principal Investigator, Royal Liverpool Unversity Hospital (RLUH), 0044 1517062000, [email protected] Scientific contact Principal Investigator, Royal Liverpool Unversity Hospital (RLUH), 0044 1517062000, [email protected] Paediatric regulatory details Is trial part of an agreed paediatric investigation plan (PIP) No Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? No Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? No Results analysis stage Analysis stage Final Date of interim/final analysis 10 Oct 2014 Is this the analysis of the primary completion data? Yes Primary completion date 13 Dec 2013 Global end of trial reached? Yes Global end of trial date 13 Dec 2013 Was the trial ended prematurely? No General information about the trial Main objective of the trial To investigate the effect of different doses of once daily nitisinone on 24-hour urinary homogentisic acid excretion (u-HGA24) in patients with alkaptonuria after 4-weeks treatment. Protection of trial subjects Short term study, so no specific protection, warning of ocular toxicity, and to inform study team if such events occured. Background therapy All and any co-coniment medications were allowed, no other background thearpy. Evidence for comparator No treatment (0mg) versus with 1, 2, 4 & 8mg. no comparator medication. Actual start date of recruitment 25 Mar 2013 Long term follow-up planned No Independent data monitoring committee (IDMC) involvement? Yes Population of trial subjects Number of subjects enrolled per country Country: Number of subjects enrolled United Kingdom: 15 Country: Number of subjects enrolled Slovakia: 25 Worldwide total number of subjects 40 EEA total number of subjects 40 Number of subjects enrolled per age group In utero 0 Preterm newborn - gestational age < 37 wk 0 Newborns (0-27 days) 0 Infants and toddlers (28 days-23 months) 0 Children (2-11 years) 0 Adolescents (12-17 years) 0 Adults (18-64 years) 37 From 65 to 84 years 3 85 years and over 0 Recruitment Recruitment details - Pre-assignment Screening details Inclusion criteria 1. Diagnosis of AKU verified by documented elevated urinary homogentisic acid excretion. 2. Age ≥18 years. 3. Willing and able to visit the investigational site for study visits. 4. Signed written informed consent given Exclusion criteria The presence of any of the following will exclude a patient from inclusion in the st Period 1 Period 1 title Overall trial (overall period) Is this the baseline period? Yes Allocation method Randomised - controlled Blinding used Not blinded Blinding implementation details The study was open label, since it is not feasible to blind a study with HGA-lowering treatment in AKU. One of the cardinal signs of AKU is urine darkening on standing as HGA is oxidised. Patients could therefore easily know whether they were on nitisinone or not. Furthermore, any personnel involved at the investigative sites who were involved in the processing of urine samples would also be able to see this difference. Arms Are arms mutually exclusive Yes Arm title Untreated Arm description No treatment provided Arm type No intervention Investigational medicinal product name No investigational medicinal product assigned in this arm Arm title 1 mg Arm description 1mg of nitisinone over 4 weeks Arm type Active comparator Investigational medicinal product name Nitisinone Investigational medicinal product code Other name Orfadin Pharmaceutical forms Suspension for oral suspension Routes of administration Oral use Dosage and administration details Suspension - oral 4 mg/mL dosage 1 mg (0.25 mL) Once daily Arm title 2mg nitisinone Arm description 2mg nitisinone daily over 4 weeks Arm type Active comparator Investigational medicinal product name Nitisinone Investigational medicinal product code Other name Orfadin Pharmaceutical forms Suspension for oral suspension Routes of administration Oral use Dosage and administration details Suspension - oral 4 mg/mL dosage 2 mg (0.50 mL) Once daily Arm title 4mg nitisinone Arm description 4mg of nitisinone daily over 4 weeks Arm type Active comparator Investigational medicinal product name Nitisinone Other name Orfadin Pharmaceutical forms Suspension for oral suspension Routes of administration Oral use Dosage and administration details Suspension - oral 4 mg/mL dosage 4 mg (1.0 mL) Once daily Arm title 8mg nitisinone Arm description 8mg of nitisinone daily over 4 weeks Arm type Active comparator Investigational medicinal product name Nitisinone Investigational medicinal product code Other name Orfadin Pharmaceutical forms Suspension for oral suspension Routes of administration Oral use Dosage and administration details Suspension - oral 4 mg/mL dosage 8 mg (2.0 mL) Once daily Number of subjects in period 1 Untreated 1 mg 2mg nitisinone 4mg nitisinone 8mg nitisinone Started 8 8 8 8 8 Completed 8 8 8 8 8 Baseline characteristics Top of page Baseline characteristics reporting groups Reporting group title Untreated Reporting group description No treatment provided Reporting group title 1 mg Reporting group description 1mg of nitisinone over 4 weeks Reporting group title 2mg nitisinone Reporting group title 4mg nitisinone Reporting group description 4mg of nitisinone daily over 4 weeks Reporting group title 8mg nitisinone Reporting group description 8mg of nitisinone daily over 4 weeks Reporting group values Untreated 1 mg 2mg nitisinone 4mg nitisinone 8mg nitisinone Total Number of subjects 8 8 8 8 8 40 Age categorical Units: Subjects In utero 0 Preterm newborn infants (gestational age < 37 wks) 0 Newborns (0-27 days) 0 Infants and toddlers (28 days-23 months) 0 Children (2-11 years) 0 Adolescents (12-17 years) 0 Adults (18-64 years) 0 From 65-84 years 0 85 years and over 0 Age continuous Units: years median (standard deviation) 45.9 ± 11.5 44.4 ± 10.9 43.9 ± 13.7 47.3 ± 10.7 54.4 ± 7.3 - Gender categorical Units: Subjects Female 4 1 3 3 2 13 Male 4 7 5 5 6 27 End points Top of page End points reporting groups Reporting group title Untreated Reporting group description No treatment provided Reporting group title 1 mg Reporting group description 1mg of nitisinone over 4 weeks Reporting group title 2mg nitisinone Reporting group description 2mg nitisinone daily over 4 weeks Reporting group title 4mg nitisinone Reporting group description 4mg of nitisinone daily over 4 weeks Reporting group title 8mg nitisinone Reporting group description 8mg of nitisinone daily over 4 weeks Primary: u-HGA24 in patients with AKU after 4 weeks of nitisinone treatment Top of page End point title u-HGA24 in patients with AKU after 4 weeks of nitisinone treatment End point description 24-hour urinary homogentisic acid excretion (u-HGA24) in patients with alkaptonuria after 4 weeks of treatment with nitisinone daily End point type Primary End point timeframe Baseline to 4 weeks End point values Untreated 1 mg 2mg nitisinone 4mg nitisinone 8mg nitisinone Number of subjects analysed 8 8 8 8 8 Units: mmol median (standard deviation) 31.0 ± 4.6 3.9 ± 1.7 1.6 ± 0.8 0.7 ± 0.4 0.1 ± 0.05 Statistical analysis title u-HGA24 at Week 4 Statistical analysis description The primary variable, u-HGA24 at Week 4, was analysed using a mixed model for repeated measures (MMRM). The model included the study site, treatment group, visit, and the interaction between treatment group and visit as fixed factors and the baseline u-HGA24 as a covariate. Comparison groups Untreated v 1 mg v 2mg nitisinone v 4mg nitisinone v 8mg nitisinone Number of subjects included in analysis 40 Analysis specification Pre-specified Analysis type other P-value = 0.523 Method Mixed models analysis Confidence interval Primary: u-HGA24 in patients with AKU after 4 weeks of nitisinone treatment Top of page Secondary: Serum HGA after 4 weeks of treatment with nitisinone Top of page End point title Serum HGA after 4 weeks of treatment with nitisinone End point description End point type Secondary End point timeframe Baseline to week 4 End point values Untreated 1 mg 2mg nitisinone 4mg nitisinone 8mg nitisinone Number of subjects analysed 8 0 [1] 0 [2] 0 [3] 0 [4] Units: mmol median (standard deviation) 30.5 ± 12.4 ± ± ± ± Notes [1] - Results not determined for this group. [2] - Results not determined for this group. [3] - Results not determined for this group. [4] - Results not determined for this group. No statistical analyses for this end point Secondary: Serum HGA after 4 weeks of treatment with nitisinone Top of page Secondary: Serum tyrosine after 4 weeks of treatment with nitisinone Top of page End point title Serum tyrosine after 4 weeks of treatment with nitisinone End point description End point type Secondary End point timeframe Baseline to week 4 End point values Untreated 1 mg 2mg nitisinone 4mg nitisinone 8mg nitisinone Number of subjects analysed 8 8 8 8 8 Units: mmol/L median (standard deviation) 56 ± 15 653 ± 106 715 ± 171 803 ± 155 813 ± 145 No statistical analyses for this end point Secondary: Serum tyrosine after 4 weeks of treatment with nitisinone Top of page Adverse events Top of page Adverse events information Timeframe for reporting adverse events The period for recording adverse events, begins from the time the subject has signed the informed consent until 28 days past the last dose of IMP Assessment type Systematic Dictionary used for adverse event reporting Dictionary name MedDRA Dictionary version 16.0 Reporting groups Reporting group title All participants Reporting group description - Serious adverse events All participants Total subjects affected by serious adverse events subjects affected / exposed 0 / 32 (0.00%) number of deaths (all causes) 0 number of deaths resulting from adverse events 0 Frequency threshold for reporting non-serious adverse events: 5% Non-serious adverse events All participants Total subjects affected by non serious adverse events subjects affected / exposed 11 / 32 (34.38%) Nervous system disorders Headache Substantial protocol amendments (globally) Were there any global substantial amendments to the protocol? Yes Date Amendment 19 Feb 2013 Following advice from the MHRA the following changes were made to the Protocol; Addition of slit-lamp eye assessment Addition of Demographics, Inclusion/exclusion criteria and slit lamp eye assessment and removal of standardized meals from Schedule of Events Change of visit 2 from home visit to hospital attendance Addition of information regarding rescue procedure Clarification of clinically significant abnormalities being reporting as adverse events in the Laboratory safety assessment section Changes to PIS/ICF; Change of visit 2 from home visit to hospital attendance Addition of eye examination to overview of study procedures Interruptions (globally) Were there any global interruptions to the trial? No Limitations and caveats None reported Online references http://www.ncbi.nlm.nih.gov/pubmed/25475116
https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005340-24/results
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In Vitro Assessment of Tolerance and Rejection Occurring After Co-Transplantation of Allogeneic Umbilical Cord Blood and Haploidentical CD34+ Cells as Treatment for Severe Aplastic Anemia | Blood | American Society of Hematology Abstract. Abstract 2352Introduction/Methods:. The administration of highly purified haploidentical peripheral blood CD34+ cells combined with an unrelated cord In Vitro Assessment of Tolerance and Rejection Occurring After Co-Transplantation of Allogeneic Umbilical Cord Blood and Haploidentical CD34+ Cells as Treatment for Severe Aplastic Anemia Nicole J. Gormley, MD , Nicole J. Gormley, MD 1 Critical Care, National Institutes of Health, CC, Bethesda, MD, USA, Aleah Smith , Blood (2010) 116 (21): 2352. https://doi.org/10.1182/blood.V116.21.2352.2352 Abstract Abstract 2352 Introduction/Methods: The administration of highly purified haploidentical peripheral blood CD34+ cells combined with an unrelated cord blood transplant results in earlier neutrophil engraftment than is typically seen with a cord blood transplant alone. Chimerism data from pilot trials evaluating this strategy have reported 3 phases of engraftment: 1) early myeloid engraftment from transplanted haplo-CD34+ cells followed by 2) cord blood engraftment resulting in dual chimerism and 3) the subsequent disappearance of haploidentical donor cells with resultant full donor cord chimerism. The mechanism accounting for the disappearance of haploidentical cells has not been defined. Here the clinical results and an in vitro assessment of alloreactivity in three patients that underwent combined haploidentical CD34+ cell and cord blood transplantation for severe aplastic anemia (SAA) are described. The conditioning regimen consisted of cyclophosphamide (60mg/kg/day on days -7 and -6), fludarabine (25mg/m2/day on days -5 to -1), horse ATG (40mg/kg/day on days -5 to -2), and total body irradiation (200cGy on day -1). GVHD prophylaxis consisted of tacrolimus and mycophenolate mofetil. PCR of STRs was used to assess chimerism in T-cell and myeloid lineages and mixed lymphocyte reaction assays(MLR) were performed on peripheral blood samples collected at different time-points post-transplant to assess for alloreactivity against the recipient, the haploidentical donor, or the cord unit. Stimulator cord blood cells for the MLR were obtained from residual cord blood cells remaining in the infusion bag after patient administration and expanded in vitro using anti-CD28/CD3 Dynabeads. Results: Prior to transplantation, all three pts had transfusion dependent SAA associated with severe neutropenia that was refractory to conventional immunosuppressive therapy. Pt 1 had an early transient myeloid recovery (ANC 400 on day+11) from the haploidentical donor followed by engraftment of the cord unit (Cord ANC > 500) on day 21. The patient is currently 2 years post transplant and has 100% cord blood chimerism and is transfusion independent. An MLR assay performed when donor T-cell chimerism was 100% cord, showed evidence for rejection of the haploid cells by cord blood T-cells, with the MLR response to haploidentical donor cells being seven fold higher than the response to fully HLA-mismatched 3 rdparty cells. In pt 2, neutrophil recovery from the transplanted haploidentical donor occurred on day +10, with chimerism studies showing no evidence for cord engraftment in either myeloid or T-cell lineages at any point post-transplant. The patient is currently 15 months post transplant and is transfusion independent with normal blood counts and sustained “split” chimerism (T-cells recipient in origin with myeloid cells being 100% haploidentical donor). MLR assays showed that the recipient was tolerant to the haploid donor, with no statistically significant difference in the alloreactive response to the haploid donor compared to self. In pt 3, neutrophil recovery from the transplanted haploidentical donor occurred on day +10, with chimerism studies showing split chimerism (T-cell chimerism >90% cord and myeloid chimerism 88–100% haploid donor in origin). MLR assays again showed evidence of rejection of the haploid cells by cord blood T-cells, with a trend towards greater alloreactivity against the haploid donor compared to an HLA mismatched 3 rdparty on post-transplant day +63. Conclusions: Combined haploidentical CD34+ cell and unrelated cord blood transplantation following highly immunosuppressive conditioning represents a viable treatment option for patients with SAA who lack an HLA-matched donor. Using this approach, 2 of 3 pts had cord blood engraftment associated with early neutrophil recovery from the haploidentical donor. In one pt, the cord unit failed to engraft. Remarkably, sustained engraftment from the haploidentical donor in this pt resulted in transfusion independence. MLR appears to be a useful approach to assess the in vitro alloreactivity of this unique stem cell graft source. In the two pts who had cord engraftment, in vitro MLR assessments established that the disappearance of haploid cells occurred as a consequence of rejection of the haploidentical cells by engrafting cord blood T-cells, rather than from non-immunological haploidentical cell graft failure. Figure 1. Results expressed as countsper minute (CPM). Pt 1 MLR was performed day + 101 post-transplant. (T-cell chemerism was 100% cord). The alloreactiveresponse to the haploidentical donor is seven fold higher than the response to HLA-mismatched 3 rdparty, suggesting, there is rejecttion of the haploid donor by the cordunit. In Pt 2. the cord unit failed to engraft, the MLR was performed on day +99 (T-cell chimerism 100% recipient, myeloid 99% hapolied donor). The alloreactiver esponse to the haploid donor was similar to the response to self. suggestomg tolerance. In pt 3. thee MLR was performed day +63 post-transplant (T-cell chimerism 79% cord. 22% recipient; Myeloid Chimerism 100% haploid donor). There is a trend to wards a greater alloreactive response against haploid donor compared to 3 rdparty, suggesting early rejection. Figure 1. Topics: aplastic anemia , rejection (psychology) , transplantation , umbilical cord blood , human leukocyte antigens , transfusion , umbilical cord blood transplantation , brachial plexus neuritis , tissue transplants ,
https://ashpublications.org/blood/article/116/21/2352/131773/In-Vitro-Assessment-of-Tolerance-and-Rejection
CONNIE gets closer to picturing reactor neutrinos | symmetry magazine A collaboration of the Americas aims to take the first pioneering images of low-energy neutrinos and provide new data to shed light on the mysterious identity of dark matter. Illustration by Sandbox Studio, Chicago with Steve Shanabruch CONNIE gets closer to picturing reactor neutrinos A collaboration of the Americas aims to take the first pioneering images of low-energy neutrinos and provide new data to shed light on the mysterious identity of dark matter. Around 2010, physicist Juan Estrada of the US Department of Energy’s Fermi National Accelerator Laboratory was working on an astrophysics instrument called the Dark Energy Camera. The camera was designed to survey a large swath of the Southern sky and provide pictures that could give insight into dark matter and dark energy, known to shape the structure and appearance of the whole universe. The remarkable sensors within the Dark Energy Camera were giving him an idea. They had gotten so sensitive that they might be able to detect other particles besides light. It seemed possible that they could even catch the whispers of faint particles called neutrinos. They would do this by using an elusive process called CEνNS (pronounced “sevens”), coherent elastic neutrino-nucleus scattering, in which neutrinos of a particularly low energy can bounce directly off of atoms in matter. Ten years later, after a great deal of work, Estrada and a team of over 30 physicists and engineers are getting close to realizing their goal. Their neutrino camera, the first of its kind, began operation in December 2014 at the Angra 2 reactor of the Angra Nuclear Power Plant, the only nuclear power plant in Brazil. The camera is called CONNIE, a friendly acronym for Coherent Neutrino Nucleus Interaction Experiment. Illustration by Sandbox Studio, Chicago with Steve Shanabruch From DECam to CONNIE CONNIE’s success hinges on those sensors found in the Dark Energy Camera, known as charged coupled devices. CCDs are a core technology behind digital cameras, used in everything from the Hubble Space Telescope to mobile phones. Over the last five years, Estrada and colleagues have made significant breakthroughs in CCD design. Funding for CONNIE has come from the Laboratory Directed Research and Development program at Fermilab, along with member institutions in Argentina, Brazil, Mexico, Paraguay and Switzerland. When CONNIE get its next upgrade, scheduled for 2021, its researchers should likely detect Angra’s neutrinos at last, via the billiard ball-like CEνNS process. Neutrinos are considered exceedingly strange compared to most other elementary particles. They are ubiquitous, created in all kinds of nuclear reactions such as fusion reactions that power the sun. But they are notoriously aloof, barely interacting with anything. A trillion solar neutrinos pass through your hand every second, but during your whole lifetime, only around a thousand will imperceptibly touch it. The neutrino measurements scientists hope to make with the CONNIE detector could eventually serve one of Estrada’s original aims: learning more about the dark matter that makes up the mass of 85% of the universe. Many models that predict the existence of low-mass dark matter particles also predict that neutrinos are more likely to interact with matter than currently expected. CONNIE will test these predictions by counting up the neutrinos that it detects outside Angra. A larger count than expected, for example, would give indirect support to these types of dark matter models. “The idea of detecting dark matter really drives my curiosity every day,” Estrada says. “At the same time, I am a person that really likes to build stuff.” The idea to build his experiment at a reactor came from recognition that reactors produce a huge flux of low-energy (about 1 MeV) neutrinos. Estrada and his team predicted that their sensitive CCDs should detect at least a few particles from out of this enormous output. But as they looked into placing their experiment at a reactor, they realized that they would have to get through a challenging amount of security and access restrictions. Fortunately, João Carlos dos Anjos, director of the National Observatory of Brazil, was already running an experiment in a shipping container at the Angra nuclear facility. Brazilian team members on the new CONNIE project connected with dos Anjos and, with his help, CONNIE moved in as a roommate with the existing experiment. After five years of on-site development, CONNIE has now reached the stage where it can be operated fully remotely via the internet. But physical intervention is still occasionally needed; for example, air conditioning units can and do fail in the Brazilian heat. Illustration by Sandbox Studio, Chicago with Steve Shanabruch Studying reactor neutrinos The site of the Angra nuclear facility is a four-hour drive west from Rio de Janeiro, along steep roads that hug the coastline and pass through the mountains. Heavy vehicles make the roads dangerous, but the area is considered one of the most beautiful in the region. The large shipping container that CONNIE lives in looks about as substantial as a gnat sitting next to the Angra 2 reactor’s giant white containment dome. CONNIE itself is small and compact. Many other experiments that detect neutrinos use huge containers of liquid, weighing in on the scale at metric tons. The bigger the target that the liquid presents, the more likely it is to catch a reclusive neutrino. When particles pass through CONNIE’s CCDs and interact with their material, the sensors build up electric charge, like rain buckets catching water. This is because the CCDs are actually printed silicon chips; incoming particles knock out charged electrons from the chips’ silicon atoms, or knock into nuclei that in turn knock out electrons from other atoms. A few times a day, researchers activate the CCD circuitry that empties this charge, the amount of which correlates with the number of particles that passed through the CCD. However, most of this charge is created by background particles other than neutrinos like cosmic rays that originate from the atmosphere and hit the detector. To tell how much of the collected charge is caused by neutrinos, physicists compare the CCD counts when the reactor is on—and neutrinos are firing—to the counts when the reactor is off. (The reactor shuts down one month out of every 14 for routine maintenance.) If CONNIE is actually catching neutrinos from the reactor, it should notice a drop in interactions when the reactor is off. “The strategy of analysis is reactor on minus reactor off, subtracting the contribution of background, and the hypothesis you’re making is that the background doesn’t change during the time,” says Carla Bonifazi, professor at Universidade Federal do Rio de Janeiro in Brazil, one of the physicists who leads the experiment locally. Though the detection process has yet to reveal neutrinos from the reactor, researchers have increasingly keyed into the obstacles. Illustration by Sandbox Studio, Chicago with Steve Shanabruch Skipper CCDs The CCDs that specialist fabricators at Lawrence Berkeley National Laboratory and Fermilab initially designed for CONNIE were extraordinarily thick and wide. That gave low-energy neutrinos plenty of space in which to bounce or scatter off atoms via the aforementioned CEνNS process. And when they send the CCD’s silicon atoms recoiling, these have the chance of knocking out electrons from other atoms—an electric charge that can be measured. But because of the low-mass and low-energy of the incoming neutrinos, the atoms that recoil away from them tend to do so too weakly to knock out electrons from other neighboring atoms. Hitting a silicon atom with a reactor neutrino is comparable to bouncing a ping pong ball off a truck—it creates only a tiny whisper of recoil. The CEνNS process was predicted theoretically over 40 years ago, but it was only measured for the first time in 2017 at the Spallation Neutron Source at Oak Ridge National Laboratory as part of a project known as COHERENT. “CONNIE is trying to do something even more challenging [than COHERENT], and it will be really awesome when they succeed,” says Kate Scholberg, a professor at Duke University and spokesperson for COHERENT. “They’re looking for neutrinos from nuclear reactors that are very copious but lower in energy by a factor of 10, so that they give really incredibly tiny recoils.” Because of the innovative design of CONNIE’s CCDs, scientists predicted the detector’s first scientific run in 2016 would catch neutrinos, but there turned out to be an unexpected problem. The recoiling nuclei in the CCD sometimes knock out electrons, but they also sometimes make the whole CCD sensor vibrate, like a ping pong ball hitting a truck but transferring its energy straight into the ground that the truck sits on. This process reduces or quenches the recoil energy available to knock out electrons. The quenching observed in the results in 2019 turned out to be larger than predicted, by a factor of five to 10, and the signal generated by neutrinos was therefore indistinguishable from electrical noise. CONNIE was sensitive enough to show only that no more than 40 times the expected neutrino interactions were present. To get much more sensitive, researchers have figured out how to get rid of the noise. Guillermo Moroni joined Estrada’s team in 2011 as a doctoral student at the Universidad Nacional del Sur in Argentina. In 2011, he led a study on how to design a modern CCD with almost no readout noise, known as a “skipper CCD.” “It was first invented in the ’90s, but nobody used it for 20 years,” Moroni says. “The problem is that it is very hard to operate. Most of the time we spent was to understand how to operate the sensor.” In the last several years, Moroni has also led development of its readout electronics. The skipper CCD uses a remarkably elegant principle to reduce noise. The neutrino-induced charge that collects in the sensor is moved to a kind of holding area, where it can be measured, moved back out, moved back in, and then measured again. The charge can be skipped in and out like this repeatedly, thousands of times. This slows down the readout process, but smears out practically all of the noise, just like rolling a die more and more times can increase the confidence that it’s fair. With a skipper CCD, even the tiniest recoils that knock out only a single electron can be precisely measured. Another experiment called SENSEI is already using skipper CCDs to get “incredible” results, Moroni says. CONNIE scientists plan to have its skipper upgrade sometime next year. Then, the detector should start catching neutrinos and measuring their interactions with matter, providing a powerful new source of data to search for phenomena like dark matter, undescribed by the Standard Model. CONNIE researchers from countries including Argentina, Brazil, Mexico, Paraguay and the USA are working to improve it in in other ways, too. They hope to move it inside the containment dome of the reactor so that it can experience an even higher flux of neutrinos, either at Angra or at a different reactor in Argentina. “It is clear that CONNIE is the most significant particle physics experiment in Brazil,” Bonifazi says. “It puts us on the front line of knowledge.”
https://www.symmetrymagazine.org/article/connie-gets-closer-to-picturing-reactor-neutrinos
Comparisons | Global Practice Guides | Chambers and Partners Corporate M&A 2023 Israel Contributed By Naschitz, Brandes, Amir & Co Law and Practice Authors Sharon Amir Tuvia Geffen Einat Rosu Idan Lidor Tal Eliasaf Naschitz, Brandes, Amir & Cois one of the largest full-service law firms in Israel, with more than 240 lawyers in all areas of commercial practice, including over 20 M&A partners and 70 M&A associates and other legal practitioners based principally in its head office in Tel Aviv. The firm has one of Israel’s powerhouse M&A practices, advising leading domestic and multinational corporations as well as investors and funds such as FIMI, Israel’s largest and most successful private equity fund. With extensive experience in cross-border M&A, the firm’s lawyers are among the most experienced and effective in Israel. They have been involved on the buy and sell sides of public and private M&A transactions that include several of the largest cross-border M&A deals ever done in Israel, such as the USD7.1 billion public merger of Frutarom with NYSE-listed International Flavors & Fragrances Inc. and the recent ILS2.5 billion public merger of TASE-listed Veridis Environment Ltd. and Infinya Ltd. The M&A practice is supplemented by the firm’s prominent capital markets, regulatory, competition, real estate, tax, labour and litigation practices. 1. Trends 1.1 M&A Market The number of mergers and acquisitions (M&A) in Israel decreased by approximately 40% in 2022, with 142 M&A deals in the year compared to 238 deals in 2021 (according to the PwC Israel 2022 M&A Report). However, the overall value of deals reached USD18 billion in 2022, an increase of 5% compared to the USD17.1 billion set in 2021 (excluding special purpose acquisition companies (SPACs) and IPOs). Overall, the number of M&A deals in 2022 (142) was greater than in 2020 (123). However, since the number of M&A deals decreased over the quarters as 2022 progressed, it is too early to determine whether the M&A market is back to the pre-2021 spike level. Average deal value rose in 2022 to USD202 million, which represents a 61% increase over the previous year’s average deal value of USD126 million. The significant increase in average deal value resulted primarily from the surge in the values of companies and from the increase in the number of megadeals in excess of USD1 billion in 2022, with three megadeals representing 37% of total 2022 deal value. 1.2 Key Trends Changes in the macro-economic environment in 2022 triggered high levels of market uncertainty, which, together with the increase in interest rates after a few years of “cheap” money, resulted in an unstable M&A market in 2022, with the number of deals decreasing as the year progressed. Given the high level of available capital that remains in the market and attractive target opportunities that are expected to surface as potential targets face cash flow concerns, the M&A volume is predicted to pick up in the mid to long term after a short-term breather to evaluate market uncertainties. The market continued to experience growth in the number of Israeli companies acquired by Israeli companies, which accounted for 19% of the deal count in 2022, with a total value of USD3.5 billion, compared with 16% of the deal count in 2021, with a total value of USD2.8 billion. An additional USD3.3 billion of deal value in 2022 was attributed to outbound M&A deals of Israeli companies acquiring targets outside of Israel. Overall, Israeli buyers contributed to 37% of the M&A deal value in 2022, reflecting the focus change of global Israeli players, shifting from M&A targets to M&A growth acquirers. Leveraged deals were at a decade low with a total of 12 deals, or 8% of all deals, reflecting the difficulty of executing attractive deals with the target prices soaring and the cost of funding increasing due to the spike in interest rate levels. 1.3 Key Industries As in previous years, hi-tech M&A deals dominated in 2022, with a deal value of USD9.3 billion – more than 50% of the total deal value in 2022. Finance, energy, consumer products and services also experienced growth in 2022 mainly due to a handful of high-value deals. 2. Overview of Regulatory Field 2.1 Acquiring a Company There are three primary methods of acquiring a public company in Israel: a statutory merger, a tender offer and a court-approved merger. Statutory Mergers Pursuant to Israel’s Companies Law 5759-1999 (Companies Law), a merger may only be effected between two Israeli companies. Therefore, most acquisitions of Israeli companies by non-Israeli buyers are effected by means of a reverse triangular merger, whereby the acquiring company forms an Israeli subsidiary, which is then merged with and into the Israeli target company. Tender Offers The second method of acquiring public companies is by way of a tender offer commenced by the buyer and directed to all company shareholders. If, as a result of the tender offer: shareholders holding less than 5% of the company’s shares had not accepted the offer and a majority of the shares held by shareholders that did not have a personal interest in the offer had accepted the offer; or shareholders holding less than 2% of the company’s shares had not accepted the offer, then, the Companies Law provides that the purchaser automatically acquires ownership of the remaining shares. However, if the purchaser is unable to purchase (together with the shares it holds) more than 95% or 98% (as applicable) of the company’s shares, the purchaser may not own more than 90% of the shares of the target company. In light of the high squeeze-out threshold, buyers rarely use a tender offer if the goal is to acquire 100% of a public company. Court-Approved Mergers (Scheme of Arrangement) The third method available for acquiring public companies is a court-approved merger. This procedure involves an application to a court in Israel on behalf of the target company. The court is authorised to approve the merger, after at least 75% of the shares participating in the vote of the target company, as well as a simple majority of those shareholders attending and voting at such a meeting (as well as creditors, if applicable), approve the merger. In addition, Israeli law permits the acquisition of all or a significant portion of the assets of an Israeli public company, in which case the approval of the selling company’s shareholders is not required. 2.2 Primary Regulators The primary regulators for M&A activity in Israel are the Israel Securities Authority (ISA), the Israel Competition Authority and the Israel Tax Authority. In addition, the Capital Market, Insurance and Savings Authority in the Ministry of Finance is the primary regulator responsible for approving acquisitions of regulated financial companies and fills a key role in such acquisitions. 2.3 Restrictions on Foreign Investments There are no general restrictions on foreign ownership of shares in Israeli companies, other than restrictions on residents of countries at war with the State of Israel. Israeli companies that participate in certain government funding programmes – eg, the research and development grants of the Israel Innovation Authority (formerly known as the Office of the Chief Scientist) and tax incentives of the Israeli Authority for Investments and Development of the Industry and Economy (formerly known as the Investment Centre) – require the approval of these agencies prior to certain changes in their shareholding, including when non-Israeli shareholders acquire specified ownership levels. 2.4 Antitrust Regulations Generally, an antitrust filing will be required in Israel for a transaction if each of the counterparties (together with controlling, controlled-by and under-common-control entities) has an annual turnover in Israel of at least ILS20 million, and both parties together have an aggregate annual turnover in Israel of at least ILS367 million. In addition, even if these thresholds are not met, a filing would still be required if: one of the parties (together with controlling, controlled-by and under-common-control entities) holds a monopoly in any given defined market in Israel; or as a result of the acquisition, the market share of the combined companies (together with controlling, controlled-by and under-common-control entities) in the production, sale, marketing or purchase of a particular asset and similar assets or in the provision of a particular service and similar services, would exceed 50%. 2.5 Labour Law Regulations Generally, the approval of employees is not required in M&A transactions. However, a change of control may, in certain circumstances, be deemed a termination of employment, entitling the employees to receive severance payment as if their employment had been terminated. It is also worth noting that employees cannot waive severance rights and certain other employee social rights, and that the enforceability of covenants not to compete in Israel is subject to limitations. 2.6 National Security Review There is currently no general national security review of acquisitions in Israel. However, the Israeli government has formed an oversight committee to review the national security aspects of foreign investments in Israel, which is tasked with evaluating and recommending whether, and in what scope, to implement such an acquisition review process. In addition, Israel may retain certain veto or other rights with respect to natural resources and companies providing essential services. 3. Recent Legal Developments 3.1 Significant Court Decisions or Legal Developments The COVID-19 pandemic triggered new challenges to the interpretation of material adverse change (MAC) clauses in M&A deals, with buyers seeking routes to walk away from deals signed before the COVID-19 pandemic had spread. A key Israeli M&A deal, which reached the Delaware Chancery Court, was the unsuccessful attempt of Nasdaq-listed Comtech Telecommunications to walk away from its USD580 million acquisition of Israeli-based and Nasdaq-listed Gilat Satellite (represented by NBA), asserting a MAC. NBA was successful in defending the case and obtaining a record USD70 million settlement fee. Since the litigation was settled before the case was fully litigated, the opportunity for a significant court decision affecting the interpretation of MAC clauses in the Israeli M&A context was missed. 3.2 Significant Changes to Takeover Law See 1. Trends. 4. Stakebuilding 4.1 Principal Stakebuilding Strategies The Companies Law provides that an acquisition of shares in a public company must be made by means of a “special tender offer” if, as a result of the acquisition, the purchaser would hold 25% or more of the voting rights in the company, unless there is already another shareholder of the company with 25% or more of the voting rights. Similarly, the Companies Law provides that an acquisition of shares in a public company must be made by means of a special tender offer if, as a result of the acquisition, the purchaser would hold more than 45% of the voting rights in the company, unless there is already a shareholder with more than 45% of the voting rights in the company. Accordingly, the ability to build a stake in a target that equals or exceeds 25% prior to launching a special tender offer or entering into merger discussions with the target is limited. 4.2 Material Shareholding Disclosure Threshold Any person who acquires an interest greater than 5% in a company listed on the Tel Aviv Stock Exchange (TASE) is required to notify the company of the acquisition. The company is then required to file a notice of this acquisition with the TASE and the ISA. Thereafter, any further sales or purchases of shares by that shareholder, for so long as the shareholder holds an interest above 5%, are subject to similar disclosure requirements. Shareholders seeking to cross the 25% or 45% ownership thresholds are required to commence a special tender offer as described in 4.1 Principal Stakebuilding Strategies. Shareholders of public Israeli companies listed on stock exchanges in the USA or the UK are subject to the reporting requirements that apply in those jurisdictions. 4.3 Hurdles to Stakebuilding Although there is no specific Israeli law that prohibits a company from introducing additional reporting thresholds beyond the mandatory statutory reporting requirements, Israeli companies do not introduce such requirements in their articles of association. Exceptions apply for companies in industries that require special regulatory approval for passing ownership thresholds, such as companies with licences from the Ministry of Communications, or banks and other regulated financial companies that require the approval of the Supervisor of the Capital Market, Insurance and Savings Authority in the Ministry of Finance when passing specified thresholds. 4.4 Dealings in Derivatives Dealing in derivatives is permitted. 4.5 Filing/Reporting Obligations Generally, the reporting obligations for derivatives are similar to the reporting obligations that apply to the underlying securities, as described in the responses to prior sections. 4.6 Transparency A shareholder is required to make known the purpose of its acquisition and intention if the shareholder commences a special tender offer as described in 4.1 Principal Stakebuilding Strategies. 5. Negotiation Phase 5.1 Requirement to Disclose a Deal A TASE-listed company is generally required to disclose active negotiations and the receipt of a non-binding letter of interest. However, other than in the case of public leakage, the company may defer disclosure until a definitive agreement is signed, if the board of directors determines that the disclosure of the negotiations and/or non-binding letter of intent may jeopardise the consummation of the transaction or have a detrimental effect on its terms. 5.2 Market Practice on Timing Generally, companies tend to rely on the exception described in 5.1 Requirement to Disclose a Dealto defer disclosure until a definitive agreement is signed. 5.3 Scope of Due Diligence In the context of friendly negotiated deals, it is common to perform detailed business, legal, accounting, finance, tax, intellectual property and other industry-specialised diligence, recognising that in general no post-closing indemnity obligations exist in public company deals. 5.4 Standstills or Exclusivity Standstills are generally not common in the Israeli market. On the other hand, it is common for the board of directors of a public company to undertake a certain exclusivity period as part of its business judgement, particularly if the company has already undertaken a market check process. “Go shop” provisions have also been included in several Israeli public deals in recent years. 5.5 Definitive Agreements Tender offer terms are generally not documented in a definitive agreement other than in the case of agreements between the bidder and a significant shareholder agreeing to accept the tender offer. 6. Structuring 6.1 Length of Process for Acquisition/Sale Mergers Following the execution of the definitive merger agreement, each merging party is required to convene a shareholders’ meeting to approve the merger (with advance notice of at least 35 days), and to file a formal merger proposal with the Israeli Companies Registrar. The Companies Registrar will effect the merger and issue a certificate of merger after the later of: 50 days after the filing of the merger proposal; or 30 days after approval of the merger by the shareholders of both merging companies. Tender Offers A tender offer must remain open for at least 14 days or, if the offer qualifies as a “special tender offer”, as discussed in the response to 4.1 Principal Stakebuilding Strategies, for at least 21 days. The maximum time period for maintaining a tender offer is 60 days, which may be extended if a competing bid is issued during that period. Court-Approved Mergers (Schemes of Arrangement) Following the execution of the definitive merger agreement, the company files a petition to the Israeli court to approve the convening of a shareholders’ meeting and a creditors’ meeting, which can take up to 30 days. The meetings to approve the merger are typically set within 30 days after the date of the court order. 6.2 Mandatory Offer Threshold See 2.1 Acquiring a Companyand 4.1 Principal Stakebuilding Strategies. 6.3 Consideration Israeli law does not regulate the types of consideration that may be paid in a takeover. In recent years, cash has been the more common acquisition consideration, but in periods when global interest rates are higher the number of deals that include share consideration tends to increase. If the consideration is paid in the form of shares or other securities, the bidder must comply with the relevant provisions of the Israeli Securities Law 5728-1968 (Israeli Securities Law), including filing and obtaining the approval of the ISA to publish an Israeli prospectus, unless a prospectus exemption is available. An exemption may apply if the buyer dual-lists its securities on the TASE. In an environment of deal uncertainty, parties may use caps, floors and collars to address fluctuation in share deals. 6.4 Common Conditions for a Takeover Offer With regard to mergers, Israeli law does not restrict the type of closing conditions that the parties may agree to include in the definitive merger agreement. Tender offers may be subject to conditions only with respect to the receipt of governmental consents, permits or licences that the bidder needs to acquire the shares; and to the affirmative offer acceptance by a minimum number of shares specified by the bidder in the tender offer document. A bidder may also withdraw a tender offer if unforeseen and unforeseeable circumstances have occurred since the announcement of the tender offer that have resulted in the offer terms being significantly different from those that a reasonable bidder would have offered had the conditions been known at the time of making the offer. 6.5 Minimum Acceptance Conditions The level of approvals varies, based on the transaction structure. Mergers A merger requires the approval of the board of directors and the shareholders of each merging company. Generally, a simple majority vote is required. However, a merger involving a controlling shareholder’s personal interest may trigger special majority vote requirements. Furthermore, a company may provide in its articles of association for a higher majority vote threshold. Shares held by the other merging company or certain affiliates are generally excluded from the vote. Tender Offers In order for the bidder to cross the 90% threshold in the full tender offer, the bidder must acquire either: more than 95% of the company’s shares (including the shares held by the bidder), and a majority of the shareholders that did not have a personal interest in the offer must have accepted the tender offer; or more than 98% of the company’s shares (including the shares held by the bidder), and in this instance the remainder of the shares are squeezed out. However, if the purchaser is unable to purchase more than 95% or 98%, as applicable, of the company’s shares, the purchaser may not own more than 90% of the shares. In the case of a special tender offer to cross the 25% or 45% ownership threshold, as described in 4.1 Principal Stakebuilding Strategies, at least 5% of the shares must accept the special tender offer. Court-Approved Mergers (Scheme of Arrangement) In addition to court approval, the merger is also subject to the approval of the holders of at least 75% of the shares present and voted as well as a simple majority of those shareholders attending and voting at the meeting. The approval of creditors may also be required in accordance with the court’s order. 6.6 Requirement to Obtain Financing The parties may agree to condition the merger upon the bidder obtaining financing. A bidder cannot condition a tender offer on obtaining financing. 6.7 Types of Deal Security Measures Merger agreements may contain provisions for break-up fees in the event that the merger is not consummated, typically due to the target company’s board exercising its “fiduciary out”. Non-solicitation, matching rights and force-the-vote provisions are also common; however, in recent years, the inclusion of limited-period “go shop” provisions, as an exception to non-solicitation, is also becoming more common, particularly in cases where the company did not perform a comprehensive market check before entering into a definitive merger agreement. As the COVID-19 pandemic has unfortunately become an ongoing concern, parties tend to negotiate the exclusion of COVID-19 pandemic effects in material adverse change (MAC) clauses, and to include representations, warranties and covenants to address compliance with COVID-19 measures. In certain cases, provisions are also included in the definitive agreements to address the need of the target and/or its global subsidiaries to repay COVID-related government grants and loans in different jurisdictions, such as the Paycheck Protection Program (PPP) loans in the USA. 6.8 Additional Governance Rights Generally, any agreement between a public company and its controlling shareholder (defined for this purpose as the holder of more than 25% of the shares) requires the special approval of shareholders without a personal interest in the matter. Accordingly, it is difficult for the bidder to obtain special rights from the public company. 6.9 Voting by Proxy Shareholders can vote by proxy in Israel. 6.10 Squeeze-Out Mechanisms See 2.1 Acquiring a Companyand 6.5 Minimum Acceptance Conditions. The squeeze-out threshold under Israeli law is very high, and therefore the acquisition of 100% of a public company is typically conducted by way of a statutory merger or court-approved merger and not by a tender offer. 6.11 Irrevocable Commitments In many friendly negotiated merger transactions, significant shareholders execute voting or support agreements with the buyer undertaking to vote in favour of the merger at the general meeting of shareholders. A voting or support undertaking typically provides that the shareholder may revoke its undertaking if the board of directors of the target company changes its recommendation in accordance with the terms of the merger agreement. 7. Disclosure 7.1 Making a Bid Public See 5.1 Requirement to Disclose a Deal. 7.2 Type of Disclosure Required As described in 6.3 Consideration, if the consideration is paid in the form of shares or other securities, the bidder must comply with the relevant provisions of the Israeli Securities Law, including filing and obtaining the approval of the ISA to publish an Israeli prospectus, unless a prospectus exemption is available. An exemption may apply if the buyer dual-lists its securities on the TASE. 7.3 Producing Financial Statements Depending on the scope of the transaction, pro forma financial statements may be required to be included in the disclosure documents. Israeli law requires financial statements to be prepared in accordance with International Financial Reporting Standards (IFRS). However, in the event the Israeli company is listed on a US stock exchange and is therefore also subject to SEC rules, then the Israeli Securities Law permits the company to report using US generally accepted accounting principles (GAAP). 7.4 Transaction Documents Generally, the Israeli Securities Law requires detailed disclosure of the key transaction documents, but it is not mandatory to file copies of the documents themselves. However, if the Israeli company, being listed on a US stock exchange, is also subject to SEC rules, then the Israeli Securities Law requires disclosure in the same manner as required under SEC rules, which would also include the filing of copies of the key transaction documents. 8. Duties of Directors 8.1 Principal Directors' Duties The approval of the board of directors is required with respect to a statutory merger and a court-approved merger. In fulfilling such a duty, the board of directors, by virtue of its duty of care and the duty of loyalty, has a duty to maximise shareholder value. In a statutory merger, the board of directors of each merging company is required to consider not only the interest of the shareholders but also the ability of the merged company to meet its obligations to its creditors. With respect to a full tender offer, in the absence of a specific provision regarding the required conduct of the board of directors, there is uncertainty as to whether the board of directors is required to evaluate the price offered and express its view, or leave the shareholders to make their own independent determination on the proposed terms, being a direct transaction between the bidder and the shareholders to which the company is not a party. In a special tender offer, the Companies Law requires the board of directors either to make a recommendation to its shareholders as to whether the offer is fair or, if it elects not to make such a recommendation, to disclose the reasons for not making one. 8.2 Special or Ad Hoc Committees In transactions involving parties in which directors, officers or significant shareholders have a personal interest or a conflict of interests, it is common for the board of directors to establish a special ad hoc committee of non-interested directors (or appoint the audit committee of the board of directors) to negotiate the transaction and present recommendations to the board of directors. 8.3 Business Judgement Rule Generally, in the absence of a conflict of interests, or of alleged self-dealing or conflict of interests scenarios, Israeli courts defer to the judgement of the board of directors of a target company in a takeover situation. It is also important to note that the Companies Law provides for specific approval procedures for transactions involving personal interests on the part of directors, officers or significant shareholders, which may trigger separate approval requirements by the independent audit committee and by a special majority vote of the non-interested shareholders. Israeli law also mandates personal interest disclosure by directors and prohibits a director from participating and voting at board and committee meetings on matters in which the director has a personal interest. In many cases, the courts focus their involvement on the manner in which the personal interest was disclosed and addressed in the context of the transaction approval. 8.4 Independent Outside Advice In transactions involving parties in which directors, officers or significant shareholders have a personal interest or a conflict of interests, it would be common for the special independent committee to engage its own legal counsel, separate from the target company’s counsel. In certain cases, the special committee would also engage a separate financial adviser, and – depending on the circumstances – that adviser would also provide a separate fairness opinion alongside, or instead of, the financial adviser of the entire board. 8.5 Conflicts of Interest Conflicts of interest have been the subject of judicial scrutiny in Israel. As noted in 8.4 Independent Outside Advice, given the specific approval procedures for transactions involving personal interests in the Companies Law, Israeli courts focus their judicial review on the manner in which the personal interest was disclosed and addressed in the context of the transaction approval. 9. Defensive Measures 9.1 Hostile Tender Offers Hostile tender offers are permitted in Israel. However, if the intent of the bidder is to acquire 100% of a target company, it is difficult to reach that with a tender offer, bearing in mind the high threshold for squeezing out shareholders who do not accept the tender offer, as described in 2.1 Acquiring a Companyand 6.5 Minimum Acceptance Conditions. Accordingly, hostile M&A activity is typically used as an avenue to engage a resisting incumbent board of directors, and, if successful, eventually leads to a merger structure recommended by the board (in its new or old composition). 9.2 Directors' Use of Defensive Measures The board of directors, by virtue of its duty of loyalty and duty of care, has a duty to maximise shareholder value, and to act in good faith and for the benefit of the company, which, depending on the circumstances, may include the use of defensive measures. 9.3 Common Defensive Measures A number of takeover defences are available to Israeli target companies, including a staggered board and the board’s ability to issue blank cheque preferred stock (which is not permitted for companies only traded on the TASE). 9.4 Directors' Duties See 9.2 Directors’ Use of Defensive Measures. 9.5 Directors' Ability to “Just Say No” In taking any action to frustrate a takeover attempt, the board of directors must carefully exercise its fiduciary duties to evaluate the proposal together with appropriate advisers, particularly in a scenario in which members of the board may be deemed to have a personal interest. The right of directors to “just say no” has not been tested in an Israeli court. 10. Litigation 10.1 Frequency of Litigation Although it has increased in recent years – an example of this being the Delaware Chancery Court MAC litigation of the Israeli M&A deal of Comtech and Gilat Satellite, as described in 3.1 Significant Court Decisions or Legal Developments– litigation is not common in M&A deals in Israel. It usually occurs in alleged self-dealing and conflict of interest scenarios. 10.2 Stage of Deal When litigation arises, it would typically be filed in the period after a definitive agreement is signed and announced and prior to the shareholders’ vote on the proposed transaction. 10.3 “Broken-Deal” Disputes See 3.1 Significant Court Decisions or Legal Developmentsfor an example. 11. Activism 11.1 Shareholder Activism Activism has become more popular in Israel in recent years, particularly in Israeli companies traded on US stock exchanges. Since many of the largest Israeli companies are traded on the NYSE and Nasdaq, the scope of activity in such companies has increased. Activists in Israeli companies typically focus on shaking up the board of directors, bringing in new blood to the board, encouraging M&A activity and cutting expenses. 11.2 Aims of Activists Activism has encouraged some companies to enter into M&A transactions. One example is the stakeholding position Starboard acquired in Mellanox, an Israeli company traded on the Nasdaq. The activist attempted to replace the board of directors and publicly encouraged Mellanox to reduce expenses and engage financial advisers to strategically evaluate M&A alternatives. Following such developments, Mellanox’s board of directors accepted an offer to sell 100% of the company to Nvidia for USD6.9 billion, and it delisted from the Nasdaq following completion of the recommended sale. As noted in 11.1 Shareholder Activism, activism has become more popular in Israel in recent years, particularly in Israeli companies traded on US stock exchanges. However, we do not believe such increase resulted from, or was impacted by, the COVID-19 pandemic. 11.3 Interference With Completion Although rare in the Israeli market, the USD800 million acquisition of Nasdaq-listed EZchip (represented by NBA) by Mellanox became the subject of activism interference by Raging Capital following the announcement of the definitive agreement and prior to the shareholders’ vote on the merger.
https://practiceguides.chambers.com/practice-guides/comparison/777/10513/17200-17204-17211-17214-17221-17227-17239-17244-17250-17256-17260
(PDF) X‑ray and Neutron Scattering of Water PDF | This review article focuses on the most recent advances in X-ray and neutron scattering studies of water structure, from ambient temperature to... | Find, read and cite all the research you need on ResearchGate X‑ray and Neutron Scattering of Water May 2016 Chemical Reviews116(13):7570–7589 DOI: 10.1021/acs.chemrev.5b00663 Authors: <here is a image f67b477b9f605ce6-9264ba135b54dc11> Katrin Amann-Winkel Johannes Gutenberg-Universität Mainz & Stockholm University <here is a image 651df8624816b54d-a90c9e086d0e4b0d> M-C Bellissent-Funel French National Centre for Scientific Research <here is a image ae357f02b2f6b0be-16da70ad58f8c641> Livia Bove French National Centre for Scientific Research (CNRS) and EPFL <here is a image 3c462af4c0e04fb6-65f28a2404174d29> Thomas Loerting University of Innsbruck Abstract and Figures This review article focuses on the most recent advances in X-ray and neutron scattering studies of water structure, from ambient temperature to the deeply supercooled and amorphous states, and of water diffusive and collective dynamics, in disparate thermodynamic conditions and environments. In particular, the ability to measure X-ray and neutron diffraction of water with unprecedented high accuracy in an extended range of momentum transfers has allowed the derivation of detailed O−O pair correlation functions. A panorama of the diffusive dynamics of water in a wide range of temperatures (from 400 K down to supercooled water) and pressures (from ambient up to multiple gigapascals) is presented. The recent results obtained by quasi-elastic neutron scattering under high pressure are compared with the existing data from nuclear magnetic resonance, dielectric and infrared measurements, and modeling. A detailed description of the vibrational dynamics of water as measured by inelastic neutron scattering is presented. The dependence of the water vibrational density of states on temperature and pressure, and in the presence of biological molecules, is discussed. Results about the collective dynamics of water and its dispersion curves as measured by coherent inelastic neutron scattering and inelastic X-ray scattering in different thermodynamic conditions are reported. <here is a image 84e872ec7f5abe1e-f85cc37705325e80> compares … <here is a image 482ce49d3b5dca8a-3f2cb2bedaea3d87> . Average O−O Coordination Number n OO (r) and First Peak Height g 1 As Determined by Three Different Studies a … <here is a image c1958b28b685b0e1-d433d26002874a32> Total X-ray differential scattering cross section dσ/dΩ(Q) of water 11 (solid red line). The sum of self-scattering, intramolecular scattering, and Compton scattering is indicated by the dashed black line. The total coherent X-ray scattering cross section, called the total structure factor S(Q) (inset, blue line), is obtained after subtraction of the self, intramolecular, and Compton scattering contributions from the total X-ray differential scattering cross section and after normalization as described in the text. The data presented here were taken from ref 11. … <here is a image 6574435aff88fffd-2897bee12e4f364b> Experimental structure factor, S(Q), derived from SAXS of H 2 O: (left, bottom to top at high Q) at 280, 284, 289, 293, 298, 302, 311, 320, 329, and 347 K; 51 (right, top to bottom at low Q) at 252, 254, 258, 263, 268, 273, 278, and 284 K. 52 Reprinted with permission from ref 51. Copyright 2009 National Academy of Sciences. Reprinted with permission from ref 52. Copyright 2010 American Institute of Physics Publishing LLC. … <here is a image cbf49a77e06d11b3-57a661bf196851f4> +2 (left) Isothermal compressibility determined from either macroscopic thermodynamic measurements (dashed line) 55 or extracted from the SAXS data (circles and squares). 51,52 (right) Concentration−concentration (S CC (k)), density−density (S(k)), and density−concentration (S NC (k)). 58 (inset) Isosurfaces at 253 K of high-density fields (yellow) and high tetrahedrality (blue) from TIP4P/2005 simulations. 59 The length of the box is ∼106 Å. Reprinted with permission from ref 51. Copyright 2009 National Academy of Sciences. Reprinted with permission from ref 52. Copyright 2010 American Institute of Physics Publishing LLC. … Figures - uploaded by Daniel Schlesinger X ‑ ray and Neutron Scattering of Water Katrin Amann-Winkel, † Marie-Claire Bellissent-Funel, * , ‡ Livia E. Bove, § , ∥ Thomas Loerting, ⊥ Anders Nilsson, † Alessandro Paciaroni, # Daniel Schlesinger, † and Lawrie Skinner ∇ † Department of Physics, AlbaNova University Center, Stockholm University, SE-106 91, Stockholm, Sweden ‡ LLB, CEA, CNRS, Universite ́ Paris-Saclay, CEA Saclay, 91191Gif-sur-Yvette, France § IMPMC, CNRS-UMR 7590, Universite ́ P&M Curie, 75252 Paris, France ∥ Institute of Condensed Matter Physics, E ́ cole Polytechnique Fe ́ de ́ rale de Lausanne, CH-1015 Lausanne, Switzerland ⊥ Institute of Physical Chemistry, University of Innsbruck, 6020 Innsbruck, Austria # Dipartimento di Fisica e Geologia, Universita ̀ di Perugia, Via Alessandro Pascoli, I-06123 Perugia, Italy ∇ Mineral Physics Institute, Stony Brook University, Stony Brook, New York 11794-2100, United States ABSTRACT: This review article focuses on the most recent advances in X-ray and neutron scattering studies of water structure, from ambient temperature to thedeeply supercooled and amorphous states, and of water di ffusive and collective dynamics, in disparate thermodynamic conditions and environments. In particular, the ability to measure X-ray and neutron di ff raction of water with unprecedented high accuracy in an extended range of momentum transfers has allowed the derivation of detailed O − O pair correlation functions. A panorama of the di ff usive dynamics of water in a wide range of temperatures (from 400 K down to supercooled water) and pressures (from ambient up to multiple gigapascals) ispresented. The recent results obtained by quasi-elastic neutron scattering under high pressure are compared with the existing data from nuclear magnetic resonance, dielectric and infrared measurements, and modeling. A detailed description of thevibrational dynamics of water as measured by inelastic neutron scattering is presented. The dependence of the water vibrational density of states on temperature and pressure, and in the presence of biological molecules, is discussed. Results about the collective dynamics of water and its dispersion curves as measured by coherent inelastic neutron scatteringand inelastic X-ray scattering in di ff erent thermodynamic conditions are reported. CONTENTS 1. IntroductionA 2. Water Structure from X-ray and Neutron Di ffrac- tion B 2.1. TheoryB 2.2. Di ff raction Measurements and Experimental Challenges C 2.3. Neutron Di ff raction Measurements of WaterD 2.4. X-ray Di ff raction Measurements of WaterE 2.5. Isotope E ff ects on the Structureof WaterE 2.6. Structure of Water as a Function of Temper- ature: From the Liquid to the Amorphous IcesF 2.6.1. Density Fluctuations(Small AngleScat- tering) F 2.6.2. Structure of Water in theLiquid StateG 2.6.3. Structure of Amorphous States of WaterG 3. Water Dynamics from Neutron ScatteringI 3.1. Di ff usive DynamicsI 3.2. Vibrational DynamicsK 3.2.1. General FeaturesK 3.2.2. Intermolecular VibrationsL 3.2.3. The Boson PeakL 3.2.4. Intramolecular VibrationsM 3.3. Collective DynamicsM 3.3.1. General FeaturesM 3.3.2. Fast SoundM 3.3.3. Low-Frequency BranchM 4. Conclusion: Going Further intothe Knowledge of the Structure and Dynamics of Water in Amor- phous States and under Extreme Conditions of Temperature and PressureN 4.1. Improvement for the Structure of WaterN 4.2. Improvement for the Dynamics of WaterN Author InformationN Corresponding AuthorN Author ContributionsN Notes N Biographies O Acknowledgments O Abbreviations P References P 1. INTRODUCTION Liquid water plays a central role in a wide range of scienti fic disciplines, such as physics, chemistry, geophysics, biology, Special Issue: Water - The Most Anomalous Liquid Received: November 10, 2015 Review pubs.acs.org/CR © XXXX American Chemical Society A DOI: 10.1021/acs.chemrev.5b00663 Chem. Rev. XXXX, XXX, XXX −XXX atmospheric chemistry, food science, cryoscience, water treat- ment, electrocatalysis, and biomedicine. It is one of the main components that have allowed life on Earth to develop. Its presence on other planets is a topic of much general interest. Water is an ever-present material in our lives. The distribution of water around the globe in fl uences weather on a daily basis, whereas on the longer time scale it has signi fi cantly shaped the geological and marine environment that we have today. Water has played and continues to play a highly signi fi cant role in the historical and political development of Man. In a scienti fi c context, water is a “ simple ” triatomic molecule with only two atomic components to constitute a hydride of oxygen, OH 2 . At room temperature water is a liquid, which distinguishes H 2 O from the hydrides of other elements close to oxygen in the periodic table, namely methane, ammonia, hydrogen sul fi de, hydrogen chloride, and so on: these compounds are all gaseous at room temperature. At subzero temperature, water nucleates to form a solid that is less dense than the liquid phase. When subject to pressure and temperature variation water shows an amazing richness of polymorphs: 16 crystalline phases have so far been identi fi ed, as well as di fferent amorphous forms. Water appears to have a number of unusual properties that account for its unique role in nature, and has frequently been termed as “ anomalous ” .Mostofwater ’ s “ anomalies ” derive from the presence of the hydrogen bond (HB), i.e. the electrostatic attraction between hydrogen atoms and the negatively charged region in the back of the oxygen site, and from the open, nearly tetrahedral, geometry of the molecule. The anomalous physical properties of water become enhanced upon supercooling below the freezing point. Lowering the temperature, the strength of the hydrogen bond network increases and both cooperative e ff ects between molecules and quantum e ff ects become relevant. Of note is that, despite its rather high energy, the dynamics of the hydrogen bond is very rapid (of the order of 1 ps), and weakly a ff ected by temperature 1 , 2 and pressure 3 variation, whereas the structural relaxation time increases by many orders of magnitude upon cooling. 4 The delicate balance between this short lifetime and the existence of a HB network linking molecules together well above its percolation threshold is not yet fully unraveled. One of the keys to disclosing water ’ s unique behavior thus resides in providing a coherent description of the hydrogen bond network structure and dynamics at the microscopic level on the broader range of thermodynamic conditions and environments. In this review article, we focus on the most recent structural and dynamic properties of water in many di ff erent conditions of temperature and pressure as derived by X-ray and neutron scattering experiments. These two techniques are complemen- tary and well appropriate to probe these properties at a microscopic level and on the time scale of the hydrogen bond dynamics. The research described here has been performed at world leading research facilities including the neutron high flux reactor at the Institut Laue-Langevin (ILL) in Grenoble, the neutron spallation source ISIS in the U.K., the X-ray synchrotron radiation source at the Argonne National Laboratory (APS) in the United States, the European Synchroton Radiation Facility (ESRF) in Grenoble, and the DESY (Deutsches Elektronen- Synchroton) in Hamburg. Several review articles have reported on water structure and dynamics, 5 − 10 but the recent advances in instrumentation for X- ray di ff raction both at synchrotron and Linac Coherent Light Source (LCLS) facilities, and for neutron di ff usion at reactor sources and pulsed sources facilities, provide nowadays extremely accurate data on water structure, 11 and gave access to previously unexplored states, 12 ,13 thermodynamic conditions, 12 ,14 , 3 ,15 and environments. 16 −18 In particular, the present article reviews the most recent X-ray and neutron di ff raction results about the structure of liquid water and amorphous ice. We discuss wide angle scattering at ambient temperature on an extended Q-range and with an unprecedented low noise contamination, small angle scattering on ambient and supercooled water performed in a large Q -range with high accuracy and reproducibility, as well as neutron di ff raction measurements on di ff erent amorphous ices produced by hyperquenching, vapor deposition, and pressure induced techniques. The translational and rotational di ffusive dynamics of water under pressure of several gigapascals, as probed by quasi-elastic neutron scattering (QENS), is discussed in comparison with NMR, dielectric relaxation, and infrared spectroscopy. Just as at colder temperature, the anomalous behavior of water becomes more pronounced at higher pressure. Vibrational dynamics of bulk liquid water and hydration water from biomolecular systems as probed by inelastic neutron scattering and inelastic X-ray scattering is presented and compared with the results of molecular modeling. 2.WATER STRUCTURE FROM X-RAY AND NEUTRON DIFFRACTION The microscopic structure of water is currently studied by using X-ray and neutron di ff raction techniques, which are comple- mentary as di ff erently sensitive to oxygen and hydrogen atoms, as described below. These di ff raction techniques allow access to the intermolecular pair correlation function g ( r) 19 of a system, i.e. the density probability of fi nding another atom lying in another molecule at a distance r from any atom. 2.1. Theory The basic theory for studies of X-ray and neutron scattering from molecular systems is well-known, 19 and only the essentials will be reported here. These scattering techniques measure the di ff erential scattering cross section d σ/d Ω that is essentially proportional to the structure factor S M of a monatomic system or to a weighted sum of partial structure factors for a polyatomic system. The di ff erential scattering cross section for scattering of neutrons or X-rays by an assembly of fi xed nuclei (forming molecules or not) is given in the static approximation by ∑∑ σ σ π Ω =⟨· ⟩+ aa i QQr d d ()exp[ ] 4 ij ij ij ij j (1) where a i is the scattering factor of atom i (for neutrons, a i = ⟨ b i ⟩is the coherent scattering length of the i nucleus; for X-rays, a i = f i is the atomic scattering factor). In the case of neutrons: we de fi ne the coherent and incoherent scattering lengths of the nucleus after averaging over all isotopes and nuclear spins: =⟨ ⟩ bb ii coh, =⟨⟩−⟨⟩ bbb [] ii i incoh, 221/2 and the incoherent scattering cross sections σ incoh, i =4 π ( b incoh, i) 2. This is simply the average and standard deviation of the sample ’s scattering length distribution respectively. Q =4 π sin θ / λ is the modulus of the scattering wave vector in the case of elastic scattering where 2 θ is the di ff raction angle and λ is the wavelength of the radiation; the vector r ij = r i − r j gives the Chemical Reviews Review DOI: 10.1021/acs.chemrev.5b00663 Chem. Rev. XXXX, XXX, XXX −XXX B relative position of scattering centers i and j . The broken brackets in eq 1 denote an average over the grand-canonical ensemble The di ff erential scattering cross section ( eq 1 ) can be split into a self-part ( i = j ) and a distinct part ( i ≠ j): σσ σ Ω= Ω+ Ω d/d(d/d )(d/d ) self distinc t (2) The self-part itself can be split into an incoherent and a self- coherent part σσσ Ω= Ω+ Ω ( d/d )(d/d )(d/d ) self coh self inco h self (3) The distinct part can be separated into intra- and intermolecular parts corresponding to correlations between atoms within the same molecule and atoms belonging to di fferent molecules, respectively: σσσ Ω=Ω+Ω ( d/d )(d/d )(d/d ) distinctintrainter (4) The di ff erential scattering cross section may thus be expressed by the relation σσ σ σ Ω= Ω+ Ω +Ω QQ Q Q d/d ()(d/d )()(d/d )( ) (d /d)() self intra inter (5) The structure factor of a molecular liquid S M ( Q )isde fi ned from the distinct part of the di ff erential scattering cross section. For a molecular liquid, it may be split into two parts: =+ S QfQDQ () ()() M 1 M (6) f 1 (Q ) is the molecular form factor and theD M ( Q ) function contains all the intermolecular contributions. For Q → 0, lim Q → 0 ( S M )= ρ k B T χ T , where ρ is the molecular number density, k B is the Boltzmann constant, T is the absolute temperature and χ T is the isothermal compressibility. S M ( ∞ )=( ∑ b i ,coh 2 )/(∑ b i ,coh 2 ) 2 is the asymptotic value of S M at large Q . For a molecular liquid it is important to remove the intramolecular contribution f 1 ( Q ) from the structure factor S M ( Q ) in order to access only the intermolecular contribution D M ( Q ). By Fourier transformation, one can calculate the pair correlation function g ( r) ∫ πρ =+ ∞ g rrQDQQrQ ()1/(2)( )sin()d1 2 0 M (7) for the intermolecular terms only. The function g ( r )isa combination of the di ff erent partial correlation functions. 2.2. Di ff raction Measurements and Experimental Challenges X-ray di ff raction studies of liquid water, which date back to the 1930s, give pair distribution functions g ( r ) with contributions mainly from oxygen − oxygen (O − O) correlations, g OO ( r ), and oxygen − hydrogen (O − H) correlations, g OH ( r ), while the hydrogen − hydrogen (H − H) correlations, g HH ( r ) give negligible contributions, as discussed below. The dominating O − O contribution exhibits peaks at 2.8 and 4.5 Å. 20 Although these peak positions have a ratio close to the 1.633 expected for a tetrahedral O − O − O angle, they are found to be broad and overlapping in ambient liquid water, leaving a wide range of O − O − O angles, rather than a well-de fi ned tetrahedral arrangement. The precise degree of tetrahedrality in ambient water thus remains a subject of debate, 5 , 21 − 23 and even though it can be easily quanti fi ed in atomistic models, the correspondence of models to actual water is often imperfect. It is clear, however, that liquid water is more disordered than the ideal tetrahedral arrangements of amorphous Si and low-density amorphous ice. Unlike ambient liquid water, these systems have well-de fi ned first peaks in their measured g ( r ) patterns, and an average number of nearest neighbors very close to 4.0. Though the four-coordinated motif is still the dominant one in water, a signi fi cant amount of three-coordinated motifs are present, consistent with the trigonal geometry of water electron density, as well as a large number of bifurcated interactions 24 accounted for by fi ve neighbors, and which play a fundamental role in the di ff usion mechanism. 25 While X-ray di ff raction patterns of water contain very little H − H information (the hydrogen atom only has one electron and its X-ray scattering cross section is thus very small), neutron di ff raction measurements on H 2 O − D 2 O mixtures can provide separated partial pair distribution functions ( g OO ( r ), g OH( r ), and g HH ( r ) assuming H − D equivalence). An early measurement of these g αβ ( r ) functions by Narten et al. 26 is shown in Figure 1. These three g αβ ( r ) patterns, and later improved measurements, provide detailed local structure information and a reference for models of liquid water. Precise partial g αβ ( r ) measurements, however, are often hard to achieve. First, three or more S( Q ) measurements must be decomposed into the three partial structure factors, and then these decomposed functions are Fourier transformed to obtain the g αβ ( r ) patterns. When obtaining g αβ ( r) functions, errors are often hard to track. Noise and systematic errors in S( Q ) can appear in the g ( r ) as unphysical oscillations and erroneous peaks. Hence precise measurements are required to obtain meaningful results, yet water poses added technical di ffi culties: X-rays scatter very weakly because of water ’ s low electron density, whereas the large incoherent neutron scattering cross section and low mass of H lead to large attenuation, multiple scattering, and recoil corrections in neutron di ff raction. The method of H − D substitution is also a bad case for isotope equivalence, resulting in H 2 O and D 2 O having slightly di ff erent structures and properties; for example, the D 2 O temperature of maximum density is 7.2 K higher than that of H 2 O. Several di fferent strategies for minimizing theseproblems are used in the literature, and inconsistencies have frequently led to disagree- ment. The di ff erent g αβ ( r ) contributions are shown in Figure 1. The more pronounced features of the g αβ ( r ) patterns are broadly correct, but as noted by the original authors, there are signi ficant errors present. These errors make the smaller features, such as the peak in g HH ( r ) ∼ 2.8Å, unreliable. Figure 1. Partial pair distribution functions obtained from neutron di ff raction and H − D substitution. Reprinted with permission from ref 26 . Copyright 1982 American Association for the Advancement of Science. Chemical Reviews Review DOI: 10.1021/acs.chemrev.5b00663 Chem. Rev. XXXX, XXX, XXX −XXX C Recently, the O − O distribution function g OO ( r ) has been determined to greatly improved accuracy from both neutron 27 and X-ray di ffraction 11 that agree almost quantitatively. 2.3. Neutron Di ff raction Measurements of Water Neutrons see nuclei, rather than the di ff use electron cloud seen by X-rays. This has the major advantage of allowing sensitivity to light atoms such as the hydrogens of water. A key property of neutron di ff raction is that the coherent scattering length b c depends on the isotope. The accepted coherent scattering lengths ( b c ) for O and H (data from ref 28 , with the exception 29 of 18 O) given in Table 1 demonstrate the large di fference between 1 H and D ( 2 H), as well as the small, but usable di fference between 16 O and 18O. Before accessing the di ff erential scattering cross section or the structure factor of water, corrections to the experimental data have to be done. Neutron di ff raction correction procedures for water have been described in detail many times. 27 ,30 ,31 Here we give an overview of the major problems and approaches taken to achieve optimum measurements. A major problem for water measurements is the large incoherent scattering cross section σ inc , which does not contain any structural information, but increases the multiple scattering and attenuation e ff ects. To reduce these multiple scattering and attenuation e ff ects arising from the large σ inc of H 2 O, it is often preferable to use H − D mixtures with less than 50% H 2 O. 31 Also, since the H − D isotope e ff ect is very similar to a temperature shift, 32 the isotope equivalence can be improved by measuring the di ff erent H − D mixtures at di ff erent temperatures, using the o ff sets determined by X-ray di ff raction as a guide. 31 −33 This e ff ect is expected to become signi fi cant in the supercooled regime where isotope e ff ects approximate a temperature shift of about ∼ 10 K. 33 By contrast, the isotope e ff ect in crystalline ices 34 is much smaller than in the supercooled liquid. Melting temper- atures, polymorphic transformation temperatures and triple points deviate by only ∼ 2 − 5 K upon H − D substitution. 31 A second problem is the Placzek fallo ff , arising from large inelasticity e ff ects due to the near-equal mass of H nuclei and incident neutrons. In general the ratio of low- Q to high- Q scattering levels from this fallo ff is approximately ( A +1) 2 / A2 , where A is the atomic mass. This shows that the fallo ff for 1 Hisa factor of 4, while for D it is 2.5, and for 16 O the factor is only 1.13. Figure 2 shows the total di ff erential scattering cross sections measured using di ff erent techniques showing the severity of the Placzek fallo ff for di ff erent measurement setups. Since the Placzek fallo ff depends most strongly on scattering angle (2 θ), one can reduce the slope over a given Q -range ( Q =4 π sin( θ )/ λ ) by using a constant θ , and varying λ . This is typically achieved using time-of- fl ight (TOF) neutron scattering at a pulsed neutron source ( Figure 2 , right). The use of high-energy neutrons in TOF measurements also reduces multiple scattering and attenuation e ff ects. In this method the wavelength of scattered neutrons is assigned according to their arrival time. TOF neutron measurements also incur technical di ffi culties: the wide range of wavelengths requires detailed analysis and modeling of e ff ects such as multiple scattering, Placzek, and sample attenuation corrections. Although we call the Placzek a fallo ff , for TOF neutron measurements the instrument geometry can result in this correction taking di ff erent shapes. Table 1. Key Neutron Scattering Parameters for Water Components (Coherent Scattering Length b c and Incoherent Scattering Cross Section σ inc a ) isotope b c 28 (fm) σ inc 28 (barn) 1 H − 3.742 80.27 2 H (D)6.6742.05 16 O 5.805 0 18 O 6.009 29 0 a Note the very large σ inc of 1 H (problematic), and the large di fference between b c values of 1 H and D (advantageous). Figure 2. Total di ff erential scattering cross sections of pure H 2 O and pure D 2O water as measuredby two di ff erent neutron scattering techniques. (left) Monochromatic neutrons ( λ = 0.5 Å) using the reactor source ILL (gray lines). The red line corresponds to the sum ofself plus intramolecular plus incoherent contributions (see section 2.1 for details). (right) Time-of- fl ight neutron di ff raction (TOF) at the pulsed neutron source ISIS, which usesa wide band of incident neutron energies ( λ ∼ 0.1 − 3 Å) (black lines). Reprinted with permission from ref 36 . Copyright 2012 IOP Publishing. Reprinted D Alternatively monochromatic neutron experiments, using a reactor source, vary only θ to collect a su ffi ciently wide Q-range ( Figure 2 , left). In this case Placzek fallo ff for H 2 O is large and problematic. One method for minimizing this problem is to use H 2 16 O and H 2 18 Odi ff erences, where the H − D content is identical in each sample; then only a small residual oxygen Placzek slope remains in the di ff erence between the two measurements, while partial structure factor information can also be obtained. 35 ,36 2.4. X-ray Di ff raction Measurements of Water X-ray scattering of water is caused by interactions of the incident X-ray photons with the electron density in the water molecule located mostly at the oxygen atom. The coherent part of the X- ray di ff raction signal is thus dominated by oxygen −oxygen correlations. This is in contrast to neutron di ff raction measure- ments, which are sensitive to scattering from both hydrogen (deuterium) and oxygen atoms. While D 2 O is a relatively strong coherent neutron scatterer it is a weak X-ray scatterer; on top of this, much of the measured scattered X-ray signal is either self- scattering or Compton scattering, leaving an extremely small coherent signal, as illustrated in Figure 3. However, an advantage of X-ray scattering compared to neutron scattering is the availability of large monochromatic flux at short wavelengths ( ∼ 0.1 Å); this allows angular corrections and statistical noise to be minimized in the measurements. Di ff erent approaches have been used in the literature to extract the X-ray structure factor quantifying the coherent intermo- lecular scattering from X-ray di ff raction measurements, and detailed comparisons of these schemes have been performed. 37 ,11 In the independent atom approximation (IAA), the concen- tration-weighted sum of the scattering intensity of the individual atoms is subtracted from the total scattering intensity. This atomic normalization scheme has been improved by the use of modi fi ed atomic form factors (MAFFs), f α , which take charge redistributions between the atoms within a water molecule and valence-electron delocalization due to chemical bonding into account. 38 In the molecular normalization scheme, on the other hand, the square of the molecular form factor (MFF), here denoted C ( Q), is subtracted from the scattering intensity. The MFF can be obtained from quantum calculations. 39 The resulting coherent intermolecular scattering intensity is commonly normalized by B ( Q )=( ∑ α c αf α (Q )) 2 and the square of the number of atoms per molecule (9 in the case of water), and the total X-ray structure factor S ( Q ) can thus be calculated: −= − S QIQCQBQ () 1 (()())/(9()) (8) The total structure factor mainly consists of contributions from O − O correlations, with a smallcontribution fromO −H correlations and a negligible contribution from H − H correla- tions ( ∼ 1% at Q <5Å − 1 and smaller elsewhere). The O −O partial structure factor can then be calculated by subtracting the intermolecular O − H contribution, which can be obtained from molecular dynamics simulations, combined X-ray and neutron di ff raction analyses, or, as recently demonstrated, from oxygen isotope substituted neutron di ff raction measurements. 35 As discussed already in section 2.1 , the real space molecular distribution can be obtained by Fourier transformation of the structure factor. For a detailed description of X-ray scattering analysis and correction procedures see refs 11 and 40. 2.5. Isotope E ff ects on the Structure of Water While the H − D substitution neutron di ff raction technique typically assumes structural equivalence between H 2 O and D 2O, X-ray di ff raction o ff ers the opportunity to investigate their di ff erences. Since isotopes have the same electron number, di ff erences observed with X-ray di ff raction between H 2 16 O, D 2 16 O, H 2 18 O, and D 2 18 O correspond directly to the non- equivalence of their structures. Such isotope di ff erence measure- ments fi nd that the H 2 O − D 2 O X-ray di ff erence is very similar to a temperature shift of 5 − 10 K, and that the di ff erence increases with decreasing temperature. 32 The H 2 18 O − H 2 16 OX-ray structure di ff erences, however, are roughly an order of magnitude smaller than the H 2 O − D 2 Odi ff erence. 35 A limitation of X-ray isotope di ff erence measurements is that they are mainly sensitive to the di ff erences in the O −O correlations ( g OO ( r )). Neutron scattering measurements, how- ever, are in principle able to give information on all three (O −O, O − H, and H − H) partial di ff erences from isotope e ff ects. This separation requires very high precision measurements, at several di ff erent concentration H − D mixtures, and/or resolving the very small scattering contrast between 16 Oand 18 Oenriched water. 35 ,41 Recent investigations about the isotope e ffect on the structure of liquid water have been focused on the r OD and r OH intramolecular bond lengths. When measured with H − D substitution, a 3% di ff erence is observed 42 in time-of- flight neutron di ff raction measurements at small angles, leading the authors to concur with an earlier X-ray Raman spectroscopy study 43 which concluded an enhanced hydrogen bond asymmetry in H 2 O in addition to the temperature o ff set reported by Hart et al. 32 Oxygen isotope substitution leads to smaller e ff ects where, e.g., monochromatic neutron di ff raction measure- ments using 18 O − 16 Odi ff erences fi nd r OD = 0.985 Å and r OD= 0.990 Å, a 0.5% di fference. 35 ,36 At least part of the di ff erence in results arises from the small size of the isotope e ff ect and the large corrections required of the data. The determination of the H −H and O − O intermolecular isotope e ff ects, especially at deep supercooling, is far from being achieved and would be of particular interest in future investigations. Figure 3. Total X-ray di ff erential scattering cross section d σ /d Ω ( Q )of water 11 (solid red line). The sum of self-scattering, intramolecular scattering, and Compton scattering is indicated by the dashed black line. The total coherent X-ray scattering cross section, called the total structure factor S ( Q ) (inset, blue line), is obtained after subtraction of the self, intramolecular, and Compton scattering contributions from the total X-ray di ff erential scattering cross section and after normalization as described in the text. The data presented here were taken from ref 11. Chemical Reviews Review DOI: 10.1021/acs.chemrev.5b00663 Chem. Rev. XXXX, XXX, XXX −XXX E 2.6. Structure of Water as a Function of Temperature: From the Liquid to the Amorphous Ices 2.6.1. Density Fluctuations (Small Angle Scattering). Small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS) are the most direct probes of density fl uctuations on diff erent length scales in a single component liquid. Through an enhancement of the structure factor at low momentum transfer, Q , small deviations from the average electron density at di ff erent length scales can be reliably identi fied. 44 Previous SAXS studies of water have mostly focused on the supercooled region and given contradictory results, reporting both positive 45 −47 and zero enhancement 48 ,49 at low Q. With the development of third-generation synchrotron light sources, the ability to perform SAXS has been greatly advanced and measurements can now be performed in a large Q -range with high accuracy and reproducibility. 50 Figure 4 depicts the scattering structure factor, S ( Q ), at di ff erent temperatures varying from 347 to 280 K 51 and from 284 K down to 252 K. 52 S ( Q ) shows an enhanced scattering asQ approaches zero where the slope of the curve changes from positive to increasingly negative and with a higher intercept with decreasing temperatures, indicating density fl uctuations in the system which increase at low temperatures. This is di fferent behavior in comparison to a simple liquid such as ethanol where instead the temperature variation is a parallel shift and there is no enhancement at low Q. 53 There is a thermodynamic relationship that relates the isothermal compressibility χ T to the structure factor at Q =0 as S (0) = ρ k B T χ T (see section 2.1). 54 Figure 5 compares the isothermal compressibility determined from measurements of the velocity of sound in water 55 and as obtained from the SAXS data
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JCM | Free Full-Text | Appropriateness of Allogeneic Red Blood Cell Transfusions in Non-Bleeding Patients in a Large Teaching Hospital: A Retrospective Study In hemodynamically stable patients, both anemia and red blood cell (RBC) transfusion may be detrimental to patients; hence, a decision regarding RBC transfusion should be based on thorough risk& ndash;benefit assessment. According to hematology and transfusion medicine organizations, RBC transfusion is indicated when recommended hemoglobin (Hb) triggers are met, and symptoms of anemia are present. The aim of our study was to examine the appropriateness of RBC transfusions in non-bleeding patients at our institution. We performed a retrospective analysis of all RBC transfusions performed between January 2022 and July 2022. The appropriateness of RBC transfusion was based on the most recent Association for the Advancement of Blood and Biotherapies (AABB) guidelines and some additional criteria. The overall incidence of RBC transfusions at our institution was 10.2 per 1000 patient-days. There were 216 (26.1%) RBC units appropriately transfused and 612 (73.9%) RBC units that were transfused with no clear indications. The incidence of appropriate and inappropriate RBC transfusions were 2.6 and 7.5 per 1000 patient-days, respectively. The most frequent clinical situations when RBC transfusion was classified as appropriate were: Hb & lt; 70 g/L plus cognitive problems/headache/dizziness (10.1%), Hb & lt; 60 g/L (5.4%), and Hb & lt; 70 g/L plus dyspnea despite oxygen therapy (4.3%). The most frequent causes of inappropriate RBC transfusions were: no Hb determination pre-RBC transfusion (n = 317) and, among these, RBC transfused as a second unit in a single-transfusion episode (n = 260); absence of anemia sings/symptoms pre-transfusion (n = 179); and Hb concentration & ge;80 g/L (n = 80). Although the incidence of RBC transfusions in non-bleeding inpatients in our study was generally low, the majority of RBC transfusions were performed outside recommended indications. Red blood cell transfusions were evaluated as inappropriate mainly due to multiple-unit transfusion episodes, absence of anemia signs and/or symptoms pre- transfusion, and liberal transfusion triggers. There is still the need to educate physicians on appropriate indications for RBC transfusion in non-bleeding patients. Appropriateness of Allogeneic Red Blood Cell Transfusions in Non-Bleeding Patients in a Large Teaching Hospital: A Retrospective Study by Piotr F. Czempik 1,2,* , Dawid Wilczek 3 , Jan Herzyk 3 and Łukasz J. Krzych 1 1 Department of Anaesthesiology and Intensive Care, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland 2 Transfusion Committee, University Clinical Center, Medical University of Silesia, 40-752 Katowice, Poland 3 Students’ Scientific Society, Department of Anaesthesiology and Intensive Care, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland Author to whom correspondence should be addressed. J. Clin. Med. 2023 , 12 (4), 1293; https://doi.org/10.3390/jcm12041293 Received: 2 January 2023 / Revised: 2 February 2023 / Accepted: 4 February 2023 / Published: 6 February 2023 Abstract In hemodynamically stable patients, both anemia and red blood cell (RBC) transfusion may be detrimental to patients; hence, a decision regarding RBC transfusion should be based on thorough risk–benefit assessment. According to hematology and transfusion medicine organizations, RBC transfusion is indicated when recommended hemoglobin (Hb) triggers are met, and symptoms of anemia are present. The aim of our study was to examine the appropriateness of RBC transfusions in non-bleeding patients at our institution. We performed a retrospective analysis of all RBC transfusions performed between January 2022 and July 2022. The appropriateness of RBC transfusion was based on the most recent Association for the Advancement of Blood and Biotherapies (AABB) guidelines and some additional criteria. The overall incidence of RBC transfusions at our institution was 10.2 per 1000 patient-days. There were 216 (26.1%) RBC units appropriately transfused and 612 (73.9%) RBC units that were transfused with no clear indications. The incidence of appropriate and inappropriate RBC transfusions were 2.6 and 7.5 per 1000 patient-days, respectively. The most frequent clinical situations when RBC transfusion was classified as appropriate were: Hb < 70 g/L plus cognitive problems/headache/dizziness (10.1%), Hb < 60 g/L (5.4%), and Hb < 70 g/L plus dyspnea despite oxygen therapy (4.3%). The most frequent causes of inappropriate RBC transfusions were: no Hb determination pre-RBC transfusion (n = 317) and, among these, RBC transfused as a second unit in a single-transfusion episode (n = 260); absence of anemia sings/symptoms pre-transfusion (n = 179); and Hb concentration ≥80 g/L (n = 80). Although the incidence of RBC transfusions in non-bleeding inpatients in our study was generally low, the majority of RBC transfusions were performed outside recommended indications. Red blood cell transfusions were evaluated as inappropriate mainly due to multiple-unit transfusion episodes, absence of anemia signs and/or symptoms pre- transfusion, and liberal transfusion triggers. There is still the need to educate physicians on appropriate indications for RBC transfusion in non-bleeding patients. Keywords: anemia ; hemoglobin ; indication ; patient blood management ; red blood cell ; transfusion ; trigger 1. Introduction The decision regarding red blood cell (RBC) transfusion constitutes a daily challenge to hospital physicians [ 1 ]. Transfusion of RBC in massive bleeding saves lives. As an unequivocally benefit in the context of bleeding, RBC transfusion is supported by clinical practice guidelines [ 2 ]. RBC transfusion performed outside bleeding emergency has a more complicated risk–benefit profile. In hemodynamically stable patients, both anemia and RBC transfusion may be detrimental to patients; hence, a decision regarding RBC transfusion should be based on thorough risk–benefit assessment. Anemia is an independent risk factor for myocardial ischemia, stroke, acute kidney injury, and infection [ 3 ]. Even mild anemia, defined as hemoglobin (Hb) concentration 110–130 g/L in men and 110–120 g/L in women, doubles long-term mortality in patients scheduled for major elective surgery or hospitalized in the intensive care unit (ICU) [ 4 , 5 ]. Anemia may lead to longer hospitalization [ 6 ]. Moreover, anemia may increase the odds of RBC transfusion [ 7 ]. On the other hand, transfusion of RBC may lead to prolonged respirator weaning or weaning failure [ 8 ], pneumonia [ 9 ] and other nosocomial infections, immunomodulation, transfusion-associated cardiac overload (TACO), transfusion-associated acute lung injury (TRALI), thromboembolic complications, allergic reactions, immunization, blood-born pathogen transmission, and early and delayed hemolytic reactions. Finally, RBC transfusion may lead to increased mortality [ 10 ] and longer hospitalization. Taking these into account, decisions regarding RBC transfusion in non-emergency setting should follow thorough risk–benefit assessment in an individual patient. Transfusion of RBC was listed by the American Board of Internal Medicine Foundation’s Choosing Wisely Campaign as one of the top five procedures for which rationale should be questioned by physicians and patients [ 11 ]. According to various organizations, RBC should be transfused at a restrictive threshold (i.e., Hb < 70 g/L) [ 12 ]. Moreover, the decision regarding RBC transfusion should be based not solely on Hb concentration but also on symptoms of anemia [ 13 ] or broader clinical context [ 14 ]. Even elderly patients may, if properly managed, tolerate very low Hb concentrations [ 15 ]. At last, in deciding on RBC transfusion, some authors suggest using the so called physiologic RBC transfusion triggers [ 16 , 17 , 18 ]. The aim of our study was to examine the appropriateness of RBC transfusions in non-bleeding patients at our institution. 2. Materials and Methods We performed a retrospective analysis of all RBC transfusions performed in non-bleeding patients between January 2022 and July 2022. We excluded RBCs that were transfused for bleeding (n = 301) or as preparation for surgery (n = 104). Our institution is a large tertiary medical center affiliated with a medical university with 644 hospital beds in two locations. Both subspecialty surgical and subspecialty medical disciplines are represented at the institution. Gastrointestinal surgery department admits patients scheduled for gastrointestinal oncologic and non-oncologic surgery. The oncologic surgery department is a small unit that admits patients scheduled for oncologic surgery of mostly the breast, thyroid, and pancreas. In the department of autoimmune and metabolic diseases, patients with various medical diagnoses are hospitalized; some of the patients are transferred from medical oncology departments due to deterioration after chemotherapy treatment. The clinical pharmacology department specializes in optimizing the pharmacotherapy of chronic conditions and treatment of patients with dyslipidemias. The intensive care unit (ICU) is a mixed medical–surgical department. There is no hematology department at the institution. Patients with hematological diseases are occasionally hospitalized in the departments of autoimmune and metabolic diseases and clinical pharmacology. All data were retrieved from the hospital electronic health records (AMMS, Asseco Medical Solutions, Rzeszów, Poland). The percentage of patients who received at least a single RBC was calculated for the institution in general and per hospital department. Incidence of RBC transfusions was calculated as the number of transfusions per 1000 patient-days. Demographic and clinical data on RBC recipients were retrieved: age, sex, hospital department, presence of signs and/or symptoms of anemia pre- and post RBC transfusion, laboratory markers of anaerobic metabolism (central venous oxygen saturation—ScvO 2 , mixed venous oxygen saturation—SvO 2 , blood lactate) pre- and post RBC transfusion, and Hb concentration up to 24 h pre- and post RBC transfusion. Hemoglobin concentration was determined using a venous blood sample, which is considered a gold standard for Hb determination. We evaluated appropriateness of RBC transfusion according to the most recent clinical practice guidelines from the Association for the Advancement of Blood and Biotherapies (AABB) [ 14 ]. When deciding on appropriateness of RBC transfusion, both Hb concentration and presence of signs and/or symptoms of anemia were taken into account. As an appropriate trigger for RBC transfusion, Hb concentration <70 g/L was used [ 12 ], whereas in patients with a history of coronary artery disease (CAD), Hb concentration < 80 g/L was used. All RBC transfusions with pre-transfusion Hb concentration < 60 g/L were classified as appropriate irrespective of anemia signs and/or symptoms. When pre-transfusion Hb concentration was 60–70 g/L, RBC transfusion was classified as appropriate when at least one sign and/or symptom of anemia was present, and/or at least one laboratory marker of anaerobic metabolism was abnormal. The signs and symptoms of anemia that were looked for in evaluating the appropriateness of RBC transfusion were: dizziness, lightheadedness, headache, problems with concentration, attention deficit, shortness of breath, tachycardia, hypotension, chest pain, and new electrocardiogram (ECG) changes. These cardiologic and respiratory signs and/or symptoms had to be present following attempts at improving patients’ tolerance of anemia through hemodynamic and oxygenation optimization. The most common markers of anaerobic metabolism at our institution, used as so-called physiologic transfusion triggers, were ScvO 2 and lactate. The other markers that are used as physiologic transfusion triggers are arterial–venous oxygen difference and oxygen extraction ratio. Physiologic transfusion triggers reflect the patient-sensitive and time-sensitive balance between global oxygen delivery and consumption. The patient’s tolerance of anemia depends on this fine balance. The cut-off value for ScvO 2 /SvO 2 (<55%), indicating a need for RBC transfusion, was derived from the published literature [ 19 ]. The cut-off value for blood lactate (>1.8 mmol/L) was based on the reference range from the local laboratory. Lactate was used in the past as a marker of an oxygen deficit, helping in the optimal timing of RBC transfusion [ 20 ]. Lactate was used as a physiologic transfusion trigger due to limited number of patients in whom ScvO 2 could be determined. Central venous oxygen saturation can only be determined in patients with a central line, with the tip of a central line being located in the lower part of superior vena cava. To sum up, clinical scenarios in which RBC transfusion was deemed appropriate are presented in Table 1 . Table 1. Appropriate red blood cell transfusion clinical scenarios. We classified as inappropriate all RBCs transfused outside the abovementioned clinical scenarios or RBCs transfused with no pre-transfusion Hb determination. At our institution, we support the one-unit transfusion policy [ 21 ]. The second unit of RBC transfused during a single-transfusion event was classified as inappropriate even if there were symptoms of anemia or positive laboratory markers of anaerobic metabolism prior to transfusion of the first unit, but no reassessment of Hb concentration, anemia signs/symptoms, or physiologic transfusion triggers was performed following the first RBC unit. Inappropriate RBC transfusions constituted RBC overuse. The incidence of RBC transfusions per 1000 patient-day was calculated as well as percentage of patients in whom at least a single RBC unit was transfused. We calculated the number of appropriately and inappropriately transfused RBCs overall and per hospital department. Statistical analysis was performed using MedCalc version 18 statistical software (MedCalc Software, Ostend, Belgium). Continuous variables were presented as median and interquartile ranges (IQR) for variables with non-normal distribution. The type of distribution was verified with Shapiro–Wilk test. Categorical variables were expressed as numbers and percentages. Statistical significance was established by the chi-square or the Fischer’s exact test. Intergroup differences were evaluated by the Mann–Whitney test. The variables pre–post RBC transfusion were analyzed using the Wilcoxson test. p < 0.05 was considered statistically significant. Due to retrospective character of the study, the local ethics committee decided that the study did not require the committee’s approval (PCN/CBN/0022/KB/292/21). 3. Results Out of 24,117 patients, 286 received at least a single RBC unit. The overall incidence of RBC transfusions at our institution was 10.2 per 1000 patient-days. The incidence of RBC transfusions and percentage of RBC-transfused patients in individual hospital departments are presented in Table 2 . Table 2. Incidence of red blood cell transfusions and percentage of transfused patients. The incidence of RBC transfusions was highest in the autoimmune and metabolic diseases department, the ICU, and the clinical pharmacology department. The percentage of RBC-transfused patients was also highest in these three locations. Demographic and clinical characteristics of patients who were transfused with RBC are presented in Table 3 . Table 3. Characteristics of patients transfused with red blood cell units. The increase in Hb concentration following RBC transfusion was significant ( p < 0.01), whereas drop in lactate concentration was not ( p = 0.96). In 173 (20.9%) patients, pre-transfusion Hb was <70 g/L, and in 27 (3.3%) patients, lactate was >1.8 mmol/L; in 16 (1.9%), both criteria were met. During the 7-month period, there were 828 RBC units transfused to non-bleeding patients. There were 171 RBCs given as single-unit transfusions and 657 RBCs as multiple-unit transfusions. The numbers of RBCs that were transfused in clinical situations deemed appropriate indications for RBC transfusion are presented in Figure 1 . Figure 1. Number of appropriate RBC transfusions (percentage of all RBC transfusions) in various clinical scenarios classified as appropriate indications for RBC transfusion ( Table 1 ). RBC, red blood cell. The most frequent clinical situations when RBC transfusion was classified as appropriate were: Hb < 70 g/L plus cognitive problems/headache/dizziness (10.1%), Hb < 60 g/L (5.4%), and Hb < 70 g/L plus dyspnea despite oxygen therapy (4.3%). Among patients with CAD in whom RBCs were transfused (n = 42), nine (21.4%) patients had cognitive symptoms, eight (19.0%) patients had dyspnea, and three (0.7%) patients had tachycardia and/or hypotension, while some patients had more than one sign/symptom. Among patients with and without CAD, the most frequent were neurological and respiratory sings/symptoms of anemia. There were 216 (26.1%) RBC units appropriately transfused and 612 (73.9%) RBC units that were transfused outside the abovementioned clinical scenarios. The most frequent causes of inappropriate RBC transfusion were: no Hb determination pre-RBC transfusion (n = 317) and among these RBC transfused as a second unit in a single-transfusion episode (n = 260), absence of anemia sings/symptoms (n = 179), and Hb concentration ≥80 g/L (n = 80). Incidence, number, and total volume of RBCs that were appropriately and inappropriately transfused is presented in Table 4 . Table 4. Incidence, number, and volume of appropriate and inappropriate red blood cell transfusions per hospital department. Overall, 26.1% RBC transfusions were classified as appropriate and 73.9% as inappropriate. The incidence of appropriate and inappropriate RBC transfusions was 2.6 and 7.5 units per 1000 patient-days, respectively. Hospital departments with the highest percentage of appropriate RBC transfusions (>80%) were the neurology department (100%), ICU (83.7%) and stroke unit (83.3%). The percentage of appropriate RBC transfusions was <34% in all other hospital departments. Comparison between patients who received appropriate and inappropriate RBC transfusions is presented in Table 5 . Table 5. Characteristics of recipients of appropriate and inappropriate RBC transfusions. The patients who received appropriate and inappropriate RBC transfusions differed in Hb concentration pre–post RBC transfusion, whereas age, sex, CAD status, and lactate pre–post transfusion were not different. 4. Discussion The overall percentage of RBC-transfused patients at our institution was 1.2%. This percentage was much lower than reported by Borkent-Raven et al. in 2011 (10.9%) [ 22 ] and 2010 (13%) [ 23 ]. This discrepancy might be due to different populations of patients and analyses performed in different time periods. The aim of our study was to analyze the appropriateness of RBC transfusions in non-bleeding patients hospitalized at our institution. At our institution, 26.1% RBC transfusions were classified as appropriate. The highest percentage of appropriate RBC transfusions was in the neurology department, the ICU, and stroke unit (83.3–100%). This percentage was below 33% in all other hospital departments. In the study analyzing appropriateness of RBC transfusion in four emergency departments, 78.6% of RBC transfusions were considered appropriate. This high percentage of appropriate RBC transfusions was due to adopted criteria. Clinical scenarios in which RBC transfusion was considered appropriate were (based on the official consensus document from 2013): Hb < 70 g/L (acute anemia irrespective of sign/symptoms), Hb < 80 g/L (chronic anemia with symptoms of anemia or risk factors), Hb < 90 g/L (acute anemia with hemodynamic instability, CAD, heart failure, cerebrovascular disease, and myocardial infarction), and Hb ≥ 90 g/L (acute anemia with hemorrhage or symptoms of anemia) [ 24 ]. In our study, we did not consider Hb < 70 g/L without anemia symptoms or Hb < 90 g/L in patients with risk factors as appropriate indications for transfusion. To evaluate the appropriateness of RBC volume, the authors defined over-transfusion as post-transfusion Hb > 20 g/L above the appropriate transfusion trigger, and they showed an over-transfusion percentage of 45%. When this volume of over-transfusion was combined with inappropriate indication, 60% of RBC transfusion episodes and 41% of RBC units were found as unnecessarily transfused [ 24 ]. In the study by Shander et al., the panel of experts rated allogeneic RBC transfusions as inappropriate in 59.3% of nonbleeding clinical situations—all scenarios with Hb ≥ 100 g/L and 71.3% of scenarios with Hb 80–99 g/L. In 28.9% of clinical scenarios, RBC transfusion appropriateness was uncertain [ 25 ]. However, the authors did not take signs/symptoms of anemia into account when deciding on the appropriateness of RBC transfusion, unlike we did in our study. The appropriateness of RBC transfusion in our study was based on the most recent AABB guidelines and some additional indications specified by the authors ( Table 1 ). RBCs are transfused to improve the oxygen-carrying capacity of blood and delivery of oxygen to cells. Most clinical practice guidelines on RBC transfusion list specific Hb concentration thresholds as an indication for RBC transfusion. Clinical Practice Guidelines from AABB set the threshold at Hb ≤ 70 g/L in hospitalized hemodynamically stable patients and critically ill patients (strength of recommendation IB) [ 14 ]. The aforementioned guidelines set the Hb threshold at ≤80 g/L in patients undergoing orthopedic or cardiac surgery and in patients with coronary artery disease (strength of recommendation IB) although the Hb trigger ≤70 g/L and ≤80 g/L are most probably comparable in these patients [ 14 ]. Restrictive transfusion trigger (i.e., Hb 70–75 g/L) was shown to be safe compared to liberal transfusion trigger (i.e., 90–100 g/L) by randomized controlled trials in different populations of patients: the critically ill [ 26 ], cardiac surgery patients [ 27 , 28 ], orthopedic surgery patients with cardiac risk factors [ 29 ], septic patients [ 30 ], and those with malignant tumors [ 31 ]. All authors agreed with that RBC transfusion should be tailored to individual situations in accordance with the strategy of individualized therapy. The decision regarding RBC transfusion should be based on patient clinical condition and not only on Hb concentration [ 32 , 33 ]. Every patient has individualized adaptation mechanisms to anemia, so hemoglobin concentration cannot be the only marker of the need for RBC transfusion [ 34 ]. There are few exceptions in the context of the non-inferiority of restrictive RBC transfusion trigger. It is not known if, in myelodysplastic syndrome patients, restrictive liberal RBC transfusion trigger is more appropriate [ 35 ]. In patients with coronary artery disease (CAD), liberal RBC transfusion triggers should be taken into account [ 36 ]. Therefore, we classified RBC transfusions given to symptomatic patients with CAD with Hb < 80g/L as appropriate. Guidelines from AABB also suggest considering clinical context (clinical signs or symptoms of anemia) when deciding on RBC transfusion in non-bleeding patients [ 13 , 14 ]. Although transfusion guidelines are meant as a support tool, they should not replace the clinical judgement of clinicians making decisions on RBC transfusions. There may be situations when patients do not tolerate anemia with Hb concentrations above the restrictive trigger (e.g., myelodysplastic syndrome patients); on the other hand, young, otherwise healthy, chronically anemic patients may tolerate Hb < 6 g/dL well and not require RBC transfusion. The imperative here is to look for signs and symptoms of anemia. The supporting role in the decision regarding RBC transfusions may have physiological transfusion triggers. The most widely available is lactate concentration. Nevertheless, clinicians should be aware of multiple factors influencing lactate concentration in sepsis patients [ 37 ]. Moreover, RBC transfusion may not produce a clinically sound drop in lactate concentration, making reassessment following RBC transfusion problematic [ 38 ]. In our study, the most frequently reported symptoms of anemia were neurological symptoms. This result is not unusual, as high oxygen consumption makes the brain particularly sensitive to anemia. Some studies even suggest that anemia is strongly associated with overall cognitive impairment and may be a risk factor for dementia (1.39, 95% CI 1.23–1.56, p < 0.001), Alzheimer’s disease (1.59, 95% CI 1.18–2.13, p = 0.002), and mild cognitive impairment (1.36, 95% CI, 1.04–1.78; p = 0.02) [ 39 , 40 ]. On the other hand, Valladao et al. did not notice the association between worse cognitive function or mental disorders and anemia [ 41 ]. To reduce unnecessary transfusions, Edwards et al. suggested examining Hb concentration after single RBC transfusion [ 42 ]. In our study, multiple-unit RBC transfusions were also classified as inappropriate. Multiple-unit RBC transfusion was also the main cause of inappropriate transfusion in our study. Discharge Hb concentration may be representative and effective retrospective indicator of appropriateness of RBC transfusion [ 42 ]. Data on discharge Hb concentration were not retrieved in our study. Although several guidelines have been proposed to reduce the RBC overuse, our study showed that the unjustified use of RBC persists. Some studies suggest that the decision regarding RBC transfusion may be based on beliefs and fixed behaviors [ 43 , 44 ]. Attempts at the reduction of inappropriate RBC transfusions is especially valid in the context of the low number of blood donors and the ever-increasing demand for blood [ 45 ]. Implementation of standardized RBC guidelines, medical staff education, and prospective transfusion-order screening may lead to the reduction of inappropriate RBCs transfusions [ 46 ]. Therefore, there is a definite need to educate physicians on appropriate indications for RBC transfusion. The educational interventions may have different results. The traditional approach to educate on appropriateness of RBC transfusions is through direct training campaigns; however, their effectiveness may be limited [ 47 ]. Introduction of clinical decision-support (CDS) electronic alerts is potentially more effective. Goodnough et al. showed that transfusions with pre-transfusion Hb > 80 g/L decreased from 60% to 30% following the introduction of CDS [ 48 ]. Tavares at al. showed that engagement of physicians may result in a 33% decrease in total number of RBC transfusions [ 49 ]. A significant reduction number of inappropriate RBC transfusion—from 25% to 15% of total RBC transfused in the medical-surgical ICU—was noticed after implementation of a transfusion bundle [ 50 ]. Introduction of patient blood management (PBM) may lead to more appropriate RBC transfusions in medical and surgical departments [ 51 , 52 ]. Ordering physicians may override the alerts on proper RBC transfusion indicators, and the main reason for this behavior is “protocolized behaviors on specialty services” [ 53 ]. Conflicting practices in various clinical specialties, potential costs, and differences in skills and knowledge of co-workers are indicated as the most important impediments to RBC transfusions based on evidence [ 54 ]. The last step in the efforts to minimize the incidence of inappropriate RBC transfusions may be the patient’s informed consent for the procedure. Such consent or lack of it should be the result of thorough discussion with the patient about benefits, risks, alternatives, and consequences of refusal of RBC transfusion. In our study, we did not look into the informed consent process specifically. Although at our institution, the consent form for RBC transfusion includes statement on alternative management, we do not know how many patients were offered alternative treatment options. Our study is not without limitations. Due to the retrospective character of the study, we did not have access to some important clinical information that was not documented in the patients’ case notes. Although we thoroughly analyzed all daily entries of the patients on the day of RBC transfusion, there is a possibility that signs or symptoms of anemia were not properly documented by ordering physicians, and some RBC transfusion episodes could be wrongly evaluated as inappropriate. The presented indications for appropriate RBC transfusions may be judged by some authors as debatable. Some patients (e.g., myelodysplastic syndrome patients) may require RBC transfusion to increase Hb concentration above 80 g/L, which according to our approach was evaluated as inappropriate. 5. Conclusions Although the incidence of RBC transfusions in non-bleeding inpatients in our study was generally low, the majority of RBC transfusions was performed outside recommended indications. 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[ Google Scholar ] [ CrossRef ][ Green Version ] Figure 1. Number of appropriate RBC transfusions (percentage of all RBC transfusions) in various clinical scenarios classified as appropriate indications for RBC transfusion ( Table 1 ). RBC, red blood cell. Table 1. Appropriate red blood cell transfusion clinical scenarios. Clinical Scenarios Hb 1 < 60 g/L; Hb < 70 g/L plus tachycardia and/or hypotension despite normal blood volume; Hb < 70 g/L plus dyspnea and/or tachypnea despite oxygen therapy (aimed at SpO 2 2 100%); Hb < 70 g/L plus problems with concentration/attention and/or headache and/or dizziness; Hb < 70 g/L plus Scv 2 O 3 /SvO 2 4 < 55% and/or lactate > 1.8 mmol/L; Hb < 80 g/L plus coronary artery disease plus any sign/symptom of anemia; Hb < 80 g/L plus acute coronary syndrome; Hb < 80 g/L plus acute cerebral ischemia. 1 Hemoglobin; 2 peripheral oxygen saturation; 3 central venous oxygen saturation; 4 mixed venous oxygen saturation. Table 2. Incidence of red blood cell transfusions and percentage of transfused patients. Hospital Department Incidence of RBC 1 Transfusions (Unit/1000 Patient-Days) RBC-Transfused Patients (%) Autoimmune and Metabolic Diseases 41.8 8.8 Intensive Care Unit 27.6 8.9 Clinical Pharmacology 25.6 7.4 Gastroenterology and Hepatology 18.7 2.9 Gastrointestinal Surgery 17.1 3.8 Gynecology and Obstetrics 14.5 1.9 Oncologic Surgery 7.7 0.7 Radiotherapy 5.2 0.8 Medical Oncology (2 units) 4.6 0.3 Neurosurgery 3.8 0.9 Stroke Unit 3.6 1.6 Endocrinology 1.6 0.2 Allergology and Immunology 1.1 0.1 Neurology 0.8 0.2 Neurologic Rehabilitation 0.5 0.9 Ophthalmology 0.2 <0.1 All departments 10.2 1.2 1 Red blood cell. Table 3. Characteristics of patients transfused with red blood cell units. Patient Characteristic Value Age, median, IQR 1 (years) 65 (47–75) Sex, male/female (n; %) 120 (42.0)/166 (58.0) Coronary artery disease (n; %) 42 (14.7) Hb 2 concentration pre RBC 3 transfusion, median, IQR (g/L) 75 (65–80) Hb concentration post RBC transfusion, median, IQR (g/L) 85 (77–95) Patients with pre RBC transfusion Hb < 70 g/L, number, % 173 (20.9) Lactate concentration pre RBC transfusion, median, IQR (mmol/L) 2.0 (1.5–2.6) Lactate concentration post RBC transfusion, median, IQR (mmol/L) 1.8 (1.4–2.4) Patients with pre RBC transfusion lactate > 1.8 mmol/L, number,% 27 (3.3) 1 Interquartile range; 2 hemoglobin; 3 red blood cell. Table 4. Incidence, number, and volume of appropriate and inappropriate red blood cell transfusions per hospital department. Hospital Department Appropriate RBC Transfusions Inappropriate RBC Transfusions Incidence (n/1000 Patient-Days) RBC * (%/n) Incidence (n/1000 Patient-Days) RBC (%/n) Neurology 0.8 100/3 0.0 0/0 Intensive Care Unit 23.1 83.7/41 4.5 16.3/8 Stroke Unit 2.9 83.3/10 0.6 16.7/2 Endocrinology 0.5 33.3/2 1.1 66.7/4 Clinical Pharmacology 8.1 31.6/30 17.5 68.4/65 Gastrointestinal Surgery 4.7 27.5/28 12.4 72.5/74 Gastroenterology and Hepatology 4.4 23.6/39 14.3 76.4/126 Medical Oncology (2 units) 1.1 22.9/8 3.6 77.1/27 Neurosurgery 0.8 20.0/4 3.0 80.0/16 Autoimmune and Metabolic Diseases 8.2 19.5/34 33.7 80.5/140 Gynecology and Obstetrics 1.7 11.5/15 12.8 88.5/115 Oncologic Surgery 0.9 11.1/2 6.8 88.9/16 Neurologic Rehabilitation 0.0 0/0 0.5 100/2 Ophthalmology 0.0 0/0 0.2 100/2 Allergology and Immunology 0.0 0/0 1.1 100/2 Radiotherapy 0.0 0/0 5.2 100/13 All departments 2.6 26.1/216 7.5 73.9/612 * Red blood cell. Table 5. Characteristics of recipients of appropriate and inappropriate RBC transfusions. Characteristic Appropriate RBC 1 Transfusion Inappropriate RBC Transfusion p Age, median, IQR 2 (years) 66.5 (50–78) 64.5 (45.5–74.0) 0.50 Sex, male/female (n) 31/35 89/131 0.35 Coronary artery disease (n; %) 14 (20.6) 28 (79.4) 0.09 Hb 3 concentration pre RBC, median, IQR (g/L) 64 (58–68) 75 (70–80) <0.01 Hb concentration post RBC, median, IQR (g/L) 80 (73–90) 95 (87–10) <0.01 Lactate concentration pre RBC, median, IQR (mmol/L) 2.0 (1.5–2.7) 1.7 (1.2–2.2) 0.28 Lactate concentration post RBC, median, IQR (mmol/L) 1.9 (1.4–2.5) 2.0 (1.3–2.3) 0.73 1 Red blood cell; 2 interquartile range; 3 hemoglobin. In bold: statistically significant values. MDPI and ACS Style Czempik, P.F.; Wilczek, D.; Herzyk, J.; Krzych, Ł.J. Appropriateness of Allogeneic Red Blood Cell Transfusions in Non-Bleeding Patients in a Large Teaching Hospital: A Retrospective Study. J. Clin. Med. 2023, 12, 1293. https://doi.org/10.3390/jcm12041293 AMA Style Czempik PF, Wilczek D, Herzyk J, Krzych ŁJ. Appropriateness of Allogeneic Red Blood Cell Transfusions in Non-Bleeding Patients in a Large Teaching Hospital: A Retrospective Study. Journal of Clinical Medicine. 2023; 12(4):1293. https://doi.org/10.3390/jcm12041293 Chicago/Turabian Style Czempik, Piotr F., Dawid Wilczek, Jan Herzyk, and Łukasz J. Krzych. 2023. "Appropriateness of Allogeneic Red Blood Cell Transfusions in Non-Bleeding Patients in a Large Teaching Hospital: A Retrospective Study" Journal of Clinical Medicine12, no. 4: 1293. https://doi.org/10.3390/jcm12041293
https://www.mdpi.com/2077-0383/12/4/1293/htm
Eulentin v Sicobo (10 of 2007) [2011] SCSC 20 (3 March 2011) - SeyLII Eulentin v Sicobo (10 of 2007) [2011] SCSC 20 (3 March 2011) Document detail Jurisdiction Seychelles Citation Eulentin v Sicobo (10 of 2007) [2011] SCSC 20 (3 March 2011) Copy Media Neutral Citation [2011] SCSC 20 Copy Case number 10 of 2007 Court Supreme Court Judges Renaud J Judgment date 3 March 2011 Language English Type Judgment Download Other documents RESPONDENT ………………………………………………………………………………………………………………………… Mr. W. Herminie for the Appellant Mrs. Amesbury for the Respondent JUDGMENT B. Renaud J On 5 thOctober, 2007 the Appellant entered a Notice of Appeal against the decision of the Learned Senior Magistrate His Worship Mr. W. Mutaki given on 21 stSeptember and in a Memorandum of Appeal he set out the grounds of Appeal as follows: The decision of His Worship is against the weight of the evidence. The Learned Magistrate having found that there was a valid contract between the parties should not have dismissed the case for lack of cause of action. Learned Counsel for the Appellant submitted that there is plenty of evidence on record to show that the work was incomplete. According to him, there is the uncontroverted evidence of Magdalen Helen Eulentin who stated – “ I do not know the detail of the contract, however part of work unfinished.”Learned Counsel also made reference to the evidence of Jean Philip Eulentin who under cross-examination stated – “…. the doors, not put on the cabinet, the cabinet have not complete.” Learned Counsel for the Appellant submitted that the work incomplete and this is supported by the finding of the Learned Senior Magistrate as follows – “the Defendant was right to terminate the contract”.Learned Counsel for the Appellant however agreed that the Learned Senior Magistrate was wrong to find that full payment had not been made to the Defendant, when the evidence shows otherwise, in that the Defendant had received a total sum of SR4,500.00 for the work over unspecified period. On the second ground of Appeal Learned Counsel for the Appellant submitted that the Defendant being in breach of contract, it cannot be said that Plaintiff had no cause of action against him. He argued that the reasoning and decision of the Learned Senior Magistrate is clearly contradictory in that in his judgment, at some stage he acknowledged that the work was incomplete and whereas he concluded that the work was completed. I have perused the record of the Learned Senior Magistrate in MC CS426/06 as well as the judgment given on 14 thSeptember, 2007. (not the 21 st September as stated by the Appellant). I note that Learned Senior Magistrate in his judgment made the finding that the payment of SR4,500.00 was not substantiated by evidence of the Plaintiff and his witnesses. He also found that – “the Defendant had yet to fix the cabinet and to complete the base of the cabinet for which the Defendant claimed a balance of SR2250.00/- otherwise the Defendant was either entitled to terminate the contract for non-payment of the balance”. The Learned Senior Magistrate then concluded that in the absence of proof of full payment and terms of contract, he was unable to award any relief to the Plaintiff. He also concluded that the Defendant had a right to terminate the contract if part of his obligation to the contract was performed and the Plaintiff failed to execute his part. The Learned Senior Magistrate also found that there was evidence from the Plaintiff’s witnesses that there was no detail of the quality of work in the contract between the parties but the work agreed was performed by the Defendant and completed. In his final analysis the Learned Senior Magistrate reiterated that the Plaintiff had no cause of action since he failed to prove that the Defendant did not complete the work they had agreed. It is obvious to me that the Learned Senior Magistrate gave his judgment based on findings of facts that he made based on the evidence before him. The Appellate Court will disturb such finding of facts if the Learned Senior Magistrate had glaringly made such findings in absence of evidence or he indeed wrongly evaluated such facts and based his judgment on such wrong premise. I find that the Learned Senior Magistrate correctly framed the issues as follows – “the question here is whether the Plaintiff paid the Defendant the SR4,500. and the Defendant failed to deliver the work.” He then apportioned the onus of proof and stated thus- “The burden of proof whether the Defendant was paid the money and did not deliver the work is upon the one who alleges, that is the plaintiff”. Based on the evidence before him, the Learned Senior Magistrate found that only SR2,250.00 was received by the Defendant from the Plaintiff in part payment. I do not find any fault in this finding as this is borne out by evidence. There is no evidence on record that would lead me to conclude otherwise than to uphold the finding of the Learned Senior Magistrate. In the final analysis I uphold the Judgment of the Learned Senior Magistrate that in the “ absence of proof of full payment and terms of contract, he was unable to award any relief to the Plaintiff”. For reasons stated above I find no merit in the grounds of appeal advanced by the Appellant. I therefore dismiss the appeal with costs. ………………………….. B. RENAUD JUDGE
https://seylii.org/akn/sc/judgment/scsc/2011/20/eng@2011-03-03
(PDF) Astrocytes express aberrant immunoglobulins as putative gatekeeper of astrocytes to neuronal progenitor conversion PDF | Using multi-omics analyses including RNAseq, RT-PCR, RACE-PCR, and shotgun proteomic with enrichment strategies, we demonstrated that newborn rat... | Find, read and cite all the research you need on ResearchGate Astrocytes express aberrant immunoglobulins as putative gatekeeper of astrocytes to neuronal progenitor conversion September 2022 DOI: 10.21203/rs.3.rs-2051344/v1 Abstract and Figures Using multi-omics analyses including RNAseq, RT-PCR, RACE-PCR, and shotgun proteomic with enrichment strategies, we demonstrated that newborn rat astrocytes produce neural immunoglobulin constant and variable heavy chains as well as light chains. However, their edification is different from the ones found in B cells and resembles aberrant immunoglobulins as observed in several cancers. Moreover, the complete enzymatic V(D)J recombination complex has also been identified in astrocytes. In addition, the constant heavy chain is also present in astrocytes adult rats, whereas in primary astrocytes from human fetal astrocytes we identified constant and variable kappa chains as well as the substitution lambda chains known to be involved in pre-B cells. To gather insights into the function of these neural IgGs, CRISPR-Cas9 IgG2B constant heavy chain (IgH6), overexpression, proximal labeling of rat astrocytes IgH6 and targets identification through 2D gels were performed. In CRISPR-Cas9 IgG2B KO, overexpression of factors involved in hematopoietic cells, neural stem cells and the regulation of neuritogenesis have been identified. Moreover, overexpression of IgG2B in astrocytes induces the CRTC1-CREB-BDNF signaling pathway known to be involved in gliogenesis whereas CRISPR-Cas9 IgG2B KO triggers the BMP/YAP1/TEAD3 pathway activated in astrocytes dedifferentiation into neural progenitors. Proximal labeling experiments revealed that IgG2B is N-glycosylated by the OST complex, addressed to vesicle membranes containing the ATPase complex; and behaves partially like CD98hc through its association with LAT1. Proximity-dependent biotin labeling experiments suggest that proximal IgG2B-LAT1 interaction occurs concomitantly with MACO-1 and C2CD2L, at the heart of a potentially novel cell signaling platform. Finally, we demonstrated that these chains are synthesized individually and associated to recognize specific targets. Indeed, intermediate filaments Eif4a2 and Pdia6 involved in astrocyte fate constitute targets for these neural IgGs. Taken together, we hypotheses that aberrant neural IgG chains may act as gatekeepers of astrocytes fate. Page 1/ 39 A s t r o c y t e s e x p r e s s a b e r r a n t i m m u n o g l o b u l i n s a s p u t a t i v e g a t e k e e p e r o f a s t r o c y t e s t o n e u r o n a l p r o g e n i t o r c o n v e r s i o n A l i c e C a p u z  Unvers ité de Lille, Inser m, CH U Lille S y l v a i n Os i e n  Unvers ité de Lille, Inser m, CH U Lille M e l o d i e k a r n o u b  Unvers ité de Lille, Inser m, CH U Lille S o u l a i m a n e A b o u l o u a r d  Universit y of L ille https:/ /or cid.or g/0000-0002-2045-4785 E s t e l l e L a u r e n t  Unvers ité de Lille, Inser m, CH U Lille E t i e n n e C o y a u d  Prince ss Margare t Cance r Ce ntre https:/ /orcid.or g/0000-0002-5893-4557 A n t o n e l l a R a f f o R o m e r o  Universit é de Lille 1 M a r i e D u h a m e l  Univ. Lille, Inser m, CH U Lille, U1192, Laboratoire Protéomique, Ré pon se I nammatoire et Spectr ométr i e de Masse (PRISM), F-59000 Lille, France https :/ / orcid.o rg/0000-0002-4006- 5605 A m e l i e B o n n e f o n d  M e h d i D e r h o u r h i  M a r c o T r e r o t o l a  M o n i k a Z i l k o v a  6Institute of Neuroimmunology , Slovak Academy of S cience s F i r a s K o b a i s s y  light chain (IgKV and IgGV) as we already demonstr ated in anti-IgKV We stern blot of LPS-stimulated Page 21/39 extr acts in re ducing conditions of primary culture s of spinal astrocytes ( S u p p . F i g u r e 6 B ). Moreove r , West er n blot analy ses in re ducing conditions with anti-IgKV o f secr etome s of L PS-stimulated CRISPR- Cas9 IgH 6 compare d to contr ols (T2, EV and CTR ) cells, showe d the lack of the band of 60 KDa in IgH6 KO cells ( S u p p . F i g u r e 6 C ). Further more , shotgun prote omic ana lyses of the ce ll extract from the 3 different const ruct s compare d to control and EVs showe d diff ere n tial specic pr oteomic re pres entation illustrated in the V enn diagram schematic ( S u p p . D a t a 6 , S u p p . F i g u r e 6 D ). Forty-six com mon prote ins to the 3 conditions have be en identied compare d to EV and contr ol and forty-one betwe en the two rst conditions. A mong these i dentied pr oteins, t he Y ap1 transcription factor is known to be implicate d in astroc ytic proliferation and is known to promot e astrocytoma 40 . Similarly, enhanced activity of Crtc 1 i s implicated in cancer s 41 . Moreover , the pre sence of the immunoglobulin superfamily (embigin) an d the immunity related GTPase family reinforce d the inamma tory and proliferative pro le of the astro cytes. Altoge ther , overe xpres sion of IgG2B constant chain (IgH 6) seems to re inforce t he astroc y te fate but also switche s it towards proliferation and astroc ytoma. I g G 2 B i n t e r a c t o r s p r o x i m a l i n t e r a c t o m e u n c o v e r s C D 9 8 h c - l i k e f e a t u r e s To ge t insight in IgG2B intracellular prot ein networ k, we performe d a serie s of proximity-based biot in labeling experime n ts ( F i g u r e 6 A ). These e xp erime n ts wer e designed to ide ntify the intracellular prote i ns at the proximity of IgH6 in a constant heavy chain domain-dependent manner . We pe rforme d a serie s of BirA* alone co ntrols and expre ssed the signal peptide (SP) fu sed to the IgG2B tr a nsmembrane ( TM) domain with a C-ter minal BirA*Flag tag (BF) to re move the BioI D basal a nd the membrane pr otein proce ssing-specic back grounds, r espe ctively . Both the SP-TM-BF and S P-Constant- TM-BF identied the ribos ome, s upporting cor re ct re cognition of the SP a nd proper proce ssing through the ER ( F i g u r e 6 B ). Comparing the SP-C onstant IgG2B domain (C)-TM-BF data to both BirA * alone and S P-TM-BF contr ols, we identie d 23 proximal high condence SP-C -TM-BF interac tors (i.e . prote in s brought to SP-C -TM-BF through the C onstant domain). Amongst those , we ide ntied 6 compone n ts of the oligosaccharyltransferase complex (DDOS T , MAGT1, RPN1, RPN2, STT 3B and T USC3) which suggest that SP-C-TM-BF is pro ces sed t hrough the N- l inked glycosylation pathway. Of note, SP-C-TM-BF harbor s a single N- X-S/T gl ycosylation sequon located at the N183 (- S -T). We also identied thre e components o f the prot on -tr ansporting two-s ector A TPase complex ( A T P5F1, A T P6AP1 and A TP6AP2) which catalyzes the synthesis or hydrolysis of A T P coupled to an H+ tr a nsport acr oss me mbranes. T ogether , these proximal interact ions stro ngly suggest a plasma, ly sosomal or ve sicular membr ane addres sing of SP-C- TM-BF . In line with this hypothesis, we de tected TMEM57 (Maco ilin), C2CD2L, ILKAP and S LC7A 5 among the re ma ining 14 hi gh condence interact ors ( S u p p D a t a 7 ) . TMEM57 association is stro ngly dependent of the IgG2B const ant domain. It is a poorly character iz ed prot ein which has solely been r epor ted t o regulate ne u ronal activity, re sulting i n Ca2+ imbalan ce 42, 43 . Of peculiar interes t, the phos pholipid transfer pr otein C2CD2L ensures t he transit of phosphatidylinositol from ER to the plasma membr ane in a Ca2+ depende nt manner 44 . We hypothesize that the interact ions betwe en IgG2B, TMEM57 a nd C2CD2L may occur at the te thering sites be twee n ER and pla sma membrane and could link membr ane Page 22/39 embedd ed IgG2B to ne uronal physiology through PIP and Ca2+ regulation. The large neutral amino acids transport er small subunit 1 (SLC7A5, LA T1) appears as another part ner of membr a ne embedd ed IgG2B. LA T1 is crucial in transporting large ne u tral amino acids as well as drugs or me ta bolites ( e.g. L-DOPA 45 across the blood- brain barrier (BBB). Beyond its function, SLC7A 5 acts thro ugh heter odimerizing with prote i n 46 and S LC7A 5 (LA T 1) is one of its associated light chain ensuring amino acids transpor t . T hese data suggest that mem brane embe dded IgG2B could substitute SLC3A2 t o form a membrane heter odimer with SLC7A5. In addition, the spe cic inte raction with ILKAP ( in tegrin- linked kinase associated phosphatase) potentially indicates a link betwee n IgG2B and the PI3K/AKT pathway through its re p orte d a bility to dephosphorylate GSK3 47 . This pa thway is downstream the c a nonical CD98hc-LAT1 complex. Our data thus sketc h an al ter native CD98 rece ptor where IgG2B could re pl ace CD98hc and associate wit h LAT -1 to form a fu nctional entity potentially impacting multiple pathway s, e.g. PI3K/AKT , Wnt (thr ough modulating GS K3b activity, thus b-c atenin regulation) and mT ORC1 (be cause of its amino acids transpor ter activity when associated with LA T- 1) . Of note, we did not de tec t in tegr ins as IgG2B interact ors, suggesting a partial rec a pitulation of CD98 organization. Toge ther , our proximal interac tomics s tudy suggests t hat IgG2B could be: (i) N- glycosylated by the OST complex; (ii) address ed at the ve sicle me mbrane through A TPase complex- containi ng vesicles ; and (iii); partially behav es as CD98hc thr ough its association with LA T 1 and a bility to recr uit ILKAP which potentially regulates do wnstre a m signaling pathway s. These e xperiments we re performe d in HEK293 and cer ta inly present c ell-type depende n t limitations. Howe ver , LAT1 is expr ess ed in astroc y tes, and we believe t his dataset uncover s a p utative CD98hc-like function which re p res ents a gre a t intere st for pharmaceutical re search (bec a use of the ability of CD98 to ensure BBB large mole cule cross ing). Further exper i ments are n eede d to characterize IgG2B-LAT1 interac tion in astrocyte s and could repr esent an intere sting pa th for astroc ytic neoplasms under standing 48 . Furthermo re, it will be of peculiar inter est to investigate whet her t he IgG2B-LA T1 proximal i nterac tion occur s conco mitantly with T MEM57 and  A n t i g e n r e c o g n i t i o n b y a s t r o c y t e s I g We e stablished that aber rant Ig have bee n identied in astroc y tes ext racts . Their se cre tion mu st be demonstr a ted and their ability to re cognize antigens and function as antibodies too. This support s the fact that all dif ferent fre e chains may associate to pr oduce a st ructur e functioning as a complete antibody ( F i g u r e 7 A ). To e v aluate whether t his IgG antibody can recognize antigens , Wes ter n blot of prote i n extract s from DI TNC1 ce l ls was perform ed on 2D gels ( F i g u r e 7 B ) .  All membr anes wer e incubated with sec ret ome of DI TNC1 ce l ls stimulated with 200 ng/mL of LPS a s a source of primary antibodies. Of note, the se secr etomes we re c oll ect ed after t he culture of cells in DMEM without FBS f or 24h. Then sec ondary antibody was added, and positive spots wer e det ect ed ( F i g u r e 7 B ). Each rec ogni zed spot was Page 23/39 then analy zed by shotgun prote omics. Their identication re vealed, pro teins involved in microt ubule cytoske leton or ganization i.e. Tubulin alpha chain an d beta chains, Vimentin as well as Eif4a2 and Pdia 6 ( S u p p . D a t a 8 ). These two factors were known to be involv ed in ste m cell pluripote ncy  49 and metastasis 50 Taken toge ther these results are in line with the CRISPR-Cas9 data. Int erme dia te laments ( IFs) are ke y players in the contr ol of cell morphology and struct ure as we l l as in active proce sse s such as ce l l polarization and migration. Previous studies have shown that IFs are major players in fetal brain developme n t. Vimentin was obse rved in astrocytes and glia l progenitor cells/glioblasts while tubulin beta memor y consolidation in the hippocampus 75 . Moreo ver , it also acts in the ER to re gu late the asse mbly or trac of ion channels or ion channel regulator s to modulate ne uronal excitability 76 . Based on thes e data and our results , it is te mpting to spec u late that IgG2B acts as a sc aff old prote in bringing together various regulator s involved in the astroc ytic phenotype. In parallel with IgG2B, we also ident ied free variable heavy cha ins synthesized without the DJ seque nces , free variable kappa l ight chains as well as a constant kappa ligh t chain linked to a joining seque nce. A s suggested by our pr evious Wes ter n blot data and proteomic e x perime n ts 9 , this doe s not exclude t he possibility that these f ree variable chains may associate with the i r re spective const a nt chains. The heavy a nd light chain s formed inde pendently may then interact t o form a struct u re r elated t o a BCR expre sse d at the membr a ne of endosome s/extraves icular vesicle s or t o be se crete d to re cognize some antigens or activate spe cic Fc γ R. In such a line, we r ece n tly demonstrate d tha t neurons e xp res s CD16 and CD32b, which a re linked t o the antibody depende n t neurite outgrowth modulation re sponse s (A. D.N .M) 8 . More over , we demonst rated t hat these ne u ral immunoglobulin s can rec ogni ze antigens in astroc ytes such as the PRSS1 prote i n, known to be involved in neuropro genitor s tem c ell conver sion 77 . This recognition of autoantigens may also constitute another wa y to stabilize the fate of astroc ytes by blocking their c onv ersion to neurons. T a ken toge ther , these res ults str ongly suggest that astro cytes
https://www.researchgate.net/publication/369497327_Astrocytes_express_aberrant_immunoglobulins_as_putative_gatekeeper_of_astrocytes_to_neuronal_progenitor_conversion
Lead acetate probing of the MS2 ssRNA genome. | Download Scientific Diagram Download scientific diagram | Lead acetate probing of the MS2 ssRNA genome. from publication: Direct Evidence for Packaging Signal-Mediated Assembly of Bacteriophage MS2 | Using cross-linking coupled to MALDI mass spectrometry and CLIP-Seq sequencing we determined the peptide and oligonucleotide sequences at the interfaces between the capsid proteins and the genomic RNA of bacteriophage MS2. The results suggest that the same coat protein... | Packaging, Assembly and Bacteriophage | ResearchGate, the professional network for scientists. Lead acetate probing of the MS2 ssRNA genome. Source publication Direct Evidence for Packaging Signal-Mediated Assembly of Bacteriophage MS2 Article Full-text available Ottar Rolfsson Stefani Middleton Iain W Manfield [...] Peter G Stockley Using cross-linking coupled to MALDI mass spectrometry and CLIP-Seq sequencing we determined the peptide and oligonucleotide sequences at the interfaces between the capsid proteins and the genomic RNA of bacteriophage MS2. The results suggest that the same coat protein (CP)-RNA and maturation protein (MP)-RNA interfaces are used in every viral part... Citations ... However, it is important to note that the present coarsegrained approaches do not include metal ions, virus RNA or host proteins and RNA. For instance, ordered genomic RNA such as is present in Leviviridae (Koning et al., 2016; Rolfsson et al., 2016; Chang et al., 2022) can also modulate the mechanism of viral assembly by coding specific sites for RNA-protein interactions called packaging signals (ElSawy et al., 2010;Stockley et al., 2016;Martín Garrido et al., 2020). Packaging signals are also present in Bromoviridae (Choi et al., 2002;Choi and Rao, 2003;Chakraborty et al., 2018), Tombusviridae (Qu and Morris, 1997) and Tymoviridae (Bink et al., 2003;Larson et al., 2005) although it is known that the RNA in Bromoviridae is much less ordered (Beren et al., 2020). ... The diversity of protein-protein interaction interfaces within T=3 icosahedral viral capsids Article Full-text available Shachi Gosavi Some non-enveloped virus capsids assemble from multiple copies of a single type of coat-protein (CP). The comparative energetics of the diverse CP-CP interfaces present in such capsids likely govern virus assembly-disassembly mechanisms. The T = 3 icosahedral capsids comprise 180 CP copies arranged about two-, three-, five- and six-fold axes of (quasi-)rotation symmetry. Structurally diverse CPs can assemble into T = 3 capsids. Specifically, the Leviviridae CPs are structurally distinct from the Bromoviridae , Tombusviridae and Tymoviridae CPs which fold into the classic “jelly-roll” fold. However, capsids from across the four families are known to disassemble into dimers. To understand whether the overall symmetry of the capsid or the structural details of the CP determine virus assembly-disassembly mechanisms, we analyze the different CP-CP interfaces that occur in the four virus families. Previous work studied protein homodimer interfaces using interface size (relative to the monomer) and hydrophobicity. Here, we analyze all CP-CP interfaces using these two parameters and find that the dimerization interface (present between two CPs congruent through a two-fold axis of rotation) has a larger relative size in the Leviviridae than in the other viruses. The relative sizes of the other Leviviridae interfaces and all the jelly-roll interfaces are similar. However, the dimerization interfaces across families have slightly higher hydrophobicity, potentially making them stronger than other interfaces. Finally, although the CP-monomers of the jelly-roll viruses are structurally similar, differences in their dimerization interfaces leads to varied dimer flexibility. Overall, differences in CP-structures may induce different modes of swelling and assembly-disassembly in the T = 3 viruses. ... Much of the MS2 genome produces stem-loop structures following transcription that prevent translation. During assembly, the coat MS2 coat protein (MCP) recognizes these stem-loop RNA structures, binds to them, and facilitates encapsidation [102] . ... Technologies Enabling Single-Molecule Super-Resolution Imaging of mRNA Article Full-text available Mark Tingey Steven J. Schnell Wenlan Yu Jason Saredy Weidong Yang The transient nature of RNA has rendered it one of the more difficult biological targets for imaging. This difficulty stems both from the physical properties of RNA as well as the temporal constraints associated therewith. These concerns are further complicated by the difficulty in imaging endogenous RNA within a cell that has been transfected with a target sequence. These concerns, combined with traditional concerns associated with super-resolution light microscopy has made the imaging of this critical target difficult. Recent advances have provided researchers the tools to image endogenous RNA in live cells at both the cellular and single-molecule level. Here, we review techniques used for labeling and imaging RNA with special emphases on various labeling methods and a virtual 3D super-resolution imaging technique. ... Several studies have found that the physical interaction force between capsids, protein and the others (CP−CP interaction) could drive the assembly of virions, and the packaging process of genome could also promote their assembly [105][106][107][108]. Accordingly, researchers inspired by these findings developed several strategies to incorporate cargo into the interior of VLPs [109, 110]. One of such strategies is achieved by adding RNA packaging signal elements (like the psi packaging sequence) to cargos, the RNA packaging elements interact with capsid proteins and mediate the packaging of cargos. ... Virus-Like Particles as Nanocarriers for Intracellular Delivery of Biomolecules and Compounds Article Full-text available Aug 2022 Junyao He Linying Yu Xiaodi Lin Xiaoyan Liu Wen Deng Virus-like particles (VLPs) are nanostructures assemble from viral proteins. Besides widely used for vaccine development, VLPs have also been explored as nanocarriers for cargo delivery as they combine the key advantages of viral and non-viral vectors. While it protects cargo molecules from degradation, the VLP has good cell penetrating property to mediate cargo passing the cell membrane and released into cells, making the VLP an ideal tool for intracellular delivery of biomolecules and drugs. Great progresses have been achieved and multiple challenges are still on the way for broad applications of VLP as delivery vectors. Here we summarize current advances and applications in VLP as a delivery vector. Progresses on delivery of different types of biomolecules as well as drugs by VLPs are introduced, and the strategies for cargo packaging are highlighted which is one of the key steps for VLP mediated intracellular delivery. Production and applications of VLPs are also briefly reviewed, with a discussion on future challenges in this rapidly developing field. View ... We, [1][2][3][4][5][6] [7] [8][9][10][11][12][13] and now others [14][15][16][17] propose that for many families of ssRNA virions assembly is regulated by multiple dispersed RNA sequences/motifs (Packaging Signals, PSs) within the viral genome (gRNA). This is also the case for the pararetrovirus Hepatitis B Virus. 10,13 PSs in many of these genomes consist of RNA stem-loops presenting a cognate coat protein (CP) recognition motif in their loops. ... Genome-regulated Assembly of a ssRNA Virus May Also Prepare It for Infection Richard J. Bingham Sam Clark Andrew J.P. Scott Peter G. Stockley Many single-stranded, positive-sense RNA viruses regulate assembly of their infectious virions by forming multiple, cognate coat protein (CP)-genome contacts at sites termed Packaging Signals (PSs). We have determined the secondary structures of the bacteriophage MS2 ssRNA genome (gRNA) frozen in defined states using constraints from X-ray synchrotron footprinting (XRF). Comparison of the footprints from phage and transcript confirms the presence of multiple PSs in contact with CP dimers in the former. This is also true for a virus-like particle (VLP) assembled around the gRNA in vitro in the absence of the single-copy Maturation Protein (MP) found in phage. Since PS folds are present at many sites across gRNA transcripts, it appears that this genome has evolved to facilitate this mechanism of assembly regulation. There are striking differences between the gRNA-CP contacts seen in phage and the VLP, suggesting that the latter are inappropriate surrogates for aspects of phage structure/function. Roughly 50% of potential PS sites in the gRNA are not in contact with the protein shell of phage. However, many of these sit adjacent to, albeit not in contact with, PS-binding sites on CP dimers. We hypothesize that these act as PSs transiently during assembly but subsequently dissociate. Combining the XRF data with PS locations from an asymmetric cryo-EM reconstruction suggests that the genome positions of such dissociations are non-random and may facilitate infection. The loss of many PS-CP interactions towards the 3' end of the gRNA would allow this part of the genome to transit more easily through the narrow basal body of the pilus extruding machinery. This is the known first step in phage infection. In addition, each PS-CP dissociation event leaves the protein partner trapped in a non-lowest free-energy conformation. This destabilizes the protein shell which must disassemble during infection, further facilitating this stage of the life-cycle. ... When the protein MS2 coat protein (MCP) is present it binds to the MS2 loop present on RNA transcripts. [76][77] [78] MCP tagged with the red fluorescent protein mCherry was co-transfected with our luciferase sequence containing the MS2 loops. The two then associate, producing a complex that contains the mRNP as well as a number of mCherry tagged MCP, thereby creating a brightly tagged mRNP that can be tracked via SPEED microscopy as it passes through the NPC. ... Unraveling docking and initiation of mRNA export through the nuclear pore complex Jun 2022 BIOESSAYS ... These techniques may be appropriate to resolve the symmetrical assemblies of the viral capsid proteins, but they can also obscure the inherently asymmetrically arranged genomic RNA within virus particles. Understanding the unique interactions with the numerous capsid proteins is important, as their relative binding positions and affinities with viral RNA must be carefully choreographed to successfully guide virus particle assembly (16) . Viral structural proteins can also engage in numerous host RNA contacts. ... ... The distribution of RNAcapsid interaction clusters also suggests that the packaged FHV genome has multiple conserved RNA-capsid binding sites. This indicates that the genome packaging mechanism of FHV could resemble that of other +ssRNA viruses (16) . Combined with DMS-MaPseq (dimethyl sulfate mutational profiling with sequencing) (130), it was also uncovered that FHV RNA-capsid interactions are enriched in dsRNA regions, and the disruption of base pairing at these vPAR-CL sites interfered with viral fitness (24). ... ... The MS2 genome encodes four proteins: maturation protein (A-protein), CP, lysis protein and replicase ( Figure 1A). Over the years, multiple studies have demonstrated the importance of direct interactions between the 129-residue CP and gRNA in MS2 capsid assembly (13,14,(20)(21)(22)(23)(24)(25) (26) . In particular, single-molecule fluorescence studies have revealed that the hydrodynamic collapse of gRNA during capsid for- (23). ... ... mation in MS2 and other +ssRNA viruses depends on specific interactions between viral gRNAs and their respective CPs (13,14). Using crosslinking and immunoprecipitation (CLIP) coupled with mass spectrometry and RNA footprinting, it was further shown that MS2 assembles via a PS-based mechanism involving direct, induced-fittype interactions between CP and gRNA (26) . In addition to its role in capsid formation, it was shown that CP also induces repression of replicase translation by binding to an RNA stem-loop encompassing the start codon of the replicase gene (21,24,27,28). ... ... All gRNA positions associated with Pearson Rs or theoretical interaction energies below or equal to a preselected cutoff were treated as the theoretically predicted interaction sites and were compared against their experimentally determined counterparts. In MS2, the latter were derived from either the cryo-EM analysis by Sun and coworkers (23) or CLIP analysis by Stockley and coworkers (26) . Specifically, all nucleotides in the 15 high-resolution stem loops that interact with the CP in the MS2 cryo-EM structure (23) (31) and EV-E (5) viruses. ... ... Given the initial requirement to package a ssRNA genome, we previously explored whether this virus assembles its NCP using the RNA Packaging Signal (PS)-mediated mechanism that we identified for spherical ssRNA viruses from a number of different viral families [27] [28][29][30][31][32][33] . These viral genomes encompass multiple, dispersed sequences, often in the form of stem-loops, that act collectively in binding CPs, thus regulating formation of the infectious virion [27][28][29]31,32,34,35 . ... [27] [28][29]31,32,34,35 . The differing PS sites within a gRNA have differential affinities for their cognate CPs defining a preferred assembly pathway (a Hamiltonian path). ... ... and bioinformatics analysis of the resulting Cp-binding aptamers, was used to identify 9 putative PSs that are conserved across the pgRNA sequences of 14 randomly selected HBV strains from GenBank. 27 ... In the remaining 30 dimers (C/C dimers) the FG-loops of both adopt the same conformation 13 (Fig. 1a). Binding of RNA stem-loops from within the viral genome can trigger the conformational change from the symmetric to the asymmetric dimer confirmation via a displacement of the kinetic energy favoring conversion from the C/C to the A/B conformer 14,15 Multiple dispersed RNA stem-loops in the genome with a shared sequence motif, termed packaging signals, cooperatively ensure efficient virus assembly [16][17][18][19][20] [21] ... These HBV sites, as isolated RNA oligonucleotides, trigger in vitro sequence-specific NCP formation at nanomolar concentrations 12 . We propose that they act as Packaging Signals (PSs) helping to ensure faithful encapsidation of the pgRNA, by analogy with the mechanism regulating assembly of many bona fide ssRNA viruses [14][15][16][17] [18] [19][20] . ...
https://www.researchgate.net/figure/Lead-acetate-probing-of-the-MS2-ssRNA-genome_fig4_284729564
Comparative effects of ivabradine, a selective heart rate-lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise | Request PDF Request PDF | Comparative effects of ivabradine, a selective heart rate-lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise | To compare in humans the effects of ivabradine and propranolol on cardiac and systemic haemodynamics at rest, during tilt and exercise. Nine... | Find, read and cite all the research you need on ResearchGate Article Comparative effects of ivabradine, a selective heart rate-lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise February 2006 British Journal of Clinical Pharmacology61(2):127-37 DOI: 10.1111/j.1365-2125.2005.02544.x Source PubMed Authors: <here is a image f2f62089ad6ff61c-d19572ff1996375a> Robinson Joannides Robinson Joannides <here is a image 764e05ad4730d962-b3651dfc94eca9a9> Nicholas D Moore Université de Bordeaux <here is a image f2f62089ad6ff61c-d19572ff1996375a> Michaela Iacob Michaela Iacob <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Patricia Compagnon Centre Hospitalier Universitaire Rouen Abstract To compare in humans the effects of ivabradine and propranolol on cardiac and systemic haemodynamics at rest, during tilt and exercise. Nine healthy volunteers randomly received single oral doses of ivabradine (Iva, 30 mg), propranolol (Propra, 40 mg) or placebo (Plac) during a double-blind cross-over study. Doses were selected to be equipotent in heart rate (HR) reduction. HR, systolic and diastolic blood pressure (SBP, DBP), cardiac index (CI, bioimpedance), rate pressure product (RPP), plasma epinephrine (E) and norepinephrine (NE), were measured at rest at baseline, before and after two tilt and exercise tests, started 2 and 5 h after drug intake. Heart rate variability (low to high frequency ratio LF/HF) was evaluated at rest and at 5 th minute of tilt. At rest, HR and RPP decreased similarly with Iva and Propra (both P < 0.01). During tilt, HR increased less with Iva than Propra (P < 0.01), LF/HF decreased after Iva (P < 0.03), SBP and mean blood pressure decreased after Propra (both P < 0.01), RPP decreased similarly after Iva and Propra (both P < 0.01) and CI decreased to a greater extent with Propra than with Iva or Plac (both P < 0.04). During exercise, Iva and Propra similarly decreased HR (both P < 0.01) and RPP (P < 0.01). These results demonstrate that for a similar decrease in HR at rest and during sympathetic stimulation, acute administration of ivabradine, a selective heart rate-lowering agent, decreased myocardial oxygen demand to the same extent as a reference beta-blocker, propranolol, but without evidence of depressant effect on cardiac function. <here is a image 175d1bd4b7439d95-754927124da715c1> ... Eight volunteers were in the young group (age=33 [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] [42] years, 6 women) and 11 volunteers were in the middle-aged group (age=53 [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] years, 8 . At baseline, HR, peripheral and central blood pressure, and diastolic internal diameter were similar in the 2 groups. ... ... These effects were in accordance with previous studies performed in healthy subjects and in coronary artery disease patients. 29,30, 42 In parallel, AP and AIx increased, confirming the unfavorable effect of bradycardic agents on central hemodynamics. [8][9][10] Thus, the longer systolic ejection time increases the likelihood that the arterial wave reflection returns to the proximal aorta relatively earlier during systole. ... Adaptation of Arterial Wall Viscosity to the Short‐Term Reduction of Heart Rate: Impact of Aging Article Full-text available Feb 2022 M. Iacob <here is a image 47101c73c8611f41-f9f330c67a18594a> Thomas Duflot Robinson Joannides <here is a image c543dc500f12e903-05671086854de83d> F. Roca Background Changes in arterial wall viscosity, which dissipates the energy stored within the arterial wall, may contribute to the beneficial effect of heart rate (HR) reduction on arterial stiffness and cardiovascular coupling. However, it has never been assessed in humans and could be altered by aging. We evaluated the effect of a selective HR‐lowering agent on carotid arterial wall viscosity and the impact of aging on this effect. Methods and Results This randomized, placebo‐controlled, double‐blind, crossover study performed in 19 healthy volunteers evaluated the effects of ivabradine (5 mg BID, 1‐week) on carotid arterial wall viscosity, mechanics, hemodynamics, and cardiovascular coupling. Arterial wall viscosity was evaluated by the area of the hysteresis loop of the pressure‐lumen cross‐sectional area relationship, representing the energy dissipated (W V ), and by the relative viscosity (W V /W E ), with W E representing the elastic energy stored. HR reduction by ivabradine increased W V and W E whereas W V /W E remained stable. In middle‐aged subjects (n=11), baseline arterial stiffness and cardiovascular coupling were less favorable, and W E was similar but W V and therefore W V /W E were lower than in youth (n=8). HR reduction increased W V /W E in middle‐aged but not in young subjects, owing to a larger increase in W V than W E . These results were supported by the age‐related linear increase in W V /W E after HR reduction ( P =0.009), explained by a linear increase in W V . Conclusion HR reduction increases arterial wall energy dissipation proportionally to the increase in W E , suggesting an adaptive process to bradycardia. This mechanism is altered during aging resulting in a larger than expected energy dissipation, the impact of which should be assessed. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: 2015/077/HP. URL: https://www . eudract.ema.europa.eu; Unique identifier: 2015‐002060‐17. ... Tým sa predĺži časový interval medzi následnými akčnými potenciálmi vznikajúcimi v sinoatriálnom uzle a dôsledkom je pokles srdcovej frekvencie (15). Ivabradín vyvoláva výraznú bradykardiu tak počas pokoja, ako aj počas fyzickej aktivity (16) . Toto farmakum preto umožňuje selektívne znížiť prenos signálov súvisiacich s kontraktilitou myokardu (respektíve frekvenciou) do NTS a tým potenciálne ovplyvniť aj spätnoväzobnú reguláciu aktivity SAS a HPA osi. ... ... Autori tejto štúdie zistili, že podanie ivabradínu viedlo k poklesu hodnôt srdcovej frekvencie, a to tak počas pokojových podmienok, ako aj počas zvýšenej aktivity SAS indukovanej fyzickou aktivitou. Autori predpokladajú, že zníženie srdcovej frekvencie počas situácií, pri ktorých dochádza k výraznej aktivácii SAS, by mohlo prospešne ovplyvňovať činnosť kardiovaskulárneho systému (16) . ... The effect of ivabradine administration on heart rate, blood pressure, and secretion of epinephrine, norepinephrine, and corticosterone during stress response in rats Article Full-text available Jan 2014 Noemi Hegedusova <here is a image d7ce0736305ad60d-e798be3d2a312436> Katarina Ondicova Lucia Mikova <here is a image 5a5c622fe69684c7-273c96f9aa61d09e> Boris Mravec Aim: The extent and duration of neuroendocrine stress response is regulated also by afferent signals from visceral organs. The aim of our study was to investigate the effect of ivabradine-induced reduction of afferent signalization from the heart on neuroendocrine stress response. Methods: Male Sprague-Dawley rats (250 - 300 g) were injected with ivabradine (5 mg/kg body weight) or saline. Thirty minutes after ivabradine or saline administration animals were exposed to stressors (handling, restraint, or immobilization). Heart rate and blood pressure were recorded in rats by telemetry method. Moreover, blood samples were collected and plasma levels of catecholamines and corticosterone were determined. Results: Administration of ivabradine attenuated stress-induced increase of heart rate and blood pressure in animals exposed to all three stressors. In rats exposed to the mild stressor, handling, ivabradine reduced secretion of epinephrine and norepinephrine compared to animals administered with saline. In contrast, in rats exposed to intense stressors (restraint or immobilization) ivabradine exaggerated epinephrine secretion, whereas plasma levels of norepinephrine were not significantly affected. Administration of ivabradine did not change plasma levels of corticosterone in animals exposed to handling, restraint or immobilization. Conclusion: We have shown that ivabradine administration reduced the activity of the sympathetic nervous system during exposure to a mild stressor. In contrast, during exposure to intensive stressors, ivabradine increased the activity of adrenal medulla but without any effect on sympathetic nervous system activity. Hypothalamo-pituitary-adrenocortical axis activity remained unaffected after ivabradine treatment in animals exposed to stressors. Our findings indicate that selective reduction of heart rate during exposure to a mild psychosocial stressor might reduce sympathoadrenal stress response and therefore protect the organism from negative impact of stressors. Fig. 2, Ref. 38, Online full text (Free, Pdf) www.cardiology.sk. ... It reduces heart rate, independently of the blood pressure or myocardial contractility. In a randomized trial, both ivabradine and metoprolol succinate reduced the incidence of ischaemia and MI significantly, when compared with placebo [159] . These findings need to be confirmed by future studies in the perioperative setting, because ivabradine might be considered for patients with a contraindication to β-blockers. ... Oxford Textbook of Advanced Critical Care Echocardiography Article Feb 2020 Anthony S McLean Stephen Huang Andrew Hilton <here is a image 6d6d54372bc1e888-3a01bbd82f0045fc> Konstantin Yastrebov This book is a physiological and evidence-based reference guide to the principles and techniques of advanced echocardiography. Both transoesophageal and transthoracic echocardiography are addressed, where appropriate. The foundations of advanced echocardiography are outlined in Part 1, preceding specific assessment methods of critical care echo which are demonstrated and discussed in Part 2. In reality, most critically ill patients do not suffer only one clinical problem, so Part 3 integrates techniques learned in Part 2 to answer both common and unexpected critical care questions. The future use of echocardiography in critical care is explored in Part 4. Important reference values for clinical use can be accessed easily in the appendices. An appendix includes videos, cases, and multiple-choice questions that can be used to reinforce understanding. ... It reduces heart rate, independently of the blood pressure or myocardial contractility. In a randomized trial, both ivabradine and metoprolol succinate reduced the incidence of ischaemia and MI significantly, when compared with placebo [159] . These findings need to be confirmed by future studies in the perioperative setting, because ivabradine might be considered for patients with a contraindication to β-blockers. ... The ESC Textbook of Intensive and Acute Cardiovascular Care Cardiovascular diseases (CVDs) are a major cause of premature death worldwide and a cause of loss of disability-adjusted life years. For most types of CVD early diagnosis and intervention are independent drivers of patient outcome. Clinicians must be properly trained and centres appropriately equipped in order to deal with these critically ill cardiac patients. This new updated edition of the textbook continues to comprehensively approach all the different issues relating to intensive and acute cardiovascular care and addresses all those involved in intensive and acute cardiac care, not only cardiologists but also critical care specialists, emergency physicians and healthcare professionals. The chapters cover the various acute cardiovascular diseases that need high quality intensive treatment as well as organisational issues, cooperation among professionals, and interaction with other specialities in medicine. ... The results of the present study demonstrate and explain why a smaller human I f has a greater effect on prolonging the diastolic depolarization phase when it is partially blocked, using both mathematical theoretical analysis and computer simulation, which is clearly distinct from the previous studies (Verkerk and Wilders, 2010;Fabbri et al., 2017). Collectively, they add mechanistic insight into the understanding of how a low dose of clinical use of ivabradine (<137 nM) can effectively slow down the human heart rate by about 18-20% (Camm and Lau, 2003; Joannides et al., 2006; Doesch et al., 2007;Jiang et al., 2013), which contrasts with a negligible effect predicted by experimental studies in the rabbit (<4% at 10 min after administration of ivabradine; Thollon et al., 2007). ... The Functional Role of Hyperpolarization Activated Current (If) on Cardiac Pacemaking in Human vs. in the Rabbit Sinoatrial Node: A Simulation and Theoretical Study The cardiac hyperpolarization-activated “funny” current ( I f ), which contributes to sinoatrial node (SAN) pacemaking, has a more negative half-maximal activation voltage and smaller fully-activated macroscopic conductance in human than in rabbit SAN cells. The consequences of these differences for the relative roles of I f in the two species, and for their responses to the specific bradycardic agent ivabradine at clinical doses have not been systematically explored. This study aims to address these issues, through incorporating rabbit and human I f formulations developed by Fabbri et al. into the Severi et al. model of rabbit SAN cells. A theory was developed to correlate the effect of I f reduction with the total inward depolarising current ( I total ) during diastolic depolarization. Replacing the rabbit I f formulation with the human one increased the pacemaking cycle length (CL) from 355 to 1,139 ms. With up to 20% I f reduction (a level close to the inhibition of I f by ivabradine at clinical concentrations), a modest increase (~5%) in the pacemaking CL was observed with the rabbit I f formulation; however, the effect was doubled (~12.4%) for the human I f formulation, even though the latter has smaller I f density. When the action of acetylcholine (ACh, 0.1 nM) was considered, a 20% I f reduction markedly increased the pacemaking CL by 37.5% (~27.3% reduction in the pacing rate), which is similar to the ivabradine effect at clinical concentrations. Theoretical analysis showed that the resultant increase of the pacemaking CL is inversely proportional to the magnitude of I total during diastolic depolarization phase: a smaller I f in the model resulted in a smaller I total amplitude, resulting in a slower pacemaking rate; and the same reduction in I f resulted in a more significant change of CL in the cell model with a smaller I total . This explained the mechanism by which a low dose of ivabradine slows pacemaking rate more in humans than in the rabbit. Similar results were seen in the Fabbri et al. model of human SAN cells, suggesting our observations are model-independent. Collectively, the results of study explain why low dose ivabradine at clinically relevant concentrations acts as an effective bradycardic agent in modulating human SAN pacemaking. ... One cardiac effect of propranolol is the reduced HR at rest leading to a lower Q . Indeed, the drug can also reduce exercise tachycardia in a dose-dependent manner (6, 21) . Noteworthy, is that the dosage in the present study was similar for men and women (i.e., 40 mg), yet the cardiac effect (i.e., SV, HR, and Q ) could be found in both. ... Sex Differences in Blood Pressure Regulation During Ischemic Isometric Exercise: The Role of the β‐Adrenergic Receptors ... Ivabradine is a selective inhibitor of the diastolic depolarizing I f current of cardiac pacemaker cells in the sinoatrial node. It reduces heart rate in patients in sinus rhythm, causing a significant decrease in the rate-pressure-product, a proxy for myocardial work [38] . Ivabradine alone or in combination with other anti-ischemic drugs was shown to significantly improve exercise tolerance, to reduce the incidence of anginal episodes, and to improve quality of life [39,40]. ... Relief of Ischemia in Ischemic Cardiomyopathy Purpose of the Review Ischemic heart disease is among the most common causes of morbidity and mortality worldwide. In its stable manifestation, obstructing coronary artery stenoses prevent myocardial blood flow from matching metabolic needs of the heart under exercise conditions, which manifests clinically as dyspnea or chest pain. Prolonged bouts of ischemia may result in permanent myocardial dysfunction, heart failure, and eventually reduced survival. The aim of the present work is to review currently available approaches to provide relief of ischemia in stable coronary artery disease (CAD). Recent Findings Several pharmacological and interventional approaches have proven effectiveness in reducing the burden of ischemia in stable CAD and allow for symptom control and quality of life improvement. However, substantial evidence in favor of improved survival with ischemia relief is lacking, and recently published randomized controlled trial suggests that only selected groups of patients may substantially benefit from this approach. Summary Pharmacological treatments aimed at reducing ischemia were shown to significantly reduce ischemic symptoms but failed to provide prognostic benefit. Myocardial revascularization is able to re-establish adequate coronary artery flow and was shown to improve survival in selected groups of patients, i.e., those with significant left main CAD or severe left ventricular dysfunction in multivessel CAD. Outside the previously mentioned categories, revascularization appears to improve symptoms control over medical therapy, but does not confer prognostic advantage. More studies are needed to elucidate the role of systematic invasive functional testing to identify individuals more likely to benefit from revascularization and to evaluate the prognostic role of chronic total occlusion recanalization. ... Ivabradine significantly reduced systolic BP at rest. However, during tilt and exercise tests, only propranolol but not ivabradine reduced systolic BP (25) . ... Ivabradine and Blood Pressure Reduction: Underlying Pleiotropic Mechanisms and Clinical Implications Elevated heart rate (HR) is a well-recognized but somewhat neglected risk factor among the healthy population and various cardiovascular pathologies. High HR is fraught with a spate of detrimental cardiovascular consequences including immense myocardial oxygen demand in reduced diastolic perfusion time and low, oscillatory vascular shear stress with high tensile stress triggering endothelial dysfunction. Although beta-blockers (BBs) are considered to be the cornerstone treatment of elevated HR in various cardiovascular pathologies, they are associated with negative inotropy, a number of side effects, and undesirable metabolic actions limiting their usage. Thus, new approaches to HR reduction are being continuously sought out. The inhibition of the If current in the sinoatrial node (SAN) seems to offer a promising approach to the reduction of elevated HR. Indeed, the SAN's pacemaker cells are inherently capable of cyclic variations of the resting membrane potential necessary for spontaneous depolarization. The SAN's spontaneous slow diastolic depolarization is administered by a mixed sodium/potassium inward current, known as an If current, through the “funny” (f)-channel. Structurally, the f-channel belongs to hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels and is activated by both hyperpolarization in the diastolic voltage range and intracellular cyclic adenosine monophosphate. Ivabradine selectively inhibits the If current, thus reducing the steepness of SAN's diastolic depolarization, ensuing diastole prolongation without affecting action potential duration or inducing negative inotropy. Several studies have assessed ivabradine's efficacy in clinical settings. In the SHIFT study, the investigation of 6,558 patients with systolic heart failure (HF) during a median 22.9 month follow-up period revealed that the addition of ivabradine to an established HF therapy significantly reduced the primary composite endpoint of hospital admission for worsening HF or cardiovascular death. Considering the results of the SHIFT study, ivabradine is recommended for patients with systolic HF and HR above 70 bpm despite an evidence-based optimal medical therapy (with or without BB) to reduce the composite endpoint of hospitalization and mortality. The BEAUTIFUL study comprised 10,917 systolic HF patients with HR above 70 bpm suffering from stable coronary artery disease (CAD), and the primary endpoint was a composite of cardiovascular death and hospital admission for acute myocardial infarction or HF. Although neither the primary endpoint nor the cardiovascular death rate improved, ivabradine reduced the secondary endpoints of hospital admissions for myocardial infarction and coronary revascularization. However, in the SIGNIFY study involving 19,102 patients with stable CAD but without HF, ivabradine did not reduce the compound primary endpoint of cardiovascular death and myocardial infarction. Hypertension, however, is a substantially different condition, and data regarding ivabradine's effect on peripheral blood pressure (BP) in a hypertensive population are scanty. Yet ivabradine's interference with central BP (CBP) was indicated in several studies. Lopatin and Vitale reviewed five studies analyzing ivabradine's effect on CBP in patients with CAD: two studies reported a neutral effect, while in two other studies and in one study, ivabradine decreased and increased CBP, respectively. In 12 normotensive patients with stable CAD and HR ≥ 70 bmp, a 3 week ivabradine treatment reduced brachial systolic and diastolic BP, while the HR reduction did not increase central aortic BP. Moreover, in patients with arterial hypertension and CAD treated with ivabradine, the increase in HR between resting conditions and early recovery post exercise showed a trend toward correlation with the radial augmentation index. Besides ivabradine's HR-reducing action, which is considered to be a principal mechanism of its benefit, ivabradine exerts a number of pleiotropic effects, some of which may partly be HR independent and some of which are still emerging. ... R. Joannides et al. (2006) investigaron la acción de un nuevo producto: el ivabradine (primer inhibidor selectivo de canales I F en el nódulo aurículosinusal), en comparación con la del propranolol. En 9 voluntarios sanos suministraron dosis únicas por vía oral de Ivabradine (30 mg) o propranolol (40 mg). ... VARIABILIDAD DE LA FRECUENCIA CARDIACA: FUNDAMENTOS FISIOLOGICOS, ASPECTOS METODOLOGICOS Y RECOMENDACIONES La presente obra constituye una compilación de diferentes trabajos que fueron realizados por un grupo de científicos cubanos de diferentes instituciones, que contribuyeron a consolidar criterios acerca de la temática abordada y de los procedimientos metodológicos que debían aplicarse para el procesamiento y análisis de las señales registradas, tomando en cuenta el desarrollo alcanzado por la Medicina en nuestro país y nuestras propias experiencias. De una manera u otra, en los últimos 10 años, estos mismos autores han continuado el desarrollo de la temática y han logrado avances importantes, pero hemos considerado conveniente agrupar los trabajos que se incluyen en la obra, porque entendemos que pueden servir de base para conocer el desarrollo de los conceptos y procederes a lo largo de un número de años y permitir a otros colegas compartir estos conocimientos y someterlos a su análisis y valoración. En cierto sentido, vemos en este material que ahora ponemos a consideración de la comunidad científica, parte de la historia del desarrollo de conceptos y desarrollos metodológicos, en el campo del estudio de ese gran olvidado: el Sistema Nervioso Autónomo. Muchos de los conceptos y procederes incluidos en la obra se encuentran vigentes, y en muchos casos resultará útil para quienes se introducen al mismo sin una preparación anterior. Agradecemos a todos los que han hecho posible que esta compilación se haya podido lograr y que sus materiales hayan sido revisados, aunque sin modificar esencialmente la información que fue publicada en la época en que cada material incluido, para que llegue al lector sin erratas. Para quien desee introducirse en este campo de la práctica clínico-fisiológica los materiales incluidos le serán de utilidad y ese es el gran deseo de todos el Colectivo de Autores. Dr. Mario Estévez Báez La Habana, Cuba, febrero 2020 ... One cardiac effect of propranolol is the reduced HR at rest leading to a lower Q . Indeed, the drug can also reduce exercise tachycardia in a dose-dependent manner (6, 21) . Noteworthy, is that the dosage in the present study was similar for men and women (i.e., 40 mg), yet the cardiac effect (i.e., SV, HR, and Q ) could be found in both. ... Sex Differences in Blood Pressure Regulation during Ischemic Isometric Exercise: the Role of the β-Adrenergic Receptors We sought to investigate whether the β-adrenergic receptors play a pivotal role in sex-related differences in arterial blood pressure (BP) regulation during isometric exercise. Sixteen volunteers (8 women) performed 2 min of ischemic isometric handgrip exercise (IHE) and 2 min of post exercise circulatory occlusion (PECO). Heart rate (HR) and beat-to-beat arterial BP were continuously measured. Beat-to-beat estimates of stroke volume (ModelFlow) were obtained and matched with HR to calculate cardiac output (Q̇) and total peripheral resistance (TPR). Two trials were randomly conducted between placebo and non-selective β-adrenergic blockade (40mg propranolol). Under the placebo condition, the magnitude of the BP response in IHE was lower in women compared with men. During PECO, the BP remained elevated and the sex differences persisted. The β-blockade attenuated the BP response during IHE in men (∆ 57±4 mmHg vs ∆ 45±7 mmHg, P=0.025) due to a reduction in Q̇ (∆ 3.7±0.5 l/min vs ∆ 1.8±0.2 l/min, P=0.012) while TPR was not affected. In women, however, the BP response during IHE was unchanged (∆ 27±3 mmHg vs ∆ 28±3mmHg, P=0.889), despite attenuated Q̇ (∆ 2.7±0.4 l/min vs ∆ 1.3±0.2 l/min, P=0.012). These responses were mediated by a robust increase in TPR under β-blockade (∆-0.2±0.4 mmHg.L-1.min vs ∆ 2.2±0.7 mmHg.L-1.min, P=0.012). These findings demonstrate that the sex differences in arterial BP regulation during ischemic IHE are mediated by β-adrenergic receptors. ... 10,24,25 At therapeutic concentrations, ivabradine has no action at other cardiac ion channels or receptors and does not act via altering intracellular cyclic adenosine monophosphate levels. Consequently, ivabradine does not depress myocardial contractility 26, 27 or intracardiac conduction 28 and has only minor effects on blood pressure as seen in this and previous studies. 12 Thus, the unique haemodynamic profile of ivabradine can provide anti-ischaemic efficacy in addition to heart rate lowering with beta-blocker therapy, and this combination therefore represents a potential therapeutic strategy to treat patients with stable angina. ... Tardiff JC et al Eur Heart J 2009 vol 30 pp 540-548 Efficacy of the If current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4-month, randomised, placebo-controlled trial. ... Ivabradine is one of the newer drugs used in patients with HF. These drugs act by inhibiting the sinoatrial node, hence reducing heart rate without lowering the blood pressure [88] . Recent trials have shown a significant reduction in hospitalization rates in patients using ivabradine (in addition to conventional treatment) compared to conventional treatment alone [89]. ... The impact of chronic kidney disease on medication choice and pharmacologic management in patients with heart failure Introduction: In the past few years, medical community, including doctors, have become increasingly aware of the fact that chronic kidney disease (CK) and heart failure (HF) have common risk factors which impacts one another in terms of choice of therapy. Areas covered: Management of these two diseases has been a challenge for physicians. The treatment goals for HF patients in CK are very important. They serve as the end-point in using a specific treatment for management and treatment of CK patients hence, decreasing mortality rates. In this review, we discuss the pharmacological approaches to managing patients with HF and CK, discussing current evidence based uptodate management strategies and guidelines in the general population with HF and CK. Expert Commentary: Newer novel drugs targeting specific signaling pathways are approaching the stages of clinical investigation including the direct renin inhibitors. They have been a highly attractive concept for the future in the management of these patients. However, while advances in technology elucidated many aspects of these diseases, many mysteries still remain. With continued research, we can expect more cost- effective and patient-friendly drug therapies to be developed in the near future. ... 4 Ivabradine, a novel HR lowering agent, is a selective and specific inhibitor of the "funny" I f current at concentrations that do not affect other cardiac ionic currents resulting in lack of hemody- namic effects such as reduction of blood pressure, cardiac contractility or atrioventricular conduction, which is often a limitation with beta blockers. 5, 6 Improvement in remodeling of the extracellular matrix has also been reported with Ivabradine in animal and experimental models of HF. 7 Despite its benefit being demonstrated in patients with CAD and LV dysfunction, 8,9 the use of Ivabradine in isolated non-ischemic HF has been less studied and only a few studies have reported its use in HF secondary to DCM. 10,11 This prospective randomized study sought to assess whether addition of Ivabradine to conventional treatment while targeting a heart rate reduction of <70/min would improve functional class, exercise tolerance, and left ventricular function in patients with HF secondary to nonischemic dilated cardiomyopathy. ... Adding ivabradine to beta-blockers in chronic heart failure: Do not rest without lowering the resting heart rate sufficiently ... First, ivabradine does not have negative inotropic or lusitropic effects; so hemodynamic and myocardial contractility are not impaired. 64, 65 Ivabradine leads to a decrease in heart rate, which reduces myocardial oxygen demand and simultaneously improves oxygen supply by prolonging diastole, which allows increased coronary flow and myocardial oxygenation. Second, Mulder et al showed that ivabradine improves the LV pressure-volume relationship, prevents LV systolic dysfunction, and increases capillary density in a rat model of congestive heart failure. ... S T A B L E A N G I N A P E C T O R I S : E V O L V I N G C O N S I D E R A T I O N S F O R S Y M P T O M A T I C M A N A G E M E N T O F P A T I E N T S Anti-ischemic therapy in patients undergoing cardiac rehabilitation-Marazia and others 34 C ardiac rehabilitation programs present an opportunity to improve the functional status of patients and help them to reach and maintain optimal physical, psychological, and social functional levels. Optimal pharmacological therapy, which improves coronary perfusion, symptoms, exercise capacity, and quality of life, is not only an essential part of patient management, but also acts in synergy with cardiac rehabilitation to achieve the goals of patient management. Heart rate is not just a physical sign; it is a biomarker and a therapeutic target in patients with cardiovascular disease. It regulates myo-cardial oxygen consumption, coronary flow, and plays a central role in adapting the cardiac output to the metabolic needs of the whole body. In many cardiac diseases, an increase in heart rate is associated with a higher mortality. Ivabradine is a pure heart rate-reducing agent with anti-ischemic and anti-anginal effects but without any influence on blood pressure and contractility, and it is therefore well tolerated. Since heart rate determines oxygen consumption and delivery, its modulation by ivabradine strongly influences cardiac performance and exercise tolerance and leads to functional status improvement in all patients taking part in cardiac rehabilitation programs. Medicographia. 2017;39:34-40 C ardiac rehabilitation-after a diagnosis of coronary artery disease (CAD), heart failure, and heart surgery-has gradually evolved over the past two decades from exercise-based interventions to comprehensive, professional, lifestyle programs that include smoking cessation, diet modification, control of cardiovascu-lar risk factors, and behavioral interventions. Patients who undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) after acute coronary syndrome and patients with heart failure have a high prevalence of modi-fiable risk factors, so the primary aim of cardiac rehabilitation programs should be lifestyle modification and optimization of medical therapy. Functional capacity improvement should be a priority of cardiac rehabilitation programs, as it is directly related to quality of life. Heart rate is a major determinant of myocardial oxygen demand, coronary blood flow, myocardial performance, and functional capacity in the general population 1,2 and in patients with cardiovascular disease. 3 In various heart conditions, increased heart rate, especially overnight, is associated with a higher mortality. The crucial role of heart rate is highlighted by the fact that maximal heart rate during exercise and heart rate recovery are the most commonly used parameters in cardiology for assessing the ef ... On the contrary, IVA lacks of the negative lusitropic effect at similar levels of HR reduction but provides similar decreases in myocardial oxygen demand without the detrimental action of LV contractility. [35] Nevertheless, with regard to IVA, the beneficial effects on HF cannot be ascribed to slowing of heart-beats, with lengthening of diastolic time alone, but also to its "pleiotropic" effects, as improvement of ventricular relaxation by enhancing the reuptake of calcium by the sarcoplasmic reticulum, increase in myocardial compliance, LV remodeling, no changes in blood pressure, or reduction of infarct size (in CAD) and improvement of endothelial function. [36] conclusIons On account of these characteristics, IVA can be considered a drug acting with an innovative mechanism both against CAD and CHF in sinus rhythm. ... The role of Ivabradine in Diastolic Heart Failure with preserved Ejection Fraction. A Doppler-Echocardiographic study Background Ivabradine (IVA) is effective in patients with coronary artery disease (CAD) or systolic heart failure in sinus rhythm. Its action consists in reducing heart rate (HR) and improving the time of left ventricular (LV) diastolic filling. The aim of this study was to evaluate the effects of IVA added to conventional therapy on patients with diastolic heart failure (DHF) and preserved ejection fraction (HFpEF). Methods We evaluated 25 patients with DHF in the New York Heart Association (NYHA) Class II-III and sinus rhythm. In these, IVA per os (5 mg/twice a day) was added to the conventional medical therapy and given for 12 weeks. Immediately before the beginning of IVA therapy and 3 months later, patients underwent echocardiographic evaluation by two-dimensional (2D) ultrasound and tissue Doppler imaging (TDI). The patterns of diastolic mitral inflow and pulmonary venous flow were recorded using 2D echocardiography, while the diastolic phase of mitral flow was recorded by TDI, from the lateral mitral annulus. Results Three months after the addition of IVA to conventional treatment, HR significantly decreased in comparison to the baseline values. On the contrary, the echocardiographic indexes of LV diastolic dysfunction improved. Conclusions These results testify that the addition of IVA to conventional therapy in patients with HFpEF can improve LV diastolic function evaluated by 2D and tissue Doppler-echocardiographic patterns. These Doppler-echocardiographic results match with the clinical improvement of patients evaluated. ... However, our conclusion needs several potential mechanisms to explain: First, ivabradine, a specific inhibitor of the If current in the sinoatrial node, is a pure RHR lowering agent, and it does not affect myocardial contractility, blood pressure, intracardiac conduction, or ventricular repolarization. [6,7, 27] However, RHR serves as a marker of autonomic nervous system activity. The depolarization rate of sinoatrial node is largely determined by the activity of autonomic nervous system. ... Ivabradine has a neutral effect on mortality in randomized controlled trials Background: It has long been a controversial hotspot whether resting heart rate (RHR) is a risk factor or a marker for death. Ivabradine, a specific inhibitor of the If current in the sinoatrial node, is a pure RHR lowering agent. The study was aimed to investigate whether ivabradine would reduce more RHR, cardiovascular disease (CVD) mortality, and all-cause mortality than those placebo or beta-blockers. Methods: The authors performed a meta-analysis of 8 randomized controlled clinical studies (with 40,357 participants), and 3 studies of those which were ivabradine versus placebo (36,069 participants) and other 5 studies ivabradine versus beta-blockers (4288 participants) were available. The authors compared the association of the RHR reduction with death from CVD causes (2674 in 40,285 participants) and the rate of all-cause death (3143 deaths in 38,037 participants), and assessed improvement in death rates with the use of ivabradine. Results: The change of RHR from baseline to endpoint was 8 to 16 beats/min (bpm) in ivabradine group, 1 to 8 bpm in placebo group, and 4 to 24 bpm in beta-blockers group. In ivabradine versus placebo, the reduced risks of CVD mortality and all-cause morbidity were not significantly (risk ratio [RR] 1.02; 95% confidence interval [CI] 0.91-1.14, P = .737; RR: 1.00, 95% CI: 0.92-1.09, P = .992, respectively). CVD and all-cause morbidity were similar for ivabradine versus beta-blockers (RR: 1.04; 95% CI: 0.80-1.37, P = .752; RR: 1.17, 95% CI: 0.53-2.60, P = .697, respectively). Conclusions: Ivabradine had a neutral effect on mortality, suggesting that a pure RHR lowering agent did not reduce CVD mortality, all-cause mortality and improve the lifespan. ... 4 Ivabradine, a novel HR lowering agent, is a selective and specific inhibitor of the "funny" I f current at concentrations that do not affect other cardiac ionic currents resulting in lack of hemodynamic effects such as reduction of blood pressure, cardiac contractility or atrioventricular conduction, which is often a limitation with beta blockers. 5, 6 Improvement in remodeling of the extracellular matrix has also been reported with Ivabradine in animal and experimental models of HF. 7 Despite its benefit being demonstrated in patients with CAD and LV dysfunction, 8,9 the use of Ivabradine in isolated non-ischemic HF has been less studied and only a few studies have reported its use in HF secondary to DCM. 10,11 This prospective randomized study sought to assess whether addition of Ivabradine to conventional treatment while targeting a heart rate reduction of <70/min would improve functional class, exercise tolerance, and left ventricular function in patients with HF secondary to nonischemic dilated cardiomyopathy. ... Heart rate manipulation in Dilated Cardiomyopathy: Assessing the role of Ivabradine Background Heart rate (HR) reduction is of benefit in chronic heart failure (HF). The effect of heart rate reduction using Ivabradine on various echocardiographic parameters in dilated cardiomyopathy has been less investigated. Methods Of 187 patients with HF (DCM, NYHA II–IV, baseline HR > 70/min), 125 patients were randomized to standard therapy (beta blockers, ACEI, diuretics, n = 62) or add-on Ivabradine (titrated to maximum 7.5 mg BD, n = 63). Beta-blockers were titrated in both the groups. Results At 3 months both groups had improvement in NYHA class, 6 min walk test, Minnesota Living With Heart Failure (MLWHF) scores and fall in BNP, however the magnitude of change was greater in Ivabradine group. Those on Ivabradine also had lower LV volumes, higher LVEF (28.8 ± 3.6 vs 27.2 ± 0.5, p = 0.01) and more favorable LV global strain (11 ± 1.7vs 12.2 ± 1.1, p = <0.001), MPI (0.72 ± 0.1 vs 0.6 ± 0.1, p = <0.001), LV mass (115.2 ± 30 vs 131.4 ± 35, p = 0.007), LV wall stress (219.8 ± 46 vs 238 ± 54) and calculated LV work (366 ± 101 vs 401 ± 102, p = 0.05). The benefit of Ivabradine was sustained at 6 months follow-up. The % change in HR was significantly higher in Ivabradine group (−32.2% vs −19.3%, p = 0.001) with no difference in blood pressure. Resting HR < 70/min was achieved in 96.8% vs 27.9% respectively in the two groups. Conclusion Addition of Ivabradine to standard therapy in patients with DCM and symptomatic HF and targeting a heart rate < 70/min improves symptoms, quality of life and various echocardiographic parameters. ... At therapeutic concentrations, ivabradine has no effect on other cardiac ion channels or receptors, and it does not act via changing cAMP levels in cardiac cells [29][30][31][32] . Ivabradine, unlike conventional heart rate-lowering agents including nondihydropyridine calcium channel blockers and beta-blockers [33] , has no direct effect on myocardial contractility, ventricular repolarization, and intracardiac conduction [34, 35] . Ivabradine does not reduce LVEF in patients with impaired left ventricular function [36] . ... The BEAUTIFUL Study: Randomized Trial of Ivabradine in Patients with Stable Coronary Artery Disease and Left Ventricular Systolic Dysfunction – Baseline Characteristics of the Study Population OBJECTIVES: Ivabradine is a selective heart rate-lowering agent that acts by inhibiting the pacemaker current If in sinoatrial node cells. Patients with coronary artery disease and left ventricular dysfunction are at high risk of death and cardiac events, and the BEAUTIFUL study was designed to evaluate the effects of ivabradine on outcome in such patients receiving optimal medical therapy. This report describes the study population at baseline. METHODS: BEAUTIFUL is an international, multicentre, randomized, double-blind trial to compare ivabradine with placebo in reducing mortality and cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction (ejection fraction <40%). RESULTS: A total of 10,917 patients were randomized. At baseline, their mean age was 65 years, 83% were male, 98% Caucasian, 88% had previous myocardial infarction, 37% had diabetes, and 40% had metabolic syndrome. Mean ejection fraction was 32% and resting heart rate was 71.6 bpm. Concomitant medications included beta-blockers (87%), renin-angiotensin system agents (89%), antithrombotic agents (94%), and lipid-lowering agents (76%). CONCLUSIONS: Main results from BEAUTIFUL are expected in 2008, and should show whether ivabradine, on top of optimal medical treatment, reduces mortality and cardiovascular events in this population of high-risk patients. ... It reduces heart rate, independently of the blood pressure or myocardial contractility. In a randomized trial, both ivabradine and metoprolol succinate reduced the incidence of ischaemia and MI significantly, when compared with placebo [158] . These findings need to be confirmed by future studies in the perioperative setting, because ivabradine might be considered for patients with a contraindication to β -blockers. ... Perioperative cardiac care of the high-risk non-cardiac patient ... Die Studie ist als zweiarmige Studie angelegt, um Unterschiede zu erkennen, die auf die jeweils eingesetzte Substanz im Vergleich zurückgeführt werden können. Eine Bewertung in Beziehung zu Ausgangswerten ist nur bedingt möglich, da auf einen dritten Placeboarm verzichtet wurde (Joannides et al. 2005) . Unsere Ergebnisse dürfen außerdem nur unter dem Aspekt einer vorhandenen Variabilität in der Medikamentenwirkung (Pharmakokinetik und Pharmakodynamik) gedeutet werden.Methodisch wäre sicherlich auch eine Verbesserung noch dadurch zu erreichen, wenn ergänzend spezifischere Darstellungen gefunden würden, mit denen sympathische und parasympathische Modulationen parallel und getrennt zu registrieren sind(Zhong et al. 2004).4.24. ... Akute Veränderungen des neurovegetativen Tonus´ bei intravenöser Molsidomin- oder Nitroglycerin-Applikation - Randomisierte doppelblinde Crossover-Studie mittels Herzfrequenzvariabilitäts-Analyse und Plasma-Katecholaminbestimmung Influences of NO donors on heart rate variability (HRV) and on plasma concentrations of catecholamines are scarcely described. In contrary to nitroglycerin (N), no data regarding to molsidomine (M) or SIN-1 are existing. Therefore, the present investigation engaded in the acutely occurring HRV effects of M and N in comparison. In a randomized observer-blind crossover study, 10 patients with mild hypertension (5 m / 5 f, 33-77 years, 66-95 kg body weight) were investigated in a medical department of an university clinic. All patients received in supine position either M or N intravenously in a comparable dose of 2 mg/h in both therapy arms over 4 hours on two successive days. Blood pressure, heart rate, HRV by Cardioscan (MTM Huenfelden) and catecholamine levels in plasma by HPLC were measured. The evaluation was performed in relation to basic values and with regard to specific agent effects in comparison as well. Because of different pharmacokinetis of M and N, the first hour of infusion was interpreted separately. In the 2nd - 4th hour of infusion, we found a smaller blood pressure decrease and a smaller heart rate increase under M than under N. Likewise, HRV in relation to basic values was more suppressed by N than by M. In direct comparison of both agents, HRV parameters which are describing the parasympathetic activity were significantly more suppressed when N was used (rMSSD: p=0.030, pNN50: p=0.015, HF Power: p=0.034). In contrary to an only small increase of baseline catecholamine concentrations in plasma by M, level of significance was reached by N (noradrenaline: p=0.004, adrenaline: p=0.010). The results suggest that the parasymapathetic mediated modulation of heart rate would be less impaired by M than by N. This could be important in patients with angina pectoris and in patients after myocardial infarction because these patients are typically showing a reduced vagal tone. ... Recientemente, la Agencia Europea para la Evaluación del Medicamento (EMEA) ha aprobado la ivabradina, el primer inhibidor específico de la corriente I f [38][39] [40] [41][42] , para el tratamiento de pacientes con angina crónica estable con función sinusal normal y en los que está contraindicado el uso de bloqueadores beta o que presenten intolerancia a estos fármacos. ... Ivabradine: A selective If current inhibitor. Pharmacological characteristics and tolerability The heart rate is the main determinant of both myocardial oxygen demand and coronary blood flow. Heart rate is determined by spontaneous electrical activity in the pacemaker cells of the sinoatrial node. These cells exhibit a diastolic depolarization phase that drives the membrane potential towards the threshold value for initiating a new action potential, which propagates throughout the myocardium and triggers a contractile response. The If current, an inward current of Na⁺ and K⁺ ions through hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels, is the main determinant of the slope of the slow diastolic depolarization phase. These channels open in response to membrane hyperpolarization and are modulated by the intracellular cAMP concentration. Ivabradine specifically blocks the I f current. To do so, it crosses the membrane and binds to a receptor located on the intracellular side of the channel pore. As a result, ivabradine produces a dose-dependent decrease in heart rate that reduces myocardial oxygen demand and increases coronary blood flow. However, at therapeutic concentrations, it does not affect other cardiac ionic currents, which is why ivabradine does not alter blood pressure, cardiac contractility, or cardiac electrophysiological parameters. This article reviews ivabradine's mechanism of action, pharmacodynamic and pharmacokinetic properties, side effects, and interactions. ... While there is evidence from animal studies showing a modest reduction in serum catecholamines with ivabridine [50], the authors have not been able to find human studies showing a reduction in catecholamine level. In the few small studies looking at catecholamine levels in HF patients [51] and healthy volunteers [52] , no significant acute change was seen in patients treated with ivabridine. ... Is Heart Rate a Norepiphenomenon in Heart Failure? There has been an increased focus on heart rate as a target in the management of cardiovascular disease and more specifically in heart failure with preserved ejection fraction in recent years with several studies showing the benefit of a lower resting heart rate on outcomes. This review paper examines the pathophysiology behind the benefits of lowering heart rate in heart failure and also the evidence for and against the pharmacological agents available to achieve this. ... Ivabradine is used in the treatment of chronic angina pectoris and chronic heart failure for decades [18]. Ivabradine blocks the funny channel (I f ) in the sinoatrial node [19] resulting in reduced heart rate without adversely affecting blood pressure and cardiac contractility [20, 21] . In late 2009, ivabradine was introduced as a pre-medication heart rate controller for CCTA examination and has been adopted by institutions at present. ... Ivabradine as an Effective Heart Rate Controlling Agent in Coronary Computed Tomography Angiography: A Systematic Review ... Following on from extensive preclinical testing, ivabradine emerged as promising candidate to selectively decrease HCN-mediated current in SAN preparations. Subsequent studies in both animal models and humans have documented that ivabradine decreases heart rate to an extent similar to that seen with clinical doses of betablockers [220] [221] . Currently ivabradine is clinically used in the treatment of stable angina pectoris and cardiac failure as selective bradycardic agent [222][223][224][225][226]. Its use is recommended in patients unable to tolerate or with contraindications to beta-blockers, because at variance with them, it does not directly affect myocardial systolic or diastolic function, nor it reduces blood pressure [227] or causes bronco-constriction in asthmatic or COPD subject. ... HCN Channels Modulators: The Need for Selectivity Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, the molecular correlate of the hyperpolarization-activated current (If/Ih), are membrane proteins which play an important role in several physiological processes and various pathological conditions. In the Sino Atrial Node (SAN) HCN4 is the target of ivabradine, a bradycardic agent that is, at the moment, the only drug which specifically blocks If. Nevertheless, several other pharmacological agents have been shown to modulate HCN channels, a property that may contribute to their therapeutic activity and/or to their side effects. HCN channels are considered potential targets for developing drugs to treat several important pathologies, but a major issue in this field is the discovery of isoform-selective compounds, owing to the wide distribution of these proteins into the central and peripheral nervous systems, heart and other peripheral tissues. This survey is focused on the compounds that have been shown, or have been designed, to interact with HCN channels and on their binding sites, with the aim to summarize current knowledge and possibly to unveil useful information to design new potent and selective modulators. ... 8 Ivabradine is a selective, pure HR-lowering agent that inhibits the If current in the sinoatrial node. 9 Several studies have shown ivabradine to be noninferior to first-line antianginal agents, such as beta-blockers and calcium channel blockers, and superior to placebo. [10][11][12][13] Ivabradine has a class IIa (level of evidence B) indication for the symptomatic treatment of chronic stable angina in patients intolerant to or inadequately controlled by beta-blockers. 2 In this issue of Angiology, Zarifis et al 14 evaluated the potential antianginal effect of ivabradine when coadministered with beta-blockers in 926 patients with chronic stable angina and history of coronary revascularization (coronary artery bypass graft or percutaneous coronary intervention) in a time period of 4 months. ... Lowering Heart Rate Post Revascularization: Angina and Quality of Life Improvement ... Препараты этого класса одновременно со снижением ЧСС проявляли отрицательные инотропный и люситропный эффекты, они способны напрямую увеличивать жесткость кардиомиоцитов [27]. В сравнении с атенололом ивабрадин не оказывал отрицательного люситропного действия при аналогичных с β-АБ урежении ЧСС [28] и снижении потребности миокарда в кислороде, но без негативного влияния на сократимость ЛЖ [29, 30] . ... Heart rate slowing therapy in patients with chronic heart failure and preserved left ventricular ejection fraction ... In those patients and in case of missing response to these drugs, the calcium channel blocker verapamil can be tried. If verapamil is ineffective as is frequently the case, 86 the funny current (I f ) blocker ivabradine, 87 which reduces heart rate in patients with sinus rhythm (but not in those with atrial fibrillation) without altering blood pressure, 88 can be used next if available (as in Europe). 86,89 b-Adrenoceptor antagonists are contraindicated in MCAD patients. ... Cardiovascular symptoms in patients with systemic mast cell activation disease Traditionally, mast cell activation disease (MCAD) has been considered as just one rare (neoplastic) disease, mastocytosis, focused on the mast cell (MC) mediators tryptase and histamine and the suggestive, blatant symptoms of flushing and anaphylaxis. Recently another form of MCAD, the MC activation syndrome, has been recognized featuring inappropriate MC activation with little to no neoplasia and likely much more heterogeneously clonal and far more prevalent than mastocytosis. Increasing expertise and appreciation has been established for the truly very large menagerie of MC mediators and their complex patterns of release, engendering complex, nebulous presentations of chronic and acute illness best characterized as multisystem polymorbidity of generally inflammatory ± allergic theme. We describe the pathogenesis of MCAD with a particular focus on clinical cardiovascular symptoms and the therapeutic options for MC mediator-induced cardiovascular symptoms. ... These results indicated that pharmacological effects of ivabradine are related to sustained tissue binding possibly associated with the presence of an active metabolite. 36, 38 Ivabradine is extensively metabolised by the liver and the gut, being oxidised by the cytochrome CYP3A4 and it is also a very weak inhibitor of this cytochrome. Metabolic clearance accounts for 80% of ivabradine total clearance and the remaining 20% is accounted for by renal clearance. ... Ivabradine - A novel treatment for chronic stable angina Heart rate is an important determinant of myocardial oxygen consumption and elevated heart rate is a known risk factor in coronary artery disease. Heart rate reduction has been the cornerstone of antianginal and antiischemic therapy for many years and is most often achieved by β-blockers. The discovery of the f-channel and its role in regulating pacemaker activity in the sinoatrial node led to the development of new pharmacological agents such as ivabradine, which target these f-channels causing a reduction in heart rate by inhibiting the I f current. Due to its specific and selective action, ivabradine does not display any of the negative inotropic peripheral vascular or central nervous system side-effects that have limited the use of β-blockers in some patients. Ivabradine efficacy has been investigated in a large clinical development programme involving 5000 participants including over 3500 patients with chronic stable angina, and was shown to reduce resting and exercise induced heart rate without modifying any electrophysiological parameters. It has been shown to reduce heart rate at rest and during exercise and improve measurable parameters of angina in a dose-dependent manner. Its antiianginal and antiischemic effects have also has been shown to be non-inferior to commonly use doses of atenolol and amlodipine. Ivabradine is currently licensed for oral use at 5 and 7.5mg twice daily for symptomatic treatment of chronic stable angina in patients with normal sinus rhythm who are either intolerant of β-blockers or for whom they are contraindicated. ... Comparative effects of ivabradine and propranolol on systemic and cardiac haemodynamics at rest and during exercise showed that for a similar decrease in heart rate at rest and during sympathetic stimulation, acute administration of ivabradine, decreased myocardial oxygen demand to the same extent as a reference betablocker, propranolol, but without evidence of depressant effect on cardiac function (Joannides and al., 2006) . ... Ivabradine: A new therapeutic perspective in cardiovascular disease ... Joannides et al. recently reported that acute administration of ivabradine has no effect on ANS activity and function in healthy subjects, as measured by HRV analysis, despite slowing of the HR during rest and exercise. 36 They also reported no evidence of a depressant effect on cardiac function. Nerla et al. also reported that the ivabradineinduced increase in vagal cardiovascular tone, in syncope patients, was very modest and less than that observed in patients who were given a βadrenoceptor antagonist. ... The Effect of Ivabradine on the Heart Rate and Sympathovagal Balance in Postural Tachycardia Syndrome Patients Background: Postural tachycardia syndrome (POTS) is a common form of chronic orthostatic intolerance. The remarkable increase in heart rate (HR) upon standing is the hallmark of this syndrome. Treatment of POTS patients is challenging and includes drugs that slow the HR. Ivabradine is a selective If channel blocker designed to slow the HR, as an anti-anginal agent. In view of its ability to slow the HR, we posited that ivabradine may be an ideal medication for treating POTS patients. This report provides the results of an investigation in which we studied ivabradine's effect on the hemodynamics and sympathovagal balance in POTS patients. Methods: An open-label trial, without a placebo control, was performed in eight patients with POTS of two years' standing. Characterization of symptoms, hemodynamics, autonomic function tests, and HR and blood pressure (BP) variability were determined while patients were in a supine position and during a 20-minute head-up tilt before and after a single oral dose of 7.5 mg ivabradine. Results: Ivabradine slowed the HR of POTS patients at rest by 4±1 bpm (P<0.05). During a 5-minute head-up tilt, the HR decreased from 118±4 bpm to 101±5 bpm (P<0.01). Ivabradine did not affect the BP when patients were at rest in a supine position or in head-up tilt position. Cardiovascular vagal and sympathetic tone, extrapolated from the time and frequency domains of the HR and BP variability, were also not affected by ivabradine. Conclusions: Ivabradine is an effective drug for slowing the HR of POTS patients at rest and during tilting, without producing significant adverse effects. Moreover, ivabradine exerts its effects without influencing the sympathovagal balance. ... Enfin, l'équipe de Joannides et al., a comparé les effets de l'IVA à ceux d'un bêtabloquant sur la fonction cardiaque et hémodynamique au repos, lors d'un test tilt et lors d'un exercice sur 9 volontaires sains ayant reçu de l'ivabradine (30 mg), du propranolol (40 mg) ouun placebo. Ces auteurs rapportent que pour une diminution semblable de la fréquence cardiaque au repos et à l'exercice, l'administration aigue d'IVA réduit la consommation en oxygène myocardique de façon similaire au bêta-bloquant mais sans induire d'altération de la fonction cardiaque [Joannides, Moore et al., 2006] . ... Functional and metabolic impact of heart rate reduction induced by a selective inhibitor of pacemaker current If, ivabradine : experimental approach in pig and mouse model Ischemic cardiopathies are a major cause of cardiovascular mortality potentially leading tosudden death by ventricular fibrillation (VF). In patients with coronary disease, onetherapeutic goal is to reduce oxygen requirements via slowing of heart rate (SHR). Severalmedicinal drugs, such as beta-blockers and calcium inhibitors can achieve this goal, but canresult in altered cardiac contractility and various adverse effects, which restricts their use. Wefocused our interest on the effects of a selective inhibitor of the pacemaker current If, namelyivabradine (IVA), which can reduce sinusal heart rate. The aim of the present work was toevaluate the impact of SHR on the propensity to VF and to better understand thephysiological and metabolism mechanisms involved. The first study was performed on a pigmodel of acute myocardial ischemia leading to VF. In the second study, the impact of SHRwas evaluated using a mouse model of isolated perfused working heart. Our resultsdemonstrated that IVA induced SHR in both models and this was associated in vivo withenhanced coronary flow, conservation of mitochondrial structure and myocardial energeticstatus, thus reducing the risk of triggering ischemia-induced VF. Moreover, ex vivo, theobserved SHR did not change the selection of substrates for energy production. From atherapeutic point of view, it is critical to improve the conditions within tissues and to reducethe loss of substrates during myocardial ischemia. IVA apparently met this goal. Indeed, viaspecific effects on sinusal automaticity, it can act both preventively and curatively ... Baseline (blue), after treatment (yellow). ns Not significant suppress myocardial contractility [28, 29], and does not cause atrioventricular conduction abnormalities [30]. Specifically, it does not alter QT interval or repolarization duration as well as conductivity or refractoriness of ventricles, His-Purkinje system, atrioventricular node and atrium [30]. ... Ivabradine and Bisoprolol on Doppler-derived Coronary Flow Velocity Reserve in Patients with Stable Coronary Artery Disease: Beyond the Heart Rate Coronary flow velocity reserve (CFVR) is an important prognostic marker in patients with stable coronary artery disease (CAD). Beta-blockers and ivabradine have been shown to improve CFVR in patients with stable CAD, but their effects were never compared. The aim of the current study was to compare the effects of bisoprolol and ivabradine on CFVR in patients with stable CAD. Patients in sinus rhythm with stable CAD were enrolled in this prospective, randomized, double-blind trial. Patients had to be in a stable condition for at least 15 days before enrollment, on their usual therapy. Patients who were receiving beta-blockers or ivabradine entered a 2-week washout period from these drugs before randomization. Transthoracic Doppler-derived CFVR was assessed in left anterior descending coronary artery, and was calculated as the ratio of hyperemic to baseline diastolic coronary flow velocity (CFV). Hyperemic CFV was obtained using dipyridamole administration using standard protocols. After CFVR assessment, patients were randomized to ivabradine or bisoprolol and entered an up-titration phase, and CFVR was assessed again 1 month after the end of the up-titration phase. Fifty-nine patients (38 male, 21 female; mean age 69 ± 9 years) were enrolled. Transthoracic Doppler-derived assessment of CFV and CFVR was successfully performed in all patients. Baseline characteristics were similar between the bisoprolol and ivabradine groups. No patient dropped out during the study. At baseline, rest and hyperemic peak CFV as well as CFVR was not significantly different in the ivabradine and bisoprolol groups. After the therapy, resting peak CFV significantly decreased in both the ivabradine and bisoprolol groups, but there was no significant difference between the groups (ivabradine group 20.7 ± 4.6 vs. 22.8 ± 5.2, P < 0.001; bisoprolol group 20.1 ± 4.1 vs. 22.1 ± 4.3, P < 0.001). However, hyperemic peak CFV significantly increased in both groups, but to a greater extent in patients treated with ivabradine (ivabradine: 70.7 ± 9.4 vs. 58.8 ± 9.2, P < 0.001; bisoprolol: 65 ± 8.3 vs. 58.7 ± 8.2, P < 0.001). Accordingly, CFVR significantly increased in both groups (ivabradine 3.52 ± 0.64 vs. 2.67 ± 0.55, P < 0.001; bisoprolol 3.35 ± 0.70 vs. 2.72 ± 0.55, P < 0.001), but it was significantly higher in ivabradine group, despite a similar decrease in heart rate (63 ± 7 vs. 61 ± 6; P not significant). Ivabradine improves hyperemic peak CFV and CFVR to a greater extent than bisoprolol in patients with stable CAD, despite a similar decrease in heart rate. These data demonstrate that the benefits from ivabradine therapy go beyond the heart rate. This could be due to a different mechanism such as diastolic perfusion time, isovolumic ventricular relaxation, end-diastolic pressure, and collaterals. Servier. ... Ivabradine is a specific HR-lowering drug that acts by selectively inhibiting the pacemaker I f current in the sinoatrial node. Unlike beta-blockers, ivabradine does not affect myocardial contractility, 22, 23 does not cause changes in blood pressure, 24 and has no effect on respiratory function. 25 Ivabradine in oral formulation is licensed for treatment of patients with stable angina, and the SHIFT trial in chronic HF demonstrated the safety of oral ivabradine in patients with symptomatic systolic HF, as well as benefit regarding clinical outcomes. ... Intravenous Ivabradine for Control of Heart Rate During Coronary CT Angiography: A Randomised, Double-Blind, Placebo-Controlled Trial Low heart rates (HRs) are preferable for coronary CT angiography (CTA). We evaluated the use of an intravenous bolus of ivabradine, a selective sinus node inhibitor, to lower HR before coronary CTA in a prospective, randomized, double-blind, placebo-controlled multicenter trial. A total of 370 patients scheduled for CTA, with sinus rhythm ≥70 beats/min but ineligible for intravenous beta-blockers, were randomized to an intravenous bolus of 10 mg (HR, 70-79 beats/min) or 15 mg (HR ≥80 beats/min) ivabradine or placebo. Primary end point was the proportion of patients achieving HR ≤65 beats/min at the initiation of coronary CTA (Ta). Baseline HR was 79 ± 8.5 beats/min. At Ta, HR ≤65 beats/min was achieved in 55% of the ivabradine group vs 23% for placebo (P < .0001) and in 68% vs 16% 1-hour after bolus administration (P < .0001). Contrast-enhanced coronary CTA was performed in 87% of the ivabradine group vs 65% for placebo (P < .0001). Mean HR at Ta was 67 ± 10 beats/min for ivabradine vs 75 ± 10 beats/min for placebo (P < .0001). Procedural convenience was scored better with ivabradine ("good" or "very good" in 79% vs 63% for placebo; P = .0005). The effective radiation dose of contrast-enhanced CTA was 13 ± 7 mSv for ivabradine vs 16 ± 7 mSv for placebo (P < .05). Ivabradine was well tolerated. An intravenous bolus of ivabradine achieves rapid, safe, and sustained HR lowering during coronary CTA, increasing procedural convenience and reducing radiation exposure vs placebo. Copyright © 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved. ... 13 The effects of the drug on ventricular repolarization in these previous experimental studies largely occurred at concentrations considerably exceeding the plasma concentration range in humans. Thus, when a 30mg oral dose of ivabradine has been administered to healthy volunteers, a mean maximum plasma level of 0.17 lmol/L has been reported 36 and, in a separate study, multiple dosing with 5 to 20 mg of ivabradine resulted in plasma C max values of 34 to 137 nmol/L. 37 In the present study, ivabradine concentrations (100 to 500 nmol/L) overlapping this range affected MAPD 50 and MAPD 90 and effective refractory period in a concentrationdependent fashion, in both apex and base of the guinea-pig left ventricle. ... hERG Potassium Channel Blockade by the HCN Channel Inhibitor Bradycardic Agent Ivabradine
https://www.researchgate.net/publication/7339399_Comparative_effects_of_ivabradine_a_selective_heart_rate-lowering_agent_and_propranolol_on_systemic_and_cardiac_haemodynamics_at_rest_and_during_exercise
Poiseuille Flow and Thermal Transpiration of a Rarefied Gas Between Parallel Plates: Effect of Nonuniform Surface Properties of the Plates in the Transverse Direction | J. Fluids Eng. | ASME Digital Collection Poiseuille Flow and Thermal Transpiration of a Rarefied Gas Between Parallel Plates: Effect of Nonuniform Surface Properties of the Plates in the Transverse Direction J. Fluids Eng . Oct 2015, 137(10): 101103 (9 pages) Paper No: FE-14-1601 https://doi.org/10.1115/1.4030490 Poiseuille flow and thermal transpiration of a rarefied gas between parallel plates with nonuniform surface properties in the transverse direction are studied based on kinetic theory. We considered a simplified model in which one wall is a diffuse reflection boundary and the other wall is a Maxwell-type boundary on which the accommodation coefficient varies periodically and smoothly in the transverse direction. The spatially two-dimensional (2D) problem in the cross section is studied numerically based on the linearized Bhatnagar–Gross–Krook–Welander (BGKW) model of the Boltzmann equation. The flow behavior, i.e., the macroscopic flow velocity and the mass flow rate of the gas as well as the velocity distribution function, is studied over a wide range of the mean free path of the gas and the parameters of the distribution of the accommodation coefficient. The mass flow rate of the gas is approximated by a simple formula consisting of the data of the spatially one-dimensional (1D) problems. When the mean free path is large, the distribution function assumes a wavy variation in the molecular velocity space due to the effect of a nonuniform surface property of the plate. Issue Section: Flows in Complex Systems Keywords: Micro-scale flows Topics: Flow (Dynamics) , Plates (structures) , Poiseuille flow , Surface properties , Boundary-value problems , Reflection , Numerical analysis References 1. Cercignani , C. , 1963 , “ Plane Poiseuille Flow and Knudsen Minimum Effect ,” Rarefied Gas Dynamics , Vol. II , J. A. Laurmann , ed., Academic , New York , pp. 92 – 101 . 2. Cercignani , C. , and Daneri , A. , 1963 , “ Flow of a Rarefied Gas Between Parallel Plates ,” J. Appl. Phys. , 34 ( 12 ), pp. 3509 – 3513 . 10.1063/1.1729249 3. Niimi , H. , 1971 , “ Thermal Creep Flow of Rarefied Gas Between Two Parallel Plates ,” J. Phys. Soc. Jpn. , 30 ( 2 ), pp. 572 – 574 . 10.1143/JPSJ.30.572 4. Loyalka , S. K. , 1971 , “ Kinetic Theory of Thermal Transpiration and Mechanocaloric Effect. I ,” J. Chem. Phys. , 55 ( 9 ), pp. 4497 – 4503 . 10.1063/1.1676780 Google Scholar Crossref 5. Kanki , T. , and Iuchi , S. , 1973 , “ Poiseuille Flow and Thermal Creep of a Rarefied Gas Between Parallel Plates ,” Phys. Fluids , 16 ( 5 ), pp. 594 – 599 . 10.1063/1.1694393 6. Loyalka , S. K. , 1974 , “ Comments on “Poiseuille Flow and Thermal Creep of a Rarefied Gas Between Parallel Plates” ,” Phys. 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Sone , Y. 2007 Thermal Transpiration for the Linearized Boltzmann Equation Commun. Pure Appl. Math. 163 . 10.1002/cpa.20167 14. Sharipov , F. , and Bertoldo , G. , 2009 , “ Poiseuille Flow and Thermal Creep Based on the Boltzmann Equation With the Lennard–Jones Potential Over a Wide Range of the Knudsen Number ,” Phys. Fluids , 21 ( 6 ), p. 10.1063/1.3156011 15. Takata , S. , and Funagane , H. , 2011 , “ Poiseuille and Thermal Transpiration Flows of a Highly Rarefied Gas: Over-Concentration in the Velocity Distribution Function ,” J. Fluid Mech. , 669 , pp. 242 – 259 . 16. Doi , T. , 2012 , “ Effect of Weak Gravitation on the Plane Poiseuille Flow of a Highly Rarefied Gas ,” Z. Angew. Math. Phys. , 63 ( 6 ), pp. 1091 – 1102 . 10.1007/s00033-012-0213-0 17. Doi , T. , 2012 , “ Effect of Weak Gravitation on the Plane Thermal Transpiration of a Slightly Rarefied Gas ,” Fluid Dyn. Res. , 44 ( 6 ), p. 065503 . 10.1088/0169-5983/44/6/065503 18. Veijola , T. , Kuisma , H. , and Lahdenperä , J. , 1998 , “ The Influence of Gas-Surface Interaction on Gas-Film Damping in a Silicon Accelerometer ,” Sens. Actuators, A , 66 , pp. 83 – 92 . 10.1016/S0924-4247(97)01732-9 19. Cercignani , C. , Lampis , M. , and Lorenzani , S. , 2004 , “ Variational Approach to Gas Flows in Microchannels ,” Phys. Fluids , 16 ( 9 ), pp. 3426 – 3437 . 10.1063/1.1764700 20. , Lampis , M. , and Lorenzani , S. , 2004 , “ Plane Poiseuille Flow With Symmetric and Nonsymmetric Gas-Wall Interactions ,” Transp. Theory Stat. Phys. , 33 ( 5–7 ), pp. 545 – 561 . 10.1081/TT-200053939 21. Scherer , C. S. , Filho , J. F. P. , and Barichello , L. B. , 2009 , “ An Analytical Approach to the Unified Solution of Kinetic Equations in Rarefied Gas Dynamics ,” Z. Angew. Math. Phys. , 60 ( 1 ), pp. 70 – 115 . 22. Doi , T. , 2014 , “ Plane Thermal Transpiration of a Rarefied Gas Between Two Walls of Maxwell-Type Boundaries With Different Accommodation Coefficients ,” ASME J. Fluids Eng. , 136 ( 8 ), p. 081203 . 10.1115/1.4026926 23. Doi , T. , 2014 , “ Plane Poiseuille Flow and Thermal Transpiration of a Highly Rarefied Gas Between the Two Walls of Maxwell-Type Boundaries With Different Accommodation Coefficients: Effect of a Weak External Force ,” Z. Angew. Math. Phys. (in press). 10.1007/s00033-014-0454-1 24. Seagate Technology , 2013 , “ Discrete Track Media ,” U.S. Patent No. 20130017413 A1. 25. Bhatnagar , P. L. , Gross , E. P. , and Krook , M. , 1954 , “ A Model for Collision Processes in Gases. I. Small Amplitude Processes in Charged and Neutral One-Component Systems ,” Phys. Rev. , 94 ( 3 ), pp. 511 – 525 . 10.1103/PhysRev.94.511 26. Welander , P. , 1954 , “ On the Temperature Jump in a Rarefied Gas ,” Ark. Fys. , 7 , pp. 507 – 553 . 27. Chu , C. K. , 1965 , “ Kinetic-Theoretic Description of the Formation of a Shock Wave ,” Phys. Fluids , 8 ( 8 ), pp. 12 – 22 . 10.1063/1.1761077 28. Sharipov , F. , and Kalempa , D. , 2008 , “ Oscillatory Couette Flow at Arbitrary Oscillation Frequency Over the Whole Range of the Knudsen Number ,” Microfluid. Nanofluid. , 4 ( 5 – 374 . 10.1007/s10404-007-0185-0 29. Doi , T. , 2010 , “ Numerical Analysis of the Oscillatory Couette Flow of a Rarefied Gas on the Basis of the Linearized Boltzmann Equation for a Hard Sphere Molecular Gas ,” Z. Angew. Math. Phys. , 61 ( 5 ), pp. 811 . 10.1007/s00033-009-0055-6 30. Doi , T. , 2011 , “ Numerical Analysis of the Time-Dependent Energy and Momentum Transfers in a Rarefied Gas Between Two Parallel Planes Based on the Linearized Boltzmann Equation ,” ASME J. Heat Transfer , 133 ( 2 ), p. 022404 . 10.1115/1.4002441 31. Wakabayashi , M. , Ohwada , T. , and Golse , F. , 1996 , “ Numerical Analysis of the Shear and Thermal Creep Flows of a Rarefied Gas Over the Plane Wall of a Maxwell-Type Boundary on the Basis of the Linearized Boltzmann Equation for Hard-Sphere Molecules ,” Eur. J. Mech. 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https://asmedigitalcollection.asme.org/fluidsengineering/article-abstract/137/10/101103/372303/Poiseuille-Flow-and-Thermal-Transpiration-of-a
(PDF) Star Carr in a Postglacial Lakescape: 60 Years of Research PDF | Star Carr has an international reputation in archaeology but it was just a small part of a former lakescape which has been systematically... | Find, read and cite all the research you need on ResearchGate November 2011 Journal of Wetland Archaeology 11(1):1-19 DOI: 10.1179/jwa.2011.11.1.1 Authors: Nicky Milner The University of York Paul Jeremy Lane Uppsala University Barry Taylor University of Chester Chantal Conneller Chantal Conneller This person is not on ResearchGate, or hasn't claimed this research yet. Show all 5 authors Hide Download full-text PDF Read full-text Download citation Copy link Link copied Read full-text Download citation Copy link Link copied Citations (16) References (77) Figures (6) Abstract and Figures Star Carr has an international reputation in archaeology but it was just a small part of a former lakescape which has been systematically investigated at various periods over the last 60 years. The palaeo-lake and associated sites were first investigated by John W. Moore, a local amateur archaeologist and his findings led to the better known excavations of Grahame Clark. After a hiatus in research, survey and excavation resumed in the 1970s and has been ongoing ever since. The support over the last 25 years of the Vale of Pickering Research Trust has enabled the palaeo-Lake Flixton to be mapped prompting the discovery of new Early Mesolithic sites, resulting in an unparalleled understanding of an Early Mesolithic lakescape. In addition, Star Carr has been revisited at various times revealing new insights and further questions that remain to be answered. This paper presents a history of the investigations from the initial discoveries of Moore to the present day, and considers a range of issues including support, resourcing and the training of future generations of archaeologists. Location of palaeo-Lake Flixton and the Vale of Pickering. … Clark's brushwood platform (photo courtesy of Scarborough Archaeological and Historical Society). … Photograph of the area excavations at Site K, Seamer Carr in 1985. … Plan of Seamer Carr excavations and survey. … +1 1: Star Carr; 2: Ling Lane; 3: Seamer Carr Site F; 4: Seamer Carr Sites L and N; 5: Seamer Carr Site K; 6: Seamer Carr Site D; 7: Seamer Carr Site B; 8: Seamer Carr Site C; 9: Manham Hill (Moore's site 6); 10: Cayton Carr (Moore's site 7); 11: Cayton Carr (Moore's Site 8); 12: Lingholme Farm Site B; 13: Lingholme Farm Site C; 14: Lingholme Farm Site A; 15: Barry's Island; 16: Flixton School Field; 17: Flixton School House Farm; 18: Woodhouse Farm; 19: VP Site E; 20: VP Site D; 21: Flixton 9; 22: Flixton Island South; 23: Flixton Island North; 24: No Name Hill (Moore's Site 3). … Figures - uploaded by Nicky Milner Author content All figure content in this area was uploaded by Nicky Milner Content may be subject to copyright. Discover the world's research 25+ million members 160+ million publication pages 2.3+ billion citations Join for free Public Full-text 1 Content uploaded by Nicky Milner Author content All content in this area was uploaded by Nicky Milner on Feb 12, 2016 Content may be subject to copyright. Abstract S tar C arr h as a n in t e r n at ion a l r epu tat ion in arc h a eology b u t i t w as ju s tas m a ll p art of a fo r me r l a ke sca pe whi c h h as b een s y st em at i ca lly inve st ig at ed at v ar iou s pe r iod s ove rt he l ast 60 ye ars . The p a l a eo-l a ke a nd ass o c i at ed s i t e s we r efi rst inve st ig at ed b y John W . Moo r e, a lo ca l a m at eu r arc h a eologi st a nd hi s fi nding s led t o t he b e Ĵ e r known ex ca v at ion s of G ra h a me Cl ar k. A Ğ e ra hi at u s in r e s e arc h, s u r vey a nd ex ca v at ion r e s umed in t he 1970 sa nd h as b een ongoing eve rs in c e. The s uppo rt ove rt he l ast 25 ye ars of t he V a le of Pi c ke r ing Re s e arc h T r u st h as en ab led t he p a l a eo-L a ke Flix t on t o b e m a pped p r omp t ing t he di sc ove r y of new E ar ly Me s oli t hi cs i t e s , r e s ul t ing in a n unp ara lleled unde rsta nding of a n E ar ly Me s oli t hi c l a ke sca pe. In a ddi t ion, S tar C arr h as b een r evi s i t ed at v ar iou st ime sr eve a ling new in s igh ts a nd fu rt he r que st ion st h at r em a in t o b e a n s we r ed. Thi s p a pe r p r e s en ts a hi st o r y of t he inve st ig at ion s f r om t he ini t i a l di sc ove r ie s of Moo r e t o t he p r e s en t d a y, a nd c on s ide rs a ra nge of i ss ue s in c luding s uppo rt , r e s ou rc ing a nd t he tra ining of fu t u r e gene rat ion s of arc h a eologi sts . Keywords : Star Carr, M e s oli t hi c, La ke F lix t on , V a le of P i c ke r ing J ou r n a lo f W e t l a nd Arc h a eology 11 , 2011, 1–19 S tar C arr in a Po st gl ac i a l L a ke sca pe: 60 Y e ars of Re s e arc h Nicky Milner , Paul Lane, Barry T aylor , Chantal Conneller and T im Schadla-Hall Authors’ addresses : N. Milner a nd P . Lane Dep art men t of A rc h a eology , The King s M a no r , Unive rs i t y of Yo r k, YO1 7EP . Em a il: ni c ky .milne r @yo r k. ac .uk; B. T aylor Geog ra phy, SED, Unive rs i t y of M a n c he st e r , Oxfo r d Ro a d, M a n c he st e r , M13 9PL. C. Conneller A rc h a eology , SAHC, Unive rs i t y of M a n c he st e r , Oxfo r d Ro a d, M a n c he st e r M13 9PL. T . Schadla-Hall In st i t u t e of A rc h a eology, Unive rs i t y College London, 31–34 Go r don Squ ar e, London, WC1H 0PY 2 N i c ky M ilne r et al . In tr odu ct ion Al t hough t he E ar ly Me s oli t hi c ‘ s i t e’ of S tar C arr (Cl ar k 1954) h as g a ined in t e r n at ion a l r e c ogni t ion, i t i st he c on t ex t of t he l a ke a nd o t he r E ar ly Me s oli t hi c act ivi t y wi t hin t h at l a ke sca pe t h at en ab le r i c he r in t e r p r e tat ion st o b e m a de. S tar C arr was t he E ar ly Me s oli t hi c ‘ t ype- s i t e’ fo r B r i ta in a nd indeed mu c h of Eu r ope un t il ve r y r e c en t ly , b u t c u rr en tr e s e arc h h as demon strat ed t h at i t i s unique wi t hin t h at l a ke sca pe s e Ĵ ing, a nd s hould no tb e c on s ide r ed at ype- s i t e at a ll (Connelle ra nd S c h a dl a -H a ll 2003), if indeed a ny Me s oli t hi cs i t e ca n b e c on s ide r ed ‘ t ypi ca l’. I t w as John W. Moo r e, a lo ca l a m at eu r , who i sc r edi t ed wi t h t he di sc ove r y of S tar C arr , b u t Moo r e did f ar mo r e t h a n t h at . Hi s fi eldw a lking act ivi t ie s led him t ofi nd 10 E ar ly Me s oli t hi cs i t e s , of whi c h S tar C arr w as s i t e 4 (Moo r e 1950). Howeve r , Moo r e w as a l s o in t e r e st ed in t he p a l a eo-l a ke a nd he w r o t e ab ou t ‘L a ke Flix t on: a L at e-Gl ac i a l S tr u ct u r e’ in t he fi rst pu b li cat ion of t he S carb o r ough a nd Di str i ct A rc h a eologi ca l So c ie t y in 1951. Ove rt he following 60 ye ars o rs o, t he r e h a ve b een a num b e r of p r og ra mme s of arc h a eologi ca l inve st ig at ion at t he e ast e r n end of t he V a le of Pi c ke r ing (Figu r e 1), whi c h h a ve a imed t o di sc ove r mo r e ab ou t S tar C arr a nd t he wide r l a ke sca pe. Thi sb eg a n wi t h t he Dep art men t of t he Envi r onmen ta nd No rt h Yo r k s hi r e Coun t y Coun c il s u r vey sa nd ex ca v at ion s ove ra 40 h a ar e a of Se a me r C arr , lo cat ed c . 1.5 km no rt h-e ast of S tar C arr Figure 1. Location of palaeo-Lake Flixton and the V ale of Pickering. Star Carr in a P o st gl ac i a l La ke sca pe : 60 Y e ars of R e s e arc h 3 b e t ween 1976–85 (S c h a dl a -H a ll a nd Clou t m a n 1985). Ano t he r key pl a ye r in t hi s hi st o r y of even ts h as b een t he V a le of Pi c ke r ing Re s e arc h T r u st (VPRT) whi c h c ele brat ed i ts 25 t h a nnive rsar y in 2010. Following t he S tar C arr s emin ar , held in C a m br idge in M a y 2010, i t w as deemed a n a pp r op r i at e poin tt o pu b li s h a n ou t line hi st o r y of explo rat ion of S tar C arr a nd p a l a eo-L a ke Flix t on. Thi s p a pe r will ou t line a ll ph as e s of s u r vey a nd ex ca v at ion ar ound t he p a l a eo- L a ke Flix t on f r om Moo r e’ s wo r k up un t il t he p r e s en t d a y ( a mo r e de ta iled acc oun t i s p r ovided in L a ne a nd S c h a dl a -H a ll, fo rt h c oming). F r om t hi s hi st o r y, t he r e ar e s eve ra l i ss ue s whi c h r el at e di r e ct ly t o t he di sc u ss ion s fo r fu rt he r wo r k at S tar C arr in c luding s uppo rt , r e s ou rc ing a nd tra ining of fu t u r e gene rat ion s of arc h a eologi sts . Ini t i a l Di sc ove r y a nd Inve st ig at ion s Moore The fi rst ph as e of fi eldwo r k ar ound p a l a eo-L a ke Flix t on w as carr ied ou tb y John W. Moo r e du r ing t he 1940 s . Moo r e w as involved in t he s e Ĵ ing up of t he S carb o r ough A rc h a eologi ca l a nd Hi st o r i ca l So c ie t y; fi eldwo r k t e rr i t o r ie s we r e d ra wn up a nd he w as given t he carr l a nd st o inve st ig at e (Te rr y M a n b y pe rs . c omm. Sep t em b e r 2011). Moo r e w a lked ar ound t he f r e s hly c le a ned d ra in a ge di tc he s in t he ar e aa nd in a num b e r of lo cat ion s pi c ked up wo r ked fl in t , b one a nd o t he r m at e r i a l r el at ing t o t he E ar ly Me s oli t hi c . He l ab elled t he s e lo cat ion ss i t e s 1–10 (Moo r e 1950). In 1948–9 Moo r e unde rt ook ex ca v at ion at S tar C arr , Flix t on 1 a nd Flix t on 2, t he l a Ĵ e rt wo b eing lo cat ed on Flix t on I s l a nd (Moo r e 1954). Moo r e d r ew hi s di sc ove r ie st o t he a Ĵ en t ion of H arr y Godwin who w as t hen Di r e ct o r of t he Su b -Dep art men t of Qu at e r n ar y Re s e arc h at t he Unive rs i t y of C a m br idge a nd who c oin c iden ta lly w as r e s e arc hing in t he V a le at t he t ime. In 1948 Godwin a nd Roy Cl a ph a m ( t hen P r ofe ss o r of Bo ta ny at She Ĝ eld Unive rs i t y) vi s i t ed Moo r e’ s ex ca v at ion s at Flix t on a nd o bta ined a pollen c o r e f r om t he vi c ini t y (Godwin 1949). Following a dvi c e f r om Godwin a nd t he t hen c u rat o r of S carb o r ough Mu s eum, M r T. C. Gw at kin, Moo r e s en tas a mple of fl in ts t o G ra h a me Cl ar k at t he Dep art men t of A rc h a eology , Unive rs i t y of C a m br idge (Cl ar k 1954, xviii). Cl ar k l at e r w r o t e of hi s ex c i t emen t on r e c eiving Moo r e’ s ‘p arc el of fl in ts ’ whi c h he ini t i a lly ass igned t o t he M a glemo s i a n: ‘I tt ook only a gl a n c e t o s ee t h at he r e w as a c lue t o s ome t hing I h a d b een s eeking fo r m a ny ye ars : t h at i s , a fl in t indu str y, a n a logou st o t h at fi rst r e c ognized b y D a ni s h arc h a eologi sts at M a glemo s e, Mulle r up, on t he i s l a nd of Ze a l a nd, f r om a B r i t i s h lo ca li t y o ě e r ing p r omi s e of r e c ove r ing as e Ĵ lemen ts i t e wi t h o r g a ni ca s well as me r ely li t hi c d ata … my fi rst que st ion on e stab li s hing c on tact wi t h M r . Moo r e w as whe t he r he h a d found a n t le r o rb one on a ny of hi ss i t e s . On he ar ing t h at he h a d, I lo st no t ime in mee t ing him’ (Cl ar k 1972, 10–3). Moo r e s howed Cl ar k hi s Si t e 4 whi c h r eve a led b one a nd a n t le r p r oje ct ing ou t of t he fi eld d ra in at t he sa me level as t he fl in t indu str y. I ts hould b e no t ed t h at ‘S tar C arr ’ w as a lw a y s known s imply as ‘Si t e 4’ un t il Cl ar k’ s monog ra ph w as pu b li s hed; i t w as r en a med ‘S tar C arr ’ a Ğ e rt he fi eld t o t he no rt h of t he He rt fo r d Cu t ( ac a n a li s ed r ive r ) in whi c h t he s i t e lie s , whi c h w as a l s o t he n a me of t he f ar m t o whi c h t hi s fi eld 4 N i c ky M ilne r et al . t hen b elonged. Moo r e’ s o bs e r v at ion of fl in ts a nd b one in t hi s fi eld d ra in led him t o c u t bac k t he di tc h b y 2.5 fee ta nd 23 fee t (0.76 × 7.01 m) acr o ss , as s een on Cl ar k’ s pl a n s ( s qu ar e s a b 14–21), p r e s um ab ly a Ğ e r Cl ar k’ s vi s i t . I t i s in t e r e st ing t o no t e t h at t he r e i sa g r e at e rc on c en trat ion of wo r ked fl in t in Moo r e’ st r en c h (Cl ar k 1954, fi g. 3, p. 5) whi c h s ugge sts t h at a di ě e r en tc olle ct ion strat egy w as employed b y Moo r e. Moo r e kep ts m a ll de b i ta ge, whe r e as we h a ve b een info r med b y s ome of t he o r igin a l volun t ee rs t h at Cl ar k di scar ded m at e r i a l s m a lle rt h a n hi st hum b n a il. Moo r e (1954) a l s o ex ca v at ed Flix t on 1 a nd 2 on Flix t on I s l a nd, t he l a Ĵ e rb eing carr ied ou ta tt he sa me t ime as t he ex ca v at ion sa t S tar C arr . He a l s o plo Ĵ ed a nd r e c ove r ed fi nd s f r om t he s e ct ion ba ulk ss ep arat ing Cl ar k’ st r en c he sa t S tar C arr at t he end of t he fi n a l s e as on t he r e in 1951 (F a g a n 2001, 155). Clark Cl ar k di r e ct ed ex ca v at ion s ove rt h r ee s e as on s , e ac h of whi c h w as a pp r oxim at ely t h r ee week s long: 1949–1951. The ex ca v at ion w as c le ar ly as u cc e ss in Cl ar k’ s view b e ca u s e i t fulfi lled hi s o b je ct ive s of fi nding a M a glemo s i a n s i t e wi t h o r g a ni c p r e s e r v at ion t h r ough whi c h he c ould explo r e t he new a pp r o ac he s ou t lined in Prehistoric Europe: The economic basis (Cl ar k 1952). The qu a li t y of fi nd s w as ex tra o r din ar y, at le ast in a B r i t i s h c on t ex t , a nd in c luded a po ss i b le wooden p a ddle, r ed dee rs kull he a dd r e ss e s , l ar ge qu a n t i t ie s of barb ed poin ts , f a un a l r em a in sa nd b e a d s . Find s of t hi s n at u r e ar e ex tr emely rar e: fo r ex a mple, no o t he r he a dd r e ss e s h a ve b een found in B r i ta in a nd t he r e ar e only a few ex a mple s known in Eu r ope, while t he barb ed poin ts acc oun t fo ra b ou t 97% of a ll Me s oli t hi c barb ed poin ts found in B r i ta in. In a ddi t ion, a l ar ge qu a n t i t y of wood w as found on t he edge of t he l a ke whi c h w as t e r med ‘ br u s hwood’ a nd in t e r p r e t ed as s ome kind of pl at fo r m on whi c h people would h a ve lived (Cl ar k 1954) (Figu r e 2). An info r m a l acc oun t of t he s e ex ca v- at ion sa nd t he m a ny p art i c ip a n ts , bas ed on de ta il s in a n unpu b li s hed memoi r b y Cl ar k, i s p r ovided in B r i a n F a g a n’ s b iog ra phy (2001, 145–55). Al t hough t he s i t e of S tar C arr h as s u bs equen t ly unde r gone m a ny r evi s ion sa nd r e- in t e r p r e tat ion s , t he r e s ul ts of Cl ar k’ s inve st ig at ion sc on t inue t o p r ovide a n imp r e ss ive pi ct u r e of t he w a y of life of a g r oup of Me s oli t hi c hun t e r -g at he r e rs . I t h as a l s o st ood t he t e st of t ime as a n ex a mple of wh at ca n b e ac hieved b y as king new que st ion sa nd ex a mining Figure 2. Clark’s brushwood platform (photo courtesy of Scarborough Archaeological and Historical Society). Star Carr in a P o st gl ac i a l La ke sca pe : 60 Y e ars of R e s e arc h 5 new c l ass e s of d ata , a nd s e tt he sta nd ar d fo r fu t u r e p r oje cts fo r m a ny ye ars t o c ome (T r igge r 1998, 268). The r e s ul ts of t he wo r k we r e pu b li s hed in a monog ra ph in 1954 a nd t he s i t e no t only b e ca me known as a ‘ t ype- s i t e’ fo rt he M a glemo s i a n in No rt he r n Engl a nd, b u tb e ca me wo r ld f a mou s wi t hin t he di sc ipline of A rc h a eology . The r e ar e s eve ra l r e as on s fo r S tar C arr ’ sr i s e t o p r ominen c e: 1. The qu a li t y of p r e s e r v at ion of t he o r g a ni cs a nd arra y of impo rta n t fi nd s ; 2. The in t eg rat ion of d ata f r om s pe c i a li st a n a ly s e s in c luding t he l a ke strat ig ra phy , pollen a nd vege tat ion a l hi st o r y (W a lke ra nd Godwin 1954) a nd t he f a un a l ass em b l a ge (F ras e ra nd King 1954); 3. Cl ar k’ s e c onomi ca nd e c ologi ca l in t e r p r e tat ion s whi c h b e ca me a model t o follow; 4. The ra pidi t y a nd qu a li t y of t he pu b li cat ion, whi c h i s well-w r i Ĵ en a nd acc e ss i b le, at a t ime when arc h a eologi ca l s i t e monog ra ph s we r e rar e; 5. Fin a lly , a nd ar gu ab ly mo st impo rta n t ly , w as t he infl uen c e of Cl ar k ( b y t hen Di s ney P r ofe ss o r ) in t he fo r m at ion of arc h a eology as a n aca demi c di sc ipline. Cl ar k’ s st uden ts sta ě ed t he arc h a eology dep art men ts of t he empi r e, a ll imp art ing t o t hei r st uden ts in t u r n t he s ignifi ca n c e of S tar C arr ( s ee Cole s et al. 1999; Smi t h 2009; M arc ini a k a nd Cole s 2010). In t he 1960 s , t he r e we r e r efe r en c e st o t he s i t e in r el at ion t o t he di sc ove r y of o t he r E ar ly Me s oli t hi cs i t e s wi t h p ara llel M a gelmo s i a n- t ype ass em b l a ge s on t he Pennine s , We st Yo r k s hi r e (R a dley a nd Mell ars 1964) a nd Dege rb øl (1961) c ondu ct ed fu rt he r inve st ig at ion of t he f a un a l ass em b l a ge. The l at e S t u art Fe at he ra l s o a m ass ed a l ar ge fi eldw a lked c olle ct ion of li t hi cs f r om t he V a le of Pi c ke r ing, in c luding S tar C arr (now in t he po ss e ss ion of t he c u rr en tt e a m). Howeve r , t he r e w as no r e ass e ss men t of S tar C arr un t il a lmo st 20 ye ars on when Cl ar k him s elf (1972) r e a pp ra i s ed t he s i t e a nd following t hi sc a me as e r ie s of new in t e r p r e tat ion s (e.g. C a ulfi eld 1978; J ac o b i 1978; Pi Ĵ s 1979; And r e s en et al. 1981; P r i c e 1982; Legge a nd Rowly-Conwy 1988; C art e r 1997; 1998; Mell ars a nd D ar k 1998; Poll ar d 2000; Connelle ra nd S c h a dl a -H a ll 2003; Ch a Ĵ e rt on 2003; Connelle r 2004). A s h as p r eviou s ly b een ou t lined, t he s e in t e r p r e tat ion s ve r y mu c h follow t he t heo r e t i ca l a nd me t hodologi ca l p r eo cc up at ion s of t hei rt ime (Connelle r 2003; L a ne a nd S c h a dl a -H a ll 2004). L at e r Fieldwo r k in t he V a le Whe r e as up t o t he mid-1980 s , s u cc e ss ive r ein t e r p r e tat ion s of S tar C arr we r e bas ed en t i r ely on r e a pp ra i sa l s of m at e r i a l r e c ove r ed b y Cl ar k, mo r e r e c en t ly in t e r p r e tat ion s of t he s i t e a nd i ts br o a de rs e Ĵ ing h a ve b een s h a ped, at le ast in p art , b y t he r e s ul t of new p r og ra mme s of fi eldwo r k at b o t h S tar C arr a nd el s ewhe r e ar ound t he fo r me r L a ke Flix t on. Thi ss e ct ion o ě e rs a br ief acc oun t of t he s e p r oje cts . The Seamer Carr Project The Se a me r C arr p r oje ct , ini t i at ed in 1976, w as join t ly e stab li s hed b y t he No rt h Y o r k s hi r e 6 N i c ky M ilne r et al . Coun t y Coun c il a nd wh at w as t hen t he A rc h a eology Divi s ion of t he Dep art men t of t he Envi r onmen t (now Engli s h He r i ta ge). The No rt h Y o r k s hi r e Coun t y Coun c il h a d m a de ac ompul s o r y pu rc h as e of Se a me r C arr F ar m, t o ta lling 40 h a , fo r developmen ta sa w ast e di s po sa l a nd p r o c e ss ing pl a n t fo rt he ne arb y t own of S carb o r ough. The Se a me r C arr p r oje ct w as s e t up t o mi t ig at e t he po t en t i a l e ě e cts of c on str u ct ion wo r k a nd w ast e dumping. Tim S c h a dl a -H a ll (TSH) w as t he Field Di r e ct o r f r om i ts in c ep t ion, wi t h Roge r Simp s on (now No rt he r n A rc h a eologi ca l A ss o c i at e s ) act ing as s enio rs upe r vi s o r t h r oughou t , ass i st ed b y a v ar ie t y of o t he r individu a l s . A st ee r ing c ommi Ĵ ee w as s e t up, c omp r i s ed of r ep r e s en tat ive s f r om t he An c ien t Monumen ts In s pe ct o rat e, t he An c ien t Monumen ts L ab o rat o r y, N o rt h Yo r k s hi r e Coun t y Coun c il, The B r i t i s h Mu s eum, Unive rs i t y of She Ĝ eld a nd Unive rs i t y of C ar di ě . P a ul L a ne (PL) b e ca me involved f r om 1977, a l b ei t in t e r mi Ĵ en t ly un t il t he e ar ly 1980 s . A p r og ra mme of s y st em at i cs a mpling a nd ar e a ex ca v at ion s w as ini t i at ed, wi t hfi eld s e as on s f r om 1976–1985. Be t ween 1976 a nd 1979, sa mpling w as carr ied ou t ove rt he en t i r e ar e a in o r de rt o de t e r mine t he ove ra ll di str i b u t ion a nd level s of p r e s e r v at ion of t he arc h a eologi ca l r em a in s . In a ddi t ion, mo r e de ta iled ar e a ex ca v at ion s we r e unde rta ken of s ele ct ed s i t e s (l at e P a l a eoli t hi ct o t he I r on Age). F r om t he 1980 s onw ar d s , a p r og ra mme of t e st -pi Ĵ ing, l ar ge sca le ex ca v at ion a nd envi r onmen ta l sa mpling w as tar ge t ed at t he E ar ly Me s oli t hi c arc h a eology (S c h a dl a -H a ll a nd Clou t m a n 1985), p art i c ul ar ly a imed at de t e r mining t he di str i b u t ion of art ef act a nd f a un a l sca Ĵ e rs , a nd t hei r ex t en t , c ompo s i t ion, fun ct ion a nd t empo ra l r e s olu t ion (Figu r e 3). By t he end of t hi sr e s e arc h, ne ar ly 2 km of t he fo r me r l a ke s ho r eline h a d b een Figure 3. Photograph of the area excavations at Site K, Seamer Carr in 1985. Star Carr in a P o st gl ac i a l La ke sca pe : 60 Y e ars of R e s e arc h 7 sa mpled fo r trac e s of E ar ly Me s oli t hi c act ivi t y, a nd ex t en s ive ar e a ex ca v at ion s h a d b een c ondu ct ed at t wo s i t e sb o t h wi t h eviden c e fo rr epe at ed o cc up at ion in t he l at e Uppe r P a l a eoli t hi ca nd E ar ly Me s oli t hi c : Se a me r C arr s i t e C a nd Se a me r C arr s i t e K. Seve ra l o t he r mo r e lo ca li s ed c on c en trat ion s of li t hi ca nd f a un a l m at e r i a l r ep r e s en t ing kn a pping stat ion s , tas k- ar e as , a nd trac e s of ‘o ě - s i t e’ act ivi t ie s we r e a l s o r e c o r ded (L a ne a nd S c h a dl a -H a ll fo rt h c oming; S c h a dl a -H a ll 1987 a ; 1987 b ; 1988; 1989; 1993) (Figu r e 4). Re s ul ts of t hi s wo r k a l s o r eve a led t h at t he envi r onmen ta l c on t ex t of t he V a le a nd p a l a eo-L a ke Flix t on w as poo r ly unde rst ood in t e r m s of t he s h a pe of t he l a ke, i ts ex t en t Figure 4. Plan of Seamer Carr excavations and survey. 8 N i c ky M ilne r et al . a nd t he hyd r ologi ca l r egime. A sac omponen t of t he Se a me r C arr p r oje ct , Edw ar d Clou t m a n a nd Al a n Smi t h (Clou t m a n1988 a ; 1988 b ; Clou t m a n a nd Smi t h 1988) carr ied ou tas u r vey of t he we st e r n end of p a l a eo-L a ke Flix t on whi c h b eg a n t o pu t S tar C arr in t o t he wide rc on t ex t of t he e c ologi ca l hi st o r y of t he l a ke. The V ale of Pickering Research T rust The V a le of Pi c ke r ing Re s e arc h T r u st (VPRT) w as s e t up in 1985 in o r de rt o c ondu ct a l a nd sca pe bas ed inve st ig at ion of t he E ar ly Me s oli t hi c p r e s en c e ar ound L a ke Flix t on, b uilding on t he r e s ul ts of Edw ar d Clou t m a n’ s p a l a eoenvi r onmen ta l wo r k (Clou t m a n 1988 a ; 1988 b ; Clou t m a n a nd Smi t h 1988). Thi s w as needed in o r de rt o unde rsta nd t he c onfl i ct ing in t e r p r e tat ion st h at h a d a l r e a dy eme r ged fo r S tar C arr , r el at ed t o t he num b e r , du rat ion, fun ct ion a nd s e as on s of o cc up at ion, a long wi t h t he dive r gen t eviden c e f r om Se a me r C arr . A fu rt he rs t imulu s w as t he g r owing eviden c e fo r acc ele rat ing de t e r io rat ion of t he w at e r logged depo s i ts a nd t he ne ar -u b iqui t y of e ar ly p r ehi st o r i c m at e r i a l ar ound t he s ho r e of t he l a ke. The T r u st i sar egi st e r ed c h ar i t y, a dmini st e r ed b y ab o ar d of T r u st ee sc omp r i s ing of mem b e rs of lo ca l b u s ine ss e sa nd f ar ming c ommuni t ie sa s well as p r ofe ss ion a l arc h a eologi sts . The r e s e arc h strat egy of t he VPRT w as t o ex a mine: 1. The en t i r e s ho r eline of t he p a l a eo-L a ke Flix t on ( c u rr en t ly b u r ied b ene at h pe at depo s i ts ) a nd i ts ass o c i at ed i s l a nd s wi t h inve st ig at ion vi at e st -pi Ĵ ing at c . 15m in t e r v a l s fo r trac e s of E ar ly Me s oli t hi c act ivi t y, a nd r el at e t he s e t o p a l a eoenvi r onmen ta l eviden c e; 2. Simil ar t opog ra phi c lo cat ion st o t ho s e a l r e a dy iden t ifi ed b y ex ca v at ion at Se a me r C arr ; 3. Known s i t e s iden t ifi ed b y John W. Moo r e in t he 1940 s ; 4. Po t en t i a l new lo cat ion sa ss ugge st ed b y e ar lie ra nd on-going p a l a eoenvi r onmen ta l wo r k a nd fi eld w a lking. In a ddi t ion, at v ar iou s poin ts ove rt he l ast 25 ye ars , fu rt he r inve st ig at ion s of S tar C arr h a ve ta ken pl ac e. Pe r h a p st he g r e at e st ac hievemen t of t he VPRT i st he m a pping of t he b u r ied s ho r eline. The me t hodology u s ed t o ac hieve t hi s h as b een s y st em at i c h a nd- a uge rs u r vey . Auge r a nd pe at c o r e rs u r vey s ar e u s ed t o me as u r e t he dep t h of t he pe at a nd t o de scr i b e, sa mple a nd cat ego r i s e t he s edimen ts . The bas e of t he pe at i st a ken t o indi cat e t he E ar ly Me s oli t hi ct opog ra phy s o t he dep t h of t he pe at i ss u btract ed f r om p r e s en t g r ound level, o r igin a lly me as u r ed b y c onven t ion a l s u r vey s u s ing dumpy level sa nd t heodoli t e s , a nd mo r e r e c en t ly wi t h a To ta l S tat ion. In 2010, 25 ye ars on a nd t h r ough t he h ar d wo r k of m a ny st uden ts a nd volun t ee rs , t he s u r vey w as c omple t ed a nd a full pi ct u r e of t he E ar ly Me s oli t hi c p a l a eo-l a ke h as b een c on str u ct ed in GIS b y B arr y T a ylo r (BT). Thi s i s c omplemen t ed b y t opog ra phi ca l s u r vey s of Flix t on I s l a nd, No N a me Hill a nd B arr y’ s I s l a nd (Figu r e 5). In a ddi t ion, as a mpling p r og ra mme t o lo cat e o t he rb u r ied E ar ly Me s oli t hi cs i t e s a long t he edge of t he l a ke h as b een s uppo rt ed b y t he VPRT (L a ne a nd S c h a dl a -H a ll fo rt h c oming). Thi s involved t he ex ca v at ion b y h a nd of ov e r 300 2 × 2 m t e st pi ts , lo cat ed Star Carr in a P o st gl ac i a l La ke sca pe : 60 Y e ars of R e s e arc h 9 at 15 m in t e r v a l s on t he 25.0–24.5 m a OD s u b - s u r f ac e c on t ou r , t he rat ion a le b eing t h at Cl ar k’ s ex ca v at ion sa t S tar C arr we r e 30 m acr o ss a nd a 15 m t e st pi Ĵ ing strat egy s hould hi t upon s imil ar s ized s i t e s . Thi s h as led t o t he deline at ion of fi ve s i t e s fi rst lo cat ed b y Moo r e (Fix t on I s l a nd 1 (Si t e 1), Flix t on I s l a nd 2 (Si t e 2), No N a me Hill (Si t e 3), M a nh a m Hill (Si t e 6 a nd Si t e 9) as well as t he di sc ove r y a nd deline at ion of fu rt he r c on c en trat ion s of li t hi ca nd f a un a l r em a in s of E ar ly Me s oli t hi c d at e ( s ee Figu r e 5). A t a num b e r of t he s e s i t e s (VP ‘D’, VP ‘E’, Flix t on I s l a nd 1, No N a me Hill, Flix t on S c hool Hou s e F ar m, B arr y’ s I s l a nd) l ar ge r ex ca v at ion s h a ve ta ken pl ac e s o as t o do c umen t t hei r in t e r n a l s p at i a l o r g a ni sat ion (e.g. L a ne a nd S c h a dl a -H a ll fo rt h c oming; T a ylo ra nd G ra y Jone s 2009). In a ddi t ion, s y st em at i c fi eld-w a lking h as ta ken pl ac e a Ğ e r ploughing Figure 5. 1: Star Carr; 2: Ling Lane; 3: Seamer Carr Site F; 4: Seamer Carr Sites L and N; 5: Seamer Carr Site K; 6: Seamer Carr Site D; 7: Seamer Carr Site B; 8: Seamer Carr Site C; 9: Manham Hill (Moore’s site 6); 10: Cayton Carr (Moore’s site 7); 11: Cayton Carr (Moore’s Site 8); 12: Lingholme Farm Site B; 13: Lingholme Farm Site C; 14: Lingholme Farm Site A; 15: Barry’s Island; 16: Flixton School Field; 17: Flixton School House Farm; 18: Woodhouse Farm; 19: VP Site E; 20: VP Site D; 21: Flixton 9; 22: Flixton Island South; 23: Flixton Island North; 24: No Name Hill (Moore’s Site 3). 10 N i c ky M ilne r et al . on ‘d r y-l a nd’ ar e as b o r de r ing t he p a l a eo-L a ke Flix t on, a long wi t h tar ge t ed sa mpling of depo s i ts fo r pollen a nd o t he r p a l a eoenvi r onmen ta l info r m at ion. Ex ca v at ion wo r k w as a l s o unde rta ken in 1996 b y No rt he r n A rc h a eologi ca l A ss o c i at e s (NAA) in a dv a n c e of a p r opo s ed ex t en s ion t o t he Se a me r l a ndfi ll s i t e at Ling L a ne, s upplemen t ed wi t h fu rt he r p a l a eoenvi r onmen ta l wo r k b y Edw ar d Clou t m a n (No rt he r n A rc h a eologi ca l A ss o c i at e s 1996). Signifi ca n t ly , t he NAA t e a m w as c omp r i s ed a lmo st en t i r ely of individu a l s who h a d wo r ked at Se a me r (mo st ly in as upe r vi s o r i a l ca p ac i t y), a nd on t he e ar ly ph as e s of t he VPRT p r oje ct (un t il 1991, when PL t ook ove ra s fi eld di r e ct o r ). The Ling L a ne ass e ss men t w as a l s o Ni c ky Milne r ’ s (NM) fi rst expe r ien c e of wo r king in t hi s p art of t he V a le. The r e s ul t of t hi s wo r k h as b een t o p r odu c e a n unde rsta nding of act ivi t y wi t hin t hi s Me s oli t hi c l a ke sca pe r eve a ling a v ar ie t y of tas k ss u c h as kn a pping, v ar ied t ool m a nuf act u r e, b u tc he r y a nd p r o bab ly pl a n t p r o c e ss ing. I t w as a f a mili ar pl ac e t h at people r e t u r ned t o r epe at edly , cac he s of ra w m at e r i a l we r e s e t up a nd l a nd sca pe m ar ke rs e stab li s hed (Connelle ra nd S c h a dl a -H a ll 2003). Howeve rt he s e s i t e sa ppe ar ve r y di ě e r en t f r om S tar C arr , b o t h in t he ra nge of m at e r i a l r e c ove r ed a nd t he t ype s of act ivi t y unde rta ken (Connelle ra nd S c h a dl a -H a ll 2003; Connelle r 2001; L a ne a nd S c h a dl a -H a ll fo rt h c oming). VPRT and Star Carr Fu rt he r wo r k at S tar C arr c ommen c ed in Augu st 1985: t he fi rst fi eld p r oje ct of t he V a le of Pi c ke r ing Re s e arc h T r u st , di r e ct ed b y TSH a nd PL. The m a in o b je ct ive of t hi s inve st ig at ion w as t o o bta in new sa mple sa nd strat ig ra phi c d ata f r om t he S tar C arr ar e a , whi c h would fo r m p art of SERC-funded inve st ig at ion s of t he mi cr oh ab i tats , li t hology a nd depo s i t ion a l c on t ex t of t he S tar C arr s i t e, b y Edw ar d Clou t m a n a nd Al a n Smi t h, Dep art men t of Pl a n t S c ien c e s , Unive rs i t y College, C ar di ě . The wo r k w as carr ied ou tb y as m a ll t e a m of expe r ien c ed arc h a eologi sts ( a ll of whom h a d wo r ked on t he Se a me r C arr p r oje ct ) a nd a ll m at e r i a l a nd strat ig ra phi c depo s i ts we r e r e c o r ded following t he p r o c edu r e sa dop t ed fo rt he Se a me r C arr P r oje ct . A n arr ow tr en c h (VP85A) w as lo cat ed a pp r oxim at ely 30 m t o t he e ast of Cl ar k’ st r en c he s (Figu r e 6). The tr en c h w as b e t ween 2–2.5 m wide a nd 18 m long (Mell ars et al . 1988 a ). T wo a ddi t ion a l 2 × 2 m t e st pi ts we r e ex ca v at ed b y h a nd in t he sa me gene ra l ar e a : VP85B w as s i t u at ed 15 m t o t he s ou t h of VP85A a nd VP85C w as lo cat ed ab ou t 175 m t o t he we st of t he ar e a ex ca v at ed b y Cl ar k. F a un a l a nd li t hi c m at e r i a l in c luding a barb ed poin t w as found in VP85A in ass o c i at ion wi t h a n ar e a of s u bsta n t i a l wo r ked t im b e rs . Thi s w as in t e r p r e t ed as p art of a deli b e rat ely l a id pl at fo r m, di ě e r ing s ignifi ca n t ly f r om t he b i rc h br u s hwood ho r izon no t ed du r ing Cl ar k’ s ex ca v at ion s men t ioned ab ove, a nd t he wood wo r king a n a ly s i ss ugge st ed t h at i t w as t he e ar lie st eviden c e of s y st em at i c car pen tr y in Eu r ope (Mell ars et al. 1998 b ). Th r ee pollen di a g ra m s we r e p r odu c ed f r om VP85A a nd one f r om VP85B whi c h a llowed a mo r e de ta iled r e c on str u ct ion of t he lo ca l vege tat ion t h a n h a d b een ac hieved du r ing Cl ar k’ s inve st ig at ion s . I t w as s ugge st ed t h at du r ing t he t ime of o cc up at ion t he s i t e w as a dj ac en tt o a n ar e a of s edge domin at ed fen, f r inged b y a n arr ow ba nd of r eed s w a mp, b eyond whi c h l a y open w at e rs ome 26 m f r om t he d r y l a nd (Clou t m a n a nd Smi t h 1988 c ). Star Carr in a P o st gl ac i a l La ke sca pe : 60 Y e ars of R e s e arc h 11 In 1986, t wo mo r e 2 × 2 m t e st pi ts we r e ex ca v at ed in t he vi c ini t y of S tar C arr : VP86 W w as s i t u at ed 17.5 m t o t he e ast of VP85A on t he edge of as ligh tr i s e in t he s u r f ac e, f r om whi c h only s even strat ifi ed fi nd s we r e r e c ove r ed; VP86X w as lo cat ed 140 m no rt h of t hi st r en c h on t he no rt h s ide of t he He rt fo r d Cu tb u t did no t p r odu c e a ny art ef act u a l o r f a un a l r em a in s . In 1989, fu rt he r wo r k w as unde rta ken b y at e a m f r om t he Unive rs i t y of C a m br idge unde rt he di r e ct ion of P a ul Mell ars wi t h ass i sta n c e f r om t he VPRT . A n arr ow m ac hine- c u t tr en c h w as ex ca v at ed t h r ough t he t op s oil t o r elo cat e Cl ar k’ s o r igin a l ex ca v at ion s . VP85A w as a l s o r eopened wi t h t he o b je ct ive of o bta ining pe at sa mple s fo ra new p r og ra mme of p a l a eoe c ologi ca l r e s e arc h a nd ab lo c k of pe at fo rc on tr olled ex ca v at ion unde r l ab o rat o r y c ondi t ion s . A fu rt he rs even 2 × 2 m t e st pi ts a ligned r oughly e ast -we st t o t he no rt h of t he m a in tr en c h we r e ex ca v at ed t o t e st fo rt he p r e s e r v at ion a nd s p at i a l di str i b u t ion of t he arc h a eologi ca l m at e r i a l s . The r e s ul ts of t hi s wo r k fo c u s ed on t he c h r onology of t he s i t e a nd e ě e cts of t he hum a n o cc up at ion of t he envi r onmen t in t hi s ar e a u s ing high r e s olu t ion pollen, c h arc o a l a nd s edimen ta n a ly s e s (D a y 1993; 1996 a ; 1996 b ; D a y a nd Mell ars 1994; D ar k 2000; 2004; D ar k et al. 2006; Mell ars a nd D ar k 1998). In Augu st 1992, t he VPRT unde rt ook s y st em at i c , g r idded fi eld w a lking ove rt he no rt he r n p art of t he fi eld in whi c h t he s i t e lie s , a Ğ e rt he fi eld h a d b een ploughed fo rt he fi rst t ime in ove ra de ca de. Colle ct ion w as b y 5 × 5 m s qu ar e s , wi t h e ac h s qu ar e s e arc hed b y as ingle fi eld w a lke ra nd fo ras e tt ime of fi ve minu t e s pe rs qu ar e. Ten di ě e r en t Figure 6. Plan of trenches on the Star Carr fi eld. 12 N i c ky M ilne r et al . p r oje ct mem b e rs p art i c ip at ed, a nd a llo cat ion of s qu ar e st o di ě e r en t fi eld w a lke rs w as ra ndomi s ed, t o minimi s e a ny e ě e cts on r e tr iev a l level st h at migh t h a ve b een ca u s ed b y di ě e r en c e s in fi eld-w a lking expe r ien c e a nd f a mili ar i t y wi t h li t hi c art ef acts . A t o ta l of 314 s qu ar e s (7850 m 2 ) we r e s e arc hed in t hi s w a y. A Ğ e rt he fi eld w a lking h a d b een c omple t ed, t he ar e as of s u bs oil di st u rb ed b y t he plough we r e plo Ĵ ed. Thi s exe rc i s e indi cat ed t h at ploughing w as di st u rb ing ar e as of t he b u r ied Me s oli t hi c l a nd- s u r f ac e, while t he v ar i ab le c on c en trat ion s of s u r f ac efl in t sca Ĵ e rs indi cat ed t he p r e s en c e of a po ss i b le act ivi t y ar e a on as pi t of l a nd p r oje ct ing in t o t he fo r me r l a ke t o t he e ast of t he VP85A tr en c h. The fi eld w as w a lked a g a in in t he a u t umn of 1999 b y t he VPRT , u s ing c o ars e r e s olu t ion (30 × 30) m c olle ct ion g r id s . Recent Research at Star Carr Sin c e 2004, NM, BT a nd CC h a ve b een di r e ct ing ex ca v at ion sa t S tar C arr (Connelle r 2007; Connelle r et al . 2009 a ; 2009 b ; Milne r 2007; T a ylo r 2007), t hei r involvemen t wi t h t he VPRT h a ving start ed in t he mid-1990 sa nd CC h a ving st udied t he fl in t ass em b l a ge s f r om Se a me ra nd t he VPRT ex ca v at ion sa s p art of he r PhD (Connelle ra nd S c h a dl a -H a ll 2003). Ini t i a l inve st ig at ion s in 2004 a nd 2005 start ed wi t hfi eld w a lking a nd as e r ie s of t e st pi ts on t he d r y-l a nd p art of t he s i t e acr o ss t he penin s ul at o t he e ast of p r eviou s inve st ig at ion. In 2006, tr en c he s we r e lo cat ed on t he l a ke m ar gin ar e as wi t h t he p r im ar y o b je ct ive of de t e r mining t he ex t en t of o r g a ni c art ef acts ; howeve r , di st u rb ingly , t he a n t le rt h at w as r e c ove r ed h a d s eve r ely de t e r io rat ed a nd h a d b een fl a Ĵ ened. Fu rt he r l a ke m ar gin wo r k w as carr ied ou t in 2007 in at r en c h whi c h c u tt h r ough one of Cl ar k’ s tr en c he s : t he rat ion a le b eing t h at t he r e s hould b e a good arra y of o r g a ni cr em a in s in t hi s ar e aa nd i t would b e po ss i b le t o t e st t he stat e of de ca y wi t h di sc ove r ie s m a de in 1950. The few pie c e s of a n t le r found we r e ex tr emely fl a Ĵ ened a nd only t wo pie c e s of b one we r e une art hed, b o t h of whi c h we r e ba dly p r e s e r ved a nd one of whi c h h a d li t e ra lly t u r ned t o gel at ine: t he ‘jelly b one’ (Milne r 2007; Milne r et al . 2011). The w ood t h at w as found w as a l s o in ab a d stat e of p r e s e r v at ion; howeve r , mo r e pl a nk s whi c h a ppe ar ed t o h a ve b een wo r ked we r e found ( ab ou t 20m t o t he we st of t he e ar lie r di sc ove r y in 1985) (Figu r e 7). Du r ing t hi ss e as on at r en c h on t he d r y-l a nd p art of t he s i t e, no rt h of t he l a id t im b e r pl at fo r m found in 1985, w as a l s o ex ca v at ed. Due t o t he in t e r n at ion a l r enown of t he s i t e, t he r e c en t ex ca v at ion sa Ĵ ract ed mu c h di sc u ss ion, r eg ar ding b o t h t he me t hod s of ex ca v at ion a nd t he i ss ue of de t e r io rat ing depo s i ts . The s ugge st ion t h at t he s i t e s hould b e b lo c k-li Ğ ed a nd ex ca v at ed unde r l ab o rat o r y c ondi t ion s w as t e st ed b y t he t e a m t h r ough t he ex tract ion of as m a ll b lo c k whi c h w as ex ca v at ed unde r l ab o rat o r y c ondi t ion st h r ough t he win t e ra nd s p r ing of 2007–8. The ove ra ll c on c lu s ion w as t h at t hi s me t hod w as no ts ui tab le fo rt he s e depo s i ts due t o t he p r o b lem s wi t h oxidi sat ion a nd t he likely c o st w as no t ju st ifi ed in t e r m s of sc ien t ifi cr e t u r n s (H a dley et al. 2010). In a ddi t ion, Engli s h He r i ta ge funded a p r oje ct t o t e st t he n at u r e of t he de t e r io rat ing depo s i ts wi t h a p art i c ul ar fo c u s on t he s oil geo c hemi str y . The s e demon strat ed c on c lu s ively, u s ing a wide ra nge of eviden c e, t h at t he depo s i ts we r e ex tr emely ac idi ca nd t h at t hi s h a d s eve r ely c omp r omi s ed t he o r g a ni cs (Bo r eh a m et al . 2011; Milne r et al . 2011). While t he inve st ig at ion s in t o t he de t e r io rat ion we r e b eing carr ied ou t , t he t e a m we r e Star Carr in a P o st gl ac i a l La ke sca pe : 60 Y e ars of R e s e arc h 13 as ked b y Engli s h He r i ta ge no tt o ex ca v at e in t he we t depo s i ts a nd s o in 2008 fu rt he r wo r k w as carr ied ou t on t he d r y-l a nd p art of t he s i t e, c on t inuing t he tr en c h whi c h w as start ed in 2007. Thi sr e s ul t ed in t he di sc ove r y of eviden c e fo ra po st -hole ‘hu t ’; t he e ar lie st known eviden c e of a str u ct u r e in t he UK. In 2008, fu rt he r wo r k w as a l s o c ondu ct ed in t he fi eld t o t he no rt h of t he He rt fo r d Cu t . He r e, as e r ie s of tr en c he s w as ex ca v at ed a nd flin t scatt e rs we r e found acr o ss t he fi eld indi cat ing t h at t he s i t e ex t ended mu c h fu rt he r no rt h t h a n w as p r eviou s ly t hough t . In a ddi t ion, at r en c h at t he l a ke m ar gin in t hi s fi eld p r odu c ed a no t he r pie c e of ‘jelly b one’ indi cat ing ex tr eme ac idi t y. A st hi s fi eld h a d no tb een p r eviou s ly ex ca v at ed (wi t h t he ex c ep t ion of t e st pi t VP86X), i ts eemed pl a u s i b le t h at t he ac idi t y w as r el at ed t o d ra in a ge a nd c h a nging w at e r tab le sa s oppo s ed t o e ar lie r arc h a eologi ca l in t e r ven t ion s , as h as b een po st ul at ed b y s ome fo r S tar C arr . The de bat e sc on c e r ning t he ex t en ta nd rat e of de t e r io rat ion c on t inued t h r ough 2008 a nd 2009. A s emin ar o r g a ni s ed b y Engli s h He r i ta ge at t he Unive rs i t y of Y o r k in Novem b e r 2008 w as held t o di sc u ss t he r e s ul ts of t he wo r k t o d at e a nd t he w a y s fo r w ar d. A tt he mee t ing Engli s h He r i ta ge unveiled t hei r pl a n s fo rt he r e c ommend at ion of sc heduling (de s ign at ed as n at ion a lly impo rta n t ) b y Engli s h He r i ta ge, unde rt he p r ovi s ion s of t he 1979 Ancient Monuments and Archaeological Areas Act (L ast et al. 2009). Fu rt he r wo r k on t he depo s i ts he a ded up b y Tony B r own (B r own et al. 2011) w as funded b y Engli s h He r i ta ge in 2009 b u t no ex ca v at ion t ook pl ac e in t h at ye ar . Ano t he r s emin ar , o r g a ni s ed b y Engli s h He r i ta ge a nd ho st ed b y t he Unive rs i t y of C a m br idge, t ook pl ac e in M a y 2010 wi t h t he a im of di sc u ss ing r e s ul ts , fu rt he r wo r k a nd t he wide r c on t ex t . In a ddi t ion, fu rt he r info r m at ion w as given r eg ar ding t he pl a nned sc heduling of S tar C arr as a N at ion a l Monumen t . Following t h at s emin ar , t he t e a m we r e given pe r mi ss ion fo r fu rt he r ex ca v at ion t h at s umme ra st he moni t o r ing indi cat ed fu rt he r ex ca v at ion w as r equi r ed in o r de rt o info r m fu t u r e m a n a gemen t de c i s ion s . The following o b je ct ive s we r e t o b e a dd r e ss ed: 1. De t e r mine t he evidential value (potential) of t he pl at fo r m/ trac kw a y, a nd a ny r em a ining o r g a ni c art ef acts a nd envi r onmen ta l d ata ; Figure 7. T rench SC24, excavated in 2007. The brushwood lies above ‘planks’ which are beginning to show through. This was the trench in which the ‘jellybone’ was found, in the layer above this wood. 14 N i c ky M ilne r et al . 2. Ev a lu at e t he ex t en t of w at e r logged archaeological deposits into the lake in o r de rt o info r m c on s ide rat ion on t he lo cat ion of t he s ou t he r n b ound ar y t o t he sc heduled monumen t ; 3. E stab li s h t he c u rr en t state of preservation a nd t he rate of decay of w at e r logged depo s i ts b y c omp ar i s on of r e s ul ts f r om p r eviou s ex ca v at ion s ; 4. Model how mu c h i t migh t cost t o s e c u r e t he r em a ining eviden t i a l v a lue (po t en t i a l). A t h r ee week s e as on of ex ca v at ion w as carr ied ou t wi t h t he s uppo rt of a l ar ge num b e r of s pe c i a li sts who h a ve a ll p r eviou s ly wo r ked on t he s i t e, funded b y t he N at u ra l Envi r onmen t Re s e arc h Coun c il a nd Engli s h He r i ta ge. Th r ee week s of ex ca v at ion r eve a led p arts of t he t im b e r pl at fo r m as well as t he b i rc h tr ee, o r igin a lly found in 1950 in Cl ar k’ s ex ca v at ion s . The r e s ul ts of t he s pe c i a li st a n a ly s e s led t o t he c on c lu s ion t h at t he w at e r logged p art of t he s i t e i s de t e r io rat ing f ast , b u t st ill yielding u s eful eviden t i a l v a lue a nd c on s equen t ly ex ca v at ion i sa dvo cat ed in o r de rt o s e c u r e t he r em a ining eviden t i a l v a lue (po t en t i a l). Di sc u ss ion A hi st o r y of inve st ig at ion s u c h as t hi sb r ing s ou ts ome impo rta n t poin ts . One ar e a of in t e r e st i st he pul s e s of act ivi t y a nd oppo rt uni t ie s fo rr e s e arc h. S tar C arr migh t neve r h a ve b een di sc ove r ed if i t w as no t fo r John Moo r e’ s involvemen t wi t h S carb o r ough A rc h a eologi ca l a nd Hi st o r i ca l So c ie t y. I t w as a l s o fo rt ui t ou st h at Moo r e c on tact ed Cl ar k. In a p a pe r pu b li s hed in 1972, Cl ar k expl a in s how he w as looking fo ras i t e wi t h t he po t en t i a l of S tar C arr . Thi s w as bas ed on hi s knowledge of t he di sc ove r y of M a gle s mo s i a n s i t e s in No rt he r n Eu r ope a nd w as c oupled wi t h hi sc oll ab o rat ion wi t h H arr y Godwin a nd t he Qu at e r n ar y Re s e arc h G r oup in C a m br idge in t he Fen s whi c h h a d p r ovided t hem wi t h t he expe r ien c e r equi r ed fo rs u c h wo r k. Cl ar k even stat e s t h at t he s i t e at S tar C arr in mo st r e s pe cts m atc hed t he ide a l he h a d s e t him s elf (Cl ar k 1972, 10–6). Repo rt ing in Antiquity on t he fi rst s e as on of wo r k he m a de s imil ar poin ts , str e ss ing a l s o t he v a lue of t he w at e r logged c on t ex t of t he s i t e: ‘The s i t e c ho s en fo r ex ca v at ion on a mo r e ex t en s ive sca le w as c ho s en wi t h t he expli c i ta im of r e c ove r ing trac e s of t he f a un a on whi c h t he M a glemo s i a n s lived a nd as wide a ra nge as po ss i b le of t hei r m at e r i a l c ul t u r e, in c luding o b je cts m a de f r om s u bsta n c e s no r m a lly lo st t o arc h a eology t h r ough de ca y’ (Cl ar k 1949, 207). We ca n only s pe c ul at e as t o why Cl ar k did no tr e t u r n a g a in t o S tar C arr o r why he did no tr e t u r n t o ex ca v at e a no t he rs i t e ar ound t he l a ke. One po ss i b le a n s we r i st h at he b elieved hi s o b je ct ive s h a d b een ac hieved: he h a d e stab li s hed t he strat ig ra phi c c on t ex t of t he m at e r i a l t h r ough pollen a n a ly s i s ; un c ove r ed t he whole ex t en t of t he s i t e; de t e r mined t he n at u r e of t he s e Ĵ lemen ta nd e stab li s hed t he likely s ize of t he s o c i a l uni t ; inve st ig at ed whe t he rt he r e w as a ny c h a nge in t he art ef acts r e c ove r ed f r om di ě e r en t level s ; r e c ove r ed as c omple t e as a mple as po ss i b le wi t h s pe c i a l a Ĵ en t ion t o t he o r g a ni c s u bsta n c e s ; a nd di sc ove r ed how people h a d u t ilized t hei r envi r onmen t , wh at t hey at e a nd t he s e as on st hey we r e p r e s en t on s i t e (Cl ar k 1972, 10–7). I t i s only wi t h t he b enefi t Star Carr in a P o st gl ac i a l La ke sca pe : 60 Y e ars of R e s e arc h 15 of hind s igh tt h at we now know t h at a num b e r of t he s e we r e no t fully a Ĵ a ined a nd m a ny h a ve b een fu rt he rr efi ned t h r ough s u bs equen t st udy . I t m a y a l s o b e t h at he did no t p art i c ul ar ly enjoy wo r king at S tar C arr , as he d ra w s a Ĵ en t ion t o t he ‘ physical remoteness of the site and its extreme una Ĵ ractiveness, compounded by the mud, ooze, rising water, and all too a Ĵ entive clegs (small horsefl ies) ’, a l t hough he doe s s ugge st t h at t he s e f act o rs only s e r ved t o enh a n c e t he mo ra le of t he p art y (Cl ar k 1972, 10–8)! Cl ar k a l s o m a ke ss ome impo rta n t stat emen ts ab ou t funding a nd r e s ou rc ing whi c h t o s ome deg r ee impeded hi s wo r k. He (1972) stat e st h at s u cc e ss depend s on t h r ee m a in r e s ou rc e s : money , help a nd good qu a li t y ex ca v at o rs . In t he po st -w ar ye ars , funding fo r r e s e arc h ex ca v at ion s w as p art i c ul ar ly di Ĝ c ul t , a nd ex ca v at ion sa t S tar C arr h a d t o b e carr ied ou t on a volun tar y bas i s wi t h in st i t u t ion sa nd individu a l s p r oviding f ac ili t ie s a nd l ab ou r wi t hou t p a ymen t . A s F a g a n (2001, 146) stat e s , a ll t h r ee s e as on s we r e r un on as hoe str ing. The money ca me f r om t h r ee s ou rc e s : t he Gene ra l Bo ar d of t he F ac ul t ie s of C a m br idge fo rt he tra ining fun ct ion of t he ex ca v at ion, a n a nonymou s dono ra nd t he P r ehi st o r i c So c ie t y du r ing t he fi n a l s e as on. Al t hough t hi ss ho rta ge of fund s inhi b i t ed t he s u cc e ss of t he wo r k t h r ough l ac k of equipmen ta nd t he s ho rt leng t h of t he s e as on s , i t w as ac knowledged t h at t he s ho rta ge of fund sa l s o enh a n c ed t he s pi r i t of c o-ope rat ion a nd help f r om in st i t u t ion sa nd individu a l s . Cl ar k (1972) r efl e cts on hi st e a m of st uden ts , t hei r tra ining a nd how m a ny wen t on t o jo bs in aca demi a , Roy a l Commi ss ion sa nd Mu s eum s ar ound t he wo r ld. The tra ining of st uden ts i sa l s o a key i ss ue fo rt he VPRT: NM, CC a nd BT s pen t m a ny s e as on s in tra ining t h r ough t he 1990 sa nd in t o t he 2000 s . They ar e now tra ining a new gene rat ion of st uden ts who h a ve wo r ked in t he ‘ mud, ooze and rising water ’ a nd h a ve b e c ome in cr edi b ly f a mili ar wi t h t he t e c hnique sr equi r ed in ex ca v at ing in t he s e depo s i ts . In a ddi t ion, a num b e r of r e s e arc h st uden ts h a ve start ed t o c ondu ct t hei r own r e s e arc h ar ound S tar C arr : e.g. Ben Ellio Ĵ ’ s (Unive rs i t y of Yo r k) ex a min at ion of t he a n t le r (Ellio Ĵ a nd Milne r 2010; Milne r et al. 2011); P at H a dley (Unive rs i t y of Yo r k) who ex ca v at ed t he b lo c k in t he l ab (H a dley et al. 2010); Andy Needh a m (Unive rs i t y of Y o r k) who fi rst di sc ove r ed t he high level s of ac idi t y (Bo r eh a m et al. 2011; Needh a m 2007), John O’H ara (New Y o r k Unive rs i t y) who i s unde rta king do ct o ra l r e s e arc h on t he b e a d s f r om S tar C arr a nd o t he r no rt hwe st Eu r ope a n s i t e s , a nd Ki rst y High (Unive rs i t y of Y o r k) who i s wo r king on t he i ss ue s of b one a nd a n t le r deg ra d at ion in r el at ion t o t he s oil c hemi str y. The wo r k of t he VPRT el s ewhe r e in t he V a le h as s imil ar ly en t hu s ed a num b e r of p r oje ct p art i c ip a n ts t o w r i t e unde r g ra du at e, m ast e rs o r do ct o ra l di ss e rtat ion s u s ing s ome of t he m at e r i a l c olle ct ed t h r ough t he wo r k of t he T r u st a nd t o pu b li s h aca demi c p a pe rs bas ed on t he s e (full de ta il s in L a ne a nd S c h a dl a -H a ll, fo rt h c oming). Looking t o t he fu t u r e S tar C arr c on t inue st o p r e s en t mo r e que st ion st h a n a n s we rs . A c on s e r v at ive e st im at e s ugge sts t h at le ss t h a n 5% of t he s i t e h as b een ex ca v at ed a nd we h a ve t o que st ion how m a ny o t he r str u ct u r e s m a y b e found on t he d r y-l a nd. In a ddi t ion, bas ed on t he r e s ul ts of t he 2010 ex ca v at ion s , t he l a id, wo r ked t im b e rs found ar ound t he l a ke edge ar e now t hough tt o c ove ra n ar e a of at le ast 30 m a l t hough t he fun ct ion of t hi s str u ct u r e r em a in s 16 N i c ky M ilne r et al . c omple t ely unknown. The r e i s eno r mou s po t en t i a l fo r fu rt he r impo rta n t di sc ove r ie s t o b e m a de wi t h mo r e ex ca v at ion. Equ a lly , wi t h a p r og ra mme of pu b li c ou tr e ac h, t he new di sc ove r ie s whi c h ar e b eing m a de ar e no t only imp act ing on aca demi a , b u t on t he wide r pu b li ca nd a n in t e r n at ion a l a udien c e. Fo r in sta n c e, t he po st -hole str u ct u r e found at S tar C arr w as fe at u r ed on ov e r 100 TV , ra dio a nd new s p a pe r ou t le ts ar ound t he wo r ld. S tar C arr h as now b een li st ed as a S c heduled An c ien t Monumen tb y t he He r i ta ge Mini st e r . Ni c k B r idgl a nd, de s ign at ion t e a m le a de r fo rt he No rt h at Engli s h He r i ta ge w as quo t ed in t he p r e ss r ele as e as sa ying: ‘The r em a in sa t S tar C arr ar e unequ a lled in B r i t i s h arc h a eology a nd de s ign at ion as a S c heduled An c ien t Monumen tr e c ogni s e st hi s impo rta n c e. I t will help arc h a eologi sts m a n a ge t he s i t e e ě e ct ively a nd carr y ou tc r i t i ca lly impo rta n t ex ca v at ion st o r e c ove rt he ra pidly de ca ying r em a in ss o we ca n a ll le ar n as mu c h as po ss i b le ab ou tt hi s f asc in at ing pe r iod of p r ehi st o r y’. A s di sc u ss ed ab ove, r e s ou rc ing t he s e inve st ig at ion s h as b een a n i ss ue eve rs in c e t he b eginning. A tt he l ast S tar C arr s emin ar i t w as s ugge st ed t h at a l ar ge g ra n t of at le ast a million pound s w as needed t o c on t inue wo r k at t he s i t e; t hi s p r omp t ed a p r opo sa l t o t he Eu r ope a n Re s e arc h Coun c il a nd we now h a ve s e c u r ed t he funding fo ra no t he r fi ve ye ars r e s e arc h. I t i s hoped t h at in p art ne rs hip wi t h Engli s h He r i ta ge a nd t he Eu r ope a n Re s e arc h Coun c il new a nd ex c i t ing di sc ove r ie s will b e m a de whi c h will c on t inue t o r ew r i t e ou r unde rsta nding of t hi s in tr iguing a nd impo rta n t , E ar ly Me s oli t hi cs i t e. A c knowledgemen ts We w ould like t o t h a nk a ll t he volun t ee rs , s upe r vi s o rs , s pe c i a li sts , c ook sa nd o t he r helpe rs who h a ve wo r ked on t he Se a me r C arr , V a le of Pi c ke r ing Re s e arc h T r u st a nd S tar C arr p r oje cts ove rt he ye ars , as wi t hou tt hei rc on tr i b u t ion st hi sr e c o r d of t he E ar ly Me s oli t hi c l a nd sca pe in t he e ast e r n p art of t he V a le of Pi c ke r ing w ould b e t he poo r e r . W e would a l s o like t o t h a nk a ll t he l a ndowne rs fo r acc e ss t o t he l a nd a nd t hei r c on t inued s uppo rt . Gene r ou st h a nk s ar e due t o t he v ar iou sa gen c ie st h at h a ve funded di ě e r en t elemen ts of t he fi eld wo r k, in c luding t he An c ien t Monumen t divi s ion of t he fo r me r dep art men t of t he Envi r onmen t , No rt h Y o r k s hi r e Coun t y Coun c il, t he V a le of Pi c ke r ing Re s e arc h T r u st ( a nd t hei r dono rs ), Engli s h He r i ta ge (g ra n t num b e rs 5536, 6064), t he B r i t i s h A ca demy (SG-44333, SG-47081, SG-50217), NERC, SERC, Unive rs i t y College London, t he Unive rs i t y of M a n c he st e r , t he Unive rs i t y of C a m br idge a nd t he Unive rs i t y of Y o r k. Fo r m a ny ye ars P r ofe ss o r Domini c Powle s l a nd (L a nd sca pe Re s e arc h c en tr e) h as o ě e r ed un st in t ing mo ra l a nd logi st i ca l s uppo rt , fo rt ifi ed b y gin sa nd t oni c a nd t he o ccas ion a l t equil a – fo r whi c h e t e r n a l t h a nk s . Star Carr in a P o st gl ac i a l La ke sca pe : 60 Y e ars of R e s e arc h 17 Refe r en c e s And r e s en, J. M., By r d, B. F., El s on, M. D., M c gui r e, R. H., Mendoz a , R. G., S tas ki, E. a nd Whi t e, J. P . 1981. The dee r hun t e rs : S tar C arr r e c on s ide r ed, World Archaeology 13, 31–46. B r own, T., B ra dley , C., G ra pe s , T. a nd Boome r , I. 2001. Hyd r ologi ca l ass e ss men t of S tar C arr a nd t he He rt fo r d catc hmen t , Yo r k s hi r e, UK, Journal of W etland Archaeology 11, 36–55. Bo r eh a m, S., Connelle r , C., Milne r , N., Needh a m, A., Bo r eh a m, J. a nd Rolfe, C. J. 2011. Geo c hemi ca l indi cat o rs of p r e s e r v at ion stat u sa nd s i t e de t e r io rat ion at S tar C arr , Journal of Archaeological Science 38, 1–25. C art e r , R. J. 1997. 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The iconic status enjoyed by Star Carr since Clark's work, therefore, is due not only to the prolific flint assemblages (Conneller and Schadla-Hall, 2003;Conneller et al., 2009), but also to the remarkable preservation and diversity of organic material associated with the site, which extended into the wetland sediments (Milner et al., 2011a) . The organic components of Early Mesolithic material culture, which do not survive on dry sites, were found in abundance and in an excellent state of preservation, stratified within the waterlogged organic deposits that accumulated in the palaeolake margin and in the reedswamp, fen and carr wetland habitats associated with it. ... ... This stratification has allowed the use of palaeobotanical analyses, including both macrofossil (Dark, 2004;Taylor, 2011) and pollen (Walker and Godwin, 1954;Cloutman and Smith, 1988;Dark, 1998aDark, , 1998bDark, , 1998cCummins, 2000), to reconstruct the vegetation history around the site, providing an environmental context for the settlement at Star Carr (Innes et al., 2011;Milner et al., 2013). This combination of preserved organic cultural remains and multi-disciplinary study has made Star Carr the 'type' site for the British early Mesolithic, and a model for subsequent studies in wetland archaeology (Milner et al., 2011a) . Not only could questions of site function, economy and seasonality of occupation be addressed, but the deeper understanding of the activities carried out at Star Carr allowed the site to be the hub of conceptual models of early Mesolithic land use, territoriality and interactions with the wider landscape (Clark, 1972(Clark, ). ... ... Boreham et al. (2011aBoreham et al. ( , 2011b) performed a series of physical and geochemical analyses at the site that also showed severe acidification of the sediments due to lowered and fluctuating water tables. Oxidation and acidification have caused very serious and rapid decay of the antler, bone and wood remains (Milner et al., 2011a) . In theory this very high acidity might not have such a severe effect upon pollen grain preservation, but watertable fluctuation, and associated peat dewatering, could well cause their corrosion (Lowe, 1982), and so the palynological record at Star Carr may be in as much danger as the rest of the organic material there. ... Degradation of the wetland sediment archive at Star Carr: an assessment of current palynological preservation. Article Mar 2016 JASR Bruce M. Albert James B. Innes J. J. Blackford Nicky Milner View ... It was the location of the Mesolithic settlement that first drew Clark to the site, as it lay on the edge of an Early Holocene lake Palmer et al., 2015), now termed Lake Flixton, and so promised to provide the palaeoenvironmental data that he needed for his research on Mesolithic economy and land use. The iconic status enjoyed by Star Carr since Clark's work, therefore, is due not only to the prolific flint assemblages (Conneller and Schadla-Hall, 2003;Conneller et al., 2009), but also to the remarkable preservation and diversity of organic material associated with the site, which extended into the wetland sediments (Milner et al., 2011a) . The organic components of Early Mesolithic material culture, which do not survive on dry sites, were found in abundance and in an excellent state of preservation, stratified within the waterlogged organic deposits that accumulated in the palaeolake margin and in the reedswamp, fen and carr wetland habitats associated with it. ... ... This stratification has allowed the use of palaeobotanical analyses, including both macrofossil (Dark, 2004;Taylor, 2011) and pollen (Walker and Godwin, 1954;Cloutman and Smith, 1988;Dark, 1998aDark, , 1998bDark, , 1998cCummins, 2000), to reconstruct the vegetation history around the site, providing an environmental context for the settlement at Star Carr (Innes et al., 2011;Milner et al., 2013). This combination of preserved organic cultural remains and multi-disciplinary study has made Star Carr the 'type' site for the British early Mesolithic, and a model for subsequent studies in wetland archaeology (Milner et al., 2011a) . Not only could questions of site function, economy and seasonality of occupation be addressed, but the deeper understanding of the activities carried out at Star Carr allowed the site to be the hub of conceptual models of early Mesolithic land use, territoriality and interactions with the wider landscape (Clark, 1972(Clark, ). ... ... Boreham et al. (2011aBoreham et al. ( , 2011b) performed a series of physical and geochemical analyses at the site that also showed severe acidification of the sediments due to lowered and fluctuating water tables. Oxidation and acidification have caused very serious and rapid decay of the antler, bone and wood remains (Milner et al., 2011a) . In theory this very high acidity might not have such a severe effect upon pollen grain preservation, but watertable fluctuation, and associated peat dewatering, could well cause their corrosion (Lowe, 1982), and so the palynological record at Star Carr may be in as much danger as the rest of the organic material there. ... Degradation of the wetland sediment archive at Star Carr: An assessment of current palynological preservation Article Apr 2016 JASR Bruce M. Albert Jim Innes J. J. Blackford Nicky Milner View ... The eastern Vale of Pickering in northeast Yorkshire has been the scene of intensive archaeological and palaeoenvironmental research since the mid-20th century [1][2][3] [4] [5][6][7] because of its rich Early Mesolithic archaeological resource, both lithic and organic. Much of this Table 1. ... Lateglacial to Mid-Holocene Vegetation History in the Eastern Vale of Pickering, Northeast Yorkshire, UK: Pollen Diagrams from Palaeolake Flixton Article Full-text available Dec 2022 I. G. Simmons Gaynor E. Cummins Barry Taylor James B. Innes Palaeolake Flixton, in the eastern Vale of Pickering in northeast Yorkshire, UK, existed as open water during the Lateglacial and early to mid-Holocene, until hydroseral succession and gradual terrestrialisation changed it to an area of fen and basin peatland by the later mid-Holocene. The environs of the lake were occupied by Late Palaeolithic and Mesolithic people over thousands of years and many Early Mesolithic sites, in particular, have been found located along the ancient lake edge, including the paradigm site for the British Early Mesolithic at Star Carr, where occupation occurred over several centuries. We have analysed eleven sediment cores, distributed in most parts of the palaeolake area, for pollen and stratigraphic data with which to reconstruct lake development and vegetation history. These new diagrams augment earlier pollen studies from the western part of the lake, particularly in the Star Carr area and near other major Mesolithic sites around Seamer Carr. Especially informative are a long core from the deepest part of the lake; cores that document the Lateglacial as well as early Holocene times, and evidence for the later Mesolithic that helps to balance the high density of Late Mesolithic sites known from research in the adjacent uplands of the North York Moors. There are many records of charcoal in the deposits but, especially for the earliest examples, it is not always possible to tie them firmly to either human activity or natural causes. Overall, the new and previously existing diagrams provide evidence for the spatial reconstruction of vegetation history across this important wetland system, including (a) for the progression of natural community successions within the wetland and on the surrounding dryland (b) the influence of climate change in bringing about changes in woodland composition and (c) for discussion of the possibility of human manipulation of the vegetation in the Late Upper Palaeolithic, Early and Late Mesolithic. Results show that climate was the main driver of longer-term vegetation change. Centennial-scale, abrupt climate events caused significant vegetation reversals in the Lateglacial Interstadial. The Lateglacial vegetation was very similar throughout the lake hinterland, although some areas supported some scrubby shrub rather than being completely open. Immigration and spread of Holocene woodland taxa comprised the familiar tree succession common in northern England but the timings of the establishment and the abundance of some individual tree types varied considerably around the lake margins because of edaphic factors and the effects of fire, probably of human origin. Woodland successions away from proximity to the lake were similar to those recorded in the wider landscape of northern England and produced a dense, homogenous forest cover occasionally affected by fire. View Show abstract ... Relatively good is also the state of research on the coasts of NW-Europe, i.e. in the Netherlands (see Out 2009) or in southern Scandinavia (see the compilation of Regnéll 1998or currently Regnell, 2011, often including the identification of parenchymatous tissue (Kubiak-Martens 1999;Kubiak-Martens et al., 2015;Perry 2002). In the British Isles, many sites were investigated (see Milner et al., 2011 , Bishop et al., 2013, every so often showing very good preservation of waterlogged organic remains while located on the coast or on lakes. In Scotland, plant remains are generally scarce in Mesolithic sites, which is partly due to the methods used for their recovery. ... The search for a needle in a haystack – New studies on plant use during the Mesolithic in southwest Central Europe Article Full-text available Feb 2022 JASR Stefanie Jacomet Patricia Vandorpe The existence of Mesolithic agriculture is a subject of debate in the archaeobotanist community. So far, reliable and AMS-dated on-site evidence of cereal macro remains are lacking to support the hypothesis. Archaeobotanical analysis of two rock shelters with Mesolithic occupation layers in NE-France and SW-Switzerland, namely Lutter, Abri St. Joseph (FR) and Arconciel, La Souche (CH), revealed the presence of cereal remains within the Mesolithic deposits. They gave rise to a possible answer to the question, however direct dating of the individual cereal grains revealed their intrusive nature in the older deposits. The main aim of this paper is to place the newly acquired data from both sites in the broader framework of archaeobotanical research on Mesolithic sites in Central Europe with a special focus on methodological and taphonomic issues often encountered at such sites. View Show abstract ... It derives from old Norse and means "brushy marsh." Star Carr in northern Yorkshire, United Kingdom, is an Early Mesolithic archaeological site that was occupied continuously for 200-500 years (Milner et al., 2011) . Its valley location, artifacts, and name reveal the pre-historical landscape even though the watercourse is now just a series of highly modified ponds. ... Rediscovering, Reevaluating, and Restoring Lost River-Wetland Corridors Article Full-text available Jun 2021 Ellen Wohl Janine M. Castro Brian Cluer Colin R. Thorne River-wetland corridors form where a high degree of connectivity between the surface (rheic) and subsurface (hyporheic) components of streamflow creates an interconnected system of channels, wetlands, ponds, and lakes. River-wetland corridors occur where the valley floor is sufficiently wide to accommodate a laterally unconfined river planform that may feature morphologically complex, multi-threaded channels with vegetated bars, islands, and floodplains. River-wetland corridors can develop anywhere there is valley expansion along a drainage network, from the headwaters to estuaries or deltas, and they are found across all latitudes and within all biomes and hydroclimates. River-wetland corridors may be longitudinally continuous but are commonly interspersed with single-thread reaches in narrower portions of the valley. The development and persistence of river-wetland corridors is driven by combinations of geologic, biotic, and geomorphic processes that create a river environment that is diverse, heterogeneous, patchy, and dynamically stable, and within which patterns of flow, sediment features, and habitats shift continually. Hence, we describe these polydimensional river corridors as “kaleidoscope rivers.” Historically, river-wetland corridors were pervasive in wide, alluvial valley reaches, but their presence has been so diminished worldwide (due to a diverse range of anthropogenic activities and impacts) that the general public and even most river managers are unaware of their former pervasiveness. Here, we define river-wetland corridors as a river type; review paleoenvironmental and historical records to establish their past ubiquity; describe the geologic, biotic, and geomorphic processes responsible for their formation and persistence; and provide examples of river-wetland corridor remnants that still survive. We close by highlighting the significance of the diverse river functions supported by river-wetland corridors, the consequences of diminution and neglect of this river type, and the implications for river restoration. View Show abstract ... The first major discovery was that the site was much larger than Clark had thought. This had first been demonstrated in 1985 when archaeology was found in the palaeoenvironmental trench, 30 metres away from Clark's trenches, and from some fieldwalking and testpitting in the field (Mellars and Dark 1998; Milner et al. 2012 ). However, further augering, fieldwalking and testpitting across the whole of the peninsular and into the field to the north revealed an extensive spread of worked flint suggesting that the site covers an area of roughly 19,500 m² and consequently demonstrating that less than 5% of this area has been excavated (Fig. 9.2) . ... "Fishing" Mesolithic Settlement-Subsistence Systems Using Notions of Economy of Debitage and Raw Material toward Production of Bone Points Book Jan 2015 Éva David Sinead Mc Cartan Frederik Molin Peter Woodman This paper examines the economy of debitage and that of raw material used in the bone industry from more or less contemporary sites located in similar comparative topographical situations, at the Cutts (Ireland) and at Strandvägen (Sweden); these are geographical bottleneck areas. Such a strategic position enabled the acquisition of large amounts of resources, of local or migratory origin, especially when situated at such a narrow spot where there would be expectations of regular profits intercepting animals and fish at certain periods of the year. Technological analysis concerning the production of recovered Mesolithic bone tools shows that human occupations at these locations produced an important amount of items enabling the capture and processing of various resources. Amongst them, a large amount of points display different types of prongs whose forms can be associated with the way they were set into different kinds of leisters used for fishing. While they were apparently utilised to acquire the same species in both these places, they reveal their rich informative potential for the discussion of the settlement-subsistence system after site function is emphasised when taking into account the whole material production. In the main, differences observed in behaviour towards the use of bone for implementing the fishing gear would be more related to differences in organising the subsistence at a large scale than solely from cultural choices. View Show abstract ... Further work in the area has been carried out by the Vale of Pickering Research Trust since the 1980s, with the aim of mapping the extent of the lake and identifying further sites (for a full account see Milner et al. (2011b) ). Since 2004, NM, CC and BT have been co-directing excavations at Star Carr and in 2012 the POSTGLACIAL project commenced: this is a five year, European Research Council funded project with the aim 'To implement an interdisciplinary, high-resolution approach to understanding hunter-gatherer lifeways within the context of climate and environment change during the early part of the post-glacial period (c. ... Scales of analysis: Evidence of fish and fish processing at Star Carr Article Feb 2018 JASR Harry Kenneth Robson Aimée Little Andrew Kenneth George Jones Nicky Milner View ... The first major discovery was that the site was much larger than Clark had thought. This had first been demonstrated in 1985 when archaeology was found in the palaeoenvironmental trench, 30 metres away from Clark's trenches, and from some fieldwalking and testpitting in the field (Mellars and Dark 1998; Milner et al. 2012 ). However, further augering, fieldwalking and testpitting across the whole of the peninsular and into the field to the north revealed an extensive spread of worked flint suggesting that the site covers an area of roughly 19,500 m² and consequently demonstrating that less than 5% of this area has been excavated ( Fig. 9.2) . ... Recent work at Star Carr: A POSTGLACIAL landscape study. Chapter Full-text available Dec 2015 Nicky Milner View Bibliography Article Apr 2022 Lee A. Newsom In this book, Lee A. Newsom offers an overview of wood in archaeology --how and where it is preserved and analyzed, its relevance to paleoecological and paleoenvironmental questions, as well as its role as an important source of information in modern archaeological science and related historical disciplines. Her book addresses a range of questions about wood reliance practices, sustainability, and the overall relevance of forest ecosystems to past cultures and cultural evolution. Newsom provides a step-by-step treatment of archaeological analysis with clear explanations and examples from various corners of the world. She also shows how the study of archaeological wood is relevant to modern restoration ecology and conservation biology that tracks long-term ancient ecosystems, including questions of global change. Demonstrating the vital role of wood and timber resources to past human societies, her book will interest scholars and students of archaeology, historical ecology, paleoecology, and wood science. View Show abstract Excavations at Star Carr: past and present Article Apr 2020 Barry Taylor Nicky Milner Chantal Conneller View Show more English Heritage seminar on Star Carr Article Full-text available Sep 2009 Jonathan Last Nicky Milner View A "Splendid Idiosyncrasy”: Prehistory at Cambridge 1915-50 Book Jan 2009 Pamela Jane Smith View A History of Archaeological Thought Article Feb 1992 Bull Am Schools Orient Res Steven A. Rosen Bruce G. Trigger View Faunal remains Article Jan 1954 F. C. Fraser J. E. King View Revised ‘absolute’ dating of the early Mesolithic site of Star Carr, North Yorkshire, in the light of changes in the early Holocene tree-ring chronology Article Jun 2000 Petra Dark Recent revision of the radiocarbon calibration curve for the early Holocene has implications for the ‘absolute’ date of Mesolithic sites such as Star Carr, and for their relationship to the timescale of early Holocene environmental change. View Show abstract Excavations in trench A: 1985 and 1989 Article Jan 1998 P. Mellars T. Schadla-Hall Paul Lane View Recent investigations of the early Mesolithic landscape in the Vale of Pickering Article Jan 1987 R.T. Schadla-Hall View One cannot dig at random in a peat bog'. The eastern Vale of Pickering and the archaeology of a buried landscape Article Jan 1985 R.T. Schadla-Hall E.W. Cloutman View New excavations at Star Carr Article Jan 2007 C. Conneller View Archaeological retrospect 5 Article Mar 1983 Stuart Piggott It has long been a source of pleasure to us both that the author of the first of these Archaeological Retrospects, Charles Phillips, should share with me independent boyhood contacts with the Vale of White Horse, then in Berkshire but since 1974 in Oxfordshire (Phillips, 1980). Piggotts had been around in Marcham, Hatford and West Challow since the early seventeenth century, and the families died out or slipped quietly downhill to the status of farm labourers or at best small peasant farmers. My great-grandfather was one of these, in Uffington beneath the famous hill-figure, and my grandfather at the age of 10 was taken up to the last of the traditional festive 'scourings' in 1857 by Thomas Hughes of Kingston Lisle, best known as the author of Tom Brown's Schooldays , who wrote up the event as The Scouring of the White Horse (1859). Among the festivities were wrestling and back-sword play: these sports 'were kept up there perhaps as long as in any portion of Middle England' wrote the son of a rector of Childrey, a village a few miles from Uffington, who came there in 1882. 'The Childrey schoolmaster', he goes on, 'when he was a boy at Uffington, could throw all his schoolfellows' (Cornish, 1939, 80). The schoolmaster was my grandfather, and my father was born in the village in 1874. View Show abstract Show more Recommendations Discover more Chapter Implementation and Performance Study November 2014 Talal H. Noor Quan Z. Sheng Athman Bouguettaya This chapter is devoted to the implementation and performance study of our proposed credibility-based trust management and automatic discovery of cloud services in distributed and highly dynamic environments. We implemented these techniques inside the Cloud Armor prototype. The Cloud Armor system, aim at providing a comprehensive platform for automatic cloud service discovery, malicious behavior ... [Show full abstract] detection, trust-based recommendation of cloud services and high availability support. To validate the feasibility and benefits of our approach, we conduct extensive experimental and performance studies of the proposed techniques using a collection of real-world trust feedbacks on cloud services. First, based on the collected data, we conduct a set of statistical analysis and present the results. These statistical results offer an overall view on the current status of cloud services. Second, we validate and study the performance of our credibility model by studying the effectiveness in distinguishing between feedbacks from experienced and amateur consumers. We study the robustness of the proposed techniques against different malicious behaviors namely: collusion and Sybil attacks under several behaviors and performed several precision and recall measurements. Finally, we validate and study our availability model from various aspects including accuracy and performance. Read more Conference Paper Full-text available The Deep Space Network Scheduling Problem. January 2005 Bradley Clement Mark Johnston We describe the Deep Space Network's scheduling problem based on a user requirement language. The problem is difficult to encode by almost all existing planning and scheduling systems. We describe how it can be mapped into a system that supports metric resources, durative action, simple temporal network constraints, and task hierarchy among other language features. We also describe how we adapted ... [Show full abstract] a local search scheduler to generate schedules. However, we argue that the application will best serve the users if local search is combined with systematic search. We describe how an implemented systematic search can be effectively applied to rescheduling. View full-text Article New SiO masers associated with bright southern IRAS sources January 1990 P. J. Hall David A. Allen Euan Troup [...] Alan E. Wright The discovery of 31 new SiO v = 1, J = 1 - 0 (43.122 GHz) masers associated with southern IRAS sources is reported. The candidate list for the search was produced systematically, and the high detection success rate (about 50 percent) led to the consideration of differences between stars associated with masers and those showing maser emission. A set of conditions is proposed which virtually ... [Show full abstract] guarantee the presence of detectable stellar SiO maser. One of the most important requirements is large optical variability (2.5 mag or greater), a condition associated with high mass-loss rate. In addition, it is found that the maser-to-infrared flux ratio is approximately proportional to the mass-loss rate. New polarization observations of the SiO maser associated with R Aqr, one of the two symbiotic stars known to show any type of maser emission, are also presented. Read more Article A bryophyte flora of South Wiltshire January 2001 · Journal of Bryology R. C. Stern Wiltshire has been the least known, bryologically, of all the counties in Southern England. The first records were not published until 1891. Since then, a number of bryologists have visited particularly the southern half of the county, which is the Watsonian vice-county 8 (v.-c. 8, South Wiltshire). Early recording was on a haphazard basis and there were many gaps in the coverage. A more ... [Show full abstract] systematic and intensive survey was undertaken in v.-c. 8 from the end of 1991 to 1999, using 10-km squares as the basic recording units. Locality details were noted for the less common species. This survey has resulted in nearly 3000 new 10-km square records and some 38 new species for the vice-county. Distribution maps are presented for all taxa except the commonest and the rarest. Lists of localities for the less common species are given. Read more Discover the world's research Join ResearchGate to find the people and research you need to help your work. Join for free ResearchGate iOS App Get it from the App Store now. Install Keep up with your stats and more Access scientific knowledge from anywhere or Discover by subject area Recruit researchers Join for free Login Email Tip: Most researchers use their institutional email address as their ResearchGate login Password Forgot password? Keep me logged in Log in or Continue with Google Welcome back! Please log in. Email · Hint Tip: Most researchers use their institutional email address as their ResearchGate login Password Forgot password? Keep me logged in Log in or Continue with Google No account? 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[MOBY-dev] [moby] Try to create service from serialized WSDL, get strange SOAP::Lite error Frank Gibbons francis_gibbons at hms.harvard.edu Tue Feb 7 21:02:27 UTC 2006 Previous message: [MOBY-dev] [moby] Try to create service from serialized WSDL, get strange SOAP::Lite error Next message: [MOBY-dev] jMoby update - creating Biomoby input dta Messages sorted by: [ date ] [ thread ] [ subject ] [ author ] Hi Mark, At 02:43 PM 2/7/2006, you wrote: > Hi Frank, > > I've read over your bug report below a few times and I can't quite > extract from it what the bug actually is... Can you paraphrase? Yeah, I don't really blame you - I've had a really hard time figuring out where the bug is myself! I've been working on this the past few days, and am happy to announce that I now have a deeper understanding of my confusion, though still no solution. [This posting turned out to be quite long.] First of all, it turns out that the specific problem I see below occurs only when I run my code under the Perl debugger, through emacs. So that may be a complete red herring, perhaps symptomatic of something else. I'm using Perl 5.8.6 from the SuSE distribution on dual-CPU i686-architecture hardware, but compiled for i586 architecture (sysadmin thought that shouldn't be a problem), with thread-support enabled (ditto). However, the problematic behaviour still exists. My code seg-faults 100% of the time. I can nail down the specifics a bit more precisely now. My goal is simple: cache WSDL locally, to avoid hitting MOBY Central too often, and to improve local performance in querying services: "discover once, use often" you might say. I can't keep service objects around, since I'm interested in using this in a web application, so services have to be constructed frequently. But they only need to be discovered sporadically (once an hour, once a day?). Simple enough. I have tried serializing with Storable and Data::Dumper, and find the same fundamental problem with both, which leads me to believe that the problem doesn't lie with serialization as a concept, or as an implementation. This is a relief, since all I want to serialize is the WSDL for each service, which is a string. If I can't serialize a string, I'm in deeper trouble than I thought! ;-D Using the serialized WSDL, I can thaw out ('deserialize'), successfully construct, and even execute services, so there is no inherent problem with the WSDL upon thawing. The MOBY::Client::Service objects returned are normal in every way. My problem comes when I try to return from the subroutine that does all this serializing, thawing, and reconstruction. The program crashes _always _and _only_ upon the return statement, and only when a MOBY::Client::Service has been created. If I simply serialize and thaw the WSDL, I get no problems upon returning. Under certain circumstances, the seg fault is accompanied by a message that "REFCNT decremented below 0!". Looks like a garbage-collection problem, where the GC tries to free something that's already been freed! A further clue is provided by Pieter Neerincx (private communication), who mentioned that he had a very similar problem which he traced back to XML::LibXML. The page http://cpan.uwinnipeg.ca/htdocs/XML-LibXML/Changes.html lists several recent bug fixes for threads from version 1.5.1 onwards (I'm using the latest, 1.5.8), including the specific one that Pieter encountered (the one using documentFragment()), which was supposedly fixed for 1.5.8. In fairness, I don't think the problem lies with MOBY itself, since it mostly just uses XML::LibXML in a fairly generic way (calls parse() a lot, but that's about it). However, the bug is serious enough to prevent caching of MOBY services, and presumably other potential uses which attempt to hide MOBY's interface in modules. So it affects MOBY in that sense, albeit indirectly. Briefly: use serialized WSDL, AND create MOBY::Client::Service, AND then return from subroutine ==> seg fault (always) use "fresh" WSDL, rest unchanged (can't cache services) ==> no seg fault don't return from subroutine, rest unchanged (can't encapsulate in other module) ==> no seg fault omit MOBY::Client::Service creation, rest unchanged (can't do anything useful at all) ==> no seg fault otherwise ==> no seg fault (ever) If you'd like to play around with it, go here: http://llama.med.harvard.edu/~fgibbons/tmp/api_moby.pl to get the self-contained stub I'm using to investigate this. Use the $config hashref to turn on caching (CACHE_SERVICE_INFO => 1), and watch it fault. (You'll have to run it twice: once to build the cache, then again to use it). Then turn off caching, and watch it return normally. I have NO IDEA where to go from here. I'd really rather not ask my sysadmin to build and reinstall Perl _without_ threads unless I'm positive that will cure my problems. If anyone has ANY ideas on where to go from here, I would be really, truly grateful. TIA, -Frank > On Fri, 2006-02-03 at 12:41 -0500, Frank Gibbons wrote: > > Hi, > > It takes MOBY about half a second to retrieve WSDL from Central, to > build a > > service. In an effort to improve performance in an application that > may need > > to build many (maybe ten) services at a time, I'm trying to cache WSDL > > locally, and build services from that, as needed. I'm using Storable for > > serialization in Perl, which has worked well for me in the past. To > > paraphrase Yogi Berra: "Half a second here, half a second there, > pretty soon > > you're talking about real time." > > I'm encountering a strange error in this, which appears to be emanating > > ultimately from SOAP::Lite (see below) In essence it says: > > Service description 'data:,<insert_wsdl_here> can't be loaded: 501 > Protocol > > scheme '' is not supported > > The WSDL is URI_encoded by MOBY, not by me - I just supply an XML-text > > description to MOBY::Client::Service->new(), pretty much exactly as > provided > > from MCentral. I DO NOT see this problem when using the WSDL supplied by > > MOBY Central directly however, so there's clearly some kind of > problem with > > serialization. I'm wondering if any of you have seen a similar > behaviour in > > the past, and how you got around it. The WSDL I retrieve from the cache > > looks fine when I print it out, but I'm wondering if there might be some > > other funkiness to it that gets messed up with I store it. > > Thanks in advance. > > -Frank > > _______________________________________________ > > MOBY-dev mailing list > > MOBY-dev at biomoby.org > > http://biomoby.org/mailman/listinfo/moby-dev > -- PhD, Computational Biologist, Harvard Medical School BCMP/SGM-322, 250 Longwood Ave, Boston MA 02115, USA. Tel: 617-432-3555 Fax: 617-432-3557 http://llama.med.harvard.edu/~fgibbons Previous message: [MOBY-dev] [moby] Try to create service from serialized WSDL, get strange SOAP::Lite error Next message: [MOBY-dev] jMoby update - creating Biomoby input dta Messages sorted by: [ date ] [ thread ] [ subject ] [ author ] More information about the MOBY-dev mailing list
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CHP notified of one additional human case of avian influenza A(H7N9) in Mainland CHP notified of one additional human case of avian influenza A(H7N9) in Mainland ************************************************************ The Centre for Health Protection (CHP) of the Department of Health (DH) yesterday (April 15) received notification of one additional human case of avian influenza A(H7N9) in Hunan from the National Health and Family Planning Commission. The patient is a 30-year-old man who is currently hospitalised for treatment.A total of 408 human cases of avian influenza A(H7N9) have been confirmed in the Mainland, including Zhejiang (138 cases), Guangdong (102 cases), Jiangsu (49 cases), Shanghai (41 cases), Fujian (22 cases), Hunan (21 cases), Anhui (12 cases), Jiangxi (six cases), Beijing (four cases), Henan (four cases), Guangxi (three cases), Shandong (three cases), Guizhou (one case, imported from Zhejiang), Hebei (one case) and Jilin (one case)."Locally, enhanced disease surveillance, port health measures and health education against avian influenza are ongoing. We will remain vigilant and maintain liaison with the World Health Organization (WHO) and relevant health authorities. Local surveillance activities will be modified upon the WHO's recommendations," a spokesman for the DH said."In view of human cases of avian influenza A(H7N9) confirmed locally and in the Mainland, further cases are expected in affected and possibly neighbouring areas. Those planning to travel outside Hong Kong should maintain good personal, environmental and food hygiene at all times," the spokesman urged."All boundary control points have implemented disease prevention and control measures. Thermal imaging systems are in place for body temperature checks of inbound travellers. Random temperature checks by handheld devices have also been arranged. Suspected cases will be immediately referred to public hospitals for follow-up investigation," the spokesman added.Regarding health education for travellers, display of posters in departure and arrival halls, in-flight public announcements, environmental health inspection and provision of regular updates to the travel industry via meetings and correspondence are proceeding.The spokesman advised travellers, especially those returning from avian influenza-affected areas and provinces with fever or respiratory symptoms, to immediately wear masks, seek medical attention and reveal their travel history to doctors. Health-care professionals should pay special attention to patients who might have had contact with poultry, birds or their droppings in affected areas and provinces.Members of the public should remain vigilant and take heed of the preventive advice against avian influenza below:* Do not visit live poultry markets and farms. Avoid contact with poultry, birds and their droppings. If contact has been made, thoroughly wash hands with soap;* Avoid entering areas where poultry may be slaughtered and contact with surfaces which might be contaminated by droppings of poultry or other animals;* Poultry and eggs should be thoroughly cooked before eating;* Wash hands frequently with soap, especially before touching the mouth, nose or eyes, handling food or eating; after going to the toilet or touching public installations or equipment (including escalator handrails, elevator control panels and door knobs); or when hands are dirtied by respiratory secretions after coughing or sneezing;* Cover the nose and mouth while sneezing or coughing, hold the spit with a tissue and put it into a covered dustbin;* Avoid crowded places and contact with fever patients; and* Wear masks when respiratory symptoms develop or when taking care of fever patients.The public may visit the CHP's avian influenza page (www.chp.gov.hk/en/view_content/24244.html) and website (www.chp.gov.hk/files/pdf/global_statistics_avian_influenza_e.pdf) for more information on avian influenza-affected areas and provinces. Ends/Wednesday, April 16, 2014Issued at HKT 12:10NNNN
http://www.info.gov.hk/gia/general/201404/16/P201404160450.htm
[v4,00/24] pSeries dynamic secure boot secvar interface + platform keyring loading - Patchwork [v4,00/24] pSeries dynamic secure boot secvar interface + platform keyring loading Message ID [email protected] ( mailing list archive ) Headers show Return-Path: <[email protected]> X-Spam-Checker-Version: SpamAssassin 3.4.0 (2014-02-07) on aws-us-west-2-korg-lkml-1.web.codeaurora.org Received: from vger.kernel.org (vger.kernel.org [23.128.96.18]) by smtp.lore.kernel.org (Postfix) with ESMTP id 22B8FC05027 for <[email protected]>; Fri, 20 Jan 2023 07:43:53 +0000 (UTC) Received: ([email protected]) by vger.kernel.org via listexpand id S230225AbjATHnw (ORCPT <rfc822;[email protected]>); Fri, 20 Jan 2023 02:43:52 -0500 Received: from lindbergh.monkeyblade.net ([23.128.96.19]:44912 "EHLO lindbergh.monkeyblade.net" rhost-flags-OK-OK-OK-OK) by vger.kernel.org with ESMTP id S230130AbjATHnt (ORCPT <rfc822;[email protected]>); Fri, 20 Jan 2023 02:43:49 -0500 Received: from mx0a-001b2d01.pphosted.com (mx0a-001b2d01.pphosted.com [148.163.156.1]) by lindbergh.monkeyblade.net (Postfix) with ESMTPS id 2E4097DFAC; 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Fri, 20 Jan 2023 07:43:31 +0000 (GMT) Received: from jarvis-ozlabs-ibm-com.ozlabs.ibm.com (haven.au.ibm.com [9.192.254.114]) (using TLSv1.2 with cipher ECDHE-RSA-AES256-GCM-SHA384 (256/256 bits)) (No client certificate requested) by ozlabs.au.ibm.com (Postfix) with ESMTPSA id 9A457602C2; Fri, 20 Jan 2023 18:43:29 +1100 (AEDT) From: Andrew Donnellan <[email protected]> To: [email protected], [email protected] Cc: [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], [email protected] Subject: [PATCH v4 00/24] pSeries dynamic secure boot secvar interface + platform keyring loading Date: Fri, 20 Jan 2023 18:42:42 +1100 Message-Id: <[email protected]> X-Mailer: git-send-email 2.39.0 X-TM-AS-GCONF: 00 X-Proofpoint-ORIG-GUID: BI_ISitNmGvVAhKCVwLPULG_EIz_thMK X-Proofpoint-GUID: BI_ISitNmGvVAhKCVwLPULG_EIz_thMK Content-Transfer-Encoding: 8bit X-Proofpoint-UnRewURL: 0 URL was un-rewritten MIME-Version: 1.0 X-Proofpoint-Virus-Version: vendor=baseguard engine=ICAP:2.0.219,Aquarius:18.0.930,Hydra:6.0.562,FMLib:17.11.122.1 definitions=2023-01-20_04,2023-01-19_01,2022-06-22_01 X-Proofpoint-Spam-Details: rule=outbound_notspam policy=outbound score=0 priorityscore=1501 impostorscore=0 mlxlogscore=999 phishscore=0 lowpriorityscore=0 malwarescore=0 spamscore=0 adultscore=0 bulkscore=0 suspectscore=0 clxscore=1015 mlxscore=0 classifier=spam adjust=0 reason=mlx scancount=1 engine=8.12.0-2212070000 definitions=main-2301200070 Precedence: bulk List-ID: <linux-integrity.vger.kernel.org> X-Mailing-List: [email protected] Series pSeries dynamic secure boot secvar interface + platform keyring loading | expand [v4,00/24] pSeries dynamic secure boot secvar interface + platform keyring loading [v4,01/24] powerpc/pseries: Fix handling of PLPKS object flushing timeout [v4,02/24] powerpc/pseries: Fix alignment of PLPKS structures and buffers [v4,03/24] powerpc/secvar: Use u64 in secvar_operations [v4,04/24] powerpc/secvar: Warn and error if multiple secvar ops are set [v4,05/24] powerpc/secvar: Use sysfs_emit() instead of sprintf() [v4,06/24] powerpc/secvar: Handle format string in the consumer [v4,07/24] powerpc/secvar: Handle max object size in the consumer [v4,08/24] powerpc/secvar: Clean up init error messages [v4,09/24] powerpc/secvar: Extend sysfs to include config vars [v4,10/24] powerpc/secvar: Allow backend to populate static list of variable names [v4,11/24] powerpc/secvar: Warn when PAGE_SIZE is smaller than max object size [v4,12/24] powerpc/secvar: Don't print error on ENOENT when reading variables [v4,13/24] powerpc/pseries: Move plpks.h to include directory [v4,14/24] powerpc/pseries: Move PLPKS constants to header file [v4,15/24] powerpc/pseries: Expose PLPKS config values, support additional fields [v4,16/24] powerpc/pseries: Implement signed update for PLPKS objects [v4,17/24] powerpc/pseries: Log hcall return codes for PLPKS debug [v4,18/24] powerpc/pseries: Make caller pass buffer to plpks_read_var() [v4,19/24] powerpc/pseries: Turn PSERIES_PLPKS into a hidden option [v4,20/24] powerpc/pseries: Add helpers to get PLPKS password [v4,21/24] powerpc/pseries: Pass PLPKS password on kexec [v4,22/24] powerpc/pseries: Implement secvars for dynamic secure boot [v4,23/24] integrity/powerpc: Improve error handling & reporting when loading certs [v4,24/24] integrity/powerpc: Support loading keys from pseries secvar Message This series exposes an interface to userspace for reading and writing secure variables contained within the PowerVM LPAR Platform KeyStore (PLPKS) for the purpose of configuring dynamic secure boot, and adds the glue required to load keys from the PLPKS into the platform keyring. This series builds on past work by Nayna Jain[0] in exposing PLPKS variables to userspace. Rather than being a generic interface for interacting with the keystore, however, we use the existing powerpc secvar infrastructure to only expose objects in the keystore used for dynamic secure boot. This has the benefit of leveraging an existing interface and making the implementation relatively minimal. This series integrates a previous series to fix some bugs in PLPKS and implement support for signed updates[1], and a cleanup patch from Michael Ellerman[2]. There are a few relevant details to note about the implementation: * New additions to the secvar API: format(), max_size(), config_attrs, var_names * New optional sysfs directory "config/" for arbitrary ASCII variables * Some OPAL-specific code has been relocated from secvar-sysfs.c to powernv platform code. Would appreciate any powernv testing! * Variable names are fixed and only those used for secure boot are exposed. This is not a generic PLPKS interface, but also doesn't preclude one being added in future. With this series, both powernv and pseries platforms support dynamic secure boot through the same interface. [0]: https://lore.kernel.org/linuxppc-dev/[email protected]/ [1]: https://lore.kernel.org/linuxppc-dev/[email protected]/ [2]: https://lore.kernel.org/linuxppc-dev/[email protected]/ v1: https://lore.kernel.org/linuxppc-dev/[email protected]/ v2: https://lore.kernel.org/linuxppc-dev/[email protected]/ v3: https://lore.kernel.org/linuxppc-dev/[email protected]/ ================= Changes in v4: Fix the build when CONFIG_PSERIES_PLPKS=n (snowpatch) Shuffled fixes to the front the series (npiggin) Pass buffer size in secvar_operations->format() (stefanb, npiggin) Return an error when set_secvar_ops() fails (npiggin) Add some extra null checks (stefanb, gjoyce) Add commit message comment elaborating on PAGE_SIZE issues (joel) Fix error handling in the kexec code (ruscur) Fix hvcall.h MAX_HCALL_OPCODE rebasing issue (npiggin) Changes in v3: Integrate Andrew's PLPKS bugfixes and enhancements series and Michael Ellerman's u64 cleanup patch into this series (and update the other patches to use u64) New patches to load keys from the PLPKS into the kernel's platform keyring (ruscur) New patches to pass PLPKS password to new kernels when kexecing (ruscur) Improve handling of format strings (ruscur) Clean up secvar error messages (ajd) Merge config attributes into secvar_operations (mpe) Add a new static variable names API rather than (ab)using get_next() (ajd/mpe) Warning message when PAGE_SIZE is smaller than the max object size (ajd) Move plpks.h to the include directory, and move a bunch of constants in there with a consistent naming scheme Refresh PLPKS config values whenever plpks_get_usedspace() is called (ajd) Extra validation on PLPKS config values (ruscur) Return maxobjlabelsize to userspace as is without subtracting overhead (ruscur) Fix error code handling in plpks_confirm_object_flushed() (ruscur) Pass plpks_var struct to plpks_signed_update_var() by reference (mpe) Make the data buffer in plpks_read_var() caller-allocated to reduce number of allocations/copies (mpe) Rework the Kconfig options so that PSERIES_PLPKS is a hidden option, turned on by enabling PPC_SECURE_BOOT, and the PLPKS secvar code is activated by PPC_SECVAR_SYSFS to match powernv (ajd) Use machine_arch_initcall() rather than device_initcall() so we don't break powernv (mpe) Improve ABI documentation (mpe) Return -EIO on most read errors (mpe) Add "grubdbx" variable (Sudhakar) Use utf8s_to_utf16s() rather than our own "UCS-2" conversion code (mpe) Fix SB_VERSION data length (ruscur) Stop prepending policy data on read (ruscur) Don't print errors to the kernel log when reading non-existent variables (Sudhakar) Miscellaneous code style, checkpatch cleanups Changes in v2: Remove unnecessary config vars from sysfs and document the others, thanks to review from Greg. If we end up needing to expose more, we can add them later and update the docs. Use sysfs_emit() instead of sprintf() for all sysfs strings Change the size of the sysfs binary attributes to include the 8-byte flags header, preventing truncation of large writes. Andrew Donnellan (8): powerpc/pseries: Fix handling of PLPKS object flushing timeout powerpc/pseries: Fix alignment of PLPKS structures and buffers powerpc/secvar: Clean up init error messages powerpc/secvar: Allow backend to populate static list of variable names powerpc/secvar: Warn when PAGE_SIZE is smaller than max object size powerpc/secvar: Don't print error on ENOENT when reading variables powerpc/pseries: Make caller pass buffer to plpks_read_var() powerpc/pseries: Turn PSERIES_PLPKS into a hidden option Michael Ellerman (1): powerpc/secvar: Use u64 in secvar_operations Nayna Jain (2): powerpc/pseries: Expose PLPKS config values, support additional fields powerpc/pseries: Implement signed update for PLPKS objects Russell Currey (13): powerpc/secvar: Warn and error if multiple secvar ops are set powerpc/secvar: Use sysfs_emit() instead of sprintf() powerpc/secvar: Handle format string in the consumer powerpc/secvar: Handle max object size in the consumer powerpc/secvar: Extend sysfs to include config vars powerpc/pseries: Move plpks.h to include directory powerpc/pseries: Move PLPKS constants to header file powerpc/pseries: Log hcall return codes for PLPKS debug powerpc/pseries: Add helpers to get PLPKS password powerpc/pseries: Pass PLPKS password on kexec powerpc/pseries: Implement secvars for dynamic secure boot integrity/powerpc: Improve error handling & reporting when loading certs integrity/powerpc: Support loading keys from pseries secvar Documentation/ABI/testing/sysfs-secvar | 75 +++- arch/powerpc/Kconfig | 1 + arch/powerpc/include/asm/hvcall.h | 1 + arch/powerpc/include/asm/plpks.h | 187 ++++++++++ arch/powerpc/include/asm/secvar.h | 21 +- arch/powerpc/kernel/secvar-ops.c | 8 +- arch/powerpc/kernel/secvar-sysfs.c | 172 +++++---- arch/powerpc/kexec/file_load_64.c | 18 + arch/powerpc/platforms/powernv/opal-secvar.c | 60 +++- arch/powerpc/platforms/pseries/Kconfig | 11 +- arch/powerpc/platforms/pseries/Makefile | 4 +- arch/powerpc/platforms/pseries/plpks-secvar.c | 215 +++++++++++ arch/powerpc/platforms/pseries/plpks.c | 338 ++++++++++++++---- arch/powerpc/platforms/pseries/plpks.h | 71 ---- .../integrity/platform_certs/load_powerpc.c | 47 ++- 15 files changed, 978 insertions(+), 251 deletions(-) create mode 100644 arch/powerpc/include/asm/plpks.h create mode 100644 arch/powerpc/platforms/pseries/plpks-secvar.c delete mode 100644 arch/powerpc/platforms/pseries/plpks.h
https://patchwork.kernel.org/project/linux-integrity/cover/[email protected]/
Danny Alexander Lib Dem conference speech in full Read chief secretary to the Treasury Danny Alexander's speech to the Liberal Democrat conference in full. * liberal-democrats-conference Danny Alexander Lib Dem conference speech in full Danny Alexander Lib Dem conference speech in full Read chief Secretary to the Treasury Danny Alexander's speech to the Liberal Democrat conference in full: I'd like to tell you about a man who's been a great source of inspiration and guidance to me behind the scenes over the last year. Gordon. Although outwardly dour, his finely tuned political antennae and no nonsense style make him the perfect sounding board. He's not flash – he's just Gordon. Gordon Birtwistle, the Liberal Democrat MP for Burnley. One of the most talented and tenacious of our 2010 intake. I'm privileged he agreed to be my PPS. Alistair Darling wasn't quite so keen on his Gordon. His Gordon racked up a record deficit fuelled by irresponsible and unsustainable spending. His Gordon denied any responsibility for the economic woes caused by his own policies. His Gordon "unleashed the forces of hell" simply for sharing his views on the severity of the economic crisis. Who was feeding Gordon Brown such advice? Was it Mandy? Or McBride? I think it's pretty obvious – it was all Balls. Unlike Labour, our party has never shied away from telling difficult truths on the economy: Vince Cable led the way in warning of the dangers that were building. And we made a historic decision last Spring. When we signed up to coalition government, we knew our country's economic stability depended on it. Returning our country to lasting prosperity is the founding purpose of this government – the overwhelming national interest that motivated two very different political parties to take responsibility together for a full 5 years. We resolved to act in the national interest and put our country first. That is what we're doing. "In government, on your side" doesn't mean telling people there's an easy answer to the horrendous problems Labour left. It means telling it straight. To get things right for the long term, we must stick to our guns now. And we shouldn't forget the impact of our unity and our resolve. Concern about both sovereign debt and economic growth is at the heart of the current market turbulence. Turbulence fuelled by uncertainty about the ability of political leaders across the globe to take the decisive action their countries need. Since we came into office, our coalition government has taken the difficult, and sometimes unpopular decisions necessary to fix our economy. This decisive action has made an immediate impact. Interest rates have stayed low, keeping workers in their jobs and families in their homes. Fellow Liberal Democrats, we played a decisive role in securing our country's financial credibility. This should make us proud. We have built a strong shelter, but the storm is still raging. Elsewhere in Europe, the struggle to establish credible deficit reduction plans goes on. In the US, political deadlock brought a historic downgrade of the country's credit rating. Yet despite all the evidence, the party that put us in this hole just want to keep digging. Labour say our motivation is dogmatic. They're wrong. It's practical. Financial discipline is necessary for effective government. It would be completely wrong to leave the bills for past mistakes to be paid for by our children. The economic case is indisputable – that's what so many of you have done in local government, and that's what we must continue to do in central government. We must stick to our plans and we will. We'll be straight with people: about how long this will take; how hard it will be, and what we will do to get it right. A huge deficit, an unbalanced economy, our trading partners in real difficulty. These are very big problems. Solving them will take years, and every one of us has a role to play. To support growth, to help families under pressure. As Liberal Democrats, our judgements about what needs to be done should be driven by the liberal economy we want to build. A liberal economy shaped by free and open competition, A liberal economy built on long-term investment, not debt and waste. A liberal economy where growth is shared across the country A liberal economy where taxation delivers fairness. Sustainable, balanced, competitive, fair. To get the kind of growth we want, we must break down the vested interests – the enemies of growth that stand in the way of future prosperity. We are prepared to take them on. We will name and shame those standing in the way of that central national purpose. On trade: Free trade has been a liberal rallying call for centuries. Offering gains to countries around the world and especially for Britain, with our quality exports and trading history. Today our trade policy is being brilliantly led by Ed Davey. The inception of the European single market a quarter of a century ago helped create hundreds of thousands of new jobs. Astonishingly, the single market is not yet complete. Huge areas of the European economy are still not fully open to British firms – especially in the services and energy sectors Completing this work will support growth, jobs and competitiveness not just in Britain but across the whole of Europe. There's an opportunity for Britain to lead this agenda right now – as we did so successfully in the 1980s. As the Eurozone seeks to deepen its integration – and we need it to do so more quickly – they will need our support. And they will get it. Sadly, eurosceptics on left and right still fail to understand Winston Churchill's insight that sharing sovereignty strengthens our influence and isolation weakens us. Scottish Nationalists make the same mistake. We'll never let the anti-European isolationists or nationalists frustrate our national interest. They are enemies of growth. Fortunately, coalition ministers are united in pursuing a policy of practical, pragmatic engagement in the EU. Nick Clegg and I are working with David Cameron and George Osborne to make deepening, strengthening, and deregulating the single market a central aim of Britain’s European policy – because it will bring jobs and growth. On infrastructure: Too many businesses are being held back by congested roads, slow railways, inadequate broadband. At the spending review last year, we looked at infrastructure spending in the round, picking only the most economically valuable projects from across government for funding. And as a result, we're investing more in the transport network over these 4 years than Labour managed in the last 4. The redevelopment of New Street Station here in Birmingham, the Mersey gateway bridge, Crossrail in London, and a national high speed rail network. And we have prioritised the money to invest to make sure that high speed broadband gets to every part of the country. Now more than ever, we need to get on with this work. But there's a major vested interest in the way. Bureaucracy, rules and red tape that mean it takes years to get things done. A planning system that can take more than a decade to allow even modest developments to go forward. It has to change. And under the coalition it will. I know there are concerns about our planning reforms. So it's important to understand what we're really doing. The presumption of sustainable development is right because it establishes the right balance. Local communities in the driving seat, local protections in place and yes more local homes and local jobs. So while it is politically contentious – we will reform planning. As chief secretary, I set the rules that control public spending. Mostly, that's about making sure we stick within our budget, which I'm sure you can imagine doesn't always make me very popular. On infrastructure, I'm pressing departments to make sure they deliver their plans on schedule. And we need to do more. More to help support jobs and growth in our communities. Because growth can't be imposed from the centre – it must be driven by businesses, communities and local authorities. They are critical to delivering the jobs and homes that our communities need. So I'd like to tell you about the next steps in our Plan for Growth. To support local growth, I can today announce my decision to reduce the interest rate offered to local authorities by the Public Works Loan Board to finance the £13bn of debt needed to leave the Housing Revenue Account subsidy system. I've listened to local authority concerns that this is a one-off transaction within the public sector and should be financed as such. Let me put it simply – an extra £100m every year that councils can then reinvest in housing. And I want to take a further step to support local growth. Across the country, projects are being held back by tough market conditions, difficult cash flow and a lack of confidence. Projects where people could be working but aren't. That is why I'm announcing today the creation of a new Growing Places Fund. Half a billion pounds that will kick start developments that are currently stalled. Half a billion pounds that will deliver key infrastructure and create jobs. Putting local areas in the driving seat, to boost the local economy and get people into work. Providing flexibility to local areas to recycle funding for other projects once development is completed. In South Gloucestershire, £300 million of private investment, 3,000 jobs and 2,200 homes is being unlocked with £6 million of public money to build a link road. Just think what we will be able to do with £500 million. Unlocking local growth by freeing businesses to grow, creating jobs, and freeing councils to build housing. Liberal Democrats in government, on your side. On banks: We're on your side when it comes to the banks too. Delivering on our promise to protect the taxpayer from the cost of future bailouts. Never again should bankers go to the casino with their stakes guaranteed by the rest of us. That's why we commissioned the Vickers report It's why we welcomed his recommendations on ring-fencing. It's why we welcomed his call to extend competition in the banking sector. And it's why we will legislate to protect future taxpayers in this Parliament. On tax: Of course, our main tool to help low and middle income families with the pressures they are facing is the tax system. Thanks to Liberal Democrats there is genuine progress. And I'm not just talking about fuel duty cuts for our remotest communities, though I expect we will have that in place next year. This year, the average worker is paying £200 less income tax than last year. Next year, the bill will come down by another £120. By the end of this parliament, most working people will be paying £700 less income tax a year. Conference, an income tax threshold of £10,000 was the first priority in our manifesto. Now it's the first tax priority of the government. We should be proud that in government our ideas are making a real difference to every working family in Britain. But we shouldn't rest on our laurels. In the next parliament, I want us to go further; our aspiration should be that someone working full time on the minimum wage should pay no income tax at all. An income tax threshold of £12,500 – think what that would do to work incentives, think what it would mean for basic fairness. Let's put that on the front page of our next manifesto. Some people have argued that we should change our tax priorities and focus our limited resources on cutting taxes for the wealthiest instead. At a time of austerity, this argument simply beggars belief. If we are all in this together, those with the broadest shoulders must bear the greatest burden. Fair taxation of the wealthiest is key to our deficit reduction plan. Of course, if a better way can be found to raise the money from this group, I will be willing to consider it. But right now we must focus relentlessly on those who are struggling. And we need to make sure tax owed is tax paid. Last year, I announced a package of investment to strengthen our fight against tax evasion, as well as tax avoidance. This year, an additional 2,250 HMRC staff will move into new anti-evasion and avoidance jobs. This month, over 1,000 of these jobs are being advertised. And already this package is bearing fruit. I promised you we'd collect an extra £7bn a year by the end of the parliament; And I can tell you we're already on track to raise £2bn this year. It took 12 years for the previous government to take action against the wealthiest 5,000 people some of who weren't paying their fair share of tax. We can do better than that. In less than a month's time, a new 'affluent team' will be place. This team will look specifically at the next 350,000 wealthiest taxpayers. These are the people who pay or should pay the 50p rate of tax. And my message to the small minority who don't pay what they owe is simple, I agree with the chancellor. "We will find you and your money" and you will pay your fair share. On conclusion: Economic credibility comes from doing the right thing – that's why Labour lost it. At the next election, we can make sure there will be only one party that people trust to both handle the economy and deliver fairness – the Liberal Democrats. We'll win that trust by sticking to our guns, especially when times are tough. We'll do that by levelling with people about the scale of the challenge we face, not offering false promises as Labour did. By delivering our aspiration to rebuild a more sustainable and balanced economy. By showing that we understand the fears and the pressures on the people of this country, and share their ambition for a better Britain. Most of all, we will do that by building a shared sense of national economic purpose so that we are working alongside every person in this country to restore our prosperity. Do you remember how Gordon Brown liked to conclude his speeches? Long lists – did you find them annoying? I know I used to. But not now, with so many Lib Dem achievements already in place, I can't resist: A clear plan to deal with the deficit, removing barriers to business growth, investing in infrastructure, promoting free trade and competition, sorting out the banks, Tackling tax avoidance, and cutting taxes for those who need it most.
https://www.politics.co.uk/comment-analysis/2011/09/19/danny-alexander-lib-dem-conference-speech-in-full/
Browse - Central Criminal Court THOMAS DUFFIELD, JAMES CLARK. Theft : theft from a specified place . 16th August 1875 Reference Number t18750816-468 Verdict Guilty > unknown Sentence Imprisonment > penal servitude ; Imprisonment 468.THOMAS DUFFIELD (35), andJAMES CLARK (25) , Breaking and entering the warehouse ofStuart Bidden, with intent to steal. MESSRS. POLAND and MEAD conducted the Prosecution; and MR. W. SLEIGH the Defence. Blackfriars Road—part of the house is Mr. Bidden's warehouse, it consists of two railway arches with gates—there is a lamp by the side of the gate—on 23rd June, about 1 o'clock, I was in bed and heard something opening, and the crash of wood; I looked out at the window and saw three men standing opposite, with their backs towards Mr. Bidden's gate, and their faces towards me—the middle one turned round and opened the gate with something; I could not see what, and then he drew it to, turned his back looked up and down the street, and then entered at the gate, and closed it after him—the prisoner Duffield then tried the gate with a push as a policeman would, and went towards Blackfriars Road, and the other man the other way and stood at the corner—I awoke Mallows, the drayman, next door, who tried the gate with the key, but he could not enter; I ran and got a policeman who returned with me—Mallows was still outside, and finding he could not enter from the front, he went to the back—I saw Mrs. Mallows standing at her door, and while I was talking to her, Duffield passed me, and I said to her "That is one of the men"—I believe Duffield heard that he looked at me and walked on in the direction in which the other had gone—Mallows and the policeman made their way in at the back and came and opened the gate, and I saw that it had been fastened with two gimblets, one at the top and the other at the bottom of the lock; I went into both the counting-houses and found the desks all open, and on the table were these eight wedges, three crowbars, and two chisels—I described the men, and on 3rd August, I was fetched to Stones End Station, where I selected the prisoners from ten or twelve men—Inspector Halse was there. Cross-examined.I am sure Clark was there—two or three weeks afterwards an officer named Stephens took me to the Borough, pointed out a man and said "That is the man I want you to see," and asked whether I knew him—I said "No, I cannot recognise him"—I said to the acting inspector "At the distance he was off he looked to me as though he had no hair about his face," I said 'nothing about his having a tuft' of hair on his chin; I described him as about my own height 5 feet 5 inches, he had no hair about his face'—there was no lantern there only a lamp at the corner of the yard—his back was turned towards me while he was prizing the door—I said that he looked to me to have a brown overcoat—I used the word "brown." GEORGE MALLOWS. I am a drayman to Mr. Bidden—I shut up the premises safely on this night, and was aroused about 1.30 by Wesson, but could not get the key to turn one way or the other—I went to the back of the premises, got over the wall, got in and found the door fastened with two gimblets. WILLIAM HALSE( Police Inspector). After the prisoners were in custody I got Wesson to go to the police-court, where I put eight or nine other persons with them in the cell passage, and Wesson picked them each out, and tapped them on the shoulder—I produce these wedges and other things. Cross-examined.I remember you handing a paper like that ( a telegram) to the Magistrate, and it was after reading that that Clark was admitted to Bail—I have not brought the scrap-book or police-sheet—the other inspector is" not here. Witnesses for the Defence. ELIZABETH CLARK. On 23rd June I was in London—at that time my husband was dangerously ill; I have got a piece of paper which I got that day. (The Court ruled that the telegram was not evidence, and could not be put in.) My son was admitted to bail by the Magistrate after the last hearing, and after he was let out I saw him start to go to Southampton—I am sure I did not see him in London either on the 22nd or 23rd June. Cross-examined.He came to London on Saturday because his father was so bad—I don't know what day of the week 23rd June was—he went away the day before Hampton Races—it was not the same week he came back, not till the week afterwards—my address is 88, Friar Street, a coffee-shop, and he lives with me—he does not attend to the coffee-shop; he deals in bladders—I do not know Duffield; I never saw him till I was at the police-court. Re-examined.My husband died soon after 23rd June—I have seen Earl Wills at these Sessions, but he could not stay any longer—I telegraphed to. him last night to Southampton. PATRICK HALL. I served a copy of a subpoena, of which this ( produced) isthe original on Earl Wills, at the Builders' Arms, Southampton—I saw him in london on the two first days of the Session—the name is blank in the original, but it is inscribed in the copy now. Cross-examined.I am a friend of the prisoners—I can't say whether they are much of companions, but they know each other. SAMUEL DAVET. I live at the Builders' Arms, Union Street, Southampton, kpt by Earl Wills—on 23rd June I went to a ball, after which I went to the Builders' Arms, and saw Clark in the parlour when I arrived—Mr. Wills was there at the same time, and he came up to London with me on Sunday morning to attend this trial, but he has gone back to Southampton—he was telegraphed for yesterday to come here to-day—there was a little bit of a shindyon this night with some Oxford gentlemen, and this knife was introduced and the blade broken; to the best of my belief Duffield is the person who broke it—Clark had a friend with him, who, to the best of my belief was Duffield—some supper was fetched and I had some crab with them—I cannot recollect whether the master, the mistress, or the servant fetched the super—the landlord did not have supper with us; I and the two men had supper together. Cross-examined.I am a musician, and played in a band at this ball, which is held every Wednesday night at the Victoria Rooms—I don't know whether Clark was there—I had not known him before; this was the first time I had seen him—I slept there—I saw him again next morning when I got up, but I had no conversation with him—I met him in London on Sunday night when I arrived from Southampton—I saw him at his mother's house—the gentleman who served the subpoena fetched me—I did not know Duffield before that night; I have no doubt about him whatever—I believe he is the man, to the best of my opinion—I said at first that I could not recognize him, but now I do—to the best of my opinion he is the man who broke the knife by playing with it, chopping it on the table—I did not know the prisoner by any name—when I came up to town I went to Mrs. Clark's, 88, Friar Street, and have been stopping there since we arrived—I am quite clear that the weekly ball is on Wednesday night—I first saw the prisoners on that night at 10.30. Re-examined.During the day of the ball I was round the Isle of Wight—I recollect two Oxford gentlemen playing games on the day of the ball and they were at the Stockbridge and Bilbury Races—I was served with a subpoena, and conduct money was paid me to pay my fare up to London—I have had opportunities of seeing Clark, but I have not seen Duffield till this morning, and while I have been giving my evidence I have been constantly looking at him—there was not a third man with us; no friends but the Oxford gentlemen were there. GEORGE WILLIAM WESSON( re-examined by MR. W. SLEIGH). This was at a little after 1 o'clock on the morning of June 23rd—it was Wednesday morning, past 12 o'clock of Tuesday night. Witness in reply. DUFFIELD was further charged with having been convicted at Newington, in October1873, to which he PLEADED GUILTY**— Seven Years' Penal Servitude. CLARK— Twleve Months' Imprisonment.
https://www.oldbaileyonline.org/browse.jsp?div=t18750816-468
Sensors | Free Full-Text | EPMOSt: An Energy-Efficient Passive Monitoring System for Wireless Sensor Networks Monitoring systems are important for debugging and analyzing Wireless Sensor Networks (WSN). In passive monitoring, a monitoring network needs to be deployed in addition to the network to be monitored, named the target network. The monitoring network captures and analyzes packets transmitted by the target network. An energy-efficient passive monitoring system is necessary when we need to monitor a WSN in a real scenario because the lifetime of the monitoring network is extended and, consequently, the target network benefits from the monitoring for a longer time. In this work, we have identified, analyzed and compared the main passive monitoring systems proposed for WSN. During our research, we did not identify any passive monitoring system for WSN that aims to reduce the energy consumption of the monitoring network. Therefore, we propose an Energy-efficient Passive MOnitoring SysTem for WSN named EPMOSt that provides monitoring information using a Simple Network Management Protocol (SNMP) agent. Thus, any management tool that supports the SNMP protocol can be integrated with this monitoring system. Experiments with real sensors were performed in several scenarios. The results obtained show the energy efficiency of the proposed monitoring system and the viability of using it to monitor WSN in real scenarios. EPMOSt: An Energy-Efficient Passive Monitoring System for Wireless Sensor Networks by Fernando P. Garcia 1,2,* , Rossana M. C. Andrade 2 , Carina T. Oliveira 2 and José Neuman De Souza 2 1 Federal Institute of Education, Science and Technology (IFCE), CEP 60040-215, Fortaleza, Ceará, Brazil 2 Group of Computer Networks, Software Engineering and Systems (GREat), Federal University of Ceará, CEP 60455-760, Fortaleza, Ceará, Brazil * Author to whom correspondence should be addressed. Sensors 2014 , 14 (6), 10804-10828; https://doi.org/10.3390/s140610804 Received: 4 April 2014 / Revised: 12 June 2014 / Accepted: 16 June 2014 / Published: 19 June 2014 Versions Notes Abstract : Monitoring systems are important for debugging and analyzing Wireless Sensor Networks (WSN). In passive monitoring, a monitoring network needs to be deployed in addition to the network to be monitored, named the target network. The monitoring network captures and analyzes packets transmitted by the target network. An energy-efficient passive monitoring system is necessary when we need to monitor a WSN in a real scenario because the lifetime of the monitoring network is extended and, consequently, the target network benefits from the monitoring for a longer time. In this work, we have identified, analyzed and compared the main passive monitoring systems proposed for WSN. During our research, we did not identify any passive monitoring system for WSN that aims to reduce the energy consumption of the monitoring network. Therefore, we propose an Energy-efficient Passive MOnitoring SysTem for WSN named EPMOSt that provides monitoring information using a Simple Network Management Protocol (SNMP) agent. Thus, any management tool that supports the SNMP protocol can be integrated with this monitoring system. Experiments with real sensors were performed in several scenarios. The results obtained show the energy efficiency of the proposed monitoring system and the viability of using it to monitor WSN in real scenarios. Keywords: passive monitoring ; energy-efficient ; wireless sensor networks 1. Introduction The miniaturization of electronic components and the evolution of wireless communication technologies have stimulated the development and use of Wireless Sensor Networks (WSNs) in various applications, such as environmental monitoring, seismic detection, structural health monitoring, and smart spaces, among others. In general, WSNs consist of small sensors which use wireless short range communication. Furthermore, these networks have severe energy consumption, processing power, memory, and bandwidth constraints [1]. Monitoring is important for debugging and analyzing the operation of WSNs. By using a monitoring system, several pieces of information about the operation of the network can be obtained, such as topology discovery, reboot of nodes, isolated nodes, routing loops, packet loss, and network latency, among others [2]. In a WSN, network monitoring can be divided into active monitoring and passive monitoring. In active monitoring, code lines are inserted in the application running in sensor nodes to obtain information about the operation of the network. In this case, the monitoring packets are sent along with data packets of the network, modifying the behavior and operation of the monitored network and consuming the resources of this network. For example, in the active monitoring system Simpathy [3] about 30% of the bandwidth is used by monitoring traffic. Furthermore, faults in the network may affect the monitoring system and prevent the delivery of monitoring information when it is most needed. In passive monitoring, a monitoring network needs to be deployed in addition to the network to be monitored, named the target network. The monitoring network captures and analyzes packets transmitted by the target network, not consuming any resources of the target network. Furthermore, a fault in the target network does not affect the operation of the monitoring system. However, the deployment of an additional network with the purpose of monitoring the target network increases the overall cost of the WSN. Therefore, passive monitoring systems are more suitable when the goal is to reduce the use of target network resources and/or isolate the faults of the target network from those of the monitoring network. In this paper, we focus on passive monitoring. The lifetime of a WSN can be up to several years and not all problems arise during the first weeks after the deployment of the network [4]. Therefore, an energy-efficient monitoring system is necessary when there is a need for monitoring a WSN in a real scenario over long periods because the lifetime of the monitoring network is extended and, consequently, the target network benefits from the monitoring for a longer time. Liu et al.[5] describe the use of a WSN for monitoring the oceans and emphasize the importance of monitoring this network using an energy-efficient passive monitoring system. All things considered, initially, we have identified, analyzed and compared the main passive monitoring systems proposed for WSN. During our research, we did not identify any passive monitoring system for WSN that aims to reduce the energy consumption of the monitoring network. Therefore, in this paper we propose an energy-efficient passive monitoring system for WSN named Energy-efficient Passive MOnitoring Sys tem (EPMOSt). The main goal of this system is to reduce the energy consumption and, consequently, extend the lifetime of the monitoring network. Furthermore, EPMOSt provides monitoring information using an SNMP agent. In this way, any management tool that supports the SNMP protocol can be integrated with this monitoring system. The remainder of the paper is organized as follows: in Section 2, the main passive monitoring systems proposed for WSN are analyzed and compared. Section 3 presents the monitoring system proposed in this paper and describes the details of its implementation. Section 4 describes the experiments and metrics used to evaluate the proposed monitoring system. Section 5 shows and discusses the results obtained from these experiments. Finally, Section 6 summarizes our contributions and identifies avenues for future work. 2. Passive Monitoring in WSNs In Sensor Network Inspection Framework (SNIF) [7], each sniffer has two radio interfaces, one of which is used to capture packets sent by the nodes of the target network and the other to send the captured packets to the sink node (e.g., a computer) through the monitoring network. The packets captured by sniffers are tagged with a timestamp and sent to the sink node, where duplicate packets are removed. Thus, the packets are analyzed and the information obtained from the monitoring is displayed in a tool developed by the authors. In Pimoto [8], the target network is subdivided into monitoring islands. A sniffer is deployed in each monitoring island. The sniffer is responsible for capturing in promiscuous mode the packets sent by the nodes of the target network that are within its island and sending theses packets to a gateway (computer) using a Bluetooth radio. A gateway can receive the packets captured by several sniffers. The gateway includes the timestamp and the sniffer address in each captured packet and then it sends the packets to a server. The server analyzes and displays the captured packets with the well-known traffic analysis tool Wireshark [9] using a plugin developed by the authors. In Pimoto, captured packets can be viewed in Wireshark, but the analysis of packets must be performed by the network administrator. Furthermore, the use of Pimoto may be impractical to monitor a WSN that has too many nodes distributed in a wide geographic area because it requires an infrastructure composed of multiple gateways interconnected to the server. In LiveNet [10], packets captured by sniffers can be stored in a flash memory or sent to a computer via a serial port for future analysis. On the computer, the captured packets are analyzed to obtain information about the behavior of the target network. Like SNTS, it is not feasible to use LiveNet to monitor WSN deployed in scenarios where it is impractical to collect the data stored in the flash memory of sniffers or to send the data collected by sniffers using a wired network, for example in military applications or environmental monitoring applications. In Passive Monitoring System in Wireless (PMSW) sensor networks [11], each sniffer captures data packets and acknowledgment packets (ACKs) sent by the nodes of the target network that are within its coverage area, and sends the captured packets to its gateway (computer). A sniffer connects to only one gateway via a radio channel with frequency different from the frequency of operation of the target network. When the gateway receives the packets captured by its sniffers, it creates a local trace. Each record of the local trace contains the information of a packet and a timestamp based on the gateway's clock. Hence, each gateway sends the local trace to a server through a TCP/IP network. The server receives the traces sent by all gateways, and generates a global trace with duplicated records removed. Then the global trace is analyzed in order to detect faults and to assess the performance of the target network. The information obtained from this analysis is displayed in a tool developed by the authors. In PMSW, only data and ACK packets are captured, while control packets, such as routing packets and packets of cluster election, are not captured or analyzed. Table 1shows the comparative analysis of the monitoring systems described in this section. We analyze the following characteristics: Energy-efficient—indicates whether the system is concerned with minimizing the energy consumption of nodes of the monitoring network; Analysis mode—indicates whether the analysis of captured packets is performed online or offline; Captured packets – types of packets (data and/or control) captured by the monitoring network; Event analysis—indicates whether the monitoring system analyzes the captured packets to obtain information about the operation of the target network; Redundant packets—verifies whether the monitoring system captures redundant packets. Redundant packets are captured when two or more sniffers capture packets sent by the same node of the target network; Aggregation—verifies whether the monitoring system uses any mechanism to aggregate information of packets captured from the target network in order to reduce the number of packets transmitted by the monitoring network and, consequently, reduce the energy consumption of this network; and Visualization tool—describes the computational tool used to display information obtained from passive monitoring. The characteristic analysis modeand event analysiswere defined in [11], while the remaining characteristics were identified from the study of passive monitoring systems discussed in this section. The capture of these characteristics is an additional contribution of this work. The main conclusions obtained by observingTable 1are: None of these systems is energy-efficient; in other words, the proposed solutions are not concerned with minimizing the energy consumption of nodes of the monitoring network. Energy efficiency is important when it is necessary to monitor sensor networks deployed in remote locations, where it is impractical to replace the batteries of sniffers; In SNIF, Pimoto and PMSW the analysis of captured packets is online. In SNTS and LiveNet captured packets are stored in non-volatile memory, which must be collected manually for future analysis (offline); SNTS, SNIF and PMSW analyze the captured data in order to detect fault events and/or assess the performance of the target network, while Pimoto and LiveNet only display the traces of captured packets; Only Pimoto does not capture redundant packets, because the target network is subdivided into monitoring islands and each island has only one sniffer. The capture of redundant packets increases the energy consumption of the monitoring network because sniffers transmit redundant packets through this network; None of these systems implements an aggregation mechanism of packets captured from a target network. Aggregation reduces the number of bytes transmitted by the monitoring network and hence reduces the energy consumption of this network; and Only Pimoto displays the monitoring information in a network management tool used by the community ( i.e., Wireshark), and none of these systems provides the monitoring information using an SNMP agent. The monitoring systems compared inTable 1have two properties: (1) they use an independent monitoring network consisting of several sniffers to capture in promiscuous mode the packets sent by the target nodes; (2) they do not perform any modification to the application executed by the target nodes. The operation of the monitoring systems which have both properties is independent of the target network. In this paper, we focus on these systems. Others passive monitoring systems for WSN are proposed in [4,5,12–15], but these systems do not have the two properties mentioned above. The monitoring system proposed by Hanninen et al.[4] does not have the property (1) because it uses only one sniffer, which should be deployed close to the target nodes to be monitored. Sommer and Kusy [12] propose Minerva, a testbed architecture for distributed debugging of WSN. Minerva does not have the property (1) because each target node is physically connected, via its pin debug, to a sniffer. In Jiangwu et al.[13], the target network faults are detected by analyzing only the data received by the sink node. Thus, this system also does not have the property (1) because it does not use any monitoring network. The monitoring systems proposed by Liu et al.[5] and Yang et al.[14] do not have the property (2) because the application that is executed by the target node is modified to include the node address ( id) in all packets which are routed through it. The system proposed by Romer and Ringwald [15] also does not have the property (2) because the application that is executed by the target node is modified to send data on the status of the node. 3. EPMOSt As mentioned in Section 1, an energy-efficient passive monitoring system is necessary when we need to monitor a WSN in a real scenario for a long time; otherwise, the lifetime of the monitoring network can be much shorter than the lifetime of the target network, due to misuse of the energy of sniffers nodes. Thus, we propose an energy-efficient passive monitoring system for WSN, named EPMOSt, which reduces the energy consumption of the monitoring network. Furthermore, the proposed system provides monitoring information using an SNMP (Simple Network Management Protocol) agent. The SNMP agent allows the integration of the proposed system with any management tool with SNMP support, such as Nagios [16], Net-SNMP [17], SNMP MIB Browser Android Tool [18] and Manage Engine MIB Browser Free Tool [19]. Figure 1shows the overview of the monitoring system EPMOSt, in which a monitoring network is deployed together with the target network. A monitoring network node (sniffer) captures, in a promiscuous mode, the packets sent by one or more nodes of the target network, inserts a timestamp for each captured packet, and aggregates the headers of several packets in a monitoring message. Then the sniffer sends this message, using the monitoring network, to the local monitor. The local monitor receives the monitoring messages from multiple sniffers and inserts the information of captured packets in a trace file (database) located on the server. The server analyzes the trace generated by one or more local monitors and obtains several pieces of information about the target network ( i.e., time at which each node awakens, packet loss, reboot of nodes, number of sent and received packets by each node, etc.). This information is available to the network administrator and it is also stored in a Management Information Base (MIB) to be accessed by an SNMP agent. Figure 2shows the Unified Modeling Language (UML) activity diagram of the EPMOSt. In this system, in general the packets of a given node of the target network are captured by only one sniffer in order to reduce the transmission of redundant packets and hence reduce the energy consumption of the monitoring network. The EPMOSt initially runs a mechanism ( Sniffer Election) to elect the nodes of the target network that will have their packets captured by each sniffer. This election mechanism is performed by the sniffers and by the local monitor, taking into account the Received Signal Strength Indicator (RSSI). This mechanism is explained in detail in Section 3.1.1. When capturing a packet of the target network, the sniffer inserts a timestamp in this packet. After capturing some packets, the sniffer may aggregate the headers of these packets in a monitoring message to send to the local monitor. The aggregation of headers aims to reduce the number of bytes sent through the monitoring network and, consequently, reduce the energy consumption of this network. In this case, only the information present in the headers of the packets sent by the target network is monitored. However, when there is a need to monitor the data (payload) sent by the target network, the system should not use this aggregation module. The aggregation mechanism is explained in detail in Section 3.1.2. The local monitor receives the monitoring messages sent by sniffers and inserts the information of captured packets in a trace file (database) located on the server. The local monitor communicates with the server through an IP network. In some scenarios, it is necessary to deploy local monitors in different parts of the network due to the limited radio range of sniffers. In a more restricted scenario, only one local monitor can be used. In this case, the same computer can act as local monitor and server. The main function of the server is to extract information about the target network from the trace generated by local monitors. For this purpose, initially, the server removes redundant packets that were inserted into the trace. Note that there may be redundant packets in the trace when two or more sniffers capture packets from the same sensor node of the target network. The algorithm to remove redundant packets is explained in detail in Section 3.3. After this, the trace is analyzed to obtain information about the target network. The information obtained is used to generate a report to display for the network administrator. In particular, it is stored in an MIB by an SNMP agent. Therefore, any management tool based on SNMP protocol can communicate with the SNMP agent and display the information obtained from the monitoring of the target network. The implementation details of the system are presented in the following subsections. 3.1. Sniffer In our implementation, the monitoring network uses, as sniffers, sensor nodes of the MicaZ platform, developed by Crossbow Technology. This platform was chosen because it is widely used in applications of WSN in general and it is used in related work in WSN [20,21] of the research group to which this work is linked. The monitoring application embedded in sniffers was developed using the programming language nesC (network embedded system C) [22] and it runs on the TinyOS [23] operating system. 3.1.1. Sniffer Election After the deployment of the monitoring network, sniffers and a local monitor start the Sniffer Electionin order to elect the nodes of the target network that will have their packets captured by each sniffer. This election mechanism is executed when a sniffer captures for the first time a packet of a given node of the target network and takes into account the RSSI. As shown in the UML sequence diagram ofFigure 3a, when a sniffer S Xcaptures for the first time a packet of the target node A, it sends a message of inclusion of a new node to the local monitor reporting the address of this node Aand the corresponding RSSI. If no other sniffer is capturing packets from node A, the local monitor sends a message to S Xto start capturing the packets sent by node A. Thus, sniffer S Xsends an ACK message to the local monitor and starts capturing packets sent by node A. However, if another sniffer S Yis capturing packets from target node A, the local monitor analyzes which of the two sniffers is receiving packets from node Awith the highest RSSI value, because, in general, the signal with the highest RSSI value has better quality. If S Yis receiving the signal from node Awith the RSSI value greater than or equal to S X, the local monitor sends a message to S Xstating that it should not capture packets sent by node A, as shown inFigure 3b. However, if S Yis receiving the signal from node Awith the RSSI value less than S X, the local monitor sends a message to S Xto start capturing packets from Aand it sends a message to S Yto stop capturing packets from A, as shown inFigure 3c. In all situations presented in sequence diagrams shown inFigure 3, after sending a message to a sniffer, the local monitor waits for an ACK message from this sniffer. If the ACK is not received after a time interval (timeout), the local monitor relays the message. If the local monitor does not receive any acknowledgment message after three transmission attempts, this sniffer is considered dead. In this case, the election mechanism is rebooted for the packets of the target nodes covered by this sniffer can be captured by another sniffer. It is important to mention that RSSI captures the signal strength observed on the receiver antenna during packet reception. Two main considerations must be taken into account when analyzing RSSI. First, the RSSI calculation is solely based on correctly received packets, which implies that RSSI will not record packets that failed because of interference [24]. Second, the RSSI is not the average of the signal strengths measured through the reception of the whole packet. In fact, the RSSI value represents the received signal strength captured only during the reception of the preamble and header of the Physical Layer Protocol [25]. Thus, in cases where the interference affects only the data portion of the frame, this effect of interference will not be captured in the RSSI measurement [26]. Despite these considerations, the RSSI is a metric frequently used for evaluating the quality of the received signal. To increase the RSSI precision, it has been suggested to use RSSI measurements together with statistical functions. For example, the RSSI value can be calculated from a fixed number of previous measurements or from the measurements in a time interval. Exponential Weighting Moving Average (EWMA) is also suitable to give more weight to recent measurements while not entirely discarding older ones. It is important to highlight that any type of statistical function can be seen as a stability mechanism able to significantly increase the representation of the specificities of wireless environments (e.g., reflections, absorptions, shadowing) [24]. Through the proposed election mechanism, in general only one sniffer captures packets sent by a given node of the target network, thereby reducing the transmission of packets captured by the monitoring network and thus reducing the energy consumption of this network. However, it is possible to capture redundant packets when the situation shown inFigure 3coccurs, due to the time interval between the messages 1.1 and 1.2. Redundant packets can also be captured due to the election mechanism to be run on the local monitor, because each local monitor assigns its monitoring nodes to target nodes, but different local monitors are not aware of each other's assignments. As shown in the results (Section 5), the proposed mechanism, although simple, considerably reduces the energy consumption of the monitoring network. 3.1.2. Packet Capture After running the sniffer election detailed in Section 3.1.1, sniffers start capturing packets, where each sniffer captures, in promiscuous mode, packets sent by the target nodes that it monitors, that is, nodes which were selected by this election mechanism. As mentioned in Section 3, the aggregation of headers is optional. When the aggregation of headers is not used, the sniffer generates, for each captured packet, a monitoring message containing its address (sniffer address), a timestamp and the bytes of the captured packet. This monitoring message is sent to the local monitor through the monitoring network using multihop routing. The format of the packet sent by the sniffer is shown inFigure 4. The header is inserted by the link layer protocol of the MicaZ platform and has fixed length of 05 bytes. The payload carries the monitoring message. The maximum payload size on the MicaZ platform is 29 bytes. Therefore, if the number of bytes of the monitoring message is larger than this value, the sniffer has to send more than one packet to the local monitor. When the aggregation of headers is used, only the information present in the headers of captured packets is sent by the sniffer to the local monitor. In this case, the headers of several packets may be sent in the same monitoring message, hence reducing the overhead of transmission and consequently reducing the energy consumption of the sniffers. The format of the packet sent by the sniffer is shown inFigure 5. The monitoring message carries the timestamp and the header of Ncaptured packets. The maximum size of Ndepends on the size of header of the packets sent by the target nodes, because the monitoring message cannot be higher than the maximum payload size in the MicaZ platform (29 bytes). 3.2. Local Monitor As described in Section 3.1.1, the local monitor runs the election mechanism together with sniffers. Moreover, the local monitor receives the monitoring messages sent by sniffers containing the packets captured from the target network and inserts the captured packets in a trace file (database) located on the server. For this purpose, the application running on the local monitor establishes a remote connection to a DBMS (DataBase Management System) installed on the server through an IP network. “MySQL Server 5.5” [27] is used in this work because it is a widely used DBMS. Besides, it is free software with GPL (General Public License). As the captured packets are stored in a database, it is easy to get information about the target network using SQL (Structured Query Language) clauses. For example, the SQL clause “ SELECT * FROM wsn WHERE source_addr= 10” shows the packets sent by the target node whose address ( source_addr) is 10. The application running on the local monitor was implemented using the Java programming language because it is a multiplatform technology and enables the same code to run on different operating systems (Linux, Windows, etc.). 3.3. Server-Trace Analysis The trace analysisapplication runs on the server (seeFigure 1) and has the main function to extract information about the target network from the trace generated by local monitors. For this purpose, initially, the redundant packets that exist in the trace (database) are removed. In the MicaZ platform, redundant packets can be detected by analyzing the Destination Sequence Number (DSN) present in the header of the packets sent by sensor nodes. The DSN has a size of 8 bits and it is incremented by the source node for each packet sent. When the DSN reaches the value of 255, the DSN of the next packet sent by the sensor node will have a value of 0 [28]. Therefore, if two or more packets have the same source address, the same DSN, and the difference between their timestamps is less than Δt, it means that they are the same packet. In this work, we assume Δt is equal to 10 s, because in our implementation a given sensor node does not send more than 255 packets in this time interval. Figure 6shows a portion of the trace with the packets sent by the target node whose address ( source_addr) is 1. As shown inFigure 6, there are two packets with DSN equal to 119 and they have the same timestamp ( exp_datetime). In this case, one of these packets is removed from the trace. After removing the redundant packets, the trace is analyzed to extract information about nodes and paths of the target network.Figure 7illustrates an example of the trace analysisapplication. Note that it exemplifies information about the nodes of a given target network used to validate this application.Table 2(Section 3.4.1) shows the description of each variable displayed inFigure 7. In this case, as shown inFigure 7, only the node with addresses ( nodeId) of 0receives data packets, because it is the sink node. Nodes with addresses from 1to 21send data packets with information collected from sensors to the sink node. The address ( nodeId) 65535corresponds to the broadcast address of the network, where all packets of the routing protocol used by the target network are sent. The scenario used to obtain this information is described in Section 4.1. The screen of the trace analysisapplication shown inFigure 8exemplifies information about some paths of the target network.Table 4(Section 3.4.1) shows the description of each variable displayed inFigure 8. Note that each sensor node is the source of two paths, with one for the broadcast address (address 65535) and the other for the sink node (address 0). The trace analysisapplication was implemented using the Java programming language. 3.4. Server-SNMP Agent As mentioned in Section 3, the information obtained from the analysis of the trace is stored in an MIB by an SNMP agent. The SNMP agent has been developed using the framework “ WebNMS SNMP Agent Toolkit Java Edition” [29]. This framework enables rapid development of Java-based SNMP agents. Section 3.4.1 describes the proposed MIB for EPMOSt and Section 3.4.2 shows the tests performed to validate the operation of the SNMP agent developed in this work. 3.4.1. MIB of the EPMOSt An SNMP agent reads and writes management information in an MIB. The MIB is a data structure that stores managed objects whose values collectively reflect the current state of the managed devices. The values of these objects can be read and/or written by a management tool by sending SNMP messages to the agent. MIB objects are named hierarchically, so that any node in the tree can be identified by a sequence of names (or numbers) that specify the path from the root to the node. The most widely used MIB is defined by RFC 1213 [30]. As shown inFigure 9, under the Internetnode in this MIB are the subtrees management, privateand experimental. Under the managementnode are the definitions of the MIB modules standardized by IETF (Internet Engineering Task Force). Under the privatenode are the definitions of objects of companies registered in the IETF. Under the experimentalnode are named objects that are being developed and tested. Therefore, the MIB of the EPMOSt has been defined under the experimentalnode. The MIB of the EPMOSt has four tables: nodesTablethat stores information about the nodes of the target network; pathTablethat stores information about the paths of the target network; monitorNetworkTablestores statistical information about the monitoring network; and snifferTablefor storing information about the sniffers. Also this MIB has two scalar objects: nodeCount, which is the number of nodes of the target network; and snifferCount, which is the number of sniffers. Objects defined in each of the MIB tables are shown inTables 23,4and5. Objects with an * beside their names have been identified from the study of passive monitoring systems for WSN, as discussed in Section 2 [6–8,10,11]. The identification of these objects is an additional contribution of this work. The remaining objects were captured in works that describe MIBs for WSN [11,31–33]. 3.4.2. Agent Validation The SNMP agent developed in this work allows the integration of the monitoring system EPMOSt with any management tool with support for the SNMP protocol. In order to test and validate the agent, the management tools “ SNMP MIB Browser Android Tool” [18] and “ Manage Engine MIB Browser Free Tool” [19] were used. The main functionality of these tools is to provide communication with the agents, by sending SNMP messages to query and/or modify objects in an MIB. The “ SNMP MIB Browser Android Tool” [18] was installed in a smartphone with Android operating system and queries were performed on all objects of the MIB of the EPMOSt to validate the operation of the agent developed in this work. All queries were performed successfully.Figure 10exemplifies the operation of this tool.Figure 10ashows the structure of the MIB of the EPMOSt. By clicking nodesTableon the screen shown inFigure 10a, the user views the nodes of the target network (Figure 10b). By clicking on a given node in the screen shown inFigure 10b, the user views the information related to this node (Figure 10c). The “ Manage Engine MIB Browser Free Tool” [19] was also used to test and validate the SNMP agent. This software was installed on a computer with the Windows 7 operating system and queries were performed on all objects of the MIB of the EPMOSt. Again, all queries were performed successfully. Therefore, the tests performed with these two tools show that the agent developed in this work enables integration of EPMOSt with any management tool with support for the SNMP protocol. 4. Experiments This section describes the experiments and the metrics used to evaluate the monitoring system EPMOSt. 4.1. Description The experiments were performed by using MicaZ nodes with the TinyOS [23] operating system. The MicaZ platform has the following main features: microprocessor ATMEGA128L, 4KB of RAM memory, 128KB of ROM memory and a single radio frequency transceiver CC2420. The CC2420 radio uses the IEEE 802.15.4 standard and operates in an unlicensed frequency band of 2.4 GHz with a transmission rate of 250 Kbps [28]. Figure 11illustrates the scenario used for the experiments. The target network is composed of 21sensor nodes and 01sink node. The sensor nodes run an application that, every minute, measures the ambient temperature and sends the information to the sink node. The payload of the packets sent by the sensor nodes carries the measured temperature and a counter incremented at each temperature measurement. The monitoring network is composed of Nsniffers and 01base station. Sniffers capture the packets sent by the nodes of the target network and send these packets to the base station by using multihop routing. The base station sends the packets received from sniffers, through a USB cable, to a computer. In this scenario, the computer performs the functions of the local monitor (generation of the trace) and of the server, as shown inFigure 1. Experiments were performed with 3, 5, 7, 9 and 11 sniffers distributed in the monitored area, as shown inFigure 12. For each scenario shown inFigure 12, three types of experiments were performed: “ election without aggregation”, “ election with aggregation” and “ without election”. In the experiment “ election without aggregation” sniffers run the application described in Section 3.1, in which the election mechanism proposed in Section 3.1.1 is implemented, but do not use the aggregation of headers proposed in Section 3.1.2. In the experiment “ elections with aggregation”, sniffers run the election mechanism and the aggregation of headers. In the experiment “ without election” sniffers do not run any election mechanism and they capture all packets sent by the nodes of the target network that are within the coverage area of their radios. Thus, sniffers send all the bytes of captured packets to the local monitor, which then inserts these packets in the database. In this case, several sniffers can capture a single packet sent by a given node of the target network. It is noteworthy that this is the strategy used by all the monitoring systems described in Section 2 (SNTS, SNIF, Pimoto, LiveNet and PMSW). 4.2. Metrics For the evaluation of the experiments the following metrics are defined: percentage of distinct packets captured by the monitoring network (% Pcaptured), energy consumed by the monitoring network for transmission of captured packets ( Et) and average energy consumed by each sniffer for transmission of captured packets ( EtSniffer). In the EPMOSt, as well as all monitoring systems analyzed in Section 2, sniffers “listen” to all packets traveling in their radio interfaces. Therefore, the energy consumed in the reception of packets in the proposed system is similar to the energy consumed by the systems described in related works, and so it was not used as a metric for evaluation. However, if the duty cycle of the target network is known, each sniffer can be programmed to activate its radio interface just before the duty cycle start and to deactivate its radio interface just after the end of the duty cycle of the target network. This strategy contributes to further reduce the energy consumption of the monitoring network. The total number of packets sent by the sensor nodes of the target network ( PsentTarget) is obtained byEquation (1), where CountInitial iand CountFinal iare, respectively, the number of the first and last temperature measurements performed by node i, and krepresents the number of sensor nodes of the target network. In the scenario used in these experiments, the value of kis 21: PsentTarget = ∑ i = 1 k ( CountInitial i − CountFinal i + 1 ) (1) The number of distinct packets sent by node icaptured by the monitoring network ( Pcaptured i) is determined by checking which packets from node iare in the interval [ CountInitial i, CountFinal i]. Therefore, the total number of distinct captured packets ( Pcaptured i) is obtained byEquation (2): Pcaptured = ∑ i = 1 k Pcaptured i (2) The percentage of distinct packets captured by the monitoring network (% Pcaptured) is determined byEquation (3): % Pcaptured = 100 ∗ Pcaptured / PsentTarget (3) As explained in Section 3.3, the number of redundant packets from node I( Predundant i) is determined by analyzing the DSN and the timestamp of the packets sent by the node. Therefore, the total number of redundant packets captured by the monitoring network ( Predundant) is obtained byEquation (4): Predundant = ∑ i = 1 k Predundant i (4) In order to calculate the energy consumed by the monitoring network for the transmission of packets, the energy model for MicaZ sensors defined in [34] and used in [20] was used. In this model, the energy consumed in the transmission ( Et) is determined byEquation (5), in which Psentis the number of packets sent, Plengthis the packet size in bytes, TBis the time spent for transmitting one byte, Itis the value of current in the transmission mode and Vis the electric voltage of the battery: E t = Psent × Plength × T B × I t × V (5) The values used for TB, Itand Vwere 32 mS, 17.4 mA and 3 volts, respectively. These values were obtained in the specification document of the MicaZ platform (datasheet), and are also equal to the values presented in [20,34]. By replacing these values inEquation (5),Equation (6)is obtained: E t = 1,6704 × 10 − 6 × Psent × Plength (6) In the experiments “ without election” and “ election without aggregation”, the number of packets sent by the sniffers is determined byEquation (7). In these two types of experiments, each packet sent by the sniffers has size ( Plength) of 23 bytes, with 05 bytes of header and 18 bytes of the monitoring message (seeFigure 4). Therefore, the energy consumed by the monitoring network for transmitting the captured packets from the target network is determined byEquation (8): Psent = Pcaptured + Predundant (7) E t = 38,42 × 10 − 6 × ( Pcaptured + Predundant ) (8) When the aggregation of headers is used, as explained in Section 3.1.2, the headers of several packets of the target network are sent in the same monitoring message in order to reduce the energy consumption of the sniffers. In our experiments, the monitoring message carries the address of the sniffer (1 byte) and, the timestamp (2 bytes) and the header (11 bytes) of two packets of the target network. Therefore, in the experiment “ election with aggregation” each packet sent by the sniffers has size ( Plength) of 32 bytes, with 05 bytes of header and 27 bytes of the monitoring message (seeFigure 5). In this experiment, the number of packets sent by the sniffers is determined byEquation (9). By replacing Psent, determined byEquation (9), and Plengthequal to 32 inEquation (6), we obtainEquation (10), which corresponds to the energy consumed by the monitoring network for transmission of captured packets when the aggregation of headers is used: Psent = ( Pcaptured + Predundant ) / 2 (9) E t = 53,45 × 10 − 6 × ( Pcaptured + Predundant ) / 2 (10) The average energy consumed by each sniffer for transmission of captured packets ( EtSniffer) is determined byEquation (11), where Nis the number of sniffers and Etmay be calculated throughEquation (8)or(10)according to the type of experiment: EtSniffer = E t / N (11) To exemplify how the variables used inEquations (1)–(11)affect the energy consumption,Table 6shows the values of each variable for a single round with duration of 15 minutes for each type of experiment for a monitoring network with 11 sniffers (Figure 12e). It can be observed inTable 6that the number of redundant packets captured by the monitoring network is zero when the election mechanism proposed in this paper is used. This occurs because in general only one sniffer captures packets sent by a given node of the target network, as explained in Section 3.1.1. 5. Results and Discussion For each of the scenarios shown inFigure 12(Section 4.1), three types of experiments were performed: “ election without aggregation”, “ election with aggregation” and “ without election”. For each scenario and for each type of experiment, 10 rounds with duration of 15 min were performed. All experiments were conducted in the same environment under the same conditions. The results shown inFigures 13,14and15refer to the average values of 10 rounds with a confidence interval of 95%. The margins of error of the experiments can be perceived only inFigure 15because, inFigures 13and14, their values are very small and cannot be viewed. We first investigate the energy consumed by the monitoring network for transmitting the captured packets as a function of the number of sniffers. As shown inFigure 13, when the election mechanism is not used, the energy consumed by the monitoring network increases when the number of sniffers increases. This occurs because the packets sent by a given node of the target network are captured by a larger number of sniffers, thereby increasing the number of redundant captured packets and consequently increasing the energy consumed by the monitoring network for the transmission of these packets. In the two types of experiments in which the election mechanism is used, the energy consumption of the monitoring network remains almost constant, because, when the number of sniffers increases, each sniffer captures packets from a smaller number of nodes of the target network, but the total number of packets sent by the monitoring network changes very little. Figure 13shows that, with 11 sniffers, the energy consumed by the monitoring network is 38.4 mJ when the election mechanism and the aggregation of headers are not used. When the election mechanism without aggregation of headers is used, the energy consumption is 11.8 mJ, which corresponds to a decrease of 69.3%. This decrease in energy consumption occurs because the use of the election mechanism significantly reduces the number of redundant packets transmitted by the sniffers. When the election mechanism and the aggregation of headers are used, the energy consumption is only 8.27 mJ, which corresponds to a decrease of 78.5%. These results prove the energy efficiency of the EPMOSt. Next, we study the average energy consumed by each sniffer for transmitting the captured packets as a function of the number of sniffers.Figure 14shows that, for all types of experiments, a decrease in the energy consumed by each sniffer when the number of sniffers is increased, occurs. This is because sniffers constitute an independent mesh network. Thus, when the number of sniffers increases, sniffers are closer to each other and the power of their radio interfaces is reduced, thereby reducing the coverage area of each sniffer and, consequently, each sniffer captures packets from a smaller number of target nodes. It can also be seen that the use of the election mechanism considerably reduces the energy consumption of the sniffers and consequently prolongs the lifetime of the monitoring network. Finally, we study the percentage of distinct packets captured by the monitoring network as a function of the number of sniffers.Figure 15shows that, for all types of experiments, when the number of sniffers increases, the percentage of captured packets also increases. This occurs because the sniffers are closer to the nodes of the target network and they receive the radio signals with higher strength (RSSI). When the election mechanism is not used, the percentage of captured packets is slightly higher than in the two types of experiments that use the election mechanism. This occurs because the same packet may be captured by more than one sniffer, thereby increasing the probability of it being captured. However, this difference between the captured packets decreases with increasing number of sniffers and it is only 0.62% at 11 sniffers. It is important to emphasize that the sniffers used in these experiments have only one radio interface and, consequently, they cannot receive and send packets at the same time. This contributes to the monitoring network to capture less than 100% of packets sent by the target network. Therefore, the results should be better if the sniffers had two radio interfaces. The results presented in this section demonstrate that EPMOSt considerably reduces the energy consumption of the monitoring network, when it is compared with the monitoring systems described in Section 2 (which do not use the election mechanism of sniffers). Besides, EPMOSt keeps the percentage of captured packets close to the values obtained without the use of the election mechanism. These results prove the viability of using EPMOSt when there is a need of monitoring a WSN in a real scenario over long periods. 6. Conclusions In this work, initially, we have analyzed and compared five passive monitoring systems proposed for WSN: SNTS, SNIF, Pimoto, LiveNet and PMSW. However, none of these systems aims to reduce the energy consumption of the monitoring network. Within this context, in this work we propose an energy-efficient passive monitoring system for WSN named EPMOSt that reduces the energy consumption of the monitoring network and provides monitoring information using an SNMP agent. All modules of the EPMOSt have been described and validated. Experiments were performed using the MicaZ platform and their results show that the election mechanism used in our system reduces, by up to 69.3% (11 sniffers), the energy consumed by the sniffers for transmitting captured packets. When the election mechanism and the aggregation of headers are used, the energy consumption decreases by 78.5% (11 sniffers). However, although the proposed election mechanism to achieve a rate of captured packets is slightly smaller, this rate increases with the number of sniffers and is reduced by only 0.62% when the monitoring network has 11 sniffers. Therefore, the results of the experiments demonstrate the viability of using the EPMOSt to monitor WSN in real scenarios, because the reduction of energy consumption of the monitoring network contributes to prolong the lifetime of this network. It was also shown that the SNMP agent developed in this work enables the integration of EPMOSt with any management tool which supports the SNMP protocol, facilitating the management of the target network. The contributions presented in this work bring up interesting perspectives for future research. We highlight three main directions. Firstly, we intend to change the election mechanism to take into account RSSI, LQI (Link Quality Indicator), level of battery of the sniffers, and the number of target nodes monitored by each sniffer, aiming to balance the energy consumption of the sniffers and prevent some sniffers from having their energy depleted long before others. 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Figure 1. Overview of the EPMOSt. Figure 1. Overview of the EPMOSt. Figure 2. UML activity diagram of the EPMOSt. Figure 2. UML activity diagram of the EPMOSt. Figure 3. Sniffer election: ( a ) When no sniffer is capturing packets sent by the target node. ( b ) When S Y is capturing packets sent by the target node and RSSI(S Y ) ≥ RSSI(S X ). ( c ) When S Y is capturing packets sent by the target node and RSSI(S Y ) < RSSI(S X ). Figure 3. Sniffer election: ( a ) When no sniffer is capturing packets sent by the target node. ( b ) When S Y is capturing packets sent by the target node and RSSI(S Y ) ≥ RSSI(S X ). ( c ) When S Y is capturing packets sent by the target node and RSSI(S Y ) < RSSI(S X ). Figure 4. Format of the packet sent by sniffers without using aggregation of headers. Figure 4. Format of the packet sent by sniffers without using aggregation of headers. Figure 5. Format of the packet sent by sniffers using aggregation of headers. Figure 5. Format of the packet sent by sniffers using aggregation of headers. Figure 6. Example of trace with redundant packets. Figure 6. Example of trace with redundant packets. Figure 7. Example of information about the nodes of the target network. Figure 7. Example of information about the nodes of the target network. Figure 8. Example of information about the paths of the target network. Figure 9. MIB of the EPMOSt. Figure 9. MIB of the EPMOSt. Figure 10. Operation of the “ SNMP MIB Browser Android Tool ”: ( a ) Viewing the MIB of the EPMOSt. ( b ) Viewing the target nodes. ( c ) Viewing information about the node 0 . Figure 10. Operation of the “ SNMP MIB Browser Android Tool ”: ( a ) Viewing the MIB of the EPMOSt. ( b ) Viewing the target nodes. ( c ) Viewing information about the node 0 . Figure 11. Scenario used in the experiments. Figure 11. Scenario used in the experiments. Figure 12. Distribution of sniffers: ( a ) 3 sniffers. ( b ) 5 sniffers. ( c ) 7 sniffers. ( d ) 9 sniffers. ( e ) 11 sniffers. Figure 12. Distribution of sniffers: ( a ) 3 sniffers. ( b ) 5 sniffers. ( c ) 7 sniffers. ( d ) 9 sniffers. ( e ) 11 sniffers. Figure 13. Energy consumed by the monitoring network vs. number of sniffers. Figure 13. Energy consumed by the monitoring network vs. number of sniffers. Figure 14. Energy consumed by each sniffer vs. number of sniffers. Figure 14. Energy consumed by each sniffer vs. number of sniffers. Figure 15. Packets captured by the monitoring network vs . number of sniffers. Figure 15. Packets captured by the monitoring network vs . number of sniffers. Table 1. Characteristics of monitoring systems. Table 1. Characteristics of monitoring systems. Characteristic SNTS [ 6 ] SNIF [ 7 ] Pimoto [ 8 ] LiveNet [ 10 ] PMSW [ 11 ] Energy-efficient No No No No No Analysis mode Offline Online Online Offline Online Captured packets Data + Control Data + Control Data + Control Data Data + ACK Event analysis Faults analysis Faults analysis None None Faults analysis and performance assessment Redundant packets Yes Yes No Yes Yes Aggregation No No No No No Visualization tool Developed by the authors Developed by the authors Wireshark plugin Developed by the authors Developed by the authors Table 2. Objects represented in the nodesTable . Table 2. Objects represented in the nodesTable . Object Name Object Description nodeId Address of the target node timeAwake Time (seconds) at which the node is active lastSeq DSN of the last packet sent by the node lastTimestamp Timestamp of the last packet sent by the node sendPacketNode Number of packets sent by the node recvPacketNode Number of packets received by the node sendDataPacket * Number of data packets sent by the node recvDataPacket * Number of data packets received by the node sendBytesNode Number of bytes sent by the node recvBytesNode Number of bytes received by the node Table 3. Objects represented in the snifferTable . Table 3. Objects represented in the snifferTable . Object Name Object Description snifferId Address of the Sniffer lastTimestampSniffer Timestamp of the last packet captured by the sniffer capturedPacket Number of packets captured by the sniffer capturedBytes Number of bytes captured by the sniffer Table 4. Objects represented in the path Table . Table 4. Objects represented in the path Table . Object Name Object Description pathId Path in format source → destination srcNode Address of the source node of the path dstNode Address of the destination node of the path sendPacketPath Number of packets sent through the path sendBytesPath Number of bytes sent through the path timeBeginning Timestamp of the first packet sent through the path timeEnding Timestamp of the last packet sent through the path Table 5. Objects represented in the monitorNetworkTable . Table 5. Objects represented in the monitorNetworkTable . Object Name Object Description targetNode Address of the target node packetSentTarget Number of packets sent by the target node packetCaptured Number of packets captured from the target node distinctPacketCaptured * Number of distinct packets captured from the target node redundantPacketCaptured * Number of redundant packets captured from the target node packetNotCaptured * Number of packets not captured from the target node Table 6. Values of variables for a single round with 11 sniffers. Table 6. Values of variables for a single round with 11 sniffers. Type of Experiment Variable without Election Election without Aggregation Election with Aggregation PsentTarget 325 324 324 Pcaptured 316 312 316 %Pcaptured 97.23% 96.30% 97.53% Predundant 679 0 0 Et (mJ) 38.23 11.99 8.45 EtSniffer (mJ) 3.48 1.09 0.77
https://www.mdpi.com/1424-8220/14/6/10804/xml#fig_body_display_f11-sensors-14-10804
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BCM-HGSC | Eric Boerwinkle, Ph.D. | page 18 Associate Director, Baylor College of Medicine Human Genome Sequencing Center Contact information [email protected] Other positions Dean, UTHealth School of Public Health M. David Low Chair in Public Health Kozmetsky Family Chair in Human Genetics Professor, Human Genetics Center and Dept. of Epidemiology Research interests The research interests of Dr. Boerwinkle encompass the Eric Boerwinkle, Ph.D. Associate Director, Baylor College of Medicine Human Genome Sequencing Center Contact information [email protected] (link sends e-mail) Other positions Dean, UTHealth School of Public Health M. David Low Chair in Public Health Kozmetsky Family Chair in Human Genetics Professor, Human Genetics Center and Dept. of Epidemiology Research interests The research interests of Dr. Boerwinkle encompass the genetic analysis of the common chronic diseases in humans, including coronary artery disease, hypertension, and non-insulin dependent (type II) diabetes. Dr. Boerwinkle received his B.S. in Biology from the University of Cincinnati in 1980, an M.A. in Statistics (1984), and M.S. and Ph.D. in Human Genetics (1985) from the University of Michigan, Ann Arbor where he served as Senior Research Associate in the Department of Human Genetics from 1985-1986. He joined the University of Texas-Houston Center for Demographic/ Population Genetics in 1986 as a Research Assistant and became Assistant Professor in the same year. In 1991 he joined the Department of Human Genetics at the School of Public Health, University of Texas-Houston Health Science Center as Associate Professor, in 1996 was promoted to Professor, and in 1997, Director of the Human Genetics Center. He became a faculty member of the Institute of Molecular Medicine in 1996 and became Professor and Director of the Research Center for Human Genetics. Dr. Boerwinkle is a member of the American Diabetes Association and the American Society of Human Genetics. The research interests of Dr. Boerwinkle encompass the genetic analysis of common chronic diseases in humans, including coronary artery disease, hypertension, and non-insulin dependent (type II) diabetes. This work includes localizing genes which contribute to disease risk, identification of potentially functional mutations within these genes, testing these candidate functional mutations in experimental systems, defining the impact of gene variation on the epidemiology of disease, and determining the extent to which these genes interact with environmental factors to contribute to disease risk. Activities include both statistical analysis and laboratory work. A large part of Dr. Boerwinkle's current research effort consist of localizing genes contributing to disease risk using modern genome-wide mapping methods. Success depends on keeping up with the latest genomic technical advances. The laboratory is set-up and operating as a high through-put sequencing and genotyping facility in which speed, accuracy and efficiency are monitored continuously. However, we are constantly seeking out more efficient methods to collect and manage genetic information. Dr. Boerwinkle and colleagues have completed the world's first genome-wide analyses for a variety of CAD risk factors, including diabetes and hypertension. These investigations have lead to the identification of novel susceptibility genes in both cases. Dr. Boerwinkle is particularly interested in methods for identifying potentially functional mutations within a gene region. This seemingly simple objective is made difficult because the functional mutations are expected to have small effects and are imbedded in a sea of silent genetic variation. Once nearly all of the variation is catalogued directly by DNA sequencing, individuals are genotyped for each variable site. Both novel and traditional statistical methods are applied to relate the array of genetic information to a wealth of phenotypic data. This algorithm generates "candidate functional mutations" that are then tested in an in vitro or mouse model system. Once a functional mutation has been identified, Dr. Boerwinkle's group evaluates the ability of the variable site to predict the onset of disease (e.g. myocardial infarction or stroke) above and beyond traditional risk factors. This work is carried out as part of multiple prospective studies of cardiovascular disease and its risk factors in tens of thousands of individuals representing the major American ethnic groups. Finally, he is working on experimental designs for studying genotype by environment interaction in humans. In particular, we are working on the extent to which interindividual variation in lipid lowering and anti-hypertensive medications are influenced by genetic factors. The practical objective of the research is to use genetic information to identify individuals at increase risk of disease and to design more efficacious interventions. Genetic studies are defining, at the molecular level, novel mechanisms of disease risk, onset and progression. Dr. Boerwinkle and collaborators address the localization of genes which contribute to disease risk in cardiovascular diseases, hypertension and diabetes. The methodology used involves screening of families having the disease and linking the presence of disease with known markers of the human genome. In this manner, the genomic region in which relevant mutations are located can be mapped and the relevant DNA sequenced. By assessing the structural change the mutation may have caused in the gene product (protein), it is possible to infer how it may affect biological function. In order to determine experimentally whether a mutation is functional, it is necessary to introduce the mutated gene into an animal, usually a mouse, and assess its biological effects on the animal's phenotype. Dr. Boerwinkle has participated in multiple notable discoveries since joining the Institute. Only two will be highlighted here. First, Dr. Boerwinkle's group has completed the first ever genome-wide search for genes contributing to inter-individual blood pressure levels. This initial effort has lead to the identification of an important gene (an adrenergic receptor) which influences blood pressure levels and the risk to hypertension. This is the first time that such a genome-wide approach has led to the identification of a susceptibility gene to a major cardiovascular disease risk factor. Second, Dr. Boerwinkle has participated in similar efforts to identify genes contributing to the risk of developing non-insulin dependent (type II) diabetes. In this case, however, there were no genes in the region that were suspects for the disease. A team of collaborating investigators have painstakingly characterized the genetic region and identified the mutated gene (in this case a protease). This is the first time that anyone has ever positionally cloned a gene contributing to any common chronic disease. This work is of obvious potential clinical importance. It may lead to improved prediction of those at increased risk of disease and the design of more efficacious intervention strategies. The technologies and information from the human genome project provide new tools for lessening the burden of ill-health. Dr. Boerwinkle's accomplishments in developing an internationally recognized team of investigators targeting the genetics of cardiovascular disease and its risk factors ensures a productive future and further discoveries. Publications 2011 Schaaf CP , Sabo A , Sakai Y , Crosby J , Muzny DM , Hawes A , et al. . Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders. Hum Mol Genet. 2011;20(17):3366-75. PubMed DOI Google Scholar Tagged Rodin AS , Gogoshin G , Boerwinkle E . Systems biology data analysis methodology in pharmacogenomics. Pharmacogenomics. 2011;12(9):1349-60. PubMed DOI Google Scholar Tagged Luu HN , Kingah PL , North K , Boerwinkle E , Volcik KA . Interaction of folate intake and the paraoxonase Q192R polymorphism with risk of incident coronary heart disease and ischemic stroke: the atherosclerosis risk in communities study. Ann Epidemiol. 2011;21(11):815-23. PubMed DOI Google Scholar Tagged Herring SM , Gokul N , Monita M , Bell R , Boerwinkle E , Wenderfer SE , et al. . Immunoglobulin locus associates with serum IgG levels and albuminuria. J Am Soc Nephrol. 2011;22(5):881-9. PubMed DOI Google Scholar Tagged Bell R , Herring SM , Gokul N , Monita M , Grove ML , Boerwinkle E , et al. . High-resolution identity by descent mapping uncovers the genetic basis for blood pressure differences between spontaneously hypertensive rat lines. Circ Cardiovasc Genet. 2011;4(3):223-31. PubMed DOI Google Scholar Tagged Fornage M , Debette S , Bis JC , Schmidt H , M Ikram A , Dufouil C , et al. . Genome-wide association studies of cerebral white matter lesion burden: the CHARGE consortium. Ann Neurol. 2011;69(6):928-39. PubMed DOI Google Scholar Tagged Luo L , Boerwinkle E , Xiong M . Association studies for next-generation sequencing. Genome Res. 2011;21(7):1099-108. PubMed DOI Google Scholar Tagged Kozlitina J , Boerwinkle E , Cohen JC , Hobbs HH . Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance. Hepatology. 2011;53(2):467-74. PubMed DOI Google Scholar Tagged Vineyard MA , Daniels MS , Urbauer DL , Deavers MT , Sun CC , Boerwinkle E , et al. . Is low-grade serous ovarian cancer part of the tumor spectrum of hereditary breast and ovarian cancer? . Gynecol Oncol. 2011;120(2):229-32. PubMed DOI Google Scholar Tagged Bressler J , Shimmin LC , Boerwinkle E , Hixson JE . Global DNA methylation and risk of subclinical atherosclerosis in young adults: the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. Atherosclerosis. 2011;219(2):958-62. PubMed DOI Google Scholar Tagged Liu X , Jian X , Boerwinkle E . dbNSFP: a lightweight database of human nonsynonymous SNPs and their functional predictions. Hum Mutat. 2011;32(8):894-9. PubMed DOI Google Scholar Tagged Barbalic M , Reiner AP , Wu C , Hixson JE , Franceschini N , Eaton CB , et al. . Genome-wide association analysis of incident coronary heart disease (CHD) in African Americans: a short report. PLoS Genet. 2011;7(8):e1002199. PubMed DOI Google Scholar Tagged 2010 Nettleton JA , Matijevic N , Follis JL , Folsom AR , Boerwinkle E . Associations between dietary patterns and flow cytometry-measured biomarkers of inflammation and cellular activation in the Atherosclerosis Risk in Communities (ARIC) Carotid Artery MRI Study. Atherosclerosis. 2010;212(1):260-7. PubMed DOI Google Scholar Tagged Coventry A , Bull-Otterson LM , Liu X , Clark AG , Maxwell TJ , Crosby J , et al. . Deep resequencing reveals excess rare recent variants consistent with explosive population growth. Nat Commun. 2010;1:131. PubMed DOI Google Scholar Tagged Bressler J , Kao WHLinda , Pankow JS , Boerwinkle E . Risk of type 2 diabetes and obesity is differentially associated with variation in FTO in whites and African-Americans in the ARIC study. PLoS One. 2010;5(5):e10521. PubMed DOI Google Scholar Tagged Barbalic M , Dupuis J , Dehghan A , Bis JC , Hoogeveen RC , Schnabel RB , et al. . Large-scale genomic studies reveal central role of ABO in sP-selectin and sICAM-1 levels. Hum Mol Genet. 2010;19(9):1863-72. PubMed DOI Google Scholar Tagged Volcik KA , Campbell S , Chambless LE , Coresh J , Folsom AR , Mosley TH , et al. . MMP2 genetic variation is associated with measures of fibrous cap thickness: The Atherosclerosis Risk in Communities Carotid MRI Study. Atherosclerosis. 2010;210(1):188-93. PubMed DOI Google Scholar Tagged Xing C , Cohen JC , Boerwinkle E . A weighted false discovery rate control procedure reveals alleles at FOXA2 that influence fasting glucose levels. Am J Hum Genet. 2010;86(3):440-6. PubMed DOI Google Scholar Tagged Morrison AC , Felix JF , L Cupples A , Glazer NL , Loehr LR , Dehghan A , et al. . Genomic variation associated with mortality among adults of European and African ancestry with heart failure: the cohorts for heart and aging research in genomic epidemiology consortium. Circ Cardiovasc Genet. 2010;3(3):248-55. PubMed DOI Google Scholar Tagged Bressler J , Folsom AR , Couper DJ , Volcik KA , Boerwinkle E . Genetic variants identified in a European genome-wide association study that were found to predict incident coronary heart disease in the atherosclerosis risk in communities study. Am J Epidemiol. 2010;171(1):14-23. PubMed DOI Google Scholar Tagged « first ‹ previous … 14 15 16 17 18 19 20 21 22 next › last »
https://www.hgsc.bcm.edu/people/boerwinkle-e?f%5Bauthor%5D=8720&page=17
The Sponge Sommelier - SCP Foundation The SCP Foundation's 'top-secret' archives, declassified for your enjoyment. The Sponge Sommelier Just a sommelier looking to serve you! The Sponge Sommelier Just a sommelier looking to serve you! S̶i̶d̶e̶ ̶e̶f̶f̶e̶c̶t̶s̶ ̶i̶n̶c̶l̶u̶d̶e̶d̶ ̶(̶a̶n̶d̶ ̶n̶o̶t̶ ̶l̶i̶m̶i̶t̶e̶d̶ ̶t̶o̶)̶ ̶d̶i̶z̶z̶i̶n̶e̶s̶s̶,̶ ̶l̶o̶s̶s̶ ̶o̶f̶ ̶s̶i̶g̶h̶t̶,̶ ̶c̶o̶m̶p̶l̶e̶t̶e̶ ̶b̶o̶d̶i̶l̶y̶ ̶d̶e̶s̶e̶c̶r̶a̶t̶i̶o̶n̶,̶ ̶v̶i̶n̶i̶f̶i̶c̶a̶t̶i̶o̶n̶,̶ ̶a̶n̶d̶ ̶e̶v̶e̶n̶t̶u̶a̶l̶ ̶b̶o̶t̶t̶l̶i̶n̶g̶ I moved and trimmed your thread summary, since it was taking up extra space in the main forum screen. Try to keep thread descriptions (the text in the little box under the thread title) and titles short so you don't crowd out other authors in the forum listing. ~Zyn Hey all,I'm shooting my shot at an SCP I've deemed the Sponge Sommelier.I got a first greenlight for this idea two years ago, a year later having written it came back searching for a second, and unfortunately had a tough time finding an available reviewer. I'd love to come back instead of sitting on the skip, and thus, here we are :) Seeking Greenlight:Yes Page Type: Horror / Drama Elevator Pitch : The sponge sommelier is a passionate man, one who worked as his own sommelier at his own vineyards. This passion extends to that of a vinter, the required materials of which he acquires during the process of "disvinification". The sponge sommelier, composed of spongin material himself, serves his guests his "wines" - he loves input - and proceeds to desiccate them of fluid. Then - when completed - the sommelier organizes the various bodily fluids, bottles, and promptly stores them for future tasting, comparison, and (naturally) guests. For context: When a subject is chosen, the sommelier's cognitohazardous abilities immediately run their course, engrossing the subject in conversation. Slowly, the subject becomes increasingly unaware of their situation. Alterations in personality, emotions, and mannerisms are commonplace, all whilst the sommelier takes the least critical fluids first to keep them alive as long as possible. The sommelier's control over hygroscopic properties is relatively short-ranged, however, when disturbed, it's effective distance increases substantially. As the subject degrades, they continue, unaware - until of course, they're dead (at which he will stop, due to fearing "tainted-by-death" fluids). Central Narrative : Contained with the addendum, incident logs, and test log, the narrative follows both the Sponge Sommelier's (failed) initial containment, arrival/incident after it's second (not failed) containment, and (most importantly) the effect of it's process of disvinification upon a human subject. Secondarily, there's the smaller, darker plot surrounding a D-Class's reason for being taken by the Foundation, with the whole shebang being the sommelier specifically "allowing" his containment to follow the D-Class's (literal) blood-line for his Sang Rougecollection. Additional Notes: If possible, I'm looking for feedback surrounding the description of the SCP itself and possibly tweaks to the story, if flow presents itself as an issue. Also Note: The first greenlight I got was a whiiiile ago now, so I am hoping it still stands. I am currently seeking a second, to pass into the review stage. The finished draft is available on the sandbox upon request. Re: The Sponge Sommelier Hey, I remember greenlighting this way back when! Still gets a greenlightfrom me. Butterfly squad, get in here and swarm on this. Re: The Sponge Sommelier Hey-o! I just saw your thread on DMFS19, and I read the linked sandbox- definitely a greenlightfrom me! Congrats on your journey. Re: The Sponge Sommelier I am absolutely flattered, I didn't expect it to be read! I just opened reddit and noticed your reply - thank you! I'll be sure to post this to the critique forum :)
https://scp-wiki.wikidot.com/forum/t-14118897/the-sponge-sommelier
Educating health professionals about evidence-based practice: still as important today as it was 20 years ago | Article | NursingCenter Educating health professionals about evidence-based practice: still as important today as it was 20 years ago Source: JBI Evidence Implementation March 2016, Volume :14 Number 1 , page 1 - 2 [Free] Munn, Zachary PhD, GradDip HlthSc, BMedRad Article Content In 1996, David Sackett and colleagues authored the seminal article regarding evidence-based medicine in the BMJ, stating that evidence-based medicine is the 'conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.'1This definition is still largely used today to describe an approach to healthcare that ensures evidence from research is used in combination with clinician expertise and patient preferences. The year 1996 was a big one for evidence-based practice, as in addition to the publication of Sackett's widely used definition, a small research organization focused on getting evidence into the hands of health professionals was formed in Adelaide, Australia. This small organization, titled the Joanna Briggs Institute, would soon grow into a large international collaboration of health professionals, academics and researchers, all aspiring to a world where evidence-based healthcare is the norm.2 When it was first proposed, evidence-based healthcare was seen by some as a radical and completely different approach to healthcare, thus requiring significant education of the health workforce. From its inception, the Joanna Briggs Institute has focused on providing education regarding the importance of evidence-based healthcare and the conduct of systematic reviews globally. From the tireless work of organizations 'spreading the good word' about the importance of evidence, since the 1990s, evidence-based healthcare has largely gained acceptance internationally.3Despite this, even 20 years later, there is still a need for widespread education regarding the principles of evidence-based healthcare for health professionals.4 One way to ensure health professionals are aware of the importance of evidence-based healthcare is to embed this learning in their undergraduate curriculum. In this issue of the International Journal of Evidence-based Healthcare, Young et al. describe the attitudes towards evidence-based healthcare of undergraduate medical programme educators, and their confidence in teaching this field. However, it is not just our future workforce who require educating, and Williams et al. report on their project to design, develop and evaluate printed education materials for evidence-based practice dissemination for those currently practising. However, education regarding evidence-based healthcare is only the beginning. Once the importance of evidence-based healthcare has been acknowledged by health professionals, the evidence regarding a particularly clinical question requires extracting and synthesizing in an unbiased way.5A systematic review is the best method to achieve this, and a highlight of this issue is the study by Atlantis et al.regarding dietary intake and supplementation of specific polyunsaturated fatty acids in chronic obstructive pulmonary disease. Once colleagues understand the importance of evidence, implementation and practice change can be initiated. The implementation of evidence into practice can be difficult; however, Pather et al.'s article in this issue provides a solid example of a process that can be undertaken to create change and improve compliance with best practice, even in time-poor and complex settings such as the intensive care unit. Practice change does not necessarily occur easily or quickly, and even when change can be achieved, it is not always sustained. Santos et al.provide an important report on their journey of sustaining falls reduction in their academic medical centre. Although the field of evidence-based healthcare has evolved significantly over the past 20 years, many of the core principles remain the same today. These include the need to ensure health professionals receive education regarding the importance of evidence-based practice, the importance of conducting systematic reviews to answer key clinical questions, and ensuring that strategies are designed to implement and sustain practice change with the aim to improve patient outcomes. This issue of the International Journal of Evidence-based Healthcareprovides key exemplars of these important processes in the evidence-based healthcare cycle. References 1. Sackett D, Rosenberg W, Gray J, Haynes R, Richardson W. Evidence based medicine: what it is and what it isn't. Br Med J1996; 312:71-72.[Context Link] 2. Jordan Z, Munn Z, Aromataris E, Lockwood C. Now that we're here, where are we? The JBI approach to evidence-based healthcare 20 years on. Int J Evidence-based Healthcare2015; 13:117-120.[Context Link] 3. Pearson A, Wiechula R, Court A, Lockwood C. A re-consideration of what constitutes 'evidence' in the healthcare professions. Nursing Sci Quarter2007; 20:85-88.[Context Link] 5. Munn Z, Tufanaru C, Aromataris E. Data extraction and synthesis: the steps following study selection in a systematic review. Am J Nurs2014; 114 7:49-54.[Context Link]
https://www.nursingcenter.com/journalarticle?Article_ID=3385101&Issue_ID=3385100&Journal_ID=1658605
China, US Tug-of-War Tightens as Both Try to Cement Friendships around Asia US and Chinese officials take part in back-to-back diplomacy in Vietnam, Cambodia, Singapore and South Korea. China, US Tug-of-War Tightens as Both Try to Cement Friendships around Asia Chinese Foreign Minister Wang Yi, left, greets with Cambodian counterpart Prak Sokhonn in Phnom Penh, Cambodia, Sept. 12, 2021. SAN FRANCISCO — Chinese Foreign Minister Wang Yi’s Asia tour this month following visits to the same region by two U.S. officials will intensify a superpower tug-of-war. Analysts say smaller countries can get a bounty of assistance from both China and the United States as long as they avoid offending Beijing. Countries in Asia stand to get military equipment and training from Washington along with economic aid from Beijing, which is already building core infrastructure in much of Eurasia. Both nations are passing out COVID-19 vaccinations. Smaller, sometimes impoverished nations stand to be rewarded by both sides unless they get too cozy with Washington, scholars believe. “This soft power competition between the U.S. and China has some benefits to the smaller countries where they can be an object of courting in the soft power competition, but at the same time the room for maneuver for them is also increasingly narrowed,” said Alexander Vuving, professor at the Daniel K. Inouye Asia-Pacific Center for Security Studies in Hawaii, a U.S. Department of Defense institute. Wang on Friday reached Vietnam, his first of four stops, to discuss trade, economic ties and political trust. Vietnam said it is taking “its relations with China as a top priority in its foreign policy.” This may cause tension with the U.S. which, since 2017, has pushed for a stronger partnership with Hanoi. The Chinese foreign minister’s visit coincided with a deal Vietnam signed with Japan to allow for exports of Japanese defense equipment and technology. Vietnam’s acquisition of these goods appears to be in response to China’s growing aggressiveness and influence in the region. The United States looks to Asia for allies in checking the expansion of China, though analysts say it is not known for punishing smaller countries that hew toward Beijing. Vaccine diplomacy Wang pledged 3 million COVID-19 vaccine doses after the U.S. government offered 1 million new doses in August. The U.S. also agreed to set up a U.S. Centers for Disease Control and Prevention regional office in Hanoi. Vietnam’s case shows “a competitive flavor” between superpowers, said Yun Sun, co-director of the East Asia program at the Stimson Center in Washington. Over the weekend Wang took another 3 million doses to Cambodia, which also accepted a $270 million grant from China, the VOA Khmer service reported. Cambodia already leans strongly toward China over the United States, Vuving said, and Wang hopes to lock in that preference. The Balancing act In Singapore on Monday, Wang said on his ministry’s website that China hopes to “deepen practical cooperation.” Both China and the United States see Singapore as a neutral, sometimes analytical force in Asia, with China particularly happy when the city-state calls for calm, Sun said. Vietnam and Singapore have achieved a “balancing act” between superpowers, Vuving said. Earlier this month, China deepened bonds with the Philippines through an aid pledge after the Southeast Asian state agreed to restore a Visiting Forces Agreement with the U.S. government, an analyst told VOA. Consequences of US ties South Korea, which Wang visited Tuesday and Wednesday, shows what China can do when a country veers too close to the United States, said Stephen Nagy, senior associate professor of politics and international studies at International Christian University in Tokyo. After Seoul agreed with Washington to install a missile detection system that might see into China as well as its archrival North Korea, in March 2017, Beijing banned package tours to South Korea and caused a double-digit percentage decline in Chinese visits. China also has “engaged in economic coercion” against Australia and Taiwan when once friendly ties became strained, Nagy added. This month South Korea became one of the world’s few countries with the capability to fire ballistic missiles from “extremely quiet” submarines. This is part of a “strategic arsenal” that will cause concern in China given Seoul’s longstanding alliance with Washington, said Steven Kim, a visiting research fellow with the Jeju Peace Institute in South Korea. Wang will probably talk to Korean counterparts about health and economic cooperation “with stern implicit comment” that it should value its economic ties with China, Nagy forecast. “I think that the overall diplomacy is one that would be characterized by trying to produce constructive engagement, but of course, telling states that Wang Yi will be visiting that they need to proceed carefully in terms of the kind of relationships they’re building with the United States,” he said. Back-to-back diplomacy Wang’s visit follows trips by U.S. Defense Secretary Lloyd Austin in July to Singapore, Vietnam and the Philippines as well as U.S. Vice President Kamala Harris’s trip to Vietnam and Singapore last month. U.S. and Chinese officials have done back-to-back diplomacy in the past, including the Chinese defense minister’s whirlwind Asia tour a year ago this month following anti-China statements by then-U.S. Secretary of State Michael Pompeo. The recent flurry of visits shows a growing Sino-U.S. “rivalry,” Sun said. For smaller countries “to maximize the benefits and minimize the risks, that’s going to be hard because with great power competition in mind, neither Beijing nor Washington is leaving stones unturned to push for their own agenda,” she said.
https://www.voacambodia.com/a/6229461.html
(PDF) Winding Fault Diagnosis of 3 Phase Induction Motor 2014 PDF | On Aug 18, 2014, Agusmian P Ompusunggu and others published Winding Fault Diagnosis of 3 Phase Induction Motor 2014 | Find, read and cite all the research you need on ResearchGate Winding Fault Diagnosis of 3 Phase Induction Motor 2014 <here is a image 853f997dae073812-0d44798e7f79f736> Agusmian Partogi Ompusunggu Cranfield University <here is a image bb6b67f850417923-68b657c46f07eec4> Zongchang Liu University of Cincinnati <here is a image 3a567fb2a30973eb-f3490f0af0f4ebf9> Hossein Davari University of Cincinnati <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Chao Jin CyberInsight Tech. Co. Ltd. Figures <here is a image 56fb6003e75ce7fe-a2e1d72cda741798> Statistics of failure modes in induction motors, adapted from [1] … Figures - uploaded by Jay Lee <here is a image e991fff7f331e484-213b4789a1a0e76b> Detection of stator short circuit faults in three-phase induction motors using motor current zero crossing instants Article Full-text available Apr 2011 ELECTR POW SYST RES <here is a image 9c004cd6b130ce14-5bdbea306fe809f3> Abhisek Ukil Shuo Chen Andrea Andenna Pattern Recognition and Machine Learning Book Jan 2006 C M Bishop SpringerLink (Service ligne Online Detection of Induction Motor's Stator Winding Short-Circuit Faults Article Dec 2014 IEEE SYST J <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Mahdi Eftekhari <here is a image b2a25ec63030ae57-6640a01aa7176953> Mehrdad Moallem Saeed Sadri <here is a image 5e4df9f0f1676782-4e156301609bfa66> Min-Fu Hsieh The main objective of this paper is to develop a new technique for detecting turn-to-turn short-circuit faults in one or two stator phases of an induction motor. Hence, modeling a turn-to-turn short-circuit fault in more than one phase and a phase-to-ground fault is the first novelty of this paper for calculating phase currents under faulty conditions. This strategy uses the extracted features from the corresponding three-phase current pattern in 3-D space. Identification of faulty phases and of the severity of the fault is the outcome of this technique. This technique is also capable of detecting a phase-to-ground fault. This method just requires current sensors that are available in most drive systems to provide good controllability, and details of the machine design are not necessary. Experimental results are included to show the ability of the proposed strategy for detecting and locating phase/phases under different faults and load conditions. Performance Similarity Based Method for Enhanced Prediction of Manufacturing Process Performance Conference Paper Jan 2004 <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Jianbo Liu Dragan Djurdjanovic <here is a image af77de74d57e5c74-641d476321082b46> Jun Ni <here is a image 7c3a49189d84c43e-1cbd9f5252710a19> Jay Lee Full realization of all potentials in predictive and proactive maintenance highly depends on the accuracy of long-term predictions of the remaining useful life of manufacturing equipment. Parametric linear prediction techniques, such as Autoregressive Moving Average modeling (ARMA), are routinely used to trend and predict future behavior of any time series, but are frequently not appropriate for long-term prediction because of the highly complicated and non-stationary nature of manufacturing processes. In this paper, we propose a novel method that is capable of achieving high long-term prediction accuracy by comparing signatures from two degradation processes using measures of similarity that form a Match Matrix. Through this concept, we can effectively include large amounts of historical information into the prediction of the current degradation process. Similarities with historical records are used to generate possible future distributions of features, which is then used to predict probabilities of failure over time by evaluating overlaps between predicted feature distributions and feature distributions related to unacceptable equipment behavior. Experimental results show that the proposed method results in a significant improvement of long-term prediction accuracy compared with ARMA modeling-based prediction. Spiral Vector Theory of AC Circuit and Machine. Jan 1989 Sakae YAMAMURA Principles & Applications of Insulation Testing with DC Jan 2004 Engr Mohammed Hanif This paper describes the common insulating materials, their application and desirable properties. In addition basic initiators of insulation degradation, causes and effects of insulation failure as well as type of insulation tests and principles and applications of insulation testing are discussed. Finally paper focuses on testing insulation quality with DC and various types of DC insulation tests performed worldwide are reviewed. Similarity based method for manufacturing process performance prediction and diagnosis Aug 2007 COMPUT IND <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Jianbo Liu Dragan Djurdjanovic <here is a image af77de74d57e5c74-641d476321082b46> Jun Ni <here is a image 7c3a49189d84c43e-1cbd9f5252710a19> Jay Lee Full realization of all the potentials of predictive maintenance highly depends on the accuracy of long-term predictions of the remaining useful life of manufacturing equipments. In this paper, we propose a new method that is capable of achieving high long-term prediction accuracy by comparing signatures from any two degradation processes using measures of similarity that form a match matrix (MM). Through this concept, we can effectively include large amounts of historical information into the prediction of the current degradation process. Similarities with historical records are used to generate possible future distributions of features indicative of process performance, which are then used to predict the probabilities of failure over time by evaluating overlaps between predicted feature distributions and feature distributions related to unacceptable equipment behavior. The analysis of experimental results shows that the proposed method can yield a noticeable improvement of long-term prediction accuracy in terms of mean prediction errors over the Elman Recurrent Neural Network (ERNN) based prediction, which was shown in the past literature to predict well behavior of highly non-linear and non-stationary time series. Detection of stator winding fault in induction motor using fuzzy logic Mar 2008 APPL SOFT COMPUT Pedro Vicente Jover Rodríguez <here is a image 949e6e50938ac0dd-d10f007d4d523cbf> Antero Arkkio The online monitoring of induction motors is becoming increasingly important. The main difficulty in this task is the lack of an accurate analytical model to describe a faulty motor. A fuzzy logic approach may help to diagnose induction motor faults. This work presents a reliable method for the detection of stator winding faults (which make up 38% of induction motor failures) based on monitoring the line/terminal current amplitudes. In this method, fuzzy logic is used to make decisions about the stator motor condition. The fuzzy system is based on knowledge expressed in rules and membership functions, which describe the behaviour of the stator winding. The finite element method (FEM) is utilised to generate virtual data that support the construction of the membership functions and give the possibility to online test the proposed system. The layout has been implemented in MATLAB/SIMULINK, with both data from a FEM motor simulation program and real measurements. The proposed method is simple and has the ability to work with variable speed drives. The fuzzy system is able to identify the motor stator condition with high accuracy. This work is an example of the fusion between soft and hard computing. Pattern Recognition and Machine Learning Jan 2006 J ELECTRON IMAGING Christopher Bishop Stator fault diagnosis in induction motors. <here is a image d4f9d35bc35c38a4-1ec06be2d412cc23> Muslum Arkan Thesis (Ph. D.)--University of Sussex, 2000. Linked Research Winding fault diagnosis of a 3-phase induction motor powered by frequency-inverter drive using the current and voltage signals Conference Paper Agusmian Partogi Ompusunggu · Zongchang Liu · Hossein Davari · Chao Jin · Flanders
https://www.researchgate.net/publication/264811747_Winding_Fault_Diagnosis_of_3_Phase_Induction_Motor_2014
Structural equation modeling results for the hypothesized model | Download Scientific Diagram Download scientific diagram | Structural equation modeling results for the hypothesized model from publication: Perceived change uncertainty and behavioral change support: the role of positive change orientation | Drawing from uncertainty reduction theory and uncertainty management theory, the aim of the research is to investigate the influence of positive change orientation (i.e. change self-efficacy, positive attitudes toward change, perceived control) on the perceived change... | Behavior Change, Uncertainty and Self-efficacy | ResearchGate, the professional network for scientists. Structural equation modeling results for the hypothesized model Perceived change uncertainty and behavioral change support: the role of positive change orientation Context in source publication Context 1 ... specific paths coefficients were tested to examine whether the relationships of the proposed model are confirmed by the empirical evidence. As shown in Figure 2 , regarding Hypothesis 5, change self-efficacy partially mediates the relationship between perceived change uncertainty and cooperation (b 5 0.27, p < 0.10). Further, positive attitudes toward change partially mediate the relationship between perceived change uncertainty and compliance (b 5 1.08, p < 0.001); cooperation (b 5 0.80, p < 0.001) as well as championing (b 5 0.75, p < 0.01), consistent with Hypothesis 6. Hypothesis 7 was not confirmed. ... Citations ... On the other hand, uncertainty management theory suggests that uncertainty reduction is related to positive Exploring behavioral change support employee attitudes (Lind and Van den Bos, 2002) as well as, to improved reactions and changerelated behaviors (Rafferty and Griffin, 2006). Thus, uncertainty reduction during organizational change is imperative as it may influence positively employees' attitudes and their reactions to change (Katsaros and Tsirikas, 2022; Vakola, 2016). ... Exploring behavioral change support: the role of perceived uncertainty and self- and other- interest in change Purpose – Both uncertainty reduction theory and uncertainty management theory suggest that uncertainty reduction during organizational change is imperative as it may influence positively employees’ attitudes and behaviors. By drawing on the theory of planned behavior that links individual’s beliefs and behavior, the study seeks to examine how employees’ self- and other-interest in change may reduce perceptions of change uncertainty and consequently, foster their behavioral change support (i.e. compliance, cooperation and championing). Design/methodology/approach –The study hypothesizes that employees’ self- and other-interest in change mediate the relationship between perceptions of change uncertainty and behavioral change support. The research was conducted in two large IT companies co-located in a big science park in an EU country in South- eastern Europe. Data were collected from 105 employees and their supervisors in three sequential phases. Findings – The research findings suggest that both self- and other-interest in change partially mediate the negative relationship between perceptions of change uncertainty and behavioral change support. Practical implications – The findings indicate that change management practitioners will benefit considerably if they try to decrease employees’ perceived change uncertainty by increasing their self- and other-interest in change to provoke supportive behaviors. Relevant suggestions are made. Originality/value – The findings provide new insights into how perceptions of change uncertainty and self- and other-interest in change can affect employees’ change participation. Further, the research findings add to the uncertainty reduction theory and uncertainty management theory as well as, other related notions. Keywords Behavioral change support, Other-interest, Perceptions of change uncertainty, Self-interest Paper type Research paper ... The current state of the contemporary world has caused unpredictable events to flow uninterruptedly, resulting in increasing uncertainty (Schulman, 2021). In this regard, organisations' internal and external factors have also been subject to many doubts (Katsaros & Tsirikas, 2022) Developing sustainable competitive advantages from the lens of resource-based view: evidence from IT sector of an emerging economy The present study examines the IT industry's sustainable competitive advantages (CAs) from a resource-based view (RBV). Therefore, a list of CAs in three areas of the triple bottom line (TBL), including economic, social, and environmental, are extracted by thoroughly studying the relevant literature. These attributes are then evaluated by small and medium enterprises (SMEs) managers in the IT sector by implementing a Multi-level hybrid Decision-Making approach. This step employs a modified Delphi technique combined with linguistic z-numbers. Further, by reviewing the literature, the list of intangible resources is counted, and the importance of these resources is measured via the linguistic z-number BWM (Best Worst Method). Finally, the degree of the controllability of critical CAs is prioritised by z-number TOPSIS (Technique for Order of Preference by Similarity to Ideal Solution) and then classified found on the resources. Consequently, different classes are discussed, and appropriate strategies for dealing with each are presented. ARTICLE HISTORY
https://www.researchgate.net/figure/Structural-equation-modeling-results-for-the-hypothesized-model_fig1_358462293
Rollston Epigraphy - Ancient Inscriptions from the Levantine World Rollston Epigraphy. Ancient Inscriptions from the Levantine World Review of _Corpus Inscriptionum Iudaeae/Palaestinae_ <here is a image 7aac9b5ddfa2cb41-709b5359809e90b5> A Review of Corpus Inscriptionum Iudaeae/Palaestinae: Volume 1, Jerusalem, Part 1: 1-704, edited by Hannah M. Cotton, Leah Di Segni, Werner Eck, Benjamin Isaac, Alla Kushnir-Stein, Haggai Misgav, Jonathan Price, Israel Roll and Ada Yardeni. Berlin: De Gruyter, 2010. ISBN: 978-3-11-022219-7. Pp. xxvi + 694. $195. This is the first volume of the new Corpus Inscriptionum Iudaeae/Palaestinaeto appear in print. Scholars working in fields such as Epigraphic Hebrew and Aramaic, Hebrew Bible, Second Temple Judaism, the History of Judaism, Hellenistic Greek, Classical Latin, Greek New Testament and Early Christianity will find this volume to be a vade mecum. Moreover, those working in fields such as Hellenistic and Roman history, Jewish burial practices, Jewish personal names (in Hebrew, Aramaic, Greek, Latin) and the history of Jerusalem will find this volume to be a particularly fertile source of primary data as well. In addition, those interested in subjects such as linguistic and cultural diversity in antiquity will find this volume to be replete with a superabundance of primary data. Ultimately, I would suggest that no scholar working within such fields can afford to be without this volume, and no library with a collection that touches on these fields can afford to be without this volume. It is a veritable sine qua non. To be sure, this volume is rather expensive, but it is certainly worth the purchase price. Within this review, I shall begin with a summary of the scope of this new Corpus, then discuss the contents of this first volume in broad strokes, and conclude with a synopsis of some of the epigraphic material contained in it. Scope of the entire Corpus. For some time now, scholars have sensed that there needed to be a new corpus of inscriptions from this period and region. After initial discussions in 1997, it was decided that the new corpus would be “restricted to the Graeco-Roman period (beginning with Alexander and ending with the Arab Conquest of Palestine.” However, rather than restricting itself to Greek and Latin (as works focusing on this period have often done), the new Corpus“was to be a comprehensive multilingual corpus of all inscriptions, both published and (so far as possible) unpublished, encompassing the ‘sovereign languages,’ Greek and Latin, alongside the Semitic languages, namely Hebrew, Phoenician and the various Aramaic dialects: Jewish Aramaic, Samaritan, Nabataean, Northern Syriac and Southern Syriac (known also as Christian Palestinian Aramaic).” Furthermore, it was also agreed that it would be important also to include “the proto-Arabic languages, Thamudic and Safaitic, and finally Armenian and Georgian” as well. It was also decided that “Early Arabic inscriptions are outside the time limits of our Corpus and hence not included.” However, it was noted that these are “being collected and edited by Moshe Sharon in the Corpus Inscriptionum Arabicarum Palaestinae” (pages v-vi). Obviously, therefore, both breadth and depth are envisioned for this new Corpus. Because this new Corpushas cast its net so widely, it was determined that “the entire Corpuswill consist of nine volumes, organized according to major geographical and/or historical divisions in ancient Judaea/Palestina: Jerusalem and its surroundings; the middle coastline north of Tel Aviv and south of Haifa with Caesarea as the focal point; the southern coastline with its urban hinterland; Galilee and the northern coastline including Acco; the Golan Heights; Samaria; Judaea (without Jerusalem) and Idumaea; the Negev.” It should be emphasized, however, that “the order in which the regions are presented here does not reflect the order in which the volumes will appear in print.” Finally, it is also stated that “a final volume will include milestones from the entire territory, including those that no longer bear an inscription, as well as items with unknown or uncertain provenance, in museums and private collections.” Parts of modern Syria and Jordan which were at different times part of the administrative unit which included Iudaea/Palestine (i.e., Batanea, Aurantis, and the Peraea) are not included since nowadays they belong to territories covered by Inscriptions Grecques et Latines de la Syrieor de la Jordanie, respectively” (p. vi). Naturally, because of the large number of inscriptions that are included in this Corpus, the editors state that “it was not our intention to provide an exhaustive commentary for every single inscription” (p. vii). Similarly, as for the bibliography, it is stated that it “does not claim to be complete; whereas the editors consulted every item in which each inscription was discussed, only the relevant literature has been cited here. Any other procedure would have resulted in an endless list of items, which would be of little interest” (p. vii). Again, this too is entirely understandable and defensible, in light of the large numbers of texts that are part of this Corpus. However, it should also be emphasized that the bibliographies in this volume are really quite thorough. To be sure, they are not exhaustive, but those using the bibliographies will not be disappointed. Regarding this first volume (parts 1 and 2) it is stated that “the following order has been adopted. First, the inscriptions were divided so far as possible into three chronological groups: (1) The Hellenistic period up to the destruction of the Second Temple in 70; (2) The Roman period from 70 to the reign of Constantine; (3) Late Antiquity, from Constantine to the Arab Conquest.” (p. vii). It is noted that there have been some exclusions, but entirely understandable ones. Namely, the editors state that “on the whole we have not included mass-produced inscriptions such as impressions of amphora-handle stamps, brick-stamps, potter-stamps, stamps on lamps, and pilgrims’ ampullae” (p. vii). Those using this volume might have wished for indices. The editors sensed the importance of this and state that “we regret the absence of a general index in this volume.” However, they do state that “a general index for all the volumes is planned. And we intend to provide a provisional general index to this volume on the Internet” (p. viii). It should also be mentioned that the preface mentions that “an index of names is provided here [in this volume].” There is no index of names in Volume 1, Jerusalem, Part 1: 1-704, but my strong assumption is that this index will be included in the forthcoming Volume 1, Jerusalem, Part 2. In any case, Volume 1, Jerusalem, Part 1: 1-704 begins with a fairly detailed synopsis of ancient literary references to the city of Jerusalem (pp. 1-37). Moreover, there is a fine summary of the caves and tombs in the region of Jerusalem. In terms of the history of Jerusalem, there are particularly good summaries of the period between the First and Second Jewish Revolts and also of the period from the time of Hadrian to Constantine, and from Constantine to the Muslim Conquest. This section of the volume is reflective of the volume as a whole, namely, detailed reference to relevant ancient sources, replete with citation of the most salient and authoritative modern studies. The remainder of this volume (i.e., Volume 1, Part 1) focuses on “Inscriptions from the Hellenistic period up to the Destruction of the Second Temple.” This material is divided up into four parts: Section A “Inscriptions of religious and public character,” (inscription numbers 1-17, pages 39-64). Section B “Funerary Inscriptions” (inscription numbers 18-608, pages 65-609). Note that the material in Section B is divided according to region or site (e.g., Ramat Eshkol, Kidron Valley [North], Diskin Street, Jason’s Tomb, French Hill, Ramat Rahel, and then a division called “Unprovenanced.” Section C “Instrumentum Domesticum” (inscription numbers 609-692, pages 611-680). Section D: “Varia” (inscription numbers 693-704, pages 681-694). The format for each entry follows a standard pattern. Namely, there is reference to the number of the inscription within this volume (i.e., numbers 1-704), then there is descriptive title for the inscription (e.g., “#357, Epitaph of Shappira with Aramaic wall inscription”), followed by a reference to the approximate date of the inscription (e.g., “1 c. CE” = 1st Century CE). A basic description of the inscription is then given (e.g., “An inscription of four letters, cut in the soft rock, and blackened in, above the loculus of one of the lower burial rooms”). Normally, there is reference to the find spot, the present location, the department of antiquity number or museum number, and the measurements (e.g., for ossuaries). The editors made a concerted effort to personally inspect all available inscriptions (sometimes requiring travel to France, Germany, etc.). Also, there is reference to the precise date that the inscription was “autopsied,” that is, inspected, collated, measured, photographed. This is followed by the inclusion of the reading, provided in block script Aramaic, that is, the Jewish Script, for the Hebrew and Aramaic inscriptions, and the Greek and Latin script for inscriptions in those languages. In addition, different readings are also often provided under the rubric of “App. Crit,” that is, as a “critical apparatus,” along with reference to the scholar that proposed the reading. There is also a transliteration and a translation of the inscription. For the majority of inscriptions in this volume, black and white photos are also provided, although for a few of the inscriptions it was not possible to provide a photo. In such cases, hand copies are normally provided. Then there is a “Commentary” on the inscription, replete with things such as a discussion of orthography, phonology, prosopography (when appropriate), inscriptions with similar contents, meanings of names (when this can be determined). Readers of this volume will find very fine, thorough entries for the inscriptions. Sometimes the inscriptions in this volume are, of course, partiucarly well known. For example, included in this volume are the “Uzziah Plaque” reading: “Here I brought the bones of Uzziah King of Judah; and not to open” (# 602) and the Greek warning sign from the Temple Mount: “No foreigner is to enter within the balustrade and forecourt around the sacred precinct. Whoever is caught will himself be responsible for his consequent death” (#2). There are particularly judicious discussions of inscriptions such as the “Ya’akov (‘James’) Ossuary” (i.e., #531, without provenance), and the Talpiyot Tomb known as the “Yeshua’ Family Tomb” (#473-478). Moreover, there is also a very useful synopsis of the salient points regarding the Sarcophagus of “Queen Sadan,” a burial inscription known for more than a century, but still the subject of substantive discussion (#123). Naturally, some will find the references to professions to be of interest. Although these are not very common, there are a few, such as the ossuary of “Yehosef son of Hananiah, the scribe” (#86). References to aspects of religion are also present at times. For example, there is reference to “Hananiya the son of Yehonatan the Nazirite” (#70), and several references to Proselytes to Judaism, including a certain” Ioudan the Proselyte of Tyre” (#174), and a certain “Ioudas son of Laganion the Proselyte” (#551). Of much interest also are the ossuary of “Megiste the priestess” (#297) and references on ossuaries to “Korban” (#466), a term also known from the Greek New Testament (among other ancient literatures). Of course, the famous ossuary inscription stating that “No one has abolished his entering [into death], not even El’azar and Shapira” (#93), receives a through treatment, replete with discussion of the different readings of Frank Cross and Joseph Naveh. There is also reference to a certain “Menahem” from the priestly course of “Yakim” (#183), and an ossuary of a certain “Yehohana” who was the granddaughter of the Caiaphate “High Priest Theophilos” (#534). Sometimes very useful linguistic data can be mined from the ossuary inscriptions, such as the fact that Semitic tsadecan be represented in Greek with the psi, as the Semitic and Greek forms of the same name are given (see #309). Naturally, there are a few references to the prohibition of removing the bones (#507, 385). In sum, this volume is a treasure trove of data for scholars working in a wide variety of fields. This really is a priceless volume. Those that purchase it will always be grateful they did. Those that do not purchase it now will regret that decision. Ultimately, these volumes will be the gold standard for the next generation, perhaps longer. I recommend this volume completely and without reservation. Those wishing to order this directly from the publisher can do so here: http://www.degruyter.de/cont/fb/at/atMbwEn.cfm?rc=42316 or Tel: 857-284-7073. Christopher Rollston, Ph.D. ‘Priests’ or ‘Priest’ in the Mariam (Miriam) Ossuary, and the Language of the Inscription* <here is a image 79a977d3a5065a41-c6ecf7dd3b25e605> Photo Courtesy of, and Copyrighted by, Dr. Boaz Zissu The editio princepsof the Mariam Ossuary (on the spelling “Mariam,” rather than “Miriam,” see previous post) is really quite masterful, a model publication in numerous ways (see Zissu and Goren, 2011). This note of mine is simply intended to be a modest refinement (correction) of word division in the editio princeps(and also, thereby, the resolution of a grammatical difficulty implicit in the editio princeps, as well as the resolution of the actual language of this inscription). Here is the relevant segment of this inscription: “ khnmm’zyhmbyt’mry.” The authors of the editio princepsdivide the inscription this way: khnm m’zyh mbyt ‘mryand render it: “priests of Ma’aziah from Beth ‘Imri.” However, I am confident that this inscription must be divided in the following way: khn mm’zyh mbyt ‘mry. That is, “priest of Ma’aziah from Beth ‘Imri.” Thus, the place name “ m’zyh” is preceded by the prepositional min(with assimilated nun, of course). Arguably, this can be classified as a partitive use of minand can be rendered “of.” In sum, therefore, the common noun khnis a singular noun, followed by the preposition minplus the name “Ma’aziah,” not a plural form of the common noun sanspreposition. Naturally, this resolves a morphological problem implicit in the editio princepsof this inscription as well. After all, the rendering in the editio princeps assumes a plural noun in construct, but with a memstill present (which would be an anomaly). The word division that I propose here eliminates that problem. It is imperative for me to emphasize (in defense of the authors of the editio princeps) that word division is something that can be quite difficult in epigraphic texts that have no word division, or have no clear word division (and the same problem certainly occurs in literary texts, especially those written in scriptio continua, for example, the great Greek Uncials of the New Testament). Moreover, I am quite confident that it was the assumption that said memwas a plural marker on khn(making it khnm) that caused the authors of the editio princepsto state that the inscription was Hebrew (Zissu and Goren, page 75). The inscription is arguably Aramaic. That is, the presence of the words brt(Aramaic for “daughter,” cf. Hebrew btfor daughter) and br(Aramaic for “son,” rather than the Hebrew word bnfor son) are strong evidence that the inscription is Aramaic. Of course, in this period (etc.), it can certainly be the case that br, for example, can occur in a Hebrew inscription (such is the case in Cotton, CIIP #70, where the word bris present, but the article on the following noun is the Hebrew article, rather than the Aramaic form of the article, thus revealing that the inscription is Hebrew, not Aramaic. Note that there is a linguistic principle operative here, that I will discuss in more detail in a forthcoming article on this ossuary). But there is nothing in this inscription that suggests it is Hebrew, and there is strong evidence that it is Aramaic, so the most cogent statement is that the inscription is indeed Aramaic. It should be emphasized that although the authors of the editio princepsdid not understand that this memwas the preposition min, they certainly perceived the sense of the text and so accurately rendered it “of” (but placed the word “of” in brackets; see the title of the editio princeps), and understood it as meaning “of [or ‘from’] the course of Maa’aizh”; see page 80). In sum, the common noun khnis singular in this text (not plural), the preposition minis attested twice (not once), and the language of this inscription is Aramaic (not Hebrew). Thus the reading and word divisions are: mrym/brt/yshw’/br/qyp’/khn/m-m’zyh/m-byt/’mry. That is, “Mariam daughter of Yeshua son of Caiaphas, priest of Ma’aziah from Beth ‘Imri.” Respectully submitted, Christopher Rollston Cotton, H., et al. Corpus Inscriptionjum Iudaeae/Palaestinae: Volume I Jerusalem, Part I. Berlin: De Gruyter, 2010. Zissu, B. and Goren Y, “The Ossuary of ‘Miriam Daughter of Yeshua Son of Caiaphas, Priests [of] Ma’aziah from Beth ‘Imri.'” IEJ61 (2011): 74-95. *I am very grateful to Professor Dr. Boaz Zissu for sending me an offprint of his co-authored article. The Ossuary of Mariam Daughter of Yeshua’ in Context: Limning the Broad Tableau of the Epigraphic and Literary Data Introduction. The recent publication of the “Mariam Daughter of Yeshua” Ossuary (Zissu and Goren 2011) has justifiably garnered substantial attention. The authors are to be congratulated for producing a very strong, detailed, useful editio princeps of this ossuary and its inscription. The ossuary is without a secure provenance, but I do not doubt that it is authentic. At this juncture, it is my intent to summarize in a fairly methodical fashion some of the ways in which this new ossuary inscription dovetails with, and augments, our knowledge. My comments are particularly philological and historical in nature. I.SALIENT ASPECTS OF EARLY LITERARY SOURCES: CAIAPHAS AND ANNAS A.JOSEPHUS. At various points, the Jewish Historian Josephus (ca. 37 C.E. – 100 C.E.) discusses the priesthood of the late Second Temple Period, and at a particular point in his historical synopsis: (1) Josephus notes that a certain: “Iōsēpos ho Kaiafas “ (Joseph Caiaphas, high priest from ca. 18-36 CE) became a high priest during a time of tumult (note, for example, the short duration of various high priests prior to that of Joseph Caiaphas). Here is the full context of the reference: “Valerius Gratus succeeded Annius Rufus as procurator over the Jews. Gratus deposed Ananus [ca. 6-14 C.E.) from his sacred office, and proclaimed Ishmael the son of Phabi as high priest [ca. 15-16 CE]. Not long afterwards, he removed him also and appointed in his place Eleazar [ca. 16-17 CE] the son of the high priest Ananus. A year later he deposed him also and entrusted the office of high priest to Simon the son of Camith [ca. 17-18 CE]. This last-mentioned held this position for not more than a year and was succeeded by Joseph, the one (who was called) Caiaphas (Greek: Iōsēpos ho Kaiafas , that is, personal name, article, then “Caiaphas”) [18-36 CE]. After these acts, Gratus retired to Rome, having stayed eleven years in Judea. It was Pontius Pilate who came as his successor” (Josephus, Jewish Antiquities XVIII,33-35). (2) Later, Josephus states that Vitellius (governor of Syria) traveled to Judea and went to Jerusalem in particular. Among the things that Vitellius did was this: “he removed from his sacred office the high priest Joseph Caiaphas and appointed in his stead Jonathan, the son of Ananus [Greek New Testament: Annas] the high priest. Then he set out on the journey back to Antioch” (Joseph, Jewish Antiquities, XVIII, 95-97). (3) Significantly, of Ananus [Annas], Josephus states that “the Elder Ananus was extremely fortunate. For he had five sons, all of whom, after he himself had previously enjoyed the office for a very long period, became high priests of God—a thing that had never happened to any other of our high priests” (Josephus, Jewish Antiquities, XX, 198). Historical Notes: These citations reveal that Joseph Caiaphas was the name of a high priest, of course (on the presence of “son” on Ossuary 461, see below). Moreover, the names of several of his predecessors are given and among them is Ananus. This figure of Josephus (Ananus) is known in the Greek New Testament as “Annas” (see Luke 3:2; John 18:13, 24; Acts 4:6). In addition, within these texts it is stated that five of his sons functioned as priests and two of them are mentioned in the pericopes cited here, namely, Eleazar (16-17 CE) and Jonathan (36-37 CE). See also below). The remaining sons are: Theophilus (37-41 CE), Matthias (42-43 CE), and Ananus II (62 CE; on Theophilus, see also Rahmani 1994, 259 [no 871], for reference to an ossuary inscription that includes the words “Theophilus the high priest”). The reference to “the Elder Ananus” is a reflection of the fact that the high priest Ananus (high priest from ca. 6-14 CE) had a son named Ananus (as noted above) who also became a high priest, namely, Ananus ben Ananus, that is, Ananus II (62 CE). B.GREEK NEW TESTAMENT. The Greek New Testament refers on several occasions to Caiaphas (namely, Matt 26:3, 57; Luke 3:2; John 11:49; 18:13, 14, 24, 28; Acts 4:6). Among the most important for this article are these references: (1) The context of this narrative is the beginning of the prophetic work of the figure known as John the Baptist (i.e., arguably sometime in the mid to late 20s CE). “During the high priest(hood) of Anna and Kaiafa (Caiaphas; some Greek mss of this verse have Kaifa, including Codex C and Codex D) the word of the Lord came upon John the son of Zechariah in the desert” (Luke 3:2). (2) These texts (below) hail from a judicial context, namely, putative events immediately prior to the crucifixion of Jesus of Nazareth. “Then the chief priests and the elders of the people gathered in the courtyard of the high priest being called Kaiafa (Caiapha; some Greek mss of this verse have Kaifa; Matt 26:3, similar variant spelling in vs. 57). (3) “But one of them, Kaiafas (Caiaphas; some Greek mss of this verse have Kaifas), being that year the high priest…” (John 11:49 “that year” is arguably a way of referring to the time frame of the trial and not, therefore, some sort of suggestion that he was only the high priest for a year). (4) “And they brought him to Annas first; he was the father-in-law of Kaiafa (Caiaphas; some Greek mss of this verse have Kaifa) who was the high priest that year” (John 18:13). (5) The setting for this text is judicial as well, but the historical context is after the crucifixion, during the early history of the then fledgling Jewish sect known as Christianity. “And Annas the high priest and Kaiafas (Caiaphas; some Greek mss of this verse have Kaifas) and John and Alexander and as many as were out of the lineage of the high priesthood were standing there…” (Acts 4:6). Historical Notes. As noted, the Ananas of Josephus is the same as the Annas of the Canonical Gospels. Moreover, the “John” mentioned in Acts 4:6 is arguably the Jonathan [ca. 36-37 CE] mentioned by Josephus as the son of Ananus, and the successor of Caiaphas. Also, it is not impossible that the Alexander mentioned in Acts 4:6 is the figure known in Josephus by the Hebrew name Eleazar son of Ananus[ca. 16-17 CE]. Note that the phenomenon of “double-names” is well attested for Jewish figures of the First and Second Temple Periods, in biblical and epigraphic sources. However, they may indeed be two different people. The fact that Caiaphas is said to be the son-in-law of Annas is a significant historical detail. I consider it reliable. Obviously, therefore, the details about Ananas (Annas) that are known from Josephus and the New Testament converge at a number of levels, and also are complementary in some respects. Note also in this connection the orthographic variation with regard to the spelling of Caiaphas: namely, Kaiapha and Kaipha. Note in this connection the variation in spelling in the epigraphic form of this name, detailed below. On the presence or absence of a final sigma (etc.) on Semitic personal names written in Greek, see the discussion below (IIA, Philological Note #2). II.ROMAN PERIOD EPIGRAPHIC SOURCES: THE INSCRIBED OSSUARIES A.THE CAIAPHAS BURIAL CAVE. Twelve ossuaries (or portions thereof) were discovered in 1990 in a tomb in southern Jerusalem (See Greenhut 1992; Reich 1992; Zias 1992; Cotton, et al., 2010, 481-488 [numbers 461-465]. There were a total of four loculi (or kokhim) in this tomb, three along one wall and one along another wall. Six of the ossuaries still contained bones (note: the tomb had been robbed at some point prior to excavation). Two of the ossuaries were still in situ. One of the ossuaries contained a coin from the sixth year of Agrippa I (ca. 42-43 CE). It is the inscribed ossuaries that are of interest for this article (note that the numbers used in this article are those of Cotton, et al. Predominant focus will be numbers 461, 463, and 462, in that order). Ossuary 461. The ossuary is lavishly decorated, reflecting affluence, and probably opulence. There are two Aramaic inscriptions on this ossuary, inscribed in a very cursive hand. The first inscription is written on two lines and the second on a single line. I shall refer to them as 461-A and 461-B. 461-A: line 1. Yhwsp br (Yehoseph bar = Yehosep son of) 461-A line 2. Qyp’ (Qaiyapha’; note that I consider yod to be the correct reading, not waw). ___ 461-B: Yhwsp br Qp’ (Yehosep bar Qaipha’) Ossuary 463. There is one inscription. The name is arguably Aramaic (see below), written in a cursive hand. Qp’ (Qaipha’) Ossuary 462. There is one inscription, written on two lines. I shall refer to these lines as 462-A and 462-B. The inscription is written in a highly cursive hand. This inscription is arguably Aramaic (see below). 462-A. Mrym brt (Maryam birat = Maryam daughter of) 462-B. Šm‘wn (Shimon). Philological, Epigraphic, and Historical Notes: (1) Greek Iōsēpos = Hebrew Yhwsp. (2) Moreover, the sigma (e.g., on Iōsēpos) attested on the end of the personal names in the Greek literary material is certainly not a problem, as it is simply the Greek case ending, which is routinely added onto Semitic (etc.) names (in legions of literary and epigraphic texts, not just these), obviously nominatives in particular (also of import: some foreign personal names in Greek are declined fully, some are not. Along those lines, and for illustrative purposes, I would note that the s of the personal name “Jesus” is simply the nominative case ending, and not really part of the name itself, per se…compare the genitive and accusative forms of that name, that is, Iēsou and Iēsoun respectively). (3) Greek kappa is often used to represent Hebrew and Aramaic qop. For example, “korban,” Aramaic Qrbn’, is represented in the Greek New Testament as korbanas (Matt 27:6). Similarly, Simon the Zealot is referred to as Simon the Kananaios (i.e., Simon the Kananean, that is, Simon the Zealot”) a spelling that is representing Aramaic Qn’n (Matt 10:4; cf Luke 6:15), obviously with the Greek kappa representing not the Semitic kap, but rather a Semitic qop. Ultimately, therefore, there is no orthographic problem that would preclude considering Greek Kaiafa to be a Greek transliteration of the Aramaic name Qyp’. (4) Significantly, the orthographic variation reflected in these ossuary inscriptions for the name Caiaphas, namely, Qyp’ and Qp’ (i.e., with or without yod) can be understood to be paralleled fairly nicely by the orthographic variants attested in the Greek New Testament, namely, Greek Kaiafa parallels Aramaic Qyp’ and Greek Kaifa parallels Aramaic Qp’. Obviously, Hebrew and Aramaic of this period do not represent vowels in anything approximating a precise fashion (the use of matres lectionis in this period is certainly helpful, but matres lectionis can hardly be said to clarify vocalization in some sort of definitive manner, but I do not consider the orthographic variant here to be inconsequential). In the case of the spellings Qyp’ and Qp’ (i.e., with or without the yod), I would simply note that one could understand the yod to be a mater lectionis or an actual consonant. Ultimately, this sort of thing could readily account for the two orthographies attested in the Greek New Testament. Also, on an ancillary note, suffice it to say that I believe it to be entirely tenable to contend that Yhwsp br Qyp’ and Yhwsp br Qp’ of Ossuary 461 refer to the same person. (5) Mariam (or Maryam) is the preferred vocalization, *not* Miriam. Basically, the Masoretic Text reflects a (fairly) late phonological shift, namely, as Waltke and O’Connor have noted (Waltke and O’Connor, 1990, 25), “an original short a in word-initial closed syllables” becomes i. Fortunately, the Septuagint preserves the original vocalization, thus, the sister of Moses is Mariam in the Septuagint (e.g., Exod 15:21), not Miriam. The same vocalization (i.e., with the vowel a in the first syllable) is still preserved in Arabic as well. Also, the same phenomenon is operative for the person name Sampson (e.g., Judg 14:1, with MT Šimšōn but LXX Sampsōn), of course. (6) The script of these inscriptions is a highly cursive script. It can be dated to the first century CE. (7) The two iron nails found in this tomb were probably used as instruments used for inscribing letters, although some other mundane function (e.g., scraping something, etc. ) is not impossible. (8) The presence of the words brt (rather than standard Hebrew bt) “daughter” and br (rather than standard Hebrew bn) “son” certainly argue strongly for Aramaic, moreover, I consider the ’alep of Caiaphas, that is, Qyp’ to be the determined form (i.e., with ’alep as the postpositive Aramaic article). Thus, the cumulative evidence reveals that this inscription is to be considered Aramaic, of course. B.THE MARIAM DAUGHTER OF YESHUA‘ OSSUARY(Zissu and Goren 2011). This ossuary is inscribed in a formal hand, arguably dating to the first century CE. The inscription is Aramaic. It can be read as follows: Mrym brt yšw‘ br Qyp’ khn m m‘zyh mbyt ‘mry Mariam the daughter of Yeshua son of Qaiyapha, a priest of Ma‘aziah of the House of ‘Imri (See the very useful note below from Ed Cook regarding the reading of a bet, not dalet before Ma’aziah). (Addendum: 15 July 2011: the editio princeps reads khnmm’zyh…so it turns out that it is not a kap as was initially suggested in press reports, nor is it a bet, but rather a mem. See now the blog post above, entitled “Priests or Priest…”) Epigraphic, Philological and Historical Notes: (1) This text is, arguably, Aramaic. Note especially the Aramaic brt “daughter” and br “son.” (2) The script of this ossuary is the formal script, deeply and carefully incised. I consider it to be reflective of the first century CE. (3) The presence of the names Yeshua‘ and Mariam are not at all surprising, as they were very common names in this period. Furthermore, it should also be noted that in the Caiaphas Burial Cave the name Mariam is also attested, although because of the patronymic it is clear that they are not the same person. (4) Regarding the vocalization of Mariam (rather than Miriam), see the discussion under note five above. (5) There has been some reference to the possibility that the place name Khirbet Kufin (in the northern Hebron Hills) may be preserved in the name of the “Caiaphas” family (i.e., Kufin = Caiaphas). Although this is not impossible (and I do think that it merits further investigation), I am rather disinclined to think that this is the case. After all, the Arabic place name Kufin is normally said to begin with a kaf, not a qaf. Compare the personal name Caiaphas, which begins with a qop in Aramaic and Hebrew. The distinction between these two consonants is (largely) lost in modern Hebrew, but is very much retained in modern Arabic (basically, k is a velar voiceless stop, while q is a velar voiceless emphatic). Of course, Greek is not a Semitic language and so the fact that it often represents the q as a kappa is not a particularly relevant argument against my statements regarding the q and k in Aramaic (and Hebrew) and Arabic. (6) Having said this, I should note that I do think that the name “Caiaphas” preserves a place name. Rather than Kufin, however, I believe that one can make a tenable case that Qeiyafa (i.e., Khirbet Qeiyafa) is the place name preserved in “Caiaphas.” There are, of course, Second Temple Period occupational remains at Khirbet Qeiyafa. I am not stating this definitively at this time, but do wish to mention it at this time as something that is arguably quite viable. (7) The use of the term “priest” and the reference to the priestly course of Ma‘aziah (cf. Neh 10:9 [English 10:8]) are very interesting (as is also the reference to the house of ‘Imri). The fact that the word priest is used, and the fact that there is reference to a priestly course, undermines even further Horbury’s contention that ossuaries 461 and 463 from the Caiaphas Burial Cave do not refer to the high priest named Caiaphas (Horbury 1994). Pace Horbury, I do not consider Horbury’s evidence (neither his reading of a waw in the epigraphic attestation of the personal name, nor his use of the Rabbinic evidence, etc.) to be sufficient to make his case that the literary sources referring to Joseph Caiaphas and Ossuary 461 with its reference to Yhsp bar Qyp’ (he reads it as Qwp’, renders it “Qopha”) are ultimately referring to different people who simply have similar sounding names. Again, I consider “Caiaphas” (in the literary and epigraphic sources) to preserve a place name and I believe that the Joseph Caiaphas of the literary material and the Joseph bar Caiaphas of the epigraphic corpus to be the same person. (8) Someone might object to the fact that Josephus does not have the word “son.” True enough. However, the fact of the matter is that sometimes the word “son” (bn or br) can be omitted in ancient texts. That is, in certain contexts, the word “son” was not deemed essential. I believe Josephus, therefore, to be reflective of this practice (naturally, I would also suggest that there was an earlier figure known as “Caiaphas,” with the term “Caiaphas” preserving a place name and the term, Joseph Caiaphas, therefore, reflects the fact that he was the son of a man named Caiaphas). Of course, the practice of papponymy is certainly well attested in antiquity and so I cannot rule this phenomenon out as an impossibility in this case. However, the totality of the archaelogical, epigraphy, and literary evidence converges quite nicely and so I am comfortable affirming that Josephus and Ossuary 461 are referring to the same person (also, I think that it is probable, but not absolutely certain, that the Joseph Caiaphas of the Caiaphas Burial Cave and Caiaphas the Priest of the Mariam Ossuary are the same person, although they are at the very least certainly of the same family). (9) In this connection, as an ancillary note, I should like to mention that personal names plus geographic names (i.e., PN + GN) are quite common, including in Greek sources. For New Testament examples, Mary Magdalene (Greek: Mariam hē Magdalēnē [Matt 27:56],that is, personal name, article, geographic name) and Judas Iscariot (Ioudas ho Iskariōtēs) [Matt 10:4], that is, personal name, article, and arguably a geographic name). I am certainly not suggesting that this structure in Greek (or in Hebrew and Aramaic) can only be used of the combination of a personal name plus a geographic name; however, I am suggesting that it is a construction that can be used for the combination of a personal name and geographic name. (10) Some have argued that the Sadducees might have had objections to ossuary burial (and thus did not practice it). I find that to be a problematic position (and the archaeological and epigraphic evidence, combined with the evidence of the first century literary sources, combine to suggest that some Sadducees were comfortable with ossuary burial). Respectfully submitted, Dr. Christopher A. Rollston *I gratefully acknowledge the assistance of Omar al-Ghul and also of Eran Arie with regard to various aspects of this article. Also, a number of my previous articles can be found on www.academia.edu . In addition, I am on facebook: search for Christopher Rollston…I often post articles on fb that revolve around the fields of archaeology, epigraphy, and anthropology in general. Select Bibliography Cotton, H., et al (eds). Corpus Inscriptionum Iudaeae/Palaestinae. Berlin: de Gruyter, 2010. Greenhut, Z. “The ‘Caiaphas’ Tomb in North Talpiyot.” ‘Atiqot 21 (1992): 63-71. Horbury, W. “The ‘Caiaphas’ Ossuaries and Joseph Caiaphas.” PEQ 126 (1994): 32-48. Rahmani, L. Y. A Catalogue of Jewish Ossuaries. Jerusalem: Israel Antiquities Authority, 1994. Reich, R. “Ossuary Inscriptions from the ‘Caiaphas’ Tomb.” ‘Atiqot 21 (1992): 72-77. Waltke, B. K. and O’Connor, M. An Introduction to Biblical Hebrew Syntax. Winona Lake: Eisenbrauns, 1990. Zias, J. “Human Skeletal Remains from the ‘Caiaphas’ Tomb.” ‘Atiqot 21 (1992): 77-80. Zissu, B. and Goren, Y. IEJ 61 (2011) Just Published, _Tel Aviv_ 38:1, including Rollston’s “The Khirbet Qeiyafa Ostracon: Methodological Musings and Caveats.” JUST PUBLISHED Tel Aviv: Journal of the Institute of Archaeology of Tel Aviv University Volume 38, Number 1, 2011 CONTENTS In Memoriam: Anson Rainey Deborah Sweeney Judahite Stamped and Incised Jar Handles: A Tool for Studying the History of Late Monarchic Judah Oded Lipschits, Omer Sergi, Ido Koch The paper probes the distribution of the various stamped and incised Judahite jars with two criteria in mind: (1) their estimated date; (2) the assumption that in addition to Jerusalem, sites that yielded large quantities of stamped handles (mainly Lachish and Ramat Raḥel) served as major collection centres while sites that yielded only a few dozen stamped handles served as secondary administrative centres of the kingdom. Based on their findings, the authors reconstruct the evolution of the royal administrative system in the late 8th through the early 6th centuries BCE. Tell Qudadi and Tel Gerisah: Two Early Bronze II Sites on the Yarkon River Ram Gophna, Yitzhak Paz Tell Qudadi and Tel Gerisah are two multi-period sites located on the Yarkon River. Recent research has revealed that they were the only settlements along the central Coastal Plain that were inhabited during the Early Bronze Age II. Tell Qudadi and Tel Gerisah could have played important roles as an outpost and as a main inner anchorage site, respectively, in maritime activities between Old Kingdom Egypt and the North Levantine coast. An Egyptian Mortuary Cult in Late Bronze II Canaan Katia Charbit Nataf The paper re-examines the significance of the banquet scenes depicted on the Late Bronze Age II Megiddo and Tell el-Far>ah ivories. The author attempts to identify and link a set of characteristics on the panels—the lotus flower, the drinking vessels, the musical instruments and the Delta papyrus marshes—to the Egyptian goddess Hathor. She then proceeds to explore the hypothesis that mortuary Hathor worship, a direct legacy of Egyptian cultic belief, was adopted by the Canaanites during this period. The archaeological context of such a cult is discussed. The Khirbet Qeiyafa Ostracon: Methodological Musings and Caveats Christopher Rollston The Qeiyafa Ostracaon is an important inscription from the late stage of Early Alphabetic. Regarding its language, some have argued that it is written in Hebrew. This article, however, contends that there are no discernable diagnostic features in the ostracon that mandate such a conclusion. Furthermore, the article also emphasizes that the script of this inscription is certainly not Old Hebrew, nor is it the immediate precursor of the Old Hebrew script. Rather the Old Hebrew script derived from Phoenician. Thus, there is some distance between the script of this inscription and the Old Hebrew script. Finally, the article contends that it would be difficult (because of the dearth of data) for grand proposals about statecraft and literacy to be made on the sole basis of this ostracon. Textual and Historical Notes on the Eliashib Archive from Arad Nadav Na’aman The first part of the article discusses in detail some letters addressed to Eliashib, possibly the commander of the fortress of Arad. New readings and interpretations are suggested for Ostraca Nos. 3, 5, 10, 12 and 18 and their structure and contents are clarified. The second part of the article offers new solutions for some problems in the history of the Negev in the late years of the Kingdom of Judah. It suggests that the elite troops of Kittiyim were hired by one of the last kings of Judah and sent to the Negev in an effort to curtail the Edomite danger. However, the efforts to defend the Negev failed and its centres were destroyed some time before the Babylonian 588–587 BCE campaign against the Kingdom of Judah. The heavy destruction brought about by the Edomites was deeply engraved in the collective memory and provides the background for the distinctive negative attitude to Edom in biblical prophecy of the exilic and post-exilic periods. Egypt and the Levant in the Iron Age I–IIA: The Ceramic Evidence Shirly Ben Dor Evian Traditionally, relations between Egypt and the Levant in the early phases of the Iron Age have been reconstructed based on the scant historical record and on biblical descriptions. This article introduces a new facet of Egyptian regional intervention into the discussion: the presence of Egyptian pottery at Iron Age sites in Israel. The Babylonia–Elam Connections in the Chaldaean and Achaemenid Periods—Part I Ran Zadok The paper discusses the political and economic connections between Babylonia and Elam during the periods of the Neo-Babylonian and Achaemenid empires (626–539 and 538–332 BCE respectively). It is based on both published and unpublished sources in Neo/Late-Babylonian as well as in Neo-Elamite and Royal Achaemenid Elamite. These are mostly implicit, as pertinent chronicles and royal inscriptions are rare. Therefore, the evidence for political history is minimal whereas the socioeconomic information is much more detailed. Nevertheless, even this information is chronologically uneven as most of it refers to the Chaldaean and early Achaemenid period with very few sources about the late Achaemenid period (483–332 BCE). An appendix is devoted to workmen from upper Mesopotamia and Syria (‘Assyrians’) in Elam including Arabians. They were—at least partly—subjects of the Neo-Babylonian empire before its demise. Editors: Israel Finkelstein, Benjamin Sass Editorial Board: Nadav a’aman, Oren Tal, David Ussishkin Managing Editor: Myrna Pollak Tel Aviv is Published by Maney Publishing for The Emery and Claire Yass Publications in Archaeology of The Institute of Archaeology of Tel Aviv University Among the Last of the Titans: Aspects of Professor Anson Rainey’s Life and Legacy (1930-2011) <here is a image 8eadec1e47df41d1-23337e46c74007b0> The contours of the life of Professor Anson Rainey are significant, well known, and well documented. He was a force of nature, and he was beloved, respected, revered, and (on occasion) feared. Within the field, he was a polymath. He was among the most capable and authoritative scholars of the Northwest Semitic languages. Indeed, he was as comfortable in Ugaritic, Phoenician, and Aramaic as he was in Old Hebrew. Moabite and Ammonite were subjects of great interest for him and he knew the preserved texts in these languages so very well. In addition, he was also a most capable scholar of Egyptian and Coptic. Moreover, he was also a formidable scholar in various fields and subfields of Assyriology, and his contributions to the Amarna Letters are substantive, diverse, and legion; arguably these are some of his most enduring contributions. Of course, among his greatest passions was historical geography, and it is my opinion that he had no peers in this field. Furthermore, he had also spent many seasons excavating, and he knew the archaeology of much of the ancient Near East so very well. Of course, in addition to his fluency in several European languages, he was also fluent in both modern Hebrew and also modern Arabic. I know of no one who was so capable in so many things. With his death, we are witnessing the loss of one of the last of the polymath “titans” of the field. Of course, throughout much of his career, he was an institution at Tel Aviv University, first teaching full-time there in 1964 and continuing at Tel Aviv until his retirement from full-time teaching there in 1998. He was also a professor, and in many ways an institution, at the American Institute of Holy Land Studies (now Jerusalem University College), something about which he was always very proud. Ultimately, research was really the bone and marrow of life for Anson. That is, his institutional affiliations and his travels revolved around his publication projects. And few can claim to have been as productive as he. He authored more than a dozen volumes, translated nearly that many more, he authored in excess of two hundred scholarly articles, wrote numerous reviews, and presented more than eighty conference papers. Not so very long ago, he told me that many students that were with him at Brandeis University (his doctoral alma mater, 1962) had earned their degrees and they were never heard from again. He considered this to be an utter waste of a good education. Anson published and presented papers and he believed this was the best course of action. One could say that Anson practiced what he preached. That is, Anson was a most assiduous, productive scholar. Philologists are often given to Wanderlust, and this was certainly the case for Professor Anson Rainey. For example, he traveled to Berlin and collated at the Vorderasiatisches Museum and to Cairo to collate at the Cairo National Museum. Moreover, he collated texts in Jordan, and he collated at both the British Museum and the Ashmolean Museum. Within the United States, he collated at the Metropolitan Museum (New York) and the University of Chicago. He was also a visiting scholar at various institutions, including Harvard University (1976-77), the University of Pennsylvania (1983-84; 1988-89; 1995-96), the University of California Los Angeles (2001), Konkuk University in Seoul, Korea (2002), and the University of Melbourne, Australia (2002). During the course of his life, Anson’s relationships with people were always of great importance to him. He would often mention his great respect, even admiration, for the work and person of W. Moran (of Harvard). In fact, in many ways, he considered himself to be a student of Moran and he understood himself to be building on the work and legacy of Moran. Moreover, he often spoke with pride about his tutelage at the feet of H. J. Polotsky (of Hebrew University) in Egyptian. Furthermore, Anson’s colleagues and students always loomed large in his worldview. He reminisced about Y. Aharoni with nostalgia so profound that I have rarely seen it equaled. And he would note the accomplishments of his own students with pride, touting them often. Through the years, many, including me, have felt that Anson was among the most accessible, kind, supportive scholars in the field. He was always available for conversation, dialogue, and I have long treasured the things that I learned from him. Many have long said that they felt similarly. Of course, Anson also seemed to take it rather personally if someone close to him differed with him about something he considered to be all too clear. And he was consistently candid about such things. But I suppose that this is a reflection of the fact that he genuinely cared deeply about the field and about the people in it. The field was important to Anson, paramount even. He wanted the field to get it “right.” Life is often a pilgrimage and this was the case for Professor Anson Rainey. The scholarship he produced is among the most original, substantive in the field. The personal and religious trajectory of his life is fascinating in and of itself. As I reflect on him, and his death on February 19th, it is not primarily Anson the productive scholar that I shall miss, though I shall miss this. Rather, it is the departure of Anson the mentor, friend, and colleague that is most difficult. Christopher Rollston Writing and Literacy in the World of Ancient Israel <here is a image 8d6b59c154a39982-91c589e4ea3af2af> The following volume is available from the Society of Biblical Literature (www.sbl-site.org > publications) Writing and Literacy in the World of Ancient Israel: Epigraphic Evidence from the Iron Age by Christopher Rollston ISBN 1589831071 Price: $21.95 Binding Paperback Publication Date October, 2010 Ancient Northwest Semitic inscriptions from Israel, Phoenicia, Syria, Moab, Ammon, Edom, and Philistia enlighten and sharpen our vision of the Old Testament world in various ways. Writing and Literacy in the World of Ancient Israel focuses on this epigraphic evidence in order to broaden our understanding of the techniques and roles of writing, education, and literacy during this biblical period. To that end, the volume systematically covers scribal education; scribal implements; writing media such as stones, potsherds, and plaster; and the religious, administrative, and personal uses of writing. Its “handbook” format makes it easily accessible, including for use as a textbook in courses addressing the cultural context of ancient Israel. Christopher A. Rollston holds a Ph.D. in Ancient Near Eastern Studies from the Johns Hopkins University. He is the editor of the scholarly journal MAARAV, has published widely in the field of epigraphy, and co-chairs the Epigraphy Sessions at the Annual Meetings of the Society of Biblical Literature and the American Schools of Oriental Research. He is currently the Toyozo W. Nakarai Professor of Old Testament and Semitic Studies at Emmanuel School of Religion in Johnson City, Tennessee. Hardback edition available from Brill Academic Publishers (www.brill.nl) The Probable Inventors of the First Alphabet:Semites Functioning as rather High Status Personnel in a Component of the Egyptian Apparatus <here is a image 70187c444398008f-ad532a28d0ad3510> Christopher Rollston Introduction: For some time, there has been discussion about the social status of those that developed (“invented”) Alphabetic Writing (i.e., elites or non-elites). Therefore, the nuanced discussion between O. Goldwasser (2010 and BAS web site) and A. Rainey (BAS web site) is the continuation of an old (and important) debate. Rainey contends that the inventors of the alphabet were sophisticated Northwest Semites that knew the Egyptian writing system. Goldwasser argues that the “inventors of the alphabet could not read Egyptian, neither Hieroglyphic nor Hieratic.” As an Ausgangspunkt for these comments of mine, and to facilitate understanding for those not familiar with the data, I should like to reiterate certain factors that have formed the basic contours of the entire discussion for some time: (1) Non-Alphabetic Writing (i.e., Mesopotamian Cuneiform and Egyptian) is first attested for the terminal chronological horizons of the fourth millennium BCE. (2) The alphabet was invented once and this arguably occurred during the early second millennium BCE. All alphabets derive, in some fashion, from this original alphabet. (3) The script of the Early Alphabetic inscriptions is modeled on (certain aspects of) the Egyptian script, as Egyptologists have noted for some time (e.g., from Gardiner to Darnell). (4) The language of the Early Alphabetic inscriptions is Northwest Semitic, *not* Egyptian (e.g., ba‘lat). I. Some Salient Moments in the Early History of the Early Alphabet: Research on the Early Alphabet began in earnest during the first two decades of the 20th century. Sir Flinders Petrie had discovered, in a temple in Serabit el-Khadem (in the Sinai), various Hieroglyphic inscriptions. However, he also discovered some inscriptions that he considered enigmatic. He initially referred to these inscriptions as a “local barbarism” (Gardiner 1906, 129-32). However, Gardiner soon began to analyze this corpus of inscriptions and he became convinced that the script was alphabetic, not some “local barbarism.” He rapidly made major strides forward in the decipherment of these inscriptions (often referred to as “Proto-Sinaitic”), based on his assumption that “the acrophonic principle” was operative. Moreover, he also argued that the intellectual soil that facilitated the invention was (certain aspects of) the ancient Egyptian writing system (Gardiner 1916, 1-16), including various Egyptian signs that represented single consonants. In addition, he became convinced that although these Early Alphabetic inscriptions “are not in Egyptian Hieroglyphic…many of the signs are obviously borrowed from that source” (Gardiner 1916, 14). Ultimately, based on the date of some of the Hieroglyphic inscriptions in the region of Serabit el-Khadem as well as the morphological similarities between these Early Alphabetic signs and certain Hieroglyphic signs, Gardiner stated that he believed that it was tenable to assign the alphabetic inscriptions to the latter portion of the Egyptian Twelfth Dynasty (i.e., early eighteenth century BCE. I provide more details in Rollston 2010). Several decades later, W.F. Albright made some significant progress regarding the history of the Early Alphabet, building on Gardiner’s seminal analyses (Albright 1966). Through the years, F. M. Cross has also made fundamental contributions to the discussion of the history of the Early Alphabet (see Cross’s collected writings, Cross 2003). Furthermore, P. K. McCarter’s contributions have been particularly important (e.g., 1975, 1996) as well. Moreover, both B. Sass (1988) and G. Hamilton (2006; this publication by Hamilton was based on his Harvard dissertation, 1985) have contributed to the discussion. More recently, two alphabetic inscriptions discovered at Wadi el-Hol (Egypt) were published (J. Darnell, F. W. Dobbs-Allsopp, M. Lundberg, P. K. McCarter, B. Zuckerman 2005) and it has been argued that these can be dated to the same basic chronological horizon as the Early Alphabetic texts from Serabit el-Khadem (although perhaps from a later component of that horizon). Significantly, J. Darnell (the Egyptologist that was part of the team working on the Wadi el-Hol Inscriptions) has argued that the Early Alphabetic inscriptions from Wadi el-Hol were modeled on Egyptian signs (i.e., his assessment was analogous to Gardiner’s analysis of the Serabit el-Hadem Inscriptions). Note the following citation in this regard: “What is most striking about the alphabetic texts from the Wadi el-Hol is how so many of the signs appear to reflect features and peculiarities best known from the paleographic, orthographic, and lapidary hieratic traditions of the early Middle Kingdom” (Darnell, et al., 2005, 86). Also of substantial import in this connection is the content of some of the Hieratic inscriptions discovered in Wadi el-Hol, inscriptions found near the Early Alphabetic inscriptions. Here is Darnell’s translation of the first four lines of one of these inscriptions: “The General of the Asiatics, Bebi; his daughter Maatherankheni; the Royal Messenger Bebi; The Express Courier Hornebkhasutemsaf” (Darnell, et al., 2005, 88, 102-103). Of course, the term “Asisatic” in Egyptian is a term used in Egyptian for Semites (especially those from the Levant). Darnell believes that the writers of the Early Alphabetic inscriptions of Wadi el-Hol were “not slaves,” but “desert experts” who learned Egyptian from “military scribes” (Darnell, et al., 2005, 90). Note that within a second Egyptian inscription from Wadi el-Hol are references to various officials, including a reference to “The Scribe of the storehouse of the mayor, Sawepwaut” (Darnell, et al., 104). NOTE: The inscriptions from Wadi el-Hol and Serabit el-Khadem are pictographic in nature and employ a principle often referred to as the acrophonic principle. So, for example, one of the letters attested has the appearance of a human head. The word for a human head in Semitic is r ’å. This pictographic letter stood for the phoneme “r.” That is, because the first sound of the word for head (r ’å) is “r,” a pictographic depiction of a head was intended to signify the “r” sound. Similarly, the word for water in Semitic is mym. Therefore, this pictographic letter (that has, in some respects, the appearance of flowing water) stood for the phoneme “m.” That is, because the first sound of the word for water (mym) is “m,” a graphic depiction of water was intended to signify the “m” sound. It should be emphasized strongly here that Early Alphabetic inscriptions are attested not only in Egypt, but also in Palestine (but from later periods). For example, an inscribed potsherd from Gezer dating to the Middle Bronze Age II (ca. 1800-1630 BCE) contains three early alphabetic letters. The Lachish Ewer is written in the Early Alphabetic script and dates to some time around the thirteenth century BCE. (Regarding the transition from Early Alphabetic to Phoenician, see Naveh 1987; Cross 2003; McCarter 1975, Rollston 2008a, 2008b; 2010). II. Literacy in the Ancient Near East and Mediterranean For the ancient Near Eastern cultural centers of Mesopotamia and Egypt, literacy rates are estimated to be low and confined to elites (e.g., scribes, government officials, priests). To be precise, for Egypt, literacy rates are often estimated to be at ca. one-percent or lower, and confined to elites (see Baines and Eyre,1983, 65-96; note that even at Deir el-Medina it is elites that are writing). For Mesopotamia, Larsen believes that one-percent is also a reasonable figure (see Larsen, 1989, 121-148, esp. 134). There is a fair amount of data from Mesopotamia and Egypt about the nature of scribal education (schools, school texts, buildings, etc.) and I discuss these data at some length in a volume on writing and literacy in the world of ancient Israel (Rollston 2010). Some have suggested that with the invention of the alphabet, literacy rates rapidly became quite high, with both elites and non-elites writing and reading (note: these two skills are related, but quite different). For example, during the middle of the twentieth century, W.F. Albright stated that “since the forms of the letters are very simple, the 22-letter alphabet could be learned in a day or two by a bright student and in a week or two by the dullest.” And he proceeded to affirm that he did “not doubt for a moment that there were many urchins in various parts of Palestine who could read and write as early as the time of the Judges” (Albright 1960, 123). At the beginning of the twenty-first century, R. Hess made similar statements. For example, regarding ancient Israel, he states that there is “continually increasing evidence for a wide variety of people from all walks of life who could read and write.” In addition, he states that he believes “the whole picture is consistent with a variety of [literate] classes and groups, not merely a few elites” (Hess 2006, passim 342-345). However, based on a detailed analysis of the Old Hebrew epigraphic evidence for Iron Age Israel, I have argued (2006; 2010) that literacy in Iron Age Israel was confined primarily to elites (e.g., scribes, high military officials, priests). That is, I do not believe that the non-elite masses could write and read (at least not beyond the most remedial of levels…and when they did attempt to do so, it is painfully apparent). The epigraphic evidence in Old Hebrew (i.e., the meticulous execution of the script, the synchronic consistency of orthography, the use of complicated hieratic numerals, etc.) demonstrates that there was formal, standardized education in Iron II Israel. Moreover, there was a strong distinction between the educated and the non-educated, with the masses falling into the second category (something even Ben Sira noted centuries after the rise of alphabetic scripts, Sira 38:24-39:11; 51:23; Rollston 2001). In addition, I. Young’s cogent analyses (1998a; 1998b) of the biblical evidence suggest the same thing: elites were the writers in ancient Israel. Of import in this connection is the fact that Greek is an alphabetic script (derived from the Phoenician script), but there is no decisive evidence that literacy of the populace in ancient Greece was the norm. Moreover, Latin is an alphabetic script as well, but there is no decisive evidence that literacy was the norm for the populace in ancient Italy. Rather, the evidence suggests that the vast majority of the population was not literate. Note, for example, that W. Harris (1989, 114, 267, 22) has argued that literacy rates in Attica were probably ca. five percent to ten percent and those in Italy were probably below fifteen percent (note: within this volume [passim], Harris has cogently critiqued those that have proposed high(er) rates of literacy). Therefore, I contend that high levels of literacy are not a necessary correlative of the presence of an alphabetic writing system. Goldwasser affirms (following in the footsteps of Albright) that “with the alphabet, writing broke out of the ‘golden cage’ of the professional scribal world,” and she contends that “alphabetic writing gave many more people control over their lives and enabled larger segments of the population to take a more active role in the cultural and administrative affairs of their respective societies” (Goldwasser 2010, 41). This is a marvelous notion, but I view it mostly a perpetuation of the older, romantic notions about literacy levels and the alphabet. Note that rather than positing rapid proficiency in alphabetic writing and literacy, recent empirical studies for modern languages have delineated developmental phases (“stages”) in the process of word-reading and word-spelling. Ehri summarizes these stages in broad terms as follows: (1) Prealphabetic; (2) Partial alphabetic; (3) Full alphabetic; (4) Consolidated alphabetic. The first stage applies to “prereaders who operate with nonalphabetic information because they know little about the alphabetic system.” The second stage applies to “novice beginners who operate with rudimentary knowledge of some letter-sound relations.” The third level applies to students who “possess more complete knowledge involving grapheme-phoneme units and how these units form words.” The fourth level “applies to more advanced students who have knowledge of letter patterns as well as grapheme-phoneme units” (Ehri 1997, 240; 253-256). Moreover, it has been argued on the basis of these empirical studies that for children to become proficient in a modern writing system (i.e., their first writing system) a few years are normally required, not a few days or weeks (Ehri 2002, 7-28; Henderson 1985). Of course, it is readily apparent that emergent writing is often attested within “initial” periods of instruction, but proficiency (e.g., capacity to produce “documents” with minimal orthographic errors, and with the letters reflecting accurate morphology and stance as well as standard relative size) requires substantial time (see also D. L. Share and I. Levin 1999; P. H. K. Seymour 2005). Arguably, literacy rates were higher in ancient societies using an alphabetic writing system than in those using a non-alphabetic writing system (because the non-alphabetic systems are more difficult). But my point is this: literacy of the masses is not a necessary correlative of the presence of alphabetic writing (regarding a definition of literacy, see Rollston 2010, 127-128 et passim). Basically, literacy continued to be something associated with elites, even after the rise of alphabetic writing. Therefore, I would contend that the inventors of the alphabet were also members of officialdom and literate (i.e., capable of writing and reading Egyptian texts) and that this literacy was a precipitating factor in their ability to invent the alphabet. III. The Inventors of the Alphabet: Varia O. Goldwasser (2010) contends that the inventors of the alphabet were illiterate. She focuses heavily on the Serabit el-Hadem inscriptions. Here are some of her statements. “The [Egyptian] turquoise expeditions to Serabit brought together high officials, scribes, priests, architects, physicians, magicians, scorpion charmers, interpreters, caravan leaders, donkey drivers, miners, builders, soldiers, and sailors” (Goldwasser 2010, 39). She also states that “some high officials who left inscriptions at the Serabit temple present themselves as Egyptians, yet they also mention that they are Asiatic in origin, or have an Asiatic mother.” In addition, she notes that “the expedition lists at Serabit also contain the names of many ‘interpreters’” (Goldwasser 2010, 40). She affirms that the bottom line is that “there were surely many more Canaanites at Serabit than are listed as such in the Hieroglyphic inscriptions at the site.” Furthermore, she notes that “Nowhere in the many inscriptions at the site is there a mention of slaves. Canaanites, yes; slaves, no” (Goldwasser 2010, 40). She believes that the inventors of the alphabet were Canaanite and even argues that we may even know the names of these inventors of the alphabet: “They apparently emerged from among the circle of one Khebeded. He is mentioned in several Egyptian Hieroglyphic inscriptions at the site and is referred to as the ‘Brother of the Ruler of Retenu’” (Goldwasser 2010, 45), with Retenu being a means of referring to the southern Levant. She also affirms that “It is clear that this ‘Khebeded, brother of the Ruler of Retenu’ is a Canaanite” (Goldwasser 2010, 45). She contends that “Khebeded was involved with Egyptian expeditions to Serabit for more than a decade” and she argues that “he is clearly the highest-ranking Canaanite who left a Hieroglyphic inscription in the Serabit temple. He was probably a leader of the Canaanite workforce.” She contends that “the quality of the Hieroglyphs in an inscription that Khebeded added on a stela…is very poor.” She also states that “his inscription on Stela 92 would have been an embarrassment for an educated Egyptian scribe….(his) Hieroglyphic signs [are of] different sizes and crammed next to each other, and vacant spaces appear at the end of the line. But the Hieroglyphic pictograms in Stela 92 bear a remarkable resemblance to the signs in the Proto-Sinaitic inscriptions” (Goldwasser 2010, 46). She also states that “it may seem strange, but I believe the inventors of the alphabet were illiterate—that is, they could not read Egyptian with its hundreds of Hieroglpyic signs.” She then queries: “Why do I think so?” and then answers herself: “The letters in the Proto-Sinaitic inscriptions are very crude. They are not the same size. They are not written in a single direction….this suggests that the writers had mastered neither Egyptian Hieroglyphic nor any other complex, rule-governed script” (Goldwasser 2010, 44). An additional piece of her argument is her contention that the “Canaanite inventors of the alphabet ” unwittingly conflated two Egyptian signs for snakes into a single alphabetic sign for /n/ (Semitic: “nahash,” i.e., “snake”) and this “confirms their ignorance of the meaning of the Egyptian Hieroglyphs.” At this juncture, a summary of Goldwasser’s argument is in order. She believes that at Serabit there were high officials, including scribes. She mentions that the names of many “interpreters” are present. She believes that there were Canaanites at Serabit el-Khadem. She does not believe that the Canaanites were slaves. She mentions that some of the high officials that left Egyptian inscriptions were Asiatic (i.e., Canaanite). She notes that among the Canaanites was one man named Khebeded and she notes that he was the “brother of the Ruler of Retenu.” She states that the “inventors of the alphabet….apparently emerged from among the circle of Khebeded.” She states that Khebeded was involved with Egyptian expeditions to Serabit for more than a decade. She states that he is a high ranking Canaanite and that he left a Hieroglyphic inscription in the Serabit temple. She indicates that the quality of his Egyptian penmanship is “very poor, an embarrassment for an educated Egyptian scribe.” She affirms that the letters in the Proto-Sinaitic inscriptions are very crude. She even contends that between Khebeded’s inscription on stela 92 and the signs in the Proto-Sinaitic inscriptions there is a “remarkable resemblance.” But in spite of all of this, Goldwasser concludes that “I believe the inventors of the alphabet were illiterate—that is, they could not read Egyptian” (Goldwasser 2010, 43). Striking however, is the fact that she has actually made a good case for precisely the reverse. Namely, she has made a case for the fact that the inventors of the alphabet were Canaanite, that they were part of the circle associated with a high ranking Canaanite official named Khebeded, who was the brother of the Ruler of Retenu. Furthermore, she contends that he himself wrote a Hieroglyphic inscription and the poor penmanship of that inscription shows striking similarity to the script of the alphabetic inscriptions from Serabit. That is, basically she has made a case for contending that the inventor(s) of the alphabet were Canaanite, that this (or these) Canaanites functioned in official circles and that at least some of them were literate in Egyptian (even if not capable of writing the script with good penmanship!). Finally, regarding the presumed combination of two Egyptian signs for two different kinds of snakes into a single alphabetic sign (that signified the phoneme /n/, from “nahash” “snake”), I would simply state that this could just as readily be understood as a conscious decision (after all, through time, humans often combine two similar entities, for any number of reasons, especially within the realm of language). Basically, I have thought for a number of years now that the cumulative weight of the evidence suggests that: (1) the Muttersprache of the inventors of the alphabet was a Northwest Semitic language, (2) and that the inventors of the alphabet functioned in a reasonably high status role within a component (or components) of the Egyptian administrative apparatus, that is, officialdom. (3) I believe that it is reasonable and tenable to argue that they learned Egyptian writing from Egyptian scribes. (4) I contend that it would be improbable that illiterate miners were capable of, or responsible for, the invention of the alphabet. (5) Ultimately, writing in antiquity was an elite venture and those that invented the alphabet were Northwest Semitic speakers, arguably they were officials in the Egyptian apparatus, quite capable with the complex Egyptian writing system. This, I believe, best accounts for the maximum amount of data. Bibliography Albright, W. F. 1960 Discussion. Pp. 94-123 in City Invincible: A Symposium on Urbanization and Cultural Development in the Ancient Near East, eds. C. H. Kraeling and R. M. Adams. Chicago: University of Chicago Press. 1966 The Proto-Sinaitic Inscriptions and their Decipherment. Harvard Theological Studies 22. Cambridge: Harvard University Press. Baines, J., and Eyre, C. J. 1983 Four Notes on Literacy. Göttinger Miszellen 62: 65-96. Cross, F. M. 2003 Leaves from An Epigrapher’s Notebook: Collected Papers in Hebrew and West Semitic Palaeography and Epigraphy. Harvard Semitic Studies 51. Winona Lake: Eisenbrauns. Darnell, J. C., Dobbs-Allsopp, F. W., Lundberg, M. J., McCarter, P. K., Zuckerman, B. 2005 Two Early Alphabetic Inscriptions from Wadi el-Hôl. Pp. 63-124 in The Annual of the American Schools of Oriental Research 59. Boston: American Schools of Oriental Research. Ehri, L. 1997 Learning to Read and Learning to Spell are One and the Same, Almost. Pp. 237-69 in Learning to Spell: Research, Theory, and Practice across Languages, eds. C. A. Perfetti, L. Rieben, and M. Fayol. Mahway: Erlbaum. 2002 Phases of Acquisition in Learning to Read Words and Implications for Teaching. Pp. 7-28 in Learning and Teaching Reading, eds. R. Stainthorp and R. Thomlinson. British Journal of Educational Psychology: Monograph Series 1. Leicester: British Psychological Society. Gardiner, A. H. 1906 Serabit. Pp. 129-32 in Researches in Sinai, ed. W. M. Flinders Petrie. London. 1916 The Egyptian Origin of the Semitic Alphabet. The Journal of Egyptian Archaeology 3: 1-16. Goldwasser, O. 2010 How the Alphabet was Born from Hieroglyphs. Biblical Archaeology Review 36/2 (March-April): 36-50, 74. Hamilton, G. J. 2006 Origins of the West Semitic Alphabet in Egyptian Scripts. Catholic Biblical Quarterly Monograph Series 40. Washington, DC: Catholic Biblical Association. Harris, W. V. 1989 Ancient Literacy. Cambridge: Harvard University Press. Hess, R. S. 2006 Writing about Literacy: Abecedaries and Evidence for Literacy in Ancient Israel. Vetus Testamentum 56: 342-346. Larsen, M. T. 1989 What They Wrote on Clay. Pp. 121-148 in Literacy and Society, eds. K. Schousboe and M. T. Larsen. Copenhagen: Akademisk Forlag. McCarter, P. Kyle, Jr. 1975 The Antiquity of the Greek Alphabet. Harvard Semitic Monographs 9. Missoula, MT: Scholars Press. 1996 Ancient Inscriptions: Voices from the Biblical World. Washington, DC: Biblical Archaeology Society. Naveh, J. 1987 Early History of the Alphabet: An Introduction to West Semitic Epigraphy and Palaeography. 2nd ed. Jerusalem: Magnes. Rollston, C. A. 2001 Ben Sira 38:24-39:11 and the Egyptian Satire of the Trades: A Reconsideration. Journal of Biblical Literature 120: 131-139. 2006 Scribal Education in Ancient Israel: The Old Hebrew Epigraphic Evidence. Bulletin of the American Schools of Oriental Research 344: 47-74. 2008a The Pheonician Script of the Tel Zayit Abecedary and Putative Evidence for Israelite Literacy. Pp. 61-96 in Literature Culture and Tenth-Century Canaan: The Tel Zayit Abecedary in Context, eds. Ron E. Tappy and P. Kyle McCarter: Eisenbrauns. 2008b The Dating of the Early Royal Byblian (Phoenician): A Response to Benjamin Sass. Maarav 15: 57-93. 2010 Writing and Literacy in the World of Ancient Israel: Epigraphic Evidence from the Iron Age. Archaeology and Biblical Studies 11, Tammi Schneider, Editor. Atlanta: Society of Biblical Literature. Sass, B. 1988 The Genesis of the Alphabet and Its Development in the Second Millenium B.C. Ägypten und Altes Testament 13. Wiesbaden: Harrassowitz. Seymour, P. H. K. 2005 Early Reading Development in European Orthographies. Pp. 296-315 in The Science of Reading: A Handbook, eds. M. J. Snowling and C. Hulme. Oxford: Blackwell. Share, D. L., and Levin, I. 1999 Learning to Read and Write in Hebrew. Pp. 89-111 in Learning to Read and Write: A Cross-Linguistic Perspective, eds. M. Harris and G. Hatano. Cambridge: Cambridge University Press. Young, I. M. 1998a Israelite Literacy: Interpreting the Evidence Part I. Vetus Testamentum 48: 239-253. 1998b Israelite Literacy: Interpreting the Evidence, Part II. Vetus Testamentum 48: 408-422. John the Baptist and the Reliquary of Sveti Ivan: Not a Match This article is a slightly revised (June 2012) version of a post published here in August 2010, at the time of the initial press release. Fortunately, the most recent press reports (June 2012) are more circumspect and cautious than those of two years ago. Furthermore, please allow me to emphasize here that these excavations are useful and impressive, with some significant archaeological material culture having been excavated. Nevertheless, the conclusion must still be that there is no good evidence to suggest that these bones are probably those of John the Baptist. _ I. Summary of the Salient Details of the ‘Sveti Ivan’ Excavation and the Claims regarding the Reliquary A portion of a small island known as ‘Sveti Ivan’ (a Bulgarian term that means “Saint John”) has been the site of excavations for a number of years.  This island is located in the Black Sea, about a kilometer from the Bulgarian town of Sozopol, one of the oldest on Bulgaria’s southern coast.  Kazimir Popkonstantinov is the director of the excavations on Sveti Ivan.   Aerial images reveal that there are (at least) two prominent sets of monumental archaeological remains on the island.  These have been affirmed to be the remains of: (1) a church of ca. the 6th century CE; (2) and a monastery (and church) of ca. the 13th and 14th centuries CE. Under the ruins of the 6th century church are the remains of an older basilica, and these older remains have been dated to ca. the 5th century CE.  It was in the ruins of this older basilica that a reliquary was found.  (1) The reliquary’s measurements are ca. 20.5 cm. x 12.5. cm. x. 14.5 cm.  The reliquary is reported to have been made of alabaster.  Within this reliquary were found bone fragments (six human bones and three animals bones), and the human bones included portions of a skull, a hand, a tooth, a rib, and an arm bone.  (2) Near the reliquary was a small sandstone box measuring ca. 4 cm. x 6 cm.  On this small sandstone box is a Greek inscription that reportedly says “May God save you, servant Thomas.  To Saint John, June 24.” Popkonstantinov had stated (in 2010) that the inscription is the “key” to the interpretation of the finds.  That is, based on this inscription, he has stated that the remains found in the alabaster reliquary may very well be those of John the Baptist, a figure of the Greek New Testament. II. Summary of the Salient Features of the Greek New Testament’s Statements regarding John the Baptist Although New Testament scholarship has cogently argued for more than a century that the New Testament documents are not historical in all of their details, it has been argued convincingly that certain things can be known about John the Baptist with a high degree of historical certainty.  Namely, (1) He was a Jewish Apocalypticist of the 1st century CE; (2) He was connected in some fashion with a movement surrounding Jesus of Nazareth; (3) John the Baptist was imprisoned in the Galilee by Herod Antipas (note: Herod was the Tetrarch of Galilee and Perea from ca. 4 BCE to ca. 39 CE).  (4)  John was martyred by Herod Antipas, arguably some time between 26 CE and 30 CE.  (5) John had followers (referred to in Greek as mathetai) and these followers buried John the Baptist after he was killed, arguably (according to the Marcan tradition), in a tomb (for these details, see Mark 6:14-29; Matt 14:1-12; Luke 9:7-9; for the birth narratives of John the Baptist, see Luke 1; for his apocalyptic message, see Mark 1:2-8; Matt 3:1-12; Luke 3:1-20).  (6) Josephus has some material about John, but this material does not alter the details about John the Baptist that I have noted here. III.  A Critique of Popkonstantinov’s (2010) Arguments, and any similar arguments made now in 2012 1. John the Baptist was buried in a tomb in Palestine, arguably in the Galilee (where he died).  (2) John the Baptist died during the early 1st century CE.  Therefore, without some compelling evidence for the moving of the body (or portions thereof) of John the Baptist (centuries later!) from the place of burial in Palestine, it is not cogent or prudent to propose that the remains found on a small island in the Black Sea, in the archaeological ruins of a basilica of the 5th century CE, are those of a Palestinian Jews named John the Baptist who lived, died, and was buried in the 1st century CE, in Palestine. 3. To be sure, Popkonstantinov has argued (2010) that the inscription on the sandstone box near the reliquary is the “key” to his interpretation.  However, this is not particularly convincing.  After all, the inscription certainly does *not* state that “these are the remains of John the Baptist.”  4. The date of June 24th is one of the feast days for John the Baptist (e.g., within Orthodox Christianity), but this cannot be construed as evidence that the bones themselves are actually those of John (indeed, the date of the founding of this church would argue against this, as the church was founded centuries after the death and burial of John the Baptist). 5. Furthermore, the inscription is not on the reliquary (where the bones were found), but rather, they are on a sandstone box that was found *near* the reliquary.  One might propose that the bones are those of a certain man named “Thomas,” but even this is not necessarily the case, for a number of reasons (not the least of which is the fact that the reliquary and sandstone box need not have belonged to the same person or been deposited at precisely the same time in the basilica). 6. Mostly, the inscription strikes me as a plea of a pious believer from the island of Sveti Ivan to a famed patron saint, namely, a plea to John the Baptist.  That’s it. That’s the way I would interpret the totality of the evidence. 7. Note that Popkonstantinov had stated (2010) that he knew of no DNA database for the relatives of John the Baptist.  This is correct…there is certainly *not* such a database of DNA data for the relatives of John the Baptist.  8. Of course, carbon tests have recently been done on three of the human bone fragments, and these are ostensibly helpful in establishing the basic chronological horizon for the interred remains (assuming they have not been handled so much that carbon dating will be very difficult or almost impossible), but even these sort of data can do no more than suggest that these bones came from the same basic chronological horizon as John the Baptist. That’s a far cry from demonstrating that these are the actual bones of John the Baptist. Ultimately, I would contend that for someone to suggest that these bones could be those of John the Baptist, a figure of 1st century CE Palestine, is tenuous in the extreme.  In this connection I should note that Popkonstantinov (knowing that his understanding of the evidence is strained to the breaking point) was quoted as saying (in 2010): “Here, I believe, the science stops.  Since we cannot prove the attribution of any of the relics with scientific methods, we have to be tolerant of those who want to believe that they are” (Popkonstantinov).  I would gently suggest, though, that archaeological and literary analyses are about evidence, not about authority, faith, or piety.  Thus, with all due respect, it is necessary to state that Popkonstantinov’s conclusions do not follow from the evidence. IV.  For the Sake of Argument, Here are the Sort of Data that would be Needed for Popkonstantinov’s Case. 1. A reliable ancient tradition, preferably from the late(r) 1st century or very early 2nd century CE, stating that the bones of John the Baptist had been moved to an island in the Black Sea;  2. An inscription on the burial box that stated something like “The bones of John the Baptist” (i.e., name and title…something such as “John” would not be sufficient); 3.  A palaeographic date for the inscription itself that was late 1st century or very early 2nd century (after all, arguably no one in later centuries would be able to locate precisely the burial site of John the Baptist in Palestine and it may be that even in the late 1st century no one would have been able to have done so!).  (4) Carbon 14 dating of the bones that yielded a 1st century CE date.  We now have a carbon date which is helpful, but without the other data just outlined above (numbers 1-3), the carbon dates cannot be considered particularly useful in identifying the remains, even if they do come from the same basic chronological horizon. 5. Thus, in light of the general dearth of necessary data, it is necessary to conclude that these bones are not those of John the Baptist himself. Sincerely, Christopher Rollston The Hazor Tablet Fragments: Further Details and Musings <here is a image bee47095d6b7b1fc-9905eeeba387847b> Fragment of Hazor Tablet Data about the Cuneiform Fragments from Hazor continue to be released.  Here are some of the most recent details: (1) There are two fragments.  One of the fragments is very small indeed. (2) Akkadian words that can be translated into English as “master,” “slave,” and arguably “tooth” have been read.  (3) Wayne Horowitz has been cited as stating that the style is reminiscent of the phrasing of the Code of Hammurabi (i.e., the famed Old Babylonian Law “Code”).  All of these are useful data.  Further details will certainly soon be forthcoming. Reflections.  At this juncture, (1) It seems that there is the assumption that these two fragments are from a single tablet.  I think that this seems reasonable.  Of course, the best means of determining this sort of thing is a certain and clear join of fragments .  Often, though (in the absence of a certain and clear join), it is reasonable to posit that two fragments are of the same tablet based on the proximity of the fragments (i.e., found in situ next to each other).  Nevertheless, proximity of fragments cannot be considered quite as definitive as a clear and certain join.  (2) Legal texts are very common in the ancient Near East and are attested at numerous sites through the course of time.  (3) Hammurabi is a very famous “Code.”  Nevertheless, “Codes” such as Eshunna and Lipit Ishtar are also known.  Also, note the Middle Assyrian Laws…a fairly large corpus of legal texts (and sometimes the term “code” is used of these as well).  That is, Hammurabi is arguably the most famous “code” (i.e., famous now, in the modern period) but it is not the only extant law “code.” Note: in terms of chronological horizon, Expedition Director Amnon Ben-Tor has recently characterized these fragments as “Mari Age” (Itamar Singer, personal correspondence).   Along these lines, it should be noted that, as Raymond Westbrook (my teacher of all things legal) often stated…the term “law code” cannot be readily used of these ancient Near Eastern texts, as they are not “codes” in anything approximating modern legal codes (as modern legal codes are considerably more extensive).  Thus, I use the term “code” of these ancient Near Eastern texts with Westbrook’s caveat in mind.  (4) Words that can be translated “man,” or “citizen,” or “master,” or “slave” are quite common in legal texts (e.g., , “awilum” meaning “man,” “citizen,” etc. or “wardu” meaning “slave,” or “servant”).  (5) “Shumma Awilum” is a phrase that can be rendered “If a man,” and it is the standard way that each consecutive Law of Hammuarib begins (the same is basically true of the various law “codes”).  As noted above, Horowitz refers to the style of these new fragments as similar to Hammurabi.  This causes me to suggest that something similar to this phrase has been deciphered in the new Hazor fragments.  (6) Within one story Horowitz is cited as saying: that this latest discovery “opens an interesting avenue for possible further investiation of a connection between Biblical Law and the Code of Hammurabi.”  I concur and suspect (as I mentioned in a previous post) that the contours of this discussion were articulated nicely in two recent Maarav articles. Christopher Rollston Legal Tablet from Hazor Here is an auspicious press release from the Hazor Expedition: Hazor Law Code Fragments The Selz Foundation Hazor Excavations in Memory of Yigael Yadin have recovered two fragments of a cuneiform tablet preserving portions of a law code at Hazor. The text parallels portions of the famous Law Code of Hammurabi, and, to a certain extent even the Biblical “tooth for a tooth”. The team is presently working its way down towards a monumental structure dating to the Bronze Age, where more tablets are expected to be found. The tablet is currently being studied at the Hebrew University. More details to follow as soon as possible. The excavations are sponsored by the Hebrew university and the Israel Exploration Society, and take place in the Hazor National Park. End of press release. _________ ________ Rollston’s Bibliographic Suggestions and Brief Reflections on this Subject… Because the Code of Hammurabi is mentioned (in the press release), readers might wish to refer to the discussion published in MAARAV between David Wright and Bruce Wells.  Namely, Wright, “The Laws of Hammurabi as a Source for the Covenant Collection…” (MAARAV 10 [2003]: 11-87), and then a response from Bruce Wells entitled “The Covenant Code and Near Eastern Legal Traditions: A Response to David P. Wright” (MAARAV 13 [2006]: 85-118), then Wright’s reply entitled “The Laws of Hammurabi and the Covenant Code: A Response to Bruce Wells” (MAARAV 13 [2006]: 211-260).  Wright subsequently published a book that revolves around this subject matter (and the substance of Wright’s MAARAV articles are contained in the book). In any case, because of the nature of this new Hazor find, and the wording of the press release, I suspect that the same issues that Wells and Wright discuss (in a very collegial, but direct, fashion) will soon surface again, this time as part of this new Hazor tablet. Most readers will already know this, but suffice it to state that the amount of extant legal material in Mesopotamian cuneiform is vast…coming from the Center (i.e., Mesopotamia proper) and also from the Periphery (e.g., Syria). Christopher Rollston
http://www.rollstonepigraphy.com/eglaterecebf/ffdfaf5207158.shtml/?paged=5
Internet Engineering Task Force (IETF) E. Ivov, Ed. Request for Comments: 6465 Jitsi Category: Standards Track E. Marocco, Ed. ISSN: 2070-1721 Telecom Italia J. Lennox Vidyo December 2011 A Real-time Transport Protocol (RTP) Header Extension for Mixer-to-Client Audio Level Indication Abstract This document describes a mechanism for RTP-level mixers in audio conferences to deliver information about the audio level of individual participants. Such audio level indicators are transported in the same RTP packets as the audio data they pertain to. Status of This Memo This is an Internet Standards Track document. This document is a product of the Internet Engineering Task Force (IETF). It represents the consensus of the IETF community. It has received public review and has been approved for publication by the Internet Engineering Steering Group (IESG). Further information on Internet Standards is available in Section 2 of RFC 5741. Information about the current status of this document, any errata, and how to provide feedback on it may be obtained at http://www.rfc-editor.org/info/rfc6465. Copyright Notice Copyright (c) 2011 IETF Trust and the persons identified as the document authors. All rights reserved. This document is subject to BCP 78 and the IETF Trust's Legal Provisions Relating to IETF Documents (http://trustee.ietf.org/license-info) in effect on the date of publication of this document. Please review these documents carefully, as they describe your rights and restrictions with respect to this document. Code Components extracted from this document must include Simplified BSD License text as described in Section 4.e of the Trust Legal Provisions and are provided without warranty as described in the Simplified BSD License. Ivov, et al. Standards Track [Page 1] RFC 6465 Mixer-to-Client Audio Level Indication December 2011 Table of Contents 1. Introduction ....................................................2 2. Terminology .....................................................4 3. Protocol Operation ..............................................4 4. Audio Levels ....................................................5 5. Signaling Information ...........................................7 6. Security Considerations .........................................9 7. IANA Considerations ............................................10 8. Acknowledgments ................................................10 9. References .....................................................10 9.1. Normative References ......................................10 9.2. Informative References ....................................11 Appendix A. Reference Implementation ..............................12 A.1. AudioLevelCalculator.java .................................12 1. Introduction "A Framework for Conferencing with the Session Initiation Protocol (SIP)" [RFC4353] presents an overall architecture for multi-party conferencing. Among others, the framework borrows from RTP [RFC3550] and extends the concept of a mixer entity "responsible for combining the media streams that make up a conference, and generating one or more output streams that are delivered to recipients". Every participant would hence receive, in a flat single stream, media originating from all the others. Using such centralized mixer-based architectures simplifies support for conference calls on the client side, since they would hardly differ from one-to-one conversations. However, the method also introduces a few limitations. The flat nature of the streams that a mixer would output and send to participants makes it difficult for users to identify the original source of what they are hearing. Mechanisms that allow the mixer to send to participants cues on current speakers (e.g., the contributing source (CSRC) fields in RTP [RFC3550]) only work for speaking/silent binary indications. There are, however, a number of use cases where one would require more detailed information. Possible examples include the presence of background chat/noise/music/typing, someone breathing noisily in their microphone, or other cases where identifying the source of the disturbance would make it easy to remove it (e.g., by sending a private IM to the concerned party asking them to mute their microphone). A more advanced scenario could involve an intense discussion between multiple participants that the user does not personally know. Audio level information would help better recognize the speakers by associating with them complex (but still human readable) characteristics like loudness and speed, for example. Ivov, et al. Standards Track [Page 2] RFC 6465 Mixer-to-Client Audio Level Indication December 2011 One way of presenting such information in a user-friendly manner would be for a conferencing client to attach audio level indicators to the corresponding participant-related components in the user interface. One possible example is displayed in Figure 1, where levels can help users determine that Alice is currently the active speaker, Carol is mute, and Bob and Dave are sending some background noise. ________________________ | | | 00:42 | Weekly Call | |________________________| | | | | | Alice |====== | (S) | | | | Bob |= | | | | | Carol | | (M) | | | | Dave |=== | | | | |________________________| Figure 1: Displaying Detailed Speaker Information to the User by Including Audio Level for Every Participant Implementing a user interface like the above requires analysis of the media sent from other participants. In a conventional audio conference, this is only possible for the mixer, since all other conference participants are generally receiving a single, flat audio stream and therefore have no immediate way of determining individual audio levels. This document specifies an RTP extension header that allows such mixers to deliver audio level information to conference participants by including it directly in the RTP packets transporting the corresponding audio data. The header extension in this document is different than, but complementary to, the one defined in [RFC6464], which defines a mechanism by which clients can indicate to audio mixers the levels of the audio in the packets they send. Ivov, et al. Standards Track [Page 3] RFC 6465 Mixer-to-Client Audio Level Indication December 2011 2. Terminology The key words "MUST", "MUST NOT", "REQUIRED", "SHALL", "SHALL NOT", "SHOULD", "SHOULD NOT", "RECOMMENDED", "MAY", and "OPTIONAL" in this document are to be interpreted as described in RFC 2119 [RFC2119]. 3. Protocol Operation According to RFC 3550 [RFC3550], a mixer is expected to include in outgoing RTP packets a list of identifiers (CSRC IDs) indicating the sources that contributed to the resulting stream. The presence of such CSRC IDs allows RTP clients to determine, in a binary way, the active speaker(s) in any given moment. The RTP Control Protocol (RTCP) also provides a basic mechanism to map the CSRC IDs to user identities through the CNAME field. More advanced mechanisms can exist, depending on the signaling protocol used to establish and control a conference. In the case of the Session Initiation Protocol [RFC3261], for example, "A Session Initiation Protocol (SIP) Event Package for Conference State" [RFC4575] defines a <src-id> tag that binds CSRC IDs to media streams and SIP URIs. This document describes an RTP header extension that allows mixers to indicate the audio level of every contributing conference participant (CSRC) in addition to simply indicating their on/off status. This new header extension uses the general mechanism for RTP header extensions as described in [RFC5285]. Each instance of this header contains a list of one-octet audio levels expressed in -dBov, with values from 0 to 127 representing 0 to -127 dBov (see Figures 2 and 3). Appendix A provides a reference implementation indicating one way of obtaining such values from raw audio samples. Every audio level value pertains to the CSRC identifier located at the corresponding position in the CSRC list. In other words, the first value would indicate the audio level of the conference participant represented by the first CSRC identifier in that packet, and so forth. The number and order of these values MUST therefore match the number and order of the CSRC IDs present in the same packet. When encoding audio level information, a mixer SHOULD include in a packet information that corresponds to the audio data being transported in that same packet. It is important that these values follow the actual stream as closely as possible. Therefore, a mixer SHOULD also calculate the values after the original contributing stream has undergone possible processing such as level normalization, and noise reduction, for example. Ivov, et al. Standards Track [Page 4] RFC 6465 Mixer-to-Client Audio Level Indication December 2011 It can sometimes happen that a conference involves more than a single mixer. In such cases, each of the mixers MAY choose to relay the CSRC list and audio level information they receive from peer mixers (as long as the total CSRC count remains below 16). Given that the maximum audio level is not precisely defined by this specification, it is likely that in such situations average audio levels would be perceptibly different for the participants located behind the different mixers. 4. Audio Levels The audio level header extension carries the level of the audio in the RTP payload of the packet with which it is associated. This information is carried in an RTP header extension element as defined by "A General Mechanism for RTP Header Extensions" [RFC5285]. The payload of the audio level header extension element can be encoded using either the one-byte or two-byte header defined in [RFC5285]. Figures 2 and 3 show sample audio level encodings with each of these header formats. 0 1 2 3 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 +-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+ | ID | len=2 |0| level 1 |0| level 2 |0| level 3 | +-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+ Figure 2: Sample Audio Level Encoding Using the One-Byte Header Format 0 1 2 3 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 +-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+ | ID | len=3 |0| level 1 |0| level 2 | +-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+ |0| level 3 | 0 (pad) | ... +-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+ Figure 3: Sample Audio Level Encoding Using the Two-Byte Header Format In the case of the one-byte header format, the 4-bit len field is the number minus one of data bytes (i.e., audio level values) transported in this header extension element following the one-byte header. Therefore, the value zero in this field indicates that one byte of data follows. In the case of the two-byte header format, the 8-bit len field contains the exact number of audio levels carried in the Ivov, et al. Standards Track [Page 5] RFC 6465 Mixer-to-Client Audio Level Indication December 2011 extension. RFC 3550 [RFC3550] only allows RTP packets to carry a maximum of 15 CSRC IDs. Given that audio levels directly refer to CSRC IDs, implementations MUST NOT include more than 15 audio level values. The maximum value allowed in the len field is therefore 14 for the one-byte header format and 15 for the two-byte header format. Note: Audio levels in this document are defined in the same manner as is audio noise level in the RTP Payload Comfort Noise specification [RFC3389]. In [RFC3389], the overall magnitude of the noise level in comfort noise is encoded into the first byte of the payload, with spectral information about the noise in subsequent bytes. This specification's audio level parameter is defined so as to be identical to the comfort noise payload's noise-level byte. The magnitude of the audio level itself is packed into the seven least significant bits of the single byte of the header extension, shown in Figures 2 and 3. The least significant bit of the audio level magnitude is packed into the least significant bit of the byte. The most significant bit of the byte is unused and always set to 0. The audio level is expressed in -dBov, with values from 0 to 127 representing 0 to -127 dBov. dBov is the level, in decibels, relative to the overload point of the system, i.e., the highest-intensity signal encodable by the payload format. (Note: Representation relative to the overload point of a system is particularly useful for digital implementations, since one does not need to know the relative calibration of the analog circuitry.) For example, in the case of u-law (audio/pcmu) audio [ITU.G711], the 0 dBov reference would be a square wave with values +/- 8031. (This translates to 6.18 dBm0, relative to u-law's dBm0 definition in Table 6 of [ITU.G711].) The audio level for digital silence -- for a muted audio source, for example -- MUST be represented as 127 (-127 dBov), regardless of the dynamic range of the encoded audio format. The audio level header extension only carries the level of the audio in the RTP payload of the packet with which it is associated, with no long-term averaging or smoothing applied. That level is measured as a root mean square of all the samples in the measured range. To simplify implementation of the encoding procedures described here, this specification provides a sample Java implementation (see Appendix A) of an audio level calculator that helps obtain such values from raw linear Pulse Code Modulation (PCM) audio samples. Ivov, et al. Standards Track [Page 6] RFC 6465 Mixer-to-Client Audio Level Indication December 2011 5. Signaling Information The URI for declaring the audio level header extension in a Session Description Protocol (SDP) extmap attribute and mapping it to a local extension header identifier is "urn:ietf:params:rtp-hdrext:csrc-audio-level". There is no additional setup information needed for this extension (i.e., no extension attributes). An example attribute line in the SDP for a conference might be: a=extmap:7 urn:ietf:params:rtp-hdrext:csrc-audio-level The above mapping will most often be provided per media stream (in the media-level section(s) of SDP, i.e., after an "m=" line) or globally if there is more than one stream containing audio level indicators in a session. Presence of the above attribute in the SDP description of a media stream indicates that RTP packets in that stream, which contain the level extension defined in this document, will be carrying such an extension with an ID of 7. Conferencing clients that support audio level indicators and have no mixing capabilities would not be able to provide content for this audio level extension and would hence have to always include the direction parameter in the "extmap" attribute with a value of "recvonly". Conference focus entities with mixing capabilities can omit the direction or set it to "sendrecv" in SDP offers. Such entities would need to set it to "sendonly" in SDP answers to offers with a "recvonly" parameter and to "sendrecv" when answering other "sendrecv" offers. This specification only defines the use of the audio level extensions in audio streams. They MUST NOT be advertised with other media types, such as video or text, for example. Figures 4 and 5 show two example offer/answer exchanges between a conferencing client and a focus, and between two conference focus entities. Ivov, et al. Standards Track [Page 7] RFC 6465 Mixer-to-Client Audio Level Indication December 2011 SDP Offer: v=0 o=alice 2890844526 2890844526 IN IP6 host.example.com s=- c=IN IP6 host.example.com t=0 0 m=audio 49170 RTP/AVP 0 4 a=rtpmap:0 PCMU/8000 a=rtpmap:4 G723/8000 a=extmap:1/recvonly urn:ietf:params:rtp-hdrext:csrc-audio-level SDP Answer: v=0 i=A Seminar on the session description protocol o=conf-focus 2890844730 2890844730 IN IP6 focus.example.net s=- c=IN IP6 focus.example.net t=0 0 m=audio 52544 RTP/AVP 0 a=rtpmap:0 PCMU/8000 a=extmap:1/sendonly urn:ietf:params:rtp-hdrext:csrc-audio-level Figure 4: A Client-Initiated Example SDP Offer/Answer Exchange Negotiating an Audio Stream with One-Way Flow of Audio Level Information Ivov, et al. Standards Track [Page 8] RFC 6465 Mixer-to-Client Audio Level Indication December 2011 SDP Offer: v=0 i=Un seminaire sur le protocole de description des sessions o=fr-focus 2890844730 2890844730 IN IP6 focus.fr.example.net s=- c=IN IP6 focus.fr.example.net t=0 0 m=audio 49170 RTP/AVP 0 a=rtpmap:0 PCMU/8000 a=extmap:1/sendrecv urn:ietf:params:rtp-hdrext:csrc-audio-level SDP Answer: v=0 i=A Seminar on the session description protocol o=us-focus 2890844526 2890844526 IN IP6 focus.us.example.net s=- c=IN IP6 focus.us.example.net t=0 0 m=audio 52544 RTP/AVP 0 a=rtpmap:0 PCMU/8000 a=extmap:1/sendrecv urn:ietf:params:rtp-hdrext:csrc-audio-level Figure 5: An Example SDP Offer/Answer Exchange between Two Conference Focus Entities with Mixing Capabilities Negotiating an Audio Stream with Bidirectional Flow of Audio Level Information 6. Security Considerations 1. This document defines a means of attributing audio level to a particular participant in a conference. An attacker may try to modify the content of RTP packets in a way that would make audio activity from one participant appear to be coming from another participant. 2. Furthermore, the fact that audio level values would not be protected even in a Secure Real-time Transport Protocol (SRTP) session [RFC3711] might be of concern in some cases where the activity of a particular participant in a conference is confidential. Also, as discussed in [SRTP-VBR-AUDIO], an attacker might be able to infer information about the conversation, possibly with phoneme-level resolution. 3. Both of the above are concerns that stem from the design of the RTP protocol itself, and they would probably also apply when using CSRC identifiers in the way specified in RFC 3550 [RFC3550]. It is therefore important that, according to the Ivov, et al. Standards Track [Page 9] RFC 6465 Mixer-to-Client Audio Level Indication December 2011 needs of a particular scenario, implementors and deployers consider the use of header extension encryption [SRTP-ENCR-HDR] or a lower-level security and authentication mechanism such as IPsec [RFC4301], for example. 7. IANA Considerations This document defines a new extension URI in the RTP Compact Header Extensions subregistry of the Real-Time Transport Protocol (RTP) Parameters registry, according to the following data: Extension URI: urn:ietf:params:rtp-hdrext:csrc-audio-level Description: Mixer-to-client audio level indicators Contact: [email protected] Reference: RFC 6465 8. Acknowledgments Lyubomir Marinov contributed level measurement and rendering code. Keith Drage, Roni Even, Miguel A. Garcia, John Elwell, Kevin P. Fleming, Ingemar Johansson, Michael Ramalho, Magnus Westerlund, and several others provided helpful feedback over the avt and avtext mailing lists. Jitsi's participation in this specification is funded by the NLnet Foundation. 9. References 9.1. Normative References [RFC2119] Bradner, S., "Key words for use in RFCs to Indicate Requirement Levels", BCP 14, RFC 2119, March 1997. [RFC3550] Schulzrinne, H., Casner, S., Frederick, R., and V. Jacobson, "RTP: A Transport Protocol for Real-Time Applications", STD 64, RFC 3550, July 2003. [RFC5285] Singer, D. and H. Desineni, "A General Mechanism for RTP Header Extensions", RFC 5285, July 2008. Ivov, et al. Standards Track [Page 10] RFC 6465 Mixer-to-Client Audio Level Indication December 2011 9.2. Informative References [ITU.G711] International Telecommunication Union, "Pulse Code Modulation (PCM) of Voice Frequencies", ITU-T Recommendation G.711, November 1988. [RFC3261] Rosenberg, J., Schulzrinne, H., Camarillo, G., Johnston, A., Peterson, J., Sparks, R., Handley, M., and E. Schooler, "SIP: Session Initiation Protocol", RFC 3261, June 2002. [RFC3389] Zopf, R., "Real-time Transport Protocol (RTP) Payload for Comfort Noise (CN)", RFC 3389, September 2002. [RFC3711] Baugher, M., McGrew, D., Naslund, M., Carrara, E., and K. Norrman, "The Secure Real-time Transport Protocol (SRTP)", RFC 3711, March 2004. [RFC4301] Kent, S. and K. Seo, "Security Architecture for the Internet Protocol", RFC 4301, December 2005. [RFC4353] Rosenberg, J., "A Framework for Conferencing with the Session Initiation Protocol (SIP)", RFC 4353, February 2006. [RFC4575] Rosenberg, J., Schulzrinne, H., and O. Levin, Ed., "A Session Initiation Protocol (SIP) Event Package for Conference State", RFC 4575, August 2006. [RFC6464] Lennox, J., Ed., Ivov, E., and E. Marocco, "A Real-time Transport Protocol (RTP) Header Extension for Client-to- Mixer Audio Level Indication", RFC 6465, December 2011. [SRTP-ENCR-HDR] Lennox, J., "Encryption of Header Extensions in the Secure Real-Time Transport Protocol (SRTP)", Work in Progress, October 2011. [SRTP-VBR-AUDIO] Perkins, C. and JM. Valin, "Guidelines for the use of Variable Bit Rate Audio with Secure RTP", Work in Progress, July 2011. Ivov, et al. Standards Track [Page 11] RFC 6465 Mixer-to-Client Audio Level Indication December 2011 Appendix A. Reference Implementation This appendix contains Java code for a reference implementation of the level calculation and rendering methods. The code is not normative and is by no means the only possible implementation. Its purpose is to help implementors add audio level support to mixers and clients. The Java code contains an AudioLevelCalculator class that calculates the sound pressure level of a signal with specific samples. It can be used in mixers to generate values suitable for the level extension headers. The implementation is provided in Java but does not rely on any of the language specifics and can be easily ported to another language. A.1. AudioLevelCalculator.java <CODE BEGINS> /* Copyright (c) 2011 IETF Trust and the persons identified as authors of the code. All rights reserved. Redistribution and use in source and binary forms, with or without modification, is permitted pursuant to, and subject to the license terms contained in, the Simplified BSD License set forth in Section 4.c of the IETF Trust's Legal Provisions Relating to IETF Documents (http://trustee.ietf.org/license-info). */ /** * Calculates the audio level of specific samples of a signal * relative to overload. */ public class AudioLevelCalculator { /** * Calculates the audio level of a signal with specific * <tt>samples</tt>. * * @param samples the samples whose audio level we need to * calculate. The samples are specified as an <tt>int</tt> * array starting at <tt>offset</tt>, extending <tt>length</tt> * number of elements, and each <tt>int</tt> element in the * specified range representing a sample whose audio level we Ivov, et al. Standards Track [Page 12] RFC 6465 Mixer-to-Client Audio Level Indication December 2011 * need to calculate. Though a sample is provided in the * form of an <tt>int</tt> value, the sample size in bits * is determined by the caller via <tt>overload</tt>. * * @param offset the offset in <tt>samples</tt> at which the * samples start. * * @param length the length of the signal specified in * <tt>samples<tt>, starting at <tt>offset</tt>. * * @param overload the overload (point) of <tt>signal</tt>. * For example, <tt>overload</tt> can be {@link Byte#MAX_VALUE} * for 8-bit signed samples or {@link Short#MAX_VALUE} for * 16-bit signed samples. * * @return the audio level of the specified signal. */ public static int calculateAudioLevel( int[] samples, int offset, int length, int overload) { /* * Calculate the root mean square (RMS) of the signal. */ double rms = 0; for (; offset < length; offset++) { double sample = samples[offset]; sample /= overload; rms += sample * sample; } rms = (length == 0) ? 0 : Math.sqrt(rms / length); /* * The audio level is a logarithmic measure of the * rms level of an audio sample relative to a reference * value and is measured in decibels. */ double db; /* * The minimum audio level permitted. */ final double MIN_AUDIO_LEVEL = -127; Ivov, et al. Standards Track [Page 13] RFC 6465 Mixer-to-Client Audio Level Indication December 2011 /* * The maximum audio level permitted. */ final double MAX_AUDIO_LEVEL = 0; if (rms > 0) { /* * The "zero" reference level is the overload level, * which corresponds to 1.0 in this calculation, because * the samples are normalized in calculating the RMS. */ db = 20 * Math.log10(rms); /* * Ensure that the calculated level is within the minimum * and maximum range permitted. */ if (db < MIN_AUDIO_LEVEL) db = MIN_AUDIO_LEVEL; else if (db > MAX_AUDIO_LEVEL) db = MAX_AUDIO_LEVEL; } else { db = MIN_AUDIO_LEVEL; } return (int)Math.round(db); } } <CODE ENDS> Ivov, et al. Standards Track [Page 14] RFC 6465 Mixer-to-Client Audio Level Indication December 2011 Authors' Addresses Emil Ivov (editor) Jitsi Strasbourg 67000 France EMail: [email protected] Enrico Marocco (editor) Telecom Italia Via G. Reiss Romoli, 274 Turin 10148 Italy EMail: [email protected] Jonathan Lennox Vidyo, Inc. 433 Hackensack Avenue Seventh Floor Hackensack, NJ 07601 US EMail: [email protected] Ivov, et al. Standards Track [Page 15]
https://www.ietf.org/proceedings/86/rfc/rfc6465.txt
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Turney, DE United Nations Environment Programme, Enivonrmental Effects Assessment Panel Urrutia-Cordero, P. V., Istvánovics Vachon, D Valerio, Giulia Valesini, Fiona J. Van de Bogert, Matthew C van der Linden, Leon van Dijk, Gijs Van Loon, E. Van Wichelen, J Vanni, M.J. Vannie, MJ Velez, Maria I. Velez, M. Venail, P. Venkiteswaran, Jason J. Verburg, P Verburg, P. Verburg, P. Verburg, Piet Vernon, F Vesala, T Vetter, Mark Viik, M Viik, Malle Vilbaste, S Viljanen, M Villamizar, S R Villamizar, S. Vincent, WF Vinçon-Leite, Brigitte Vinebrooke, RD Visser, P. von Schiller, Daniel von Schiller, D. Vourenmaa, J. Voutilainen, Ari Waajen, G Wagner, J Wain, D. Waite, AM Wallin, Marcus B. Wallin, Marcus B. Wang, Junbo Wang, R Wang, H. Ward, N.K. Warnecke, Falk Warren, Susan Waterfield, Holly Watkinson, Andrew J. Watras, Carl J Watras, A.J. Watras, C.J. Watson, Simon R. Weather, K.C. Weathers, K.C. Weathers, Kathleen C. Weathers, K.C. Weathers, Kathleen C Weathers, K. C. Weathers, KC Weber, E Weber, M. Weber, Michael Weigelhofer, Gabriele Welkie, David G. Wells, Britney Wemple, B. Weng, W. Wentzky, VC Weyhenmeyer, G.A. Weyhenmeyer, Gesa A. Weyhenmeyer, Gesa A Weyhenmeyer, GA Weyhenmeyer, Gesa A. Whitaker, RJ White, D. S. White, D. S. White, M. Wickramaratne, Chaturangi Wigdahl-Perry, C. Wilk-Woźniak, E. William, Colom Williamson, Craig E. Williamson, T.J. Williamson, C.E. Williamson, T.J. Williamson, Craig C. Williamson, C.E. Wilson, Louise Wilson, H.L. Winder, M Winegardner, A.K. Winn, N Winslow, L.A. Winslow, Luke A Winslow, L. A. Winslow, L.A. Winslow, L. A. Winslow, Luke Winters, Kirsten M. Wiśniewski, Grzegorz Wittkop, Chad Wolinski, Laura Woolverton, C. Woolway, Iestyn Woolway, R.I. Woolway, RI Woolway, R.I. Woolwya, R.I. Wooward, G Worrest, R C Woyke, Tanja Wright, RW Wu, Chin H Wu, J T Wu, Chin H. 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The Oxford Oratory A sanctuary in the midst of the city The Oxford Oratory is a vibrant centre of Catholic life. Our church is open every day: join us for Mass, pop in for some quiet prayer, or come and discover more at one of our groups. Our historic church of St Aloysius has been a key feature in the lives of the city’s Catholics for 150 years, attracting people of all ages and from every walk of life. We use beauty to raise hearts and minds to God, faithful to the traditions of St Philip Neri and St John Henry Newman. The Oratory Prayer Book is now shipping internationally! We’ve made it even easier to buy the Oratory Prayer Book from anywhere in the world. And we’ve made it easier to order multiple copies too — in the UK and worldwide. Order your copy here:https://tinyurl.com/opb-buy If you have one, we’d love to hear what you think about it. Let us know in the comments, or tag a photo of your prayer book in the wild with #oratoryprayerbook Thanks to @acatholicinoxford for the photo. #oxfordoratory Worship What does it actually mean to worship God? In the New Testament, the word we most often translate as ‘worship’ doesn’t mean to reverence another in some abstract sense. It always involves some kind of bodily action. When we think about the magi visiting the Holy Family, we sometimes convey this motion by describing them — after they fall to their knees — as ‘doing homage’. But it’s actually that same word here we might translate elsewhere as ‘worship’. It’s just that we recognise the need to describe the bodily sign of their submission and adoration of the new born King with something that sounds a bit more physical. The word we usually translate as ‘worship’ ( proskuneo) comes literally from a root meaning ‘to make yourself like a dog before the other person’. It originally meant prostrating yourself on the floor to show your humble submission before another. By the time of the New Testament, people wouldn’t necessarily have had the root of this word in mind whenever they used it,* but the word still carries with it the idea of doing something with your body to express your worship. The feast of Corpus Christi is all about this kind of bodily worship. It’s tied to the fact that we are not pure spirits, but that we are human beings, body and soul. To worship God is not just a spiritual act. The right worship of God does not consist in simply having the right kinds of thoughts towards him. But the worship of God involves the humble submission of our entire human being, body and soul, before the God who is greater than all of us. And ever since the Incarnation, we do this not just before an abstract spirit. Because, from the moment of the Incarnation, God really does have a human body, that we can worship, that we fall down on our knees before, like the magi and the Canaanite woman, and so many others in the Gospel who kneel down and worship Christ. When we worship God, we kneel before God who is present in the flesh, under the appearances of bread and wine, in our churches all over the world. Corpus Christi is a joyful celebration of Christ’s presence among us, and it gives us an opportunity to think about how we respond to that gift. All this talk of kneeling and worship might not sound so joyful, but one of the great paradoxes of Christianity is that we find our greatest freedom in the humble service of God. Our greatest joy really should be found in finding ways to express this loving worship. So at least once a year, it is no bad thing to think about how we express with our own bodies that worship of God’s body, and what ways we can find to worship him even more perfectly. This Sunday, we will carry Christ’s Body through the streets of our city. We have a chance to demonstrate to the world our love, our joyful service, our worship of him, through our presence. The procession leaves our church at 2:30pm. Make sure you are there. But we should also think about the more ordinary things, like making sure we show that worship whenever we are in his presence. We should show through our behaviour in church that we believe him to be there: by genuflecting before him in the tabernacle of the church, and by keeping the church quiet and prayerful. We show our worship above all by kneeling down before him — like all those people in the Gospel — for the moment of Holy Communion. And we allow the priest to place the Host on our tongues, so that we don’t handle unnecessarily what is holy and precious, and no particles of Our Lord’s Body are ever dropped or lost through carelessness. We continue that worship in our prayers of thanksgiving after Communion and once the Mass has ended. We certainly never leave church during Communion. And we might think of ways of extending the time we spend with Christ present in the Blessed Sacrament: by attending Mass during the week sometimes, or visiting him during the times each week when his Body is exposed solemnly on the altar for Adoration, or even just by visiting an empty church, where he is waiting for us to show him our worship. Our Lord is hidden there, waiting for us to come and visit him, and make our request to him. See how good he is! He is there in the Sacrament of his love, sighing and interceding incessantly with his Father for sinners. To what outrages does he not expose himself, that he may remain in the midst of us! He is there to console us; and therefore we ought often to visit him. How pleasing to him is the short quarter of an hour that we steal from our occupations, from something of no use, to come and pray to him, to visit him, to console him for all the outrages he receives! When he sees pure souls coming eagerly to him, he smiles upon them. They come with that simplicity which pleases him so much, to ask his pardon for all sinners, for the outrages of so many ungrateful men. What happiness do we not feel in the presence of God, when we find ourselves alone at his feet before the holy tabernacles! ‘Come, my soul, redouble thy fervour; thou art alone adoring thy God. His eyes rest upon thee alone.’ — St John Mary Vianney * One exception is that I do think Christ had this root meaning in mind when he spoke to the Canaanite woman in Matthew 15:21–28. He wasn’t randomly insulting her by comparing her to a dog, but drawing attention to the fact that she was making herself like a dog before him — i.e. worshipping him — because she recognised him to be God. In other words, he was acknowledging her worship as proof of her faith and humility. On Saturday, Fr Rupert led Men’s Oratory on a walking pilgrimage to Islip, birthplace of St Edward the Confessor. #oxfordoratory Congratulations to Elizabeth who was received into the Church yesterday evening on the Feast of the Visitation. #oxfordoratory Congratulations to Livi, baptised on the vigil of Pentecost. “Therefore, Lord, we pray: graciously accept this oblation of our service, that of your whole family, which we make to you also for those to whom you have been pleased to give the new birth of water and the Holy Spirit, granting them forgiveness of all their sins; order our days in your peace, and command that we be delivered from eternal damnation and counted among the flock of those you have chosen. Through Christ our Lord. Amen.” #oxfordoratory Courtesy I recall how, as a child at school, we were sometimes made to learn poetry. At the time I hated it, and baulked at the idea of having to commit to memory The Ancient Mariner, and in fact, never did. But one poem which did touch me, was Belloc’s Courtesy. It began: Of Courtesy, it is much lessThan Courage of Heart or Holiness,Yet in my Walks it seems to meThat the Grace of God is in Courtesy. The poet goes on to tell us how, on one occasion he visited the ‘monks’ at Storrington in Sussex, and that ‘They took me straight into their Hall’where he ‘saw Three Pictures on a wall, And Courtesy was in them all.’ He then tells us the subject of those paintings: The first the Annunciation;The second the Visitation;The third the Consolation,Of God that was Our Lady’s Son. The first was of St. Gabriel;On Wings a-flame from Heaven he fell;And as he went upon one kneeHe shone with Heavenly Courtesy. Our Lady out of Nazareth rode —It was Her month of heavy load;Yet was her face both great and kind,For Courtesy was in Her Mind. The third it was our Little Lord,Whom all the Kings in arms adored;He was so small you could not seeHis large intent of Courtesy. Today is the feast of the Visitation, when we celebrate how our Lady made the long and uncomfortable journey to see her older kinswoman, Elizabeth, and her husband Zachariah, who lived in the hill country of Judah. Courtesy seems to me to be a perfect description of what this moment is all about. Imagine the cordial welcome extended to Mary by the older woman, solicitous for her health and how both women were eager to share with one another the joy of the forthcoming births of their sons. Our Lady had herself gone to visit her older cousin, not simply because she wanted to ‘be there’ for her, but because she wanted to share her own good news, which was not hers alone but for her people and, ultimately for the entire world. This is something Elizabeth seemed to know already! Her enthusiastic greeting is wonderful when she cries out ‘Oh that I should be visited by the Mother of my Lord’. Her unborn son joins in the greeting, kicking and letting his mother know that he too is part of this exciting thing that is happening. Elizabeth’s gracious words: ‘Blessed art thou among women and blessed is the fruit of thy womb’ have been enshrined in our prayer to the Virgin, incorporated with the Angelic Salutation: ‘Hail Mary, full of grace!’ And if today’s feast is about courtesy (so much more than stiff politeness or polished manners, but a warm and real concern for the wellbeing and interest of the other) then it is also about joy. Mary’s presence, together with that of her Divine Son, transformed the home of Elizabeth and Zachariah. ‘Elizabeth was filled with the Holy Spirit’ because of it. St Jose Maria puts it thus: ‘Mary brought joy to her cousin’s home, because she “brought” Christ’. Dame Julian liked to call Jesus ‘our courteous Lord,’ no doubt on account of his gracious dealings with us, flowing from his ‘large intent of Courtesy’! Julian writes in her Showings: And this is a supreme friendship of our courteous Lord, that he protects us so tenderly whilst we are in our sins; and furthermore he touches us most secretly, and shows us our sins by the sweet light of mercy and grace. But when we see ourselves so foul, then we believe that God may be angry with us because of our sins. Then we are moved by the Holy Spirit through contrition to prayer, and we desire with all our might an amendment of ourselves to appease God’s anger, until the time that we find rest of soul and ease of conscience. And then we hope that God has forgiven us our sin; and this is true. And then our courteous Lord shows himself to the soul, happily and with the gladdest countenance, welcoming it as a friend, as if it had been in pain and in prison, saying: My dear darling, I am glad that you have come to me in all your woe. I have always been with you, and now you see me loving, and we are made one in bliss. So sins are forgiven by grace and mercy, and our soul is honourably received in joy, as it will be when it comes into heaven, as often as it comes by the operation of grace of the Holy Spirit and the power of Christ’s Passion. Even though we have just changed all the light bulbs, our church looks its best when we don’t need to use them. #oxfordoratory The flag goes up on feast days! #oxfordoratory Blessings with St Philip’s relic after Vespers on Thursday. #oxfordoratory Look down from heaven, Holy Father, from the loftiness of that mountain to the lowliness of this valley; from that harbour of quietness and tranquillity to this calamitous sea. And now that the darkness of this world hinders no more those benignant eyes of thine from looking clearly into all things, look down and visit, O most diligent keeper, this vineyard which thy right hand planted with so much labour, anxiety and peril. To thee then we fly; from thee we seek for aid; to thee we give our whole selves unreservedly. Thee we adopt for our patron and defender; undertake the cause of our salvation, protect thy clients. To thee we appeal as our leader; rule thine army fighting against the assaults of the devil. To thee, kindest of pilots, we give up the rudder of our lives; steer this little ship of thine, and, placed as thou art on high, keep us off all the rocks of evil desires, that with thee for our pilot and our guide, we may safely come to the port of eternal bliss. #oxfordoratory Our celebrations for St Philip began with First Vespers last night and continue with Masses today. Here St Philip’s relic and altar are incensed during Vespers. #oxfordoratory Our new longer term temporary digital organ was hoisted up to the gallery this week in time for First Vespers of Our Holy Father St Philip. Catch up on our YouTube channel if you missed it, and join us for the Solemn Mass at 6pm this Friday. #oxfordoratory Vessel of the Holy Spirit This year the novena in preparation for the feast of Our Holy Father St Philip corresponds almost exactly with the novena of novenas, the first novena, the nine days of prayer between the Ascension and Pentecost when we wait once more with the Apostles for the outpouring of the Holy Spirit. And this is most appropriate, as St Philip was, more than anything else, a man of the Spirit — as we say in his litany, he is the “vessel of the Holy Spirit”. The story of his life, which we read during the novena, really begins with his singular experience of the Spirit on the Vigil of Pentecost 1544 in the catacomb of St Sebastian when the Spirit descended like a ball of fire, entering his mouth and then into his heart. After that experience — Philip’s own Pentecost — his life would never be the same again. Behind his holiness of life, and his preaching, and his miracles, and his founding of our Institute, there is something fundamental we can learn from St Philip — conveniently for this time in the Church’s liturgical calendar, something about the Holy Spirit. St Philip’s life shows us what happens when we do not simply possess the Holy Spirit, but allow ourselves to be possessed by him. We all have the Holy Spirit dwelling in us — all of us who have been baptised and confirmed. He is in us as much as he was in St Philip Neri, as much as he was in the Apostles at Pentecost. But we are very good at closing ourselves to the Spirit — we, through our sins and our selfishness, our attachments and our self-will, block him out; we ignore his prompting and are deaf to his call, we partition him away into a little forgotten compartment in our souls. Or we make of him a very petty little thing indeed, our God — a God who always agrees with what we say, who wants us to do precisely what we want to do, and makes me right and everyone else wrong. But this is not the Holy Spirit whom we worship; this is not the awesome power of Almighty God, who hovered over the waters at creation, who raised Jesus from the dead, who came down on the Apostles and Our Lady in the Upper Room, who wonderfully penetrated the heart of St Philip, and who gives power and authority to the Church. The Holy Spirit blows where he wills; his ways are not always our ways; and if we give ourselves to him and allow him to possess us completely — as St Philip did — then we will find that he will do more for us than we ask or even imagine; do more through us and with us. St Philip wanted to be a layman — the Spirit called him to the priesthood; he wanted to be a martyr, the Spirit made him a martyr not of blood, but of charity; Philip wanted to preach the Gospel to the pagans in the Indies, the Holy Spirit had other plans. He wanted to be a humble, hidden servant of the Church, living at San Girolamo and doing what good he could, but the Spirit gave him the gift of preaching and teaching and working miracles and reading men’s hearts and winning souls, and brought him to the Vallicella, and through him founded the Congregation of the Oratory, spread, as it now is, across the world. St Philip loved to be unknown — the Holy Spirit moulded and fashioned and transformed him into one of the most popular saints, the Apostle of Rome. St Philip wanted to reform the hearts and souls of those men and women he met — the Spirit used him to reform the very heart of the Church herself. It is not enough to have the Holy Spirit — it is not enough even to think we are serving God or doing great things in his honour. We must allow ourselves to be led by the Spirit, formed and transformed by the Spirit. We must be prepared to give up our own desires and plans — even the good ones — and be taken over by the Holy Spirit to be used for his own purposes. If we do this, if we open up to the Spirit who dwells in our hearts, then the life of St Philip Neri, and indeed of all the saints, shows us that the Spirit will do great things for, in, and through us. St Philip, Vessel of the Holy Spirit and Sweetest of Fathers. Pray for us. A Prayer of Our Holy Father St Philip: My Lord Jesus, I want to love you but you cannot trust me. If you do not help me, I will never do any good. I do not know you; I look for you but I do not find you. Come to me, O Lord. If I knew you, I would also know myself. If I have never loved you before, I want to love you truly now. I want to do your will alone; putting no trust in myself, I hope in you, O Lord. The Paschal Candle has been lit for Masses since the Easter Vigil to represent Christ’s presence among us, as with his disciples for forty days. After the Gospel of the Solemn Mass yesterday, it is extinguished to symbolise his ascension into heaven. #oxfordoratory Look up to heaven On Monday this week some of the Fathers and Brothers spent the day erecting and moving scaffolding — with all due health and safety measures observed — in order to change and improve the lighting on the sanctuary of our church. It is already a great boon for us to see more clearly the beautiful decoration which adorns that focal point of the whole building, as well as being a great help for the priest reading from the missal. Tomorrow as we celebrate the feast of the Ascension, our eyes are directed upwards once more as Our Risen Lord ascends to heaven and for a moment like the Apostles we gaze upwards as he is taken from our sight. How very much more clearly do we see when we make that effort to lift up our eyes towards the Lord. We not only contemplate his glory but from that vantage point are able to see all things in their fullness, seeing them from the perspective of heaven. Prayer, the lifting of the mind and heart to God, enables us to understand and to see clearly, all those other things of life in which we are otherwise immersed. That daily shifting our focus from the things of this world to the vantage point of heaven is that great encouragement for our daily striving for God, so that where Christ goes we too may follow him. It is often an effort for us to pull ourselves out of the daily round in order to lift up our heads and our hearts to the things of heaven, but if we are to have the desire for heaven to drive us on, it is essential that we always keep our goal before us. Not only in prayer, but all those things which form the way we see things must have heaven as their vantage point and aim. Monsignor Knox wrote: In all ages, in all countries, the world acts as a solvent to Catholic piety; breathes an air in which Catholic piety languishes. Man’s intellect always wants to approach things from the human side, from the side from which they can be known by man; shirks and burkes discussion of things from the side of reality, from the side which relates them to God. Man’s art and literary genius is constantly concerned with man at his most human level, his passions, his craven fears, the rebellion of his will against the order in which he lives. All that breathes a poison, for which writers who care about the truth as it is in God have to provide an antidote; they must fight, they must react, but still more they must see things, they must record things, from that higher standpoint which is God’s. You must, sometimes, give the lungs of your soul an airing on these heights, even if the atmosphere of it is more rare, is breathed with more effort, than the other. Or else, the miasma of the modern world will get you down, will weaken your resistance; you will be a prey to the germs of infidelity, to the infection of bad example. And you will forget your Friend. As the Church invites us then on the Ascension to gaze up towards heaven, to contemplate Our Lord, Risen and Ascended, it is perhaps a good time for us to think on the place we give to the things of heaven in our life each day — not only in terms of the time we give to heaven, but also in terms of what we strive for, on what really all our efforts are in fact based. And from our gazing upon heaven, we can then go on like the Apostles, down from that mountain and into the world — to teach the Good News and make disciples of all nations, keeping ever in mind that he whom we meet on those heights of prayer is with us always, even to the end of time. Q: How many Oratorians does it take to change a lightbulb?A: “Change”? Actually the real answer turns out to be three, plus one very helpful volunteer and a lot of scaffolding. The sanctuary lighting is all working at full brightness again! #oxfordoratory Monday 15 May 2023 Congratulations to David who was baptised on Saturday! #oxfordoratory Saturday 13 May 2023 One of this month’s relics on display is St Philip’s own copy of Jacapone da Todi’s “Laude”, which St Philip has written his name in. The story of how it was rediscovered in our church — only days before the first Fathers of the Oratory arrived here from Birmingham — is extraordinary. You might find it hard to believe, unless you heard it straight from the priest who found them, who is now the Bishop of Leeds. Read his account from his St Philip’s day sermon on our website: www.oxfordoratory.org.uk/blog/post/1335-solemnity-of-our-holy-father-saint-philip The novena to St Philip begins on Tuesday after the evening Mass. You will be able to place your own prayer intentions for the novena in St Philip’s chapel over the weekend. There will be Solemn Choral Vespers on Thursday 25 May at 6:30pm. We will welcome Fr Robert Ombres OP from Blackfriars to preach at the Solemn Mass for the feast day itself on Friday 26 May at 6pm. #oxfordoratory Friday 12 May 2023 May Music Sunday 7 MaySolemn Mass 11:005th Sunday of EasterMissa Simile est regnum caelorum LoboJubilate Deo universa terra PalestrinaCaro mea vere est cibus Guerrero Sunday 14 MaySolemn Mass 11:006th Sunday of EasterMissa Regina caeli PalestrinaBenedicite gentes PalestrinaPortio mea White Thursday 18 MaySolemn Mass 18:00The Ascension of the LordMissa Ascendens Christus VictoriaAscendit Deus PhilipsO Rex gloriae Marenzio Sunday 21 MaySolemn Mass 11:007th Sunday of EasterMissa Jam Christus astra ascenderat PalestrinaViri Galilaei PalestrinaEgo sum panis vivus Palestrina Thursday 25 MaySolemn Vespers 18:30Our Holy Father St Philip NeriDeus in adjutorium PadillaMagnificat primi toni VictoriaPangamus Nerio SewellO salutaris hostia LalouxTantum ergo WidorAlleluia GabrieliRespice de caelo Sewell Friday 26 MaySolemn Mass 18:00Our Holy Father St Philip NeriMissa Papae Marcelli PalestrinaIn spiritu humilitatis CroceJubilate Deo a8 G Gabrieli Sunday 28 MaySolemn Mass 11:00PentecostMissa De la Batalla GuerreroConfirma hoc deus LassusLoquebantur variis linguis Palestrina The Oratory 25 Woodstock Road © 2023 Oxford Oratory. All rights reserved. The Oxford Oratory of St Philip Neri is a Registered Charity number 1018455
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Reno County, Kansas World War II Army Enlistment Records - Surnames O through R From: Electronic Army Serial Number Merged File, ca. 1938 - 1946 [Electronic Records]; Data Table: ENLISTMENT RECORDS; Record Group 64: Records of the National Archives and Records Administration; Series: World War II Army Enlistment Records, 6/1/2002 - 9/30/2002. (Online version on July 16, 2005 at http://www.archives.gov/aad/index.html.) Extracted by Maureen Reed, July 2005 --------------------------------------------------------------------- KSGENWEB INTERNET GENEALOGICAL SOCIETY COPYRIGHT NOTICE: In keeping with the KSGenWeb policy of providing free information on the Internet, this data may be used by non-commercial entities, as long as this message remains on all copied material. These electronic pages cannot be reproduced in any format for profit or other gain. Copying of the files within by non-commercial individuals and libraries is encouraged. Any other use, including publication, storage in a retrieval system, or transmission by electronic, mechanical, or other means requires the written approval of the file's author. --------------------------------------------------------------------- This dataset is very large so regretfully it is left in its original coded form. To determine the meaning of the columns, go to http://www.ksgenweb.org/archives/military/WWIIarmy.html Alternatively, you may view the original database at the National Archives website by following these directions: 1. Go to http://www.archives.gov/aad/index.html and click on "Search". 2. In the "Subject" option, select "World War, 1939-1945" and click "Submit." 3. Select the link for "World War II Army Enlistment Records, 6/1/2002 - 9/30/2002." 4. Select the link for "Electronic Army Serial Number Merged File, 1938-1946." 5. Select Enlistment Records. 6. You are now at the search from where you can enter the name or other data you are looking for. (These instructions are correct as of the date of posting of this text file. This text file is not updated, so if NARA decides to change its website, these instructions would no longer be valid. Review the NARA website for information on searching their databases.) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 ------------------------------------------------------------------------------------------------------------------------------------------------------- 07067460 O HS N L/VTVQ V 7325 08 APR 1946 7VT 8 1MD 12 3 2 73 25 1 5 010 6 6 0259 2.116 37755416 OBRIEN CONARD P 3274 31 OCT 1945 PFC 7 NO 2 1 6 73 26 1 1 010 6 1 1259 6.25 37757274 OBRIEN EUGENE F 7325 09 DEC 1944 PVT 8 NO 2 5 0 73 18 1 0 057 2 7 1259 6.25 20733534 OCONNELL PAUL R 7325 30 MAR 1946 M SG 1 FA 30 3 7 76 16 1 4 195 6 1 9 0359 3.80 17078430 ODONNELL THOMAS G 7628 04 AUG 1942 PVT 8 BI 0 5 0 73 18 1 8 085 6 6 0248 2.105 67167602 OETLS EZ/L E 7325 29 MAY 1946 PVT 8 INF 10 3 2 73 25 1 0 345 8 9 9 0259 2.116 20733276 OLIPHANT ROBERT C 7350 23 DEC 1940 PVT 8 FA 30 1 7 73 19 1 4 758 6 4 0359 3.80 20733307 OLSON CHARLES A 7350 23 DEC 1940 PVT 8 FA 30 1 7 73 18 1 4 134 6 4 0359 3.80 20733358 OLSON HARRY H 7350 23 DEC 1940 CPL 6 FA 30 1 7 73 19 1 4 175 6 4 0359 3.80 17056107 ONEAL CHESTER D 7325 18 JAN 1942 PVT 8 BI 0 5 0 73 21 1 1 781 6 6 0245 2.102 20733277 ORME DARRELL M 7350 23 DEC 1940 PVT 8 FA 30 1 7 73 12 1 0 781 6 4 0359 3.80 37743010 ORME DONALD H 7325 12 MAY 1944 PVT 8 NO 2 5 0 73 14 1 2 170 2 7 1257 6.23 20726016 ORTH ELMER A 7390 23 DEC 1940 PVT 8 INF 10 0 7 73 21 1 0 316 6 4 0358 3.79 37534116 OSWALT DONALD S 7325 14 JUL 1943 PVT 8 NO 2 5 0 73 24 1 3 992 1 7 1228 4.138 37504282 OUSLEY ROBERT G 7325 05 FEB 1943 PVT 8 BI 0 5 0 73 23 1 5 992 6 7 1224 4.134 37750745 OUTHWAITE ERIC R 7325 23 AUG 1944 PVT 8 NO 2 5 0 K9 21 1 4 316 6 7 1258 6.24 06931707 OVERTON GLEN E 5694 18 SEP 1939 55 7 84 55 6 459 8 1 0043 1.36 06856689 OWSTON ROBERT D 7163 20 NOV 1940 PVT 8 CE 82 9 2 73 15 1 0 316 6 1 0039 1.107 37811136 OXLEY ELLIS H 7325 25 MAY 1945 PVT 8 NO 2 5 0 73 17 1 4 478 2 7 1268 6.34 20733249 OYLER ERNEST R 7350 23 DEC 1940 PFC 7 FA 30 1 7 73 19 1 5 781 6 4 0359 3.80 37751990 OZBUN HAROLD C 7325 12 SEP 1944 PVT 8 NO 2 5 0 73 26 1 4 992 6 7 1258 6.24 17138064 OZBUN ORVILLE R 7379 05 AUG 1946 PVT 8 INF 10 3 2 73 24 1 0 345 6 1 9 0255 2.112 37731943 PACKEBUSH GEORGE A 7325 27 JAN 1944 PVT 8 NO 2 5 0 84 22 1 0 760 2 7 1256 6.22 17177433 PACKEBUSH OTTO J 7325 14 DEC 1945 PVT 8 NO 2 6 2 84 27 1 4 480 1 1 0260 2.117 37761207 PADGETT WARREN P 7325 07 FEB 1945 PVT 8 NO 2 5 0 73 26 1 3 678 6 7 1260 6.26 17178559 PALSTRING FREDRICK C JR 7347 04 FEB 1946 PVT 8 NO 2 6 2 84 28 1 3 000 2 1 0260 2.117 37732077 PANEY JOHN P 7325 28 JAN 1944 PVT 8 NO 2 5 0 73 23 1 0 316 6 7 1256 6.22 37755962 PANKRATZ OLIN V 7325 20 NOV 1944 PVT 8 NO 2 5 0 73 26 1 2 590 6 7 1259 6.25 17177271 PARKER EVERETT E 7347 19 NOV 1945 PVT 8 AC 20 3 2 70 27 1 3 590 1 1 + 0260 2.117 37881424 PARKER JAMES D 3315 05 DEC 1945 PVT 8 56 6 6 70 27 1 4 259 6 1 1271 6.37 37760430 PARKER LOREE S 7325 27 JAN 1945 PVT 8 NO 2 5 0 70 25 1 4 992 6 7 1260 6.26 20733402 PARKER REX O 7350 23 DEC 1940 PVT 8 FA 30 1 7 85 14 1 4 107 2 4 0359 3.80 37735987 PARKHURST RICHARD E 5254 24 NOV 1945 PFC 7 MP 6 3 6 84 25 1 1 480 6 1 1256 6.22 20733403 PARRISH DARYL W 7350 23 DEC 1940 PVT 8 FA 30 1 7 73 22 1 3 102 6 4 0359 3.80 20733556 PARSONA EUGENE F 7350 23 DEC 1940 CPL 6 FA 30 0 7 73 20 1 4 003 6 4 0359 3.80 20733347 PARSONS PAUL J 7350 23 DEC 1940 SGT 5 FA 30 1 7 73 18 1 2 232 6 4 0359 3.80 37741241 PARSONS RAYMOND SR 7325 24 APR 1944 PVT 8 NO 2 5 0 73 19 1 7 118 2 7 1257 6.23 20733015 PATTERSON ALLEN F 7350 23 DEC 1940 PVT 8 MD 70 0 7 73 20 1 4 999 6 4 - 0359 3.80 20733430 PATTERSON RAYMOND S 7325 22 FEB 1946 M SG 1 AC 20 3 7 48 14 1 5 356 2 1 0359 3.80 17061931 PATTERSON ROBERT E L JR 7325 09 AUG 1943 P0T 8 NO 2 5 0 75 13 1 4 050 2 7 0246 2.103 20733016 PATTERSON ROBERT F 7350 23 DEC 1940 PVT 8 MD 70 0 7 73 21 1 3 508 6 4 0359 3.80 37721579 PAYNE DOYLE W 7325 09 SEP 1943 PVT 8 NO 2 5 0 73 25 1 3 586 6 7 1254 6.20 20733308 PAYNE HARRY A 7325 01 MAR 1946 M SG 1 AC 20 3 7 73 14 1 4 114 2 1 0359 3.80 17012426 PAYNE JACK Q 7390 08 FEB 1941 F C 9 AC 20 0 0 73 20 1 6 002 6 1 0239 2.96 37735663 PEDERSON MELVIN J 7325 24 JUL 1944 PVT 8 NO 2 5 0 73 24 1 4 316 6 7 1256 6.22 20733424 PEERY JACK R 7350 23 DEC 1940 PVT 8 FA 30 0 7 84 22 1 1 102 6 4 0359 3.80 20733348 PEMBERTON ARCHIE L 7350 23 DEC 1940 SGT 5 FA 30 1 7 84 17 1 4 781 6 4 0359 3.80 37729157 PENNINGTON ROBERT T 7325 16 DEC 1943 PVT 8 NO 2 5 0 73 25 1 4 992 6 7 1255 6.21 37725969 PETER ON GILBERT H 7325 05 NOV 1943 PVT 8 NO 2 5 0 91 22 1 4 074 1 7 1255 6.21 37767530 PETERS NORMAN W 7325 18 APR 1945 PVT 8 NO 2 5 0 73 17 1 4 185 2 7 1261 6.27 20733017 PETRIE JACK C 7117 26 JUN 1941 PVT 8 AC 20 0 3 73 21 1 2 316 6 1 0359 3.80 37755806 PETRIE RICHARD E 7325 18 NOV 1944 PVT 8 NO 2 5 0 73 26 1 3 992 6 7 1259 6.25 17020173 PFAFFLY ARNOLD L 7325 26 SEP 1941 AV C 9 AC 20 0 0 73 17 1 6 030 6 1 - 0240 2.97 17175858 PFEIFER WARREN L 7325 14 DEC 1942 PVT 8 AC 20 5 0 73 23 1 4 999 6 6 0260 2.117 37511356 PHELPS BILL G 7325 26 FEB 1943 PVT 8 BI 0 5 0 73 23 1 4 068 6 7 1225 4.135 17045998 PHELPS JOHN D 7545 31 MAR 1942 PV0 8 B+ 0 5 0 73 15 1 4 072 2 6 0244 2.101 17199999 PHILLIPS DANIEL E JR 7325 22 FEB 1944 PVT 8 AC 20 5 5 73 25 1 3 992 6 3 0262 2.119 20733018 PHIPPS ALVIN J 7350 23 DEC 1940 PVT 8 MD 70 0 7 73 20 1 0 525 6 4 0359 3.80 20733360 PIATT JACOB L 7350 23 DEC 1940 PVT 8 FA 30 0 7 73 18 1 3 002 6 4 0359 3.80 06936769 PIEPLOW HARRY R 4022 05 JAN 1940 42 3 73 22 4 403 2 1 0044 1.37 37759081 PIERCE CHARLES R 7325 10 JAN 1945 PVT 8 NO 2 5 0 84 21 1 2 736 2 7 1260 6.26 20733279 PIERSON RAY V 7325 20 NOV 1945 CPL 6 QMC 50 3 K 73 22 1 3 017 2 1 0359 3.80 17200048 PIERSON WILLIAM D 7325 15 FEB 1945 PVT 8 AC 20 5 5 73 26 1 5 992 6 3 0262 2.119 17137833 PIFER FRANK L 7379 12 JUL 1946 PVT 8 AC 20 3 2 73 28 1 0 199 1 1 9 0255 2.112 37765452 PINA ELLIS J 7330 24 OCT 1945 PFC 7 INF 10 6 6 73 27 9 0 188 6 1 1 1261 6.27 17002112 PINA LEWIS 7330 26 JUL 1940 PVT 8 CE 83 7 0 73 19 9 2 999 6 1 0238 2.95 37525681 PINKSTON CHARLES A 7325 13 MAY 1943 PVT 8 NO 2 5 0 84 14 1 0 932 3 7 1226 4.136 20733251 PIPER JAMES R 7350 23 DEC 1940 PFC 7 FA 30 1 7 76 16 1 0 409 6 4 0359 3.80 17179153 PITCHFORD MONROE D 7325 21 FEB 1946 PVT 8 NO 2 6 2 73 27 1 1 188 1 1 0260 2.117 37729150 PITTS NORRIS H 7325 16 DEC 1943 PVT 8 NO 2 5 0 73 25 1 2 992 6 7 1255 6.21 17128062 PITTS ROBERT E 7325 02 NOV 1942 PVT 8 AC 20 5 0 73 23 1 3 580 6 6 0254 2.111 16027341 PITZER KENNETH H 6119 08 AUG 1940 PVT 8 AC 20 7 0 84 22 1 4 316 6 1 0208 2.65 37741138 PODSUZUS HANS A 7325 22 APR 1944 PVT 8 NO 2 5 0 76 17 1 3 316 2 7 1257 6.23 37823279 PODSZUS HARRY M 2359 24 JUN 1946 PFC 7 NO 2 1 6 73 27 1 1 367 6 1 9 1269 6.35 20733228 POE ELMER A 7350 23 DEC 1940 SGT 5 FA 30 1 7 61 17 1 5 497 6 4 0359 3.80 18032748 POHLMAN CLARENCE E 7379 30 AUG 1946 TEC4 N FA 30 3 S 96 11 1 0 050 6 1 8 0269 2.126 17021000 POPP GAROLD E 7325 15 JAN 1942 PVT 8 BI 0 5 0 73 17 1 4 783 6 6 0240 2.97 20733280 PORTER LLOYD A 7350 23 DEC 1940 PVT 8 FA 30 1 7 73 16 1 1 316 6 4 0359 3.80 17177265 POSTIER MERVIN L 7325 23 NOV 1945 PVT 8 AC 20 3 2 73 28 1 0 499 1 1 0260 2.117 20733404 POTTER DALE E 7350 23 DEC 1940 PVT 8 FA 30 1 7 73 20 1 4 999 6 4 0359 3.80 20732997 POTTER HAROLD L 7350 23 DEC 1940 PFC 7 MD 70 0 7 73 20 1 6 002 6 4 0359 3.80 37723406 POUNDS ANDREW B 7325 25 SEP 1943 PVT 8 NO 2 5 0 84 18 1 4 524 2 7 1254 6.20 17209925 POWELL DONALD L 7379 01 OCT 1946 T SG 3 AC 20 3 8 91 21 1 4 321 2 1 8 0264 2.121 37747002 POWERS NORMAN N 7325 23 JUN 1944 PVT 8 NO 2 5 0 75 21 1 0 513 2 7 1258 6.24 20733281 POWNALL OTIS H 7117 12 AUG 1941 PV0 8 AC 20 0 3 33 18 1 4 736 6 1 0359 3.80 37754665 PREISSER CHARLES F 7325 27 OCT 1944 PVT 8 NO 2 5 0 73 25 1 3 306 6 7 1259 6.25 17196211 PRICE ARCHIE E JR 7325 01 MAR 1946 PVT 8 NO 2 6 2 73 28 1 0 188 6 1 0262 2.119 17002178 PRICER HAROLD A 7330 13 AUG 1940 PVT 8 A+ 20 0 0 73 20 1 4 999 6 1 0238 2.95 17028276 PRICER PAUL H 7330 21 NOV 1941 PVT 8 AC 20 0 0 84 21 1 4 735 6 1 0241 2.98 17002215 PRINGLE GILBERT J 7330 19 AUG 1940 PVT 8 ORD 87 7 0 73 09 1 3 999 6 1 0238 2.95 17177527 PROTER WILLIAM H 7325 29 DEC 1945 PVT 8 AC 20 3 2 73 28 1 0 345 6 1 0260 2.117 20733252 PUCKETT CHARLES G 7350 23 DEC 1940 PFC 7 FA 30 1 7 61 20 1 4 999 6 4 0359 3.80 17166920 PUIRN T THOMAS H 7330 10 DEC 1942 PVT 8 AC 20 3 07 31 5 9 807 6 9 0259 2.116 17137829 PUTNAM JOHN F 7379 12 JUL 1946 PVT 8 AC 20 3 2 87 29 1 2 251 1 1 9 0255 2.112 17175847 PUTNAM LYLE A 7325 14 DEC 1942 PVT 8 AC 20 5 0 73 17 1 5 175 2 6 0260 2.117 37524153 QUIRING RAYMOND R 7325 28 APR 1943 PVT 8 NO 2 5 0 73 24 1 4 992 6 7 1226 4.136 37812957 RAILSBACK LEONARD E 7325 12 JUN 1945 PVT 8 NO 2 5 0 73 27 1 4 798 6 7 1268 6.34 06936729 RANDALL HOWARD J 9141 30 OCT 1945 M SG 4 AC 20 3 B 73 20 1 4 480 2 1 4 0044 1.37 37736567 RANDALL REGINALD A 7325 10 MAR 1944 PVT 8 NO 2 5 0 75 14 1 3 583 2 7 1256 6.22 37524214 RATCLIFF VON E 7325 05 JAN 1946 PVT 8 CE 82 3 S 87 21 1 0 341 2 1 1226 4.136 A-701594 RATCLIFFE HELEN H 7348 02 MAR 1943 AUX 8 WAC 9 5 0 73 18 1 4 175 7 9 0014 1.14 17190976 RATLEY JAMES G 7379 08 MAR 1946 PVT 8 AC 20 3 2 73 27 1 0 345 2 1 0261 2.118 06931767 RATLEY KENNETH W 4464 27 OCT 1939 55 7 73 55 6 446 6 1 0043 1.36 17196309 RATLEY LLOYD R 7325 06 MAR 1946 PVT 8 AC 20 3 2 73 29 1 0 590 1 1 0262 2.119 37735654 RATZLAFF RAYMOND E 7325 24 JUL 1944 PVT 8 NO 2 5 0 73 26 1 4 992 6 7 1256 6.22 37518904 RATZLAFF ROBERT 6074 02 NOV 1945 SGT 5 NO 2 1 6 73 22 1 3 201 6 1 1226 4.136 37731950 RATZLOFF ALFRED W 7325 27 JAN 1944 PVT 8 NO 2 5 0 73 19 1 0 736 2 7 1256 6.22 20733019 RAUH CHARLES E 7350 23 DEC 1940 PVT 8 MD 70 0 7 73 13 1 8 022 6 4 0359 3.80 A-701595 RAWLINGS JOYCE W 7354 03 MAR 1943 +UX 8 WAC 9 5 0 73 16 1 1 105 2 9 0014 1.14 06935511 RAY CECIL J 0008 06 DEC 1939 0 0 73 00 0 000 0 1 0043 1.36 A-701849 RAY EMMA G 7548 23 APR 1943 AUX 8 WAC 56 5 0 84 16 0 4 104 6 9 0015 1.15 17210009 RAYA BACILIO J 8442 17 AUG 1946 PVT 8 AC 20 3 2 73 28 1 0 590 6 1 9 0264 2.121 17210001 RAYA MIKE J 8442 16 AUG 1946 PVT 8 AC 20 3 2 73 29 1 0 590 1 1 9 0264 2.121 37735397 RAYA TIBURCIA J 7325 22 JUL 1944 PVT 8 NO 2 5 0 73 26 1 2 922 6 7 1256 6.22 37737801 RAYL HARLESS H 7325 23 MAR 1944 PVT 8 NO 2 5 0 73 13 1 4 544 4 7 1256 6.22 17200004 RAYL WILLARD C 7325 20 DEC 1943 PVT 8 AC 20 5 5 73 25 1 4 992 6 3 0262 2.119 37818784 RAYMOND GERALD F 6180 22 MAR 1946 PFC 7 NO 2 1 6 73 23 1 4 010 6 1 1269 6.35 37742850 RAYMOND WILFORD D 7325 10 MAY 1944 PVT 8 NO 2 5 0 73 26 1 5 992 6 7 1257 6.23 17020865 RAYNER HAROLD L 7325 11 JAN 1942 PVT 8 BI 0 5 0 73 19 1 5 043 2 6 0240 2.97 06931633 REDD LEROY M 7325 17 OCT 1945 1 SG 2 AC 20 3 3 73 20 1 5 480 2 1 1 0043 1.36 20733406 REDD ORVILLE L 7350 23 DEC 1940 PVT 8 FA 30 1 7 73 13 1 4 999 6 4 0359 3.80 37815248 REDFORD WILLIAM E 5175 09 FEB 1946 PFC 7 AC 20 3 6 73 27 1 0 499 1 1 1268 6.34 37730926 REDINGER CECIL 7325 13 JAN 1944 PVT 8 NO 2 5 0 73 22 1 2 485 1 7 1255 6.21 37817433 REED CLARENCE L 9124 19 NOV 1945 PVT 8 QMC 50 3 6 62 27 1 1 345 6 1 1268 6.34 20733318 REED FRED A 7350 23 DEC 1940 PVT 8 FA 30 0 7 71 10 1 4 232 6 4 0359 3.80 37828964 REED HARVEY LEONARD 7628 18 SEP 1946 PVT 8 NO 2 5 0 73 19 1 4 306 6 7 1270 6.36 17211847 REED JAMES C 7330 06 NOV 1946 PVT 8 NO 2 6 2 75 29 1 0 480 6 1 9 0264 2.121 37811487 REED JOHN M 7325 29 MAY 1945 PVT 8 NO 2 5 0 73 12 1 3 789 2 7 1268 6.34 17002292 REEVES EUGENE L 7330 30 AUG 1940 PVT 8 CAC 40 7 0 85 20 1 4 768 6 1 0238 2.95 20733253 REGER TED E 7350 23 DEC 1940 PFC 7 FA 30 1 7 73 22 1 3 999 6 4 0359 3.80 37735522 REGIER ELMER H 7325 22 JUL 1944 PVT 8 NO 2 5 0 73 24 1 0 580 6 7 1256 6.22 37747043 REGIER LOUIS R 7325 23 JUN 1944 PVT 8 NO 2 5 0 73 26 1 4 992 6 7 1258 6.24 37730693 REGIER OTTO J 7325 08 DEC 1943 PVT 8 5O 2 5 0 73 15 1 1 768 2 7 1255 6.21 37825499 REH RICHARD E 3138 28 MAY 1946 PVT 8 NO 2 6 6 73 27 1 5 480 6 1 9 1270 6.36 37741240 REH VINCENT J 7325 24 APR 1944 PVT 8 NO 2 5 0 73 22 1 8 992 6 7 1257 6.23 37521480 REICH JACK J 7325 10 APR 1943 PVT 8 NO 2 5 0 09 12 1 0 072 2 7 1226 4.136 37822237 REICHENBERGER JAMES N 7325 29 NOV 1945 PVT 8 NO 2 5 0 73 27 1 4 306 6 7 1269 6.35 37758753 REICHENBERGER RAYMOND M 7325 05 JAN 1945 PVT 8 NO 2 5 0 73 22 1 4 306 6 7 1260 6.26 37511462 REID CLEO W 7325 26 FEB 1943 PVT 8 BI 0 5 4 73 23 1 0 736 2 7 1225 4.135 17002238 REIFF WILLIAM M 7330 21 AUG 1940 PVT 8 CAC 40 4 0 73 16 1 4 781 6 1 0238 2.95 37755819 REIMER JOEL M 7325 18 NOV 1944 PVT 8 NO 2 5 0 73 24 1 4 306 6 7 1259 6.25 37721545 REUSSER LEROY M 7325 09 SEP 1943 PVT 8 NO 2 5 0 73 23 1 1 736 2 7 1254 6.20 37724270 REVEL RUSSEL J 8618 13 DEC 1943 PVT 8 AC 20 5 5 73 24 1 4 373 6 3 1254 6.20 37519294 REXROAD BENJAMIN W 7325 27 MAR 1943 PVT 8 NO 2 5 0 73 24 1 1 170 6 7 1226 4.136 37745206 REYNOLDS WILLIAM L 7325 06 JUN 1944 PVT 8 NO 2 5 0 73 18 1 7 118 6 7 1258 6.24 06825053 RHOADES JOHN S 7545 11 SEP 1942 TEC3 M ORD 87 5 5 73 12 1 0 583 2 4 0038 1.106 37761205 RHYNES DELBERT R 7325 07 FEB 1945 PVT 8 NO 2 5 0 84 20 1 1 485 2 7 1260 6.26 20733433 RICE CHARLES B 7350 23 DEC 1940 PVT 8 FA 30 0 7 73 16 1 3 949 1 4 0359 3.80 37763234 RICE ESTA L 7325 03 MAR 1945 PVT 8 NO 2 5 0 73 26 1 1 736 6 7 1260 6.26 20759955 RICE JACK E 7390 23 DEC 1940 PVT 8 FA 30 0 7 73 17 1 5 175 6 4 0361 3.82 20733283 RICH GARETH O 7350 23 DEC 1940 PVT 8 FA 30 0 7 73 19 1 2 999 6 4 0359 3.80 17138218 RICHARDSON BILLY J 7379 28 FEB 1946 PVT 8 AC 20 3 2 85 28 1 1 345 1 1 0255 2.112 37737820 RICHARDSON EDWARD O JR 7325 23 MAR 1944 PVT 8 NO 2 5 0 75 15 1 1 736 2 7 1256 6.22 37729984 RICHARDSON JACK G 7325 29 DEC 1943 PVT 8 NO 2 5 0 73 25 1 1 992 6 7 1255 6.21 17190978 RICHARDSON JAMES E 7379 08 MAR 1946 PVT 8 AC 20 3 2 73 28 1 0 590 6 1 0261 2.118 37721521 RICHARDSON JOHN P JR 7325 08 SEP 1943 PVT 8 NO 2 5 0 73 15 1 6 575 2 7 1254 6.20 37747081 RIFFEL JOHN J 7325 23 JUN 1944 PVT 8 NO 2 5 0 73 19 1 4 775 2 7 1258 6.24 37748039 RIGGS WILLIAM H 4625 01 FEB 1946 PFC 7 DML 8 1 6 73 25 1 0 000 6 1 1258 6.24 17179014 RIGGS WILLIAM W 7325 18 FEB 1946 PV3 8 AC 20 3 2 91 27 1 4 154 6 1 0260 2.117 17096540 RINGER HAROLD E 7325 21 JUN 1944 PVT 8 AC 20 5 5 73 26 1 4 992 6 3 0250 2.107 17028084 RINGER ROBERT G 7330 15 SEP 1941 PVT 8 AC 20 0 0 73 22 1 5 002 6 1 0241 2.98 39916868 RIPPEE WILLIAM E 9210 16 JUN 1943 PVT 8 NO 2 5 0 75 24 1 0 316 6 7 1483 7.54 20733068 RISHEL JOHN B 7350 23 DEC 1940 PFC 7 FA 30 0 7 73 09 1 3 170 6 4 0359 3.80 17100383 RISLEY GLEN M 7330 26 OCT 1942 PVT 8 AC 20 5 0 73 17 1 5 783 2 6 0251 2.108 37757205 RISLEY WILLIAM L 7325 08 DEC 1944 PVT 8 NO 2 5 0 73 22 1 4 306 6 7 1259 6.25 A-701451 ROACH EVELYN M 7354 03 FEB 1943 AUX 9 WAC 9 5 0 73 11 1 4 132 6 9 0014 1.14 17209532 ROACH GARLAND G 7379 12 SEP 1946 PVT 8 AC 20 3 2 1 28 1 1 144 6 1 9 0264 2.121 06936772 ROACH GEORGE T 0000 05 JAN 1940 0 0 73 00 0 000 0 1 0044 1.37 37722054 ROBERTS ARNOLD E 7325 14 SEP 1943 PVT 8 NO 2 5 0 73 14 1 3 475 2 7 1254 6.20 20733309 ROBERTS DICK C 7350 23 DEC 1940 PVT 8 FA 30 1 7 73 20 1 4 175 6 4 0359 3.80 A-413606 ROBERTS DORCIS R 4261 14 SEP 1944 PVT 8 WAC 18 5 0 73 22 1 2 175 6 9 0009 1.9 37811962 ROBERTS HAROLD E 8689 07 DEC 1945 PFC 7 NO 2 1 6 73 26 1 4 480 6 1 1268 6.34 20733489 ROBERTS NEIL I 7350 23 DEC 1940 PVT 8 FA 30 0 7 73 17 1 3 497 6 4 0359 3.80 20733310 ROBERTS ROBERT B 7117 10 MAY 1941 P5T 8 AC 20 0 1 73 15 1 6 316 6 1 - 0359 3.80 20733407 ROBERTSON CLEVE W 7350 23 DEC 1940 PV3 8 FA 30 1 7 73 18 1 4 760 6 4 - 0359 3.80 37740193 ROBERTSON KELL D SR 7325 12 APR 1944 PVT 8 NO 2 5 0 73 12 1 4 597 2 7 1257 6.23 37767571 ROBERTSON PAUL E 7325 18 APR 1945 PVT 8 NO 2 5 0 73 17 1 3 105 2 7 1261 6.27 06931733 ROBINSON CLIFFORD E 5564 09 OCT 1939 55 7 73 55 6 446 8 1 0043 1.36 20733437 ROBINSON CLINTON L 7350 23 DEC 1940 PVT 8 FA 30 1 7 73 21 1 3 170 6 4 0359 3.80 37737828 ROBINSON KELLEY E 7325 23 MAR 1944 PVT 8 NO 2 5 0 73 10 1 4 583 2 7 1256 6.22 37763330 ROBINSON ROBERT C 7325 05 MAR 1945 PVT 8 NO 2 5 0 73 22 1 1 441 2 7 1260 6.26 06936796 RODARMEL RAY C 4664 10 JAN 1940 64 2 73 65 6 536 6 1 0044 1.37 17128336 ROGERS NORMAN V 7325 03 NOV 1942 PVT 8 AC 20 5 0 73 23 1 0 222 6 6 0254 2.111 17059038 ROHR ALVIN 7325 28 AUG 1942 PVT 8 AC 20 5 0 73 22 1 4 781 1 6 0245 2.102 20733020 ROHR ISADORE F 7350 23 DEC 1940 PVT 8 MD 70 0 7 73 13 1 4 138 6 4 0359 3.80 17002702 ROHR VICTOR E 7339 20 DEC 1940 PVT 8 AC 20 0 0 73 20 1 4 781 6 1 0238 2.95 38277836 ROLLOW CECIL B 8459 08 DEC 1942 PVT 8 BI 0 5 0 84 18 1 5 097 6 7 1313 6.79 16027320 ROSIER RICHARD L 6119 08 AUG 1940 PVT 8 AC 20 7 0 73 17 1 4 402 6 1 0208 2.65 37763228 ROTH RAYMOND L 7325 03 MAR 1945 PVT 8 NO 2 5 0 73 26 1 2 306 6 7 1260 6.26 17196621 ROUSH ALLEN E 7325 16 MAR 1946 PVT 8 NO 2 6 2 84 28 1 2 000 1 1 0262 2.119 37811668 ROVENSTINE JOHN M 7325 30 MAY 1945 PVT 8 NO 2 5 0 70 15 1 4 485 2 7 1268 6.34 37728702 ROWEN DONALD K 7325 06 JAN 1944 PVT 8 AC 20 5 5 74 20 1 4 485 2 3 1255 6.21 17041941 ROYCE CLARE H 7354 22 JAN 1942 PVT 8 AC 20 5 0 73 15 1 8 583 6 6 0243 2.100 37767778 RUBLE WILLIAM H 7325 20 APR 1945 PVT 8 NO 2 5 0 73 13 1 0 720 2 7 1261 6.27 18305527 RUCKER EUGENE D 8567 19 OCT 1946 PVT 8 AC 20 3 8 78 25 1 0 259 6 1 9 0298 3.20 37747041 RUCKER LESTER E 8004 19 JAN 1946 CPL 6 NO 2 1 6 73 26 1 4 480 6 1 9 1258 6.24 37766066 RUCKER RAYMOND R 7325 04 APR 1945 PVT 8 NO 2 5 0 73 09 1 1 809 2 7 1261 6.27 20726348 RUDDELL BRUCE G 9109 17 NOV 1945 PFC 7 NO 2 1 4 73 17 1 1 499 2 1 0358 3.79 37762930 RUDICEL CHARLES E 7325 24 FEB 1945 PVT 8 NO 2 5 0 73 25 1 4 306 6 7 1260 6.26 37741478 RUE JOHN R 7325 26 APR 1944 PVT 8 NO 2 5 0 75 13 1 0 772 2 7 1257 6.23 37767542 RUESCHHOFF ALBERT J 7325 18 APR 1945 PVT 8 NO 2 5 0 73 16 1 5 091 2 7 1261 6.27 37757197 RUMFORD CHARLES F JR 7325 08 DEC 1944 PVT 8 NO 2 5 0 73 20 1 4 306 6 7 1259 6.25 17059128 RUSSELL EDGAR A 7325 31 AUG 1942 PVT 8 BI 0 5 0 73 22 1 0 316 6 6 0245 2.102 --------------------------------------------------------------------- KSGENWEB INTERNET GENEALOGICAL SOCIETY COPYRIGHT NOTICE: In keeping with the KSGenWeb policy of providing free information on the Internet, this data may be used by non-commercial entities, as long as this message remains on all copied material. 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Conference looks at blowing agents. - Free Online Library Free Online Library: Conference looks at blowing agents.(Meetings) by " Rubber World" ; Business Chemicals, plastics and rubber Conference looks at blowing agents. Rapra Technology Ltd. will hold its Seventh International Conference on Blowing Agents and Foaming Processes May 10-11 at the Millennium Hotel in Stuttgart, Germany. The technical program is said to provide excellent coverage of the key topics of interest to the industry. Papers will cover innovations in foaming technology and new applications of blowing agents, with sessions on foaming polyurethane and thermoplastics. An overview paper is planned on environmental issues and new legislation affecting the industry, particularly in construction applications. This event is said to bring together major blowing agent manufacturers and suppliers, processors, end users and academics to present an insight into the latest industrial progress in foam production. With constantly changing legislation on gas emissions, this is said to be a rapidly changing field, and it is said to be essential for users and manufacturers of foams to keep up with the latest developments. Session 1 on markets and legislation will include the presentation, "Impact of regulatory developments on the demand for blowing agents in foam," by Paul Ashford, Caleb Management Services Ltd., U.K. Session 2 on developments in foaming technology will include the following presentations: "The nucleation mechanisms investigated on polystyrene/HFC-134a mixtures," Jacques Tatibouet and Richard Gendron, Industrial Materials Institute/National Research Council Canada; "Customized interfaces to foam models for formulation advancement," Christian Ritter, Maria Key Prato and Jurgen Maebe, Shell Global Solutions, Belgium; "Mold technology," Sasan HabibiNaini, Sulzer Chemtech Ltd., Switzerland; "Repeatable processing and quality control systems for production of microcellular parts," Hartmut Traut, Trexel GmbH, Germany, and Levi Kishbaugh, Trexex; "Nanostructured polymer foams," Hans Luinge, E.J. Vorenkamp and A.J. Schouten, University of Groningen, The Netherlands; "The new rotating roller die and its application to environmentally friendly foaming of plastics using liquid C[O.sub.2]," Hadj Benkreira, M. Gale, R. Patel, M. Cox and J. Paragreen, IRC Polymer Science & Technology, U.K.; and "Physics of plastic foams: An industrial perspective," Andre Moreira and Volker Schadler, BASF AG, Germany. Session 3 on foaming thermoplastics will include the following presentations: "How to choose a polyolefin grade for physical foaming," Henk Ruinaard, Sabic EuroPetrochemicals BV, The Netherlands; "Flexible polypropylene foam solutions," Manfred Stadlbauer, Rick Folland and Paul De Mink, Borealis GmbH, Austria; "Effects of the convergent-filamentary die geometry on volume expansion of PS foams blown with C[O.sub.2]," Chul Park and Dong Lai Xu, University of Toronto, Canada; and "The effect of extrusion conditions on the morphology of chemically foamed thermoplastic elastomers," Denis Rodrigue and Ramin Khodabashkh, Universite Laval, Canada. Session 4 on foaming polyurethanes will include the following presentations: "HFC blowing agents for rigid insulation foams," Lotbar Zipfel and Christoph Meurer, Solvay Fluor, Germany; "Recent developments in the use of HFC-245fa blowing agent for rigid polyurethane foam," Saskia Walraedt, Honeywell, Belgium; "New developments in applications of methylal as blowing agent for rigid, flexible, integral skin and microcellular polyurethane foams," Michel Beaujean, Lambiotte & Cie, S.A., Belgium; "Pentane spray system: An effective and safe technology," Claudio Chittolini and Valentina Robles, Ediltec Srl, Italy; and "Cell structure and thermal conductivity of rigid polyurethane foams blown with cyclopentane in different molds," Aleksander Prociak, Cracow University of Technology, Poland. Session 5 on biodegradable and natural fiber-composite foams will include the following presentations: "Biodegradable foams based on PLA and PCL: How to improve the foaming process by means of nanocomposites and reactive processing," Ernesto Di Maio, University of Naples, Italy, and Salvatore Iannace and Yingwei Di, Institute of Composite & Biomedical Materials, Italy; "Natural fiber and wood foam composites--2005," Michael E. Reedy, Reedy International; and "Microcellular wood--PP composites in extrusion, injection and compression molding process," Abu Nasher Omar Faruk and Andrzej K. Bledzki, University of Kassel, Germany. Session 6 on development in foamed products will include the following presentations: "High frequency coaxial cable--an application for microcellular foaming technology in extrusion," Karl Audenaerde and Johannes Lorenz, Kabelwerk Eupen AG, Germany; and "Development of an environmentally friendly thermoplastic printed circuit board manufactured by foam extrusion," Dieter Langenfelder, J.K.W. Sandier and V. Altstadt, University of Bayreuth, Germany. Registration fees range from EUR 850 to EUR 1,050. Further information is available from Sharon Garrington, tel.: +44 (0) 1939 250383; fax: +44 (0) 1939 251118. Article Details Title Annotation: Meetings Publication: Rubber World Date: Apr 1, 2005 Words:
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? - [Help] Jai Jai - The Vet has suggested 1 unit of Lantus | Page 2 | Feline Diabetes Message Board - FDMB Hi Hollis, I've just had a look at Jai Jai's spreadsheet. I know the numbers are high, but you appear to be getting a much smoother curve on the 0.5IU... ? [Help] Jai Jai - The Vet has suggested 1 unit of Lantus Hi Hollis, I've just had a look at Jai Jai's spreadsheet. I know the numbers are high, but you appear to be getting a much smoother curve on the 0.5IU dose of Lantus. If we can stabilise that curve over the next 5 cycles on 0.5 IU, then it will give a much better guide to where Jai Jai's dose needs to go next. The general idea is to keep a smooth curve then in stages tweak the dose a little every 6 cycles to lower that smooth curve into regulated numbers. (But there may well be bounces along the way.) Maybe think of it like going downstairs. At each step, Jai Jai's body needs to get used to the slightly lower numbers (otherwise the liver panics and starts dumping glucose into the blood and it sets off swings again.) . heyhollis said: ↑ I got a lot of blood last night when I hit on his sweet spot, I was still very light handed...hmm hmm It'll get easier and easier with practice, Hollis. When you get the knack, maybe you can show the vet techs how to do it! Morning, Rhonda and Mogs. I have tried to test his BG before feeding him........No success, he was very fierce. I have just tested him right after his meal (hoping that not much influence by food), his AMPS is 436 (24.2 mmol/L). Mogs you are right, his curve was flatten now. Let us see how the food affects his numbers then. Fingers crossed. Right after the food is pretty OK, Hollis. Good to see an improvement in the preshot number - much better than those nasty blacks! The 1.0 unit dose on the Aug 1 AM cycle dropped Jai Jai's BG very hard and fast. Sharp drops like that can set off bounces, so I'm hoping that's behind those black preshot numbers. What we are hoping to over the next few cycles is fairly similar preshots and a curve with a gentler dip mid-cycle - smile-shaped. I am also hoping that now you're working on getting rid of the wild swings and those dangerous drops that Jai Jai's system won't be under as much strain and he'll start feeling better in himself. After all, that's what this sugar dance is all about! . Critter Mom said: ↑ The 1.0 unit dose on the Aug 1 AM cycle dropped Jai Jai's BG very hard and fast. This is exactly the reason I asked the vet to consider 0.5 units given that there was a drastic increase from + 6 (155) to +8 (268). My vet agreed that it was a drastic increase but insisted on giving 1 unit......meh That steep U-shaped curve is what you'd expect from a harsher insulin such as Caninsulin. 'Good' Lantus curves tend to be shallower. If a Caninsulin curve were a bucket, then an ideal Lantus curve would be a saucer. How is the little fella doing this morning? And did you get some better sleep? . That steep U-shaped curve is what you'd expect from a harsher insulin such as Caninsulin. 'Good' Lantus curves tend to be shallower. If a Caninsulin curve were a bucket, then an ideal Lantus curve would be a saucer. How is the little fella doing this morning? And did you get some better sleep? . Thank you for asking. I got up at +6 to get his reading, a little bit unsettled and did not have a deep sleep after that. Jai Jai is have a sleep, still bright and a little playful. I hope that you have a good sleep too. I'm glad that you at least managed to get some rest, Hollis. It can be fairly tough going in the early days after diagnosis. And with the too-high doses, you've really had a baptism of fire. Here's hoping that the 'reset' will help steady Jai Jai's system and that things will progress more smoothly now. It's grand to hear that Jai Jai is perky and playful in himself. He's got such a cute face - and you'd never think to look at him that he's 15 years young!!! It won't be long before weariness overtakes me now. Wishing you, your hubby and Jai Jai a lovely day. I'll check in to see how you're doing later. Mogs . heyhollis Member Critter Mom said: ↑ I'm glad that you at least managed to get some rest, Hollis. It can be fairly tough going in the early days after diagnosis. And with the too-high doses, you've really had a baptism of fire. Here's hoping that the 'reset' will help steady Jai Jai's system and that things will progress more smoothly now. It's grand to hear that Jai Jai is perky and playful in himself. He's got such a cute face - and you'd never think to look at him that he's 15 years young!!! It won't be long before weariness overtakes me now. Wishing you, your hubby and Jai Jai a lovely day. I'll check in to see how you're doing later. Mogs . I feel so warm and blessed when reading your message. If it is not your and some experience member's guidance and support, I must be panicking about his numbers. Looking at your Saoirse picture reminds me of my black cat. Mine is a boy and he is very muscular. I took a day off and I tested Jai Jai several times. Not good numbers but his curve is a saucer. I am hoping that his figures will not reach the black zone. Fingers crossed. May I wish you, Saoirse, and your family a wonderful day. Hi Hollis! Sorry I didn't get to you sooner. In a bit of a heap today. Thank you so much for your kind wishes. I hope by the time you read this that you've all had a good day, too. I'm also very glad to hear that you're not feeling as panicked. I have chronic PTSD and I suffer from panic attacks. Panicking is no fun, and it is really draining too. Just had a look at Jai Jai's spreadsheet: much smoother - no nassssssty blacks and no scary lows! All going well, he'll stay nice and smooth over the next two 0.5IU cycles. We should have a much better idea of how the 0.5IU is working by then, all going well, because Jai Jai should have cleared the bounce by then. I know it's tough seeing the higher numbers and waiting to go through the right number of cycles before making a change. The temptation to push things can be unbearable. Trouble is that nature can't be pushed (as Jai Jai's readings have shown us very clearly). We do a very good line in Patience Pants. Here's a special 'Superkitty' pair just for you ... Mogs . @Critter Mom I have been busy all day, and I have just settle a bit to update Jai Jai's BG records. Looks still going fine but he is apparently more tired and thirsty these two days. I think I will start a new post for your views after his 6 cycles of 0.5 units of Lantus. Thank you very much for your Patience Pants, I need that very much. heyhollis said: ↑ Thank you very much for your Patience Pants, All part of the FDMB Experience, Hollis! (I need a wardrobe full of 'em: patience was never my forté ... ) heyhollis said: ↑ Looks still going fine but he is apparently more tired and thirsty these two days. Jai Jai hasn't been getting down into lower numbers over the past few days so he will have needed to drink more water to replace the fluids lost when the kidneys are excreting the glucose that has spilled over into his urine. Having read that, I think it better to do the 0.25 IU Lantus dose increase on the next cycle but please ask for dosing advice again (with the question mark ) before the morning dose of insulin. If by chance you don't get a prompt reply on Feline Health, go back to the main forum index page, select the Lantus and Levemir insulin support group and post asking for advice there (with a link to today's thread). All going well there'll be someone who'll be able to keep an eye on things with you. (I'll check in when I surface later.) When you get a chance, Hollis, can you confirm to me whether you're testing Jai Jai's urine for ketones now. Blessings and scritches, Mogs . Critter Mom , Aug 4, 2015 Critter Mom said: ↑ When you get a chance, Hollis, can you confirm to me whether you're testing Jai Jai's urine for ketones now. Yes, on both Sunday and Monday, the results were negative. I will try another test today. That's good news. We'll have all of that we can get, Hollis. You're doing great! . Critter Mom said: ↑ That's good news. We'll have all of that we can get, Hollis. You're doing great! . Thank you, Mogs. I have got an update of his AMPS, it is in the black zone..... , do I have to change my mind of 0.75 dose? I will post this information and question on the new thread to seek views. Will follow your progress on the new thread now, Hollis. .
https://www.felinediabetes.com/FDMB/threads/help-jai-jai-the-vet-has-suggested-1-unit-of-lantus.141902/page-2?_params=Array
_BY T. W. SPEIGHT._ =The Mysteries of Heron Dyke.= _BY R. A. STERN DALE._ =The Afghan Knife.= _BY BERTHA THOMAS._ =Cressida.= =Proud Maisie.= =The Violin-Player.= _BY WALTER THORNBURY._ =Tales for the Marines.= _BY T. ADOLPHUS TROLLOPE._ =Diamond Cut Diamond.= _BY ANTHONY TROLLOPE._ =The Way We Live Now.= =The American Senator.= _BY MARK TWAIN._ =Tom Sawyer.= =An Idle Excursion.= =A Pleasure Trip on the Continent of Europe.= _BY SARAH TYTLER._ =What She Came Through.= _BY LADY WOOD._ =Sabina.= _BY EDMUND YATES._ =Castaway.= =The Forlorn Hope.= =Land at Last.= _ANONYMOUS._ =Paul Ferroll.= =Why Paul Ferroll Killed his Wife.= Fcap. 8vo, picture covers, =1s.= each. =Jeff Briggs’s Love Story.= By BRET HARTE. =The Twins of Table Mountain.= By BRET HARTE. =Mrs. Gainsborough’s Diamonds.= By JULIAN HAWTHORNE. =Kathleen Mavourneen.= By Author of “That Lass o’ Lowrie’s.” =Lindsay’s Luck.= By the Author of “That Lass o’ Lowrie’s.” =Pretty Polly Pemberton.= By the Author of “That Lass o’ Lowrie’s.” =Trooping with Crows.= By Mrs. PIRKIS. =The Professor’s Wife.= By LEONARD GRAHAM. =A Double Bond.= By LINDA VILLARI. =Esther’s Glove.= By R. E. FRANCILLON. =The Garden that Paid the Rent.= By TOM JERROLD. 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Publications - Global Disability Innovation Hub The GDI Hub brings together academic excellence, innovative practice and co-creation; harnessing the power of technology for good. Search & Filter Filter by type All PhD Working Paper Workshop Editorial Conference Paper Journal Paper Landscape review Toolkit Book Article Report Filter by theme All Assistive & Accessible Technology Inclusive Design Culture and Participation Climate & Crisis Resilience Inclusive Educational Technology Filter by research group All Disability Interactions Physiological Computing Social Justice Humanitarian & Disasters Local Productions Sort Date descending Date ascending A-Z by title Type Report Themes Assistive & Accessible Technology Assistive Technology Changes Lives: an assessment of AT need and capacity in England Vicki Austin , Dilisha Patel , Jamie Danemayer , Kate Mattick , Anna Landre , Marketa Smitova , Maryam Bandukda , Aoife Healy, Nachiappan Chockalingam, Diane Bell , Cathy Holloway This report was prepared by Global Disability Innovation (GDI) Hub for the Disability Unit in the Cabinet Office His Majesty’s Government (HMG). The report presents findings from a Country Capacity Assessment (CCA) of AT access in England. Findings illustrate a complex state of AT in England. While delivery systems tend to provide quality products that have a strong, positive impact on people’s lives, processes are often slow and stressful for users and providers alike. Startlingly, there is also an AT access gap of 31% of disabled people not having the assistive products they need to flourish, thrive, or even participate in daily life. The Cabinet Office; 2023 Cite Download Share Read Abstract Abstract Assistive Technology Changes Lives: an assessment of AT need and capacity in England The aim of this research was to undertake a Country Capacity Assessment (CCA) to inform a more integrated approach to Assistive Technology (AT) provision in England. The results aim to support policymakers in identifying actions to strengthen service delivery to better meet disabled people’s needs, improving outcomes for AT users and reducing inefficiencies in the current approach. The research was undertaken from November 2022 to March 2023 and led by the Global Disability Innovation (GDI) Hub, which is the World Health Organization (WHO) Global Collaborating Centre on AT access, using WHO tools in the Assistive Technology Assessment (ATA) suite. Cite Assistive Technology Changes Lives: an assessment of AT need and capacity in England Suggested Citation: Austin, V, Patel, D, Danemayer, J, Mattick, K, Landre, A, Smitova, M, Bandukda, M, Healy, A, Chockalingam, N, Bell D, and Holloway, C; Assistive Technology Changes Lives: an assessment of AT need and capacity in England; Cabinet Office, HMG; 2023 Share Assistive Technology Changes Lives: an assessment of AT need and capacity in England Type Conference Paper Themes Assistive & Accessible Technology Culture and Participation The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya Giulia Barbareschi , Catherine Holloway , Katherine Arnold, Grace Magomere, Wycliffe Ambeyi Wetende, Gabriel Ngare, Joyce Olenja We present the findings of a case study of mobile technology use by People with Visual Impairment (VIPs) in Kibera, an informal settlement in Nairobi. We used contextual interviews, ethnographic observations and a co-design workshop to explore how VIPs use mobile phones in their daily lives, and how this use influences the social infrastructure of VIPs. Our findings suggest that mobile technology supports and shapes the creation of social infrastructure. However, this is only made possible through the existing support networks of the VIPs, which are mediated through four types of interaction: direct, supported, dependent and restricted. CHI '20: Proceedings of the 2020 CHI Conference; 2020 Cite Share Read Abstract Visit publisher Abstract The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya Living in an informal settlement with a visual impairment can be very challenging resulting in social exclusion. Mobile phones have been shown to be hugely beneficial to people with sight loss in formal and high-income settings. However, little is known about whether these results hold true for people with visual impairment (VIPs) in informal settlements. We present the findings of a case study of mobile technology use by VIPs in Kibera, an informal settlement in Nairobi. We used contextual interviews, ethnographic observations and a co-design workshop to explore how VIPs use mobile phones in their daily lives, and how this use influences the social infrastructure of VIPs. Our findings suggest that mobile technology supports and shapes the creation of social infrastructure. However, this is only made possible through the existing support networks of the VIPs, which are mediated through four types of interaction: direct, supported, dependent and restricted. Cite The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya Giulia Barbareschi, Catherine Holloway, Katherine Arnold, Grace Magomere, Wycliffe Ambeyi Wetende, Gabriel Ngare, and Joyce Olenja. 2020. The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya. In Proceedings of the 2020 CHI Conference on Human Factors in Computing Systems (CHI '20). Association for Computing Machinery, New York, NY, USA, 1–15. https://doi.org/10.1145/331383... Share The Social Network: How People with Visual Impairment use Mobile Phones in Kibera, Kenya Type Editorial Themes Culture and Participation COVID-19 as social disability: the opportunity of social empathy for empowerment Ikenna D Ebueny, Emma M Smith, Catherine Holloway , Rune Jensen, Lucía D'Arino, Malcolm MacLachlan Social empathy is ‘the ability to more deeply understand people by perceiving or experiencing their life situations and as a result gain insight into structural inequalities and disparities’. Social empathy comprises three elements: individual empathy, contextual understanding and social responsibility. COVID-19 has created a population-wide experience of exclusion that is only usually experienced by subgroups of the general population. Notably, persons with disability, in their everyday lives, commonly experience many of the phenomena that have only recently been experienced by members of the general population. COVID-19 has conferred new experiential knowledge on all of us. We have a rare opportunity to understand and better the lives of persons with disabilities for whom some aspects of the COVID- 19 experience are enduring. This allows us greater understanding of the importance of implementing in full a social and human rights model of disability, as outlined in the UNCRPD. BMJ Global Health; 2020 Cite Share Read Abstract Visit publisher Abstract COVID-19 as social disability: the opportunity of social empathy for empowerment COVID-19 has conferred new experiential knowledge on society and a rare opportunity to better understand the social model of disability and to improve the lives of persons with disabilities. The COVID-19 experience may offer contextual knowledge of the prepandemic lives of persons with disabilities and foster greater social awareness, responsibility and opportunities for change towards a more inclusive society. Information, family and social relationships, health protection and healthcare, education, transport and employment should be accessible for all groups of the population. The means must be developed and deployed to ensure equity – the deployment of resources so that people with different types of needs have the same opportunities for living good lives in inclusive communities. We have learnt from COVID-19 that inclusive healthcare and universal access should be the new normal, that its provision as a social good is both unifying and empowering for society as a whole. Cite COVID-19 as social disability: the opportunity of social empathy for empowerment Ebuenyi ID, Smith EM, Holloway C , et al COVID-19 as social disability: the opportunity of social empathy for empowerment BMJ Global Health 2020; 5: e003039. Share COVID-19 as social disability: the opportunity of social empathy for empowerment Type Editorial Themes Assistive & Accessible Technology Research Group Social Justice Developing inclusive and resilient systems: COVID-19 and assistive technology Emma M. Smith, Malcolm MacLachlan, Ikenna D. Ebuenyi, Catherine Holloway & Victoria Austin While the inadequacies of our existing assistive technology systems, policies, and services have been highlighted by the acute and rapidly changing nature of the COVID-19 pandemic, these failures are also present and important during non-crisis times. Each of these actions, taken together, will not only address needs for more robust and resilient systems for future crises, but also the day-to-day needs of all assistive technology users. We have a responsibility as a global community, and within our respective countries, to address these inadequacies now to ensure an inclusive future. Disability & Society; 2020 Cite Share Read Abstract Visit publisher Abstract Developing inclusive and resilient systems: COVID-19 and assistive technology Assistive technology is a critical component of maintaining health, wellbeing, and the realization of rights for persons with disabilities. Assistive technologies, and their associated services, are also paramount to ensuring individuals with functional limitations have access to important health and social service information, particularly during a pandemic where they may be at higher risk than the general population. Social isolation and physical distancing have further marginalized many within this population. We have an opportunity to learn from the COVID-19response to develop more inclusive and resilient systems that will serve people with disabilities more effectively in the future. In this Current Issues piece, we present a starting point for discussion, based on our experiences working to promote access to assistive technologies through inclusive and sustainable systems and policies. Cite Developing inclusive and resilient systems: COVID-19 and assistive technology Emma M. Smith, Malcolm MacLachlan, Ikenna D. Ebuenyi, Catherine Holloway & Victoria Austin (2021) Developing inclusive and resilient systems: COVID-19 and assistive technology, Disability & Society, 36:1, 151-154, DOI: 10.1080/09687599.2020.1829558 Share Developing inclusive and resilient systems: COVID-19 and assistive technology Type Conference Paper Disability design and innovation in computing research in low resource settings Dafne Zuleima Morgado-Ramirez, Giulia Barbareschi , Maggie Kate Donovan-Hall, Mohammad Sobuh, Nida' Elayyan, Brenda T Nakandi, Robert Tamale Ssekitoleko, joyce Olenja, Grace Nyachomba Magomere, Sibylle Daymond, Jake Honeywill, Ian Harris, Nancy Mbugua, Laurence Kenney, Catherine Holloway 80% of people with disabilities worldwide live in low resourced settings, rural areas, informal settlements and in multidimensional poverty. ICT4D leverages technological innovations to deliver programs for international development. But very few do so with a focus on and involving people with disabilities in low resource settings. Also, most studies largely focus on publishing the results of the research with a focus on the positive stories and not the learnings and recommendations regarding research processes. ASSETS '20: Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility; 2020 Cite Share Read Abstract Visit publisher Abstract Disability design and innovation in computing research in low resource settings 80% of people with disabilities worldwide live in low resourced settings, rural areas, informal settlements and in multidimensional poverty. ICT4D leverages technological innovations to deliver programs for international development. But very few do so with a focus on and involving people with disabilities in low resource settings. Also, most studies largely focus on publishing the results of the research with a focus on the positive stories and not the learnings and recommendations regarding research processes. In short, researchers rarely examine what was challenging in the process of collaboration. We present reflections from the field across four studies. Our contributions are: (1) an overview of past work in computing with a focus on disability in low resource settings and (2) learnings and recommendations from four collaborative projects in Uganda, Jordan and Kenya over the last two years, that are relevant for future HCI studies in low resource settings with communities with disabilities. We do this through a lens of Disability Interaction and ICT4D. Cite Disability design and innovation in computing research in low resource settings Dafne Zuleima Morgado-Ramirez, Giulia Barbareschi, Maggie Kate Donovan-Hall, Mohammad Sobuh, Nida' Elayyan, Brenda T Nakandi, Robert Tamale Ssekitoleko, joyce Olenja, Grace Nyachomba Magomere, Sibylle Daymond, Jake Honeywill, Ian Harris, Nancy Mbugua, Laurence Kenney, and Catherine Holloway. 2020. Disability design and innovation in computing research in low resource settings. In Proceedings of the 22nd International ACM SIGACCESS Conference on Computers and Accessibility (ASSETS '20). Association for Computing Machinery, New York, NY, USA, Article 11, 1–7. https://doi.org/10.1145/337362... Share Disability design and innovation in computing research in low resource settings Type Editorial Research Group Social Justice Assistive Technology (AT), for What? Vicki Austin , Catherine Holloway This year (2022) has seen the publication of the World’s first Global Report on Assistive Technology (GReAT) [ 1 ]. This completes almost a decade of work to ensure assistive technology (AT) access is a core development issue. The lack of access to assistive products (APs), such as wheelchairs, hearing aids, and eyeglasses, as well as less well-referenced products such as incontinence pads, mobile phone applications, or walking sticks, affects as many as 2.5 billion people globally. Furthermore, the provision of APs would reap a 1:9 return on investment [ 2 ]. This could result in a family in need netting (or living without) over GBP 100,000 in their lifetime [ 2 ] or more, if we count dynamic overspills in the economy such as employment of assistive technology services and manufacturing of devices [ 3 ]. Societies; 2021 Cite Share Read Abstract Visit publisher Abstract Assistive Technology (AT), for What? Amartya Sen’s seminal Tanner lecture: Equality of What? began a contestation on social justice and human wellbeing that saw a new human development paradigm emerge—the capability approach (CA)—which has been influential ever since. Following interviews with leading global assistive technology (AT) stakeholders, and users, this paper takes inspiration from Sen’s core question and posits, AT for what? arguing that AT should be understood as a mechanism to achieve the things that AT users’ value. Significantly, our research found no commonly agreed operational global framework for (disability) justice within which leading AT stakeholders were operating. Instead, actors were loosely aligned through funding priorities and the CRPD. We suggest that this raises the possibility for (welcome and needed) incoming actors to diverge from efficiently designed collective action, due to perverse incentives enabled by unanchored interventions. The Global Report on Assistive Technology (GReAT) helps, greatly! However, we find there are still vital gaps in coordination; as technology advances, and AT proliferates, no longer can the device-plus-service approach suffice. Rather, those of us interested in human flourishing might explore locating AT access within an operational global framework for disability justice, which recognizes AT as a mechanism to achieve broader aims, linked to people’s capabilities to choose what they can do and be. Cite Assistive Technology (AT), for What? Austin, V.; Holloway, C. Assistive Technology (AT), for What? Societies 2022 , 12 , 169. https://doi.org/10.3390/soc120... Share Assistive Technology (AT), for What? Type Editorial Themes Assistive & Accessible Technology Research Group Disability Interactions The Digital and Assistive Technologies for Ageing initiative: learning from the GATE initiative Chapal Khasnabis, Catherine Holloway , Malcolm MacLachlan We are now in an era of assistive care and assistive living—whereby many people, of all ages, in good health, and those who are more frail, or with cognitive or functional impairments, are using a broad range of technologies to assist and enhance their daily living. Assistive living 1 is becoming an important part of population health and rehabilitation, which can help to maximise an individual's abilities, regardless of age or functional capacity. This encouraging shift in ethos has been strengthened by the response to the COVID-19 pandemic, in which a plethora of digital and remote technologies have been used. The Lancet; 2020 Share Visit publisher Share The Digital and Assistive Technologies for Ageing initiative: learning from the GATE initiative Type Editorial Themes Assistive & Accessible Technology Culture and Participation Research Group Social Justice Critical Junctures in Assistive Technology and Disability Inclusion Dr Maria Kett , Catherine Holloway , Vicki Austin , Dr Maria Kett It is clear from the events of the last 18 months that while technology has a huge potential for transforming the way we live and work, the entire ecosystem—from manufacturing to the supply chain—is vulnerable to the vagaries of that ecosystem, as well as having the potential to exacerbate new and existing inequalities [ 1 ]. Nowhere has this been more apparent than in the lives of people with disabilities, who make up around 15% of the world’s population and already face barriers to accessing education, employment, healthcare and other services [ 2 ]. Some of these barriers are a result of unequal access and opportunities. However, there is a growing movement to better understand how assistive technology systems and services can be designed to enable more robust and equitable access for all. As part of this growing movement, the Paralympic Games in Tokyo this autumn saw the launch of a new global campaign to transform the lives of the world’s 1.2 bn persons with disabilities: the ‘WeThe15’ campaign reached more than 4.5 billion people through its marketing and stands ready to be the biggest of its kind in history. Next year, the World Health Organization (WHO) and the United Nations Children’s Fund (UNICEF), AT scale and GDI Hub will publish the first World Report on Access to Assistive Technology, which will include research from the £20 million, UK Aid funded, GDI Hub-led, programme, AT2030. Ahead of that, in this Special Issue, we focus on how some events and situations—as diverse as the coronavirus pandemic and the Paralympics—can act as ‘critical junctures’ that can enable a rethink of the status quo to facilitate and promote change. Sustainability; 2021 Cite Share Visit publisher Cite Critical Junctures in Assistive Technology and Disability Inclusion Kett, M.; Holloway, C.; Austin, V. Critical Junctures in Assistive Technology and Disability Inclusion. Sustainability 2021 , 13 , 12744. https://doi.org/10.3390/su1322... Share Critical Junctures in Assistive Technology and Disability Inclusion Type Editorial Themes Assistive & Accessible Technology Research Group Disability Interactions Introduction to the companion papers to the global report on assistive technology Johan Borg, Wei Zhang, Emma M. Smith, Cathy Holloway GReAT, but do we care? If accessible, assistive technology would be life changing for a billion people across the world today – and two billion people in 2050 (WHO, 2018 ). It would make the difference between independence and dependence, inclusion and exclusion, life and death. It holds the potential to improve and transform health, education, livelihood and social participation; fundamental human rights everyone is entitled to. And if we are lucky to grow old, the chances are that we all would use assistive technology by then. But do we care? Assistive Technology, The Official Journal of RESNA; 2021 Cite Share Visit publisher Cite Introduction to the companion papers to the global report on assistive technology Johan Borg, Wei Zhang, Emma M. Smith & Cathy Holloway (2021) Introduction to the companion papers to the global report on assistive technology, Assistive Technology, 33:sup1, 1-2, DOI: 10.1080/10400435.2021.2003658 Share Introduction to the companion papers to the global report on assistive technology Type Conference Paper Themes Assistive & Accessible Technology Value beyond function: analyzing the perception of wheelchair innovations in Kenya Barbareschi, G ; Daymond, S; Honeywill, J; Singh, A; Noble, D; Mbugua, N; Harris, I; Austin, V ; Holloway, C The World Health Organization (WHO) defines Assistive Technology (AT) as “an umbrella term covering the systems and services related to the delivery of assistive products and services” [6]. This definition highlights how AT encompasses not only the physical and digital products used by millions of persons with disabilities (PWDs) worldwide, but also the systems and services that accompany the provision of these devices [78]. ASSETS '20: The 22nd International ACM SIGACCESS Conference on Computers and Accessibility.; 2020 Share Read Abstract Visit publisher Abstract Value beyond function: analyzing the perception of wheelchair innovations in Kenya Innovations in the field of assistive technology are usually evaluated based on practical considerations related to their ability to perform certain functions. However, social and emotional aspects play a huge role in how people with disabilities interact with assistive products and services. Over a five months period, we tested an innovative wheelchair service provision model that leverages 3D printing and Computer Aided Design to provide bespoke wheelchairs in Kenya. The study involved eight expert wheelchair users and five healthcare professionals who routinely provide wheelchair services in their community. Results from the study show that both users and providers attributed great value to both the novel service delivery model and the wheelchairs produced as part of the study. The reasons for their appreciation went far beyond the practical considerations and were rooted in the fact that the service delivery model and the wheelchairs promoted core values of agency, empowerment and self-expression. Share Value beyond function: analyzing the perception of wheelchair innovations in Kenya Type Conference Paper Themes Assistive & Accessible Technology Culture and Participation Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh Nusrat Jahan, Giulia Barbareschi , Clara Aranda Jan, Charles Musungu Mutuku, Naemur Rahman, Victoria Austin , Catherine Holloway Worldwide it is estimated that there are over a billion people who live with some form of disability [1] . Approximately 80% of people with disabilities live in low-and-middle income countries (LMICs). The combination of an inaccessible environment compounded by socio-economic factors such as poverty and stigma, makes it more likely for people with disabilities to be marginalised and excluded from society [1] . Assistive Technologies (ATs) are known to bridge the accessibility gaps and allow for greater social inclusion. However, there is a lack of adequate access to ATs in LMICs, combined with often poorly designed services, which only magnifies these challenges, thus limiting the opportunities for persons with disabilities to live an independent life [2] . Despite the importance of AT, access to AT globally is inadequate with only 10 percent of those in need having access to the ATs that they need [2] . 2020 IEEE Global Humanitarian Technology Conference Cite Share Read Abstract Visit publisher Abstract Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh Globally, mobile technology plays a significant role connecting and supporting people with disabilities. However, there has been limited research focused on understanding the impact of mobile technology in the lives of persons with disabilities in low or middle- income countries. This paper presents the findings of a participatory photovoice study looking at the role that mobile phones play in the daily lives of 16 persons with disabilities in Kenya and Bangladesh. Participants used a combination of pictures and voice recordings to capture their own stories and illustrate the impact that mobile phone use has on their lives. Through thematic analysis, we categorized the benefits of mobile phones captured by participants as 1) Improved social connection; 2) Increased independence and 3) Access to opportunities. While mobile phones are ubiquitously used for communication, for persons with disabilities they become essential assistive technologies that bridge barriers to opportunities which are not accessible otherwise. Our paper adds evidence to the need for mobile phones for persons with disabilities to enable communication and connectivity in support of development. Cite Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh N. Jahan et al ., "Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh," 2020 IEEE Global Humanitarian Technology Conference (GHTC) , Seattle, WA, USA, 2020, pp. 1-8, doi: 10.1109/GHTC46280.2020.9342934. Share Inclusion and Independence: The impact of Mobile Technology on the Lives of Persons with Disabilities in Kenya and Bangladesh Type Conference Paper Themes Assistive & Accessible Technology Research Group Local Productions A Preliminary Study to Understand How Mainstream Accessibility and Digital Assistive Technologies Reaches People in Lower- and Middle-Income Countries Tigmanshu Bhatnagar , George Torrens, Ben Oldfrey, Priya Morjaria Felipe Ramos Barajas , Katherine Perry and Catherine Holloway Access to information on digital platforms not only facilitates education, employment, entertainment, social interaction but also facilitates critical governmental services, ecommerce, healthcare services and entrepreneurship [1]. Article 9 of United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) enforces its signatories to commit to provide full accessibility to every citizen of the nation [2]. This has helped to spearhead accessibility directives such as the European Accessibility Act [3] that aims to improve the functioning of markets for accessible products and services. Such directives contribute to ensure that mainstream digital technologies (smartphones, computers etc.) are accessible for everyone and without being socially remarkable, they are able to assist in daily living. Additionally, there is evidence that improving access in mainstream technologies improves product experience and usability for everyone [4]. However, mainstream access has not been fully realized, leading to inferior opportunities for people with disabilities, a disparity which is more prominent in lower and middle-income countries [5]. RESNA Annual Conference; 2021 Share Visit publisher Share A Preliminary Study to Understand How Mainstream Accessibility and Digital Assistive Technologies Reaches People in Lower- and Middle-Income Countries Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design Troy Bodkin Doctoral Thesis. This work is one of four multidisciplinary research studies conducted by members of this research cluster, focusing on the area of Computer Aided Design (CAD) for improving the interface with Additive Manufacture (AM) to solve some of the challenges presented with improving prosthetic socket design, with an aim to improve and streamline the process to enable the involvement of clinicians and patients in the design process. Loughborough University Cite Share Read Abstract Visit publisher Abstract Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design For many years, the biggest issue that causes discomfort and hygiene issues for patients with lower limb amputations have been the interface between body and prosthetic, the socket. Often made of an inflexible, solid polymer that does not allow the residual limb to breathe or perspire and with no consideration for the changes in size and shape of the human body caused by changes in temperature or environment, inflammation, irritation and discomfort often cause reduced usage or outright rejection of the prosthetic by the patient in their day to day lives. To address these issues and move towards a future of improved quality of life for patients who suffer amputations, Loughborough University formed the Next Generation Prosthetics research cluster. This work is one of four multidisciplinary research studies conducted by members of this research cluster, focusing on the area of Computer Aided Design (CAD) for improving the interface with Additive Manufacture (AM) to solve some of the challenges presented with improving prosthetic socket design, with an aim to improve and streamline the process to enable the involvement of clinicians and patients in the design process. The research presented in this thesis is based on three primary studies. The first study involved the conception of a CAD criteria, deciding what features are needed to represent the various properties the future socket outlined by the research cluster needs. These criteria were then used for testing three CAD systems, one each from the Parametric, Non Uniform Rational Basis Spline (NURBS) and Polygon archetypes respectively. The result of these tests led to the creation of a hybrid control workflow, used as the basis for finding improvements. The second study explored emerging CAD solutions, various new systems or plug-ins that had opportunities to improve the control model. These solutions were tested individually in areas where they could improve the workflow, and the successful solutions were added to the hybrid workflow to improve and reduce the workflow further. The final study involved taking the knowledge gained from the literature and the first two studies in order to theorise how an ideal CAD system for producing future prosthetic sockets would work, with considerations for user interface issues as well as background CAD applications. The third study was then used to inform the final deliverable of this research, a software design specification that defines how the system would work. This specification was written as a challenge to the CAD community, hoping to inform and aid future advancements in CAD software. As a final stage of research validation, a number of members of the CAD community were contacted and interviewed about their feelings of the work produced and their feedback was taken in order to inform future research in this area. Cite Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design Bodkin, Troy L. (2017): Specifying a hybrid, multiple material CAD system for next-generation prosthetic design. Loughborough University. Thesis. https://hdl.handle.net/2134/25... ; Share Specifying a Hybrid, Multiple Material CAD System for Next Generation Prosthetic Design Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers Giulia Barbareschi Doctoral Thesis. This thesis makes two contributions to facilitate wheelchair users’ engagement in the participatory design process for ATs, while being mindful of the burden of participation. The first contribution is a framework that provides a modular structure guiding the participatory design process from initial problem identification and analysis to facilitating collaborations between wheelchair users and designers. The framework identifies four factors determining the need and adoption process for ATs: (i) People focuses on the target population, (ii) Person includes personal characteristics, (iii) Activity refers to the challenges associated with the task, and (iv) Context encompasses the effect of the environment in which the activity takes place. The second contribution constitutes a rich picture of personal and external elements influencing real world wheelchair transfers that emerged from four studies carried out to investigate the effect of the framework factors on the design process for ATs. UCL (University College London) Cite Share Read Abstract Visit publisher Abstract YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers Transferring independently to and from their wheelchair is an essential routine task for many wheelchair users but it can be physically demanding and can lead to falls and upper limb injuries that reduce the person’s independence. New assistive technologies (ATs) that facilitate the performance of wheelchair transfers have the potential to allow wheelchair users to gain further independence. To ensure that users’ needs are addressed by ATs, the active involvement of wheelchair users in the process of design and development is critical. However, participation can be burdensome for many wheelchair users as design processes where users are directly involved often require prolonged engagement. This thesis makes two contributions to facilitate wheelchair users’ engagement in the participatory design process for ATs, while being mindful of the burden of participation. The first contribution is a framework that provides a modular structure guiding the participatory design process from initial problem identification and analysis to facilitating collaborations between wheelchair users and designers. The framework identifies four factors determining the need and adoption process for ATs: (i) People focuses on the target population, (ii) Person includes personal characteristics, (iii) Activity refers to the challenges associated with the task, and (iv) Context encompasses the effect of the environment in which the activity takes place. The second contribution constitutes a rich picture of personal and external elements influencing real world wheelchair transfers that emerged from four studies carried out to investigate the effect of the framework factors on the design process for ATs. A related outcome based on these contributions is a framing document to share knowledge between wheelchair users and designers to provide focus and promote an equal collaboration among participants. Cite YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers Barbareschi, Giulia. “YouTransfer, YouDesign : a Participatory Approach to Design Assistive Technology for Wheelchair Transfers / Giulia Barbareschi.” Thesis (Ph.D.)--University College London, 2018., 2018. Print. Share YouTransfer, YouDesign: A Participatory Approach to Design Assistive Technology for Wheelchair Transfers Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions Understanding wrist splint user needs and personalisation through codesign Charlotte Pyatt A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy at Loughborough University. Loughborough University Cite Share Read Abstract Visit publisher Abstract Understanding wrist splint user needs and personalisation through codesign Wrist splints are a common treatment for rheumatoid arthritis, however their effectiveness is compromised by patients not wearing splints as often as prescribed. Previous research has identified a number of reasons for non-compliance, but typically lacks insights that could lead to improved splint design. This thesis investigates the motivators for patients to wear and not wear their wrist splints and, the impact of personalisation of splint appearance on patient wear. The work is based on the premise that digital design and manufacturing processes, such as Computer-Aided Design (CAD) and 3D Printing, can produce bespoke splints on demand. The research begins with a literature review across the core areas of: splinting, additive manufacture, product appearance and personalisation. This literature review identifies gaps in knowledge from which research questions are established for the work. The research employs a qualitative, generative design research approach and, follows a codesign framework employing telling, making and enacting tools. The thesis is made up of three studies. The first study is a sensitisation study and uses design probes to prepare the participants for the research and begin exploring the problem space. The second is a comprehensive study into participants splint wear behaviour and uses context mapping and scenario picture card tools to investigate the motivators for participants to wear and not wear wrist splints, along with positive and negative outcomes or wearing/not wearing splints. The final study uses a personalisation toolkit to elicit patient needs for a future wrist splint design and investigate self-reported expectations regarding compliance of patients who used the toolkit. The research finds that patient compliance is affected by practical and aesthetic limitations of current splints. It identifies 4 motivating factors to wear a splint and 10 motivating factors to not wear a splint. Additionally, it identifies 6 positive outcomes of wearing splints, 6 negative outcomes of wearing splints, 3 positive outcomes of not wearing splints and 3 negative outcomes of not wearing splints. Requirements for an improved splint design are established and form the basis of the design for a prototype personalisation toolkit. Testing of this toolkit reveals that patients are keen to own more than one splint and personalise splints to match the scenario in which it is to be worn. Patients reported that they expected to be more compliant with a personalised splint when compared to their current splint. Cite Understanding wrist splint user needs and personalisation through codesign Pyatt, Charlotte (2018): Understanding wrist splint user needs and personalisation through codesign. Loughborough University. Thesis. https://doi.org/10.26174/thesi... ; Share Understanding wrist splint user needs and personalisation through codesign Type PhD Themes Assistive & Accessible Technology Shared Control for Wheelchair Interfaces Dr Chinemelu Ejiamatu Muoma Ezeh Doctoral Thesis. Independent mobility is fundamental to the quality of life of people with impairment. Most people with severe mobility impairments, whether congenital, e.g., from cerebral palsy, or acquired, e.g., from spinal cord injury, are prescribed a wheelchair. A small yet significant number of people are unable to use a typical powered wheelchair controlled with a joystick. Instead, some of these people require alternative interfaces such as a head- array or Sip/Puff switch to drive their powered wheelchairs. However, these alternative interfaces do not work for everyone and often cause frustration, fatigue and collisions. This thesis develops a novel technique to help improve the usability of some of these alternative interfaces, in particular, the head-array and Sip/Puff switch. UCL (University College London) Cite Share Read Abstract Visit publisher Abstract Shared Control for Wheelchair Interfaces Independent mobility is fundamental to the quality of life of people with impairment. Most people with severe mobility impairments, whether congenital, e.g., from cerebral palsy, or acquired, e.g., from spinal cord injury, are prescribed a wheelchair. A small yet significant number of people are unable to use a typical powered wheelchair controlled with a joystick. Instead, some of these people require alternative interfaces such as a head- array or Sip/Puff switch to drive their powered wheelchairs. However, these alternative interfaces do not work for everyone and often cause frustration, fatigue and collisions. This thesis develops a novel technique to help improve the usability of some of these alternative interfaces, in particular, the head-array and Sip/Puff switch. Control is shared between a powered wheelchair user, using an alternative interface and a pow- ered wheelchair fitted with sensors. This shared control then produces a resulting motion that is close to what the user desires to do but a motion that is also safe. A path planning algorithm on the wheelchair is implemented using techniques in mo- bile robotics. Afterwards, the output of the path planning algorithm and the user’s com- mand are both modelled as random variables. These random variables are then blended in a joint probability distribution where the final velocity to the wheelchair is the one that maximises the joint probability distribution. The performance of the probabilistic approach to blending the user’s inputs with the output of a path planner, is benchmarked against the most common form of shared control called linear blending. The benchmarking consists of several experiments with end users both in a simulated world and in the real-world. The thesis concludes that probabilistic shared control provides safer motion compared with the traditional shared control for difficult tasks and hard-to-use interfaces. Cite Shared Control for Wheelchair Interfaces Ezeh, Chinemelu Ejiamatu Muoma. Shared Control for Wheelchair Interfaces. UCL (University College London), 2018. Print. Share Shared Control for Wheelchair Interfaces Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions Materials For Facial Prostheses In Resource Limited Countries Sophia Esther Liiba Tetteh A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy of Loughborough University Loughborough University Cite Share Read Abstract Visit publisher Abstract Materials For Facial Prostheses In Resource Limited Countries Facial prostheses are artificial devices that replace a missing body part in the facial and neck regions of the body. Defects or deformities in these regions can lead to functional deficiencies; social and psychological effects in addition to cosmetic defects. Restoration or rehabilitation in resource limited countries is usually provided by charities and organisations volunteering assistance overseas, with some training of local staff in the fabrication of these prostheses. Furthermore, these countries typically lack technical knowhow and trained personnel. In industrialised nations maxillofacial prosthetics has developed into a sophisticated medical speciality requiring highly skilled staff and expensive facilities. In resource limited countries surgical procedures may be an option for rehabilitation of these deformities/defects however, they tend to be unavailable or unaffordable and donated prostheses are not suitable. Hence, this research explores, from first principles, the appropriate and affordable local provision of maxillofacial prostheses in resource constrained regions. The investigation provides knowledge on identifying requirements for resource limited areas, resulting in the creation of a guideline constituting priorities, requirements and specifications. It further explores the viability of potentially cheaper, locally available candidate materials via weathering and antimicrobial methods in ascertaining material longevity. Cite Materials For Facial Prostheses In Resource Limited Countries Tetteh, Sophia (2019): Materials for facial prostheses in resource-limited countries. Loughborough University. Thesis. https://doi.org/10.26174/thesi... ; Share Materials For Facial Prostheses In Resource Limited Countries Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers Rhys James Williams Thesis: Firstly, the research provides a methodological contribution showing how to conduct mixed-methods research to obtain rich insights into complex prosthesis phenomena. Secondly, the research highlights the need to appreciate psychological and contextual factors when researching prosthesis wearer thermal comfort. The research contributions are also converted into an implication for prosthesis design. The concept of 'regaining control' to psychologically mitigate thermal discomfort could be incorporated into technologies by using 'on-demand' thermal discomfort relief, rather than 'always-on' solutions, as have been created in the past. UCL, ProQuest Dissertations Publishing Cite Share Read Abstract Visit publisher Abstract Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers Amongst lower-limb prosthesis wearers, thermal discomfort is a common problem with an estimated prevalence of more than 50%. Overheating does not just create discomfort to the user, but it has been linked to excessive sweating, skin damage caused by a moist environment and friction. Due to impermeable prosthetic components and a warm moist environment, minor skin damage can result in skin infections that can lead to prosthesis cessation, increased social anxiety, isolation and depression. Despite the seriousness of thermal discomfort, few studies explore the issue, with research predominantly constrained to controlled laboratory scenarios, with only one out of laboratory study. In this thesis, studies investigate how thermal discomfort arises and what are the consequences of thermal discomfort for lower-limb prosthesis wearers. Research studies are designed around the principles of presenting lived experiences of the phenomenon and conducting research in the context of participants' real-life activities. A design exploration chapter investigates modifying liner materials and design to create a passive solution to thermal discomfort. However, this approach was found to be ineffective and unfeasible. Study 1 presents a qualitative study which investigates the user experience of a prosthesis, thermal discomfort and related consequences. Study 2 explores limb temperature of male amputees inside and outside the laboratory, with the latter also collecting perceived thermal comfort (PTC) data. Finally, Study 3 investigates thermal discomfort in the real-world and tracks limb temperature, ambient conditions, activities, and experience sampling of PTC. While there were no apparent relationships presented in sensor data, qualitative data revealed that in situations where prosthesis wearers perceived a lack of control, thermal discomfort seemed to be worse. When combined, the studies create two knowledge contributions. Firstly, the research provides a methodological contribution showing how to conduct mixed-methods research to obtain rich insights into complex prosthesis phenomena. Secondly, the research highlights the need to appreciate psychological and contextual factors when researching prosthesis wearer thermal comfort. The research contributions are also converted into an implication for prosthesis design. The concept of 'regaining control' to psychologically mitigate thermal discomfort could be incorporated into technologies by using 'on-demand' thermal discomfort relief, rather than 'always-on' solutions, as have been created in the past. Cite Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers Williams, Rhys James. “Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers.” ProQuest Dissertations Publishing, 2020. Print. Share Exploring Thermal Discomfort Amongst Lower-Limb Prosthesis Wearers Type PhD Themes Assistive & Accessible Technology Research Group Disability Interactions Design rules for additively-manufactured wrist splints Sarah Kelly A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy of Loughborough University. Loughborough University Cite Share Read Abstract Visit publisher Abstract Design rules for additively-manufactured wrist splints Additive Manufacturing (AM) often known by the term three-dimensional printing (3DP) has been acknowledged as a potential manufacturing revolution. AM has many advantages over conventional manufacturing techniques; AM techniques manufacture through the addition of material - rather than traditional machining or moulding methods. AM negates the need for tooling, enabling cost-effective low-volume production in high-wage economies and the design & production of geometries that cannot be made by other means. In addition, the removal of tooling and the potential to grow components and products layer-by-layer means that we can produce more from less in terms of more efficient use of raw materials and energy or by making multifunctional components and products. The proposed Centre for Doctoral Training (CDT) in Additive Manufacturing and 3D Printing has the vision of training the next generation of leaders, scientists and engineers in this diverse and multi-disciplinary field. As AM is so new current training programmes are not aligned with the potential for manufacturing and generally concentrate on the teaching of Rapid Prototyping principles, and whilst this can be useful background knowledge, the skills and requirements of using this concept for manufacturing are very different. This CDT will be training cohorts of students in all of the basic aspects of AM, from design and materials through to processes and the implementation of these systems for manufacturing high value goods and services. The CDT will also offer specialist training on aspects at the forefront of AM research, for example metallic, medical and multi-functional AM considerations. This means that the cohorts graduating from the CDT will have the background knowledge to proliferate throughout industry and the specialist knowledge to become leaders in their fields, broadening out the reach and appeal of AM as a manufacturing technology and embedding this disruptive technology in company thinking. In order to give the cohorts the best view of AM, these students will be taken on study tours in Europe and the USA, the two main research powerhouses of AM, to learn from their international colleagues and see businesses that use AM on a daily basis. One of the aims of the CDT in AM is to educate and attract students from complementary basic science, whether this be chemistry, physics or biology. This is because AM is a fast moving area. The benefits of having a CDT in AM and coupling with students who have a more fundamental science base are essential to ensure innovation & timeliness to maintain the UK's leading position. AM is a disruptive technology to a number of industrial sectors, yet the CDTs industrial supporters, who represent a breadth of industrial end-users, welcome this disruption as the potential business benefits are significant. Growing on this industry foresight, the CDT will work in key markets with our supporters to ensure that AM is positioned to provide a real and lasting contribution & impact to UK manufacturing and provide economic stability and growth. This contribution will provide societal benefits to UK citizens through the generation of wealth and employment from high value manufacturing activities in the UK. Cite Design rules for additively-manufactured wrist splints Kelly, Sarah (2020): Design rules for additively-manufactured wrist splints. Loughborough University. Thesis. https://doi.org/10.26174/thesi... ; Share Design rules for additively-manufactured wrist splints Type PhD Themes Assistive & Accessible Technology Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece Anna Vlachaki The literature shows that research into the aesthetic aspects of prostheses is limited. Although there are suggestions that prostheses with high levels of emotionally-driven design may improve users’ well-being, they are based only on theoretical findings. Therefore, in this thesis the effects of emotionally-driven prostheses on users’ lives and society’s attitudes were explored, with respect to culture and more specifically, the theories of individualism/ collectivism. In order to investigate the effects of culture, the research was conducted in two countries with different cultures; the UK (individualistic) and Greece (collectivistic). The thesis began with a literature review across three core areas: user, product and environment, and revealed the importance of investigating an additional area; that of prosthetists. The research employed a qualitative approach and consisted of four studies. Loughborough University Cite Share Read Abstract Visit publisher Abstract Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece The literature shows that research into the aesthetic aspects of prostheses is limited. Although there are suggestions that prostheses with high levels of emotionally-driven design may improve users’ well-being, they are based only on theoretical findings. Therefore, in this thesis, the effects of emotionally-driven prostheses on users’ lives and society’s attitudes were explored, with respect to culture and more specifically, the theories of individualism/ collectivism. In order to investigate the effects of culture, the research was conducted in two countries with different cultures; the UK (individualistic) and Greece (collectivistic). The thesis began with a literature review across three core areas: user, product and environment, and revealed the importance of investigating an additional area; that of prosthetists. The research employed a qualitative approach and consisted of four studies. Study I was an online questionnaire to explore users’ preferences towards prostheses, with respect to their culture. Study II consisted of semi-structured interviews and informational probes to comprehend the role of prostheses on users’ lives, with respect to prosthetic appearance. In Study III, the aim was to investigate prosthetists’ attitudes towards the needs of prosthetic users by conducting semi-structured interviews. Finally, Study IV was an online questionnaire to explore non-users’ attitudes towards the design of prostheses. The research showed that the use of prostheses for the completion of users’ body was not an adequate factor to improve their well-being, and a shift on users’ desires towards emotionally-driven prostheses has occurred. From the variables that were tested, sex, age, cause and area of limb-loss may affect people’s attitudes towards the design of prostheses. Furthermore, the results showed that prostheses with high emotionally-driven design evoked emotions, in both users and non-users, with higher levels of pleasantness and arousal than the emotions that were elicited by the prostheses of lower emotionally-driven designs and thus, they may trigger a greater behavioural reaction. This suggested that emotionally-driven prostheses may eliminate users’ stigmatisation by increasing their self-confidence and altering society’s attitudes. However, attention needs to be paid in collectivistic countries, as emotionally-driven prostheses may enhance users’ stigmatisation. Cite Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece Vlachaki, Anna (2020): Emotionally-driven prostheses: exploring the effects on users’ lives and societies’ attitudes in the UK and Greece. Loughborough University. Thesis. https://doi.org/10.26174/thesi... ; Share Emotionally driven Prostheses: Exploring the Effects on Users’ Lives and Societies’ Attitudes in the UK and Greece Type Conference Paper Themes Assistive & Accessible Technology Opportunities for Supporting Self-efficacy through Orientation and Mobility Training Technologies for Blind and Partially Sighted People Maryam Bandukda , Catherine Holloway , Aneesha Singh, Giulia Barbareschi , Nadia Berthouze We conducted semi-structured interviews with 20 BPS people and 8 Mobility and Orientation Trainers (MOT). The interviews were thematically analysed and organised into four overarching themes discussing factors influencing the self-efficacy belief of BPS people: Tools and Strategies for O&M training, Technology Use in O&M Training, Changing Personal and Social Circumstances, and Social Influences. We further highlight opportunities for combinations of multimodal technologies to increase access to and effectiveness of O&M training. ASSETS '21: Proceedings of the 23rd International ACM SIGACCESS Conference on Computers and Accessibility Share Read Abstract Visit publisher Abstract Opportunities for Supporting Self-efficacy through Orientation and Mobility Training Technologies for Blind and Partially Sighted People Orientation and mobility (O&M) training provides essential skills and techniques for safe and independent mobility for blind and partially sighted (BPS) people. The demand for O&M training is increasing as the number of people living with vision impairment increases. Despite the growing portfolio of HCI research on assistive technologies (AT), few studies have examined the experiences of BPS people during O&M training, including the use of technology to aid O&M training. To address this gap, we conducted semi-structured interviews with 20 BPS people and 8 Mobility and Orientation Trainers (MOT). The interviews were thematically analysed and organised into four overarching themes discussing factors influencing the self-efficacy belief of BPS people: Tools and Strategies for O&M training, Technology Use in O&M Training, Changing Personal and Social Circumstances, and Social Influences. We further highlight opportunities for combinations of multimodal technologies to increase access to and effectiveness of O&M training. Share Opportunities for Supporting Self-efficacy through Orientation and Mobility Training Technologies for Blind and Partially Sighted People Type Conference Paper Themes Assistive & Accessible Technology What difference does tech make? Conceptualizations of Disability and Assistive Technology among Kenyan Youth: Conceptualizations of Disability and AT Giulia Barbareschi , Norah Shitawa Kopi, Ben Oldfrey , Catherine Holloway In this paper, we examine how young Kenyans without disabilities view people with disabilities and AT users. Findings show that while the portrayal of disability is often shaped by negative emotion, participants felt that many of the barriers affecting people with disabilities were created by society. Perceptions of AT differed –devices were not only seen as a mark of disability but also as a sign of access to resources. Therefore, what we see is an emergent picture where social barriers can be reinforced by poverty, and where poverty reinforces social barriers faced by people with disabilities. We conclude that access to appropriate technology alongside societal interventions tackling incorrect beliefs about disability can help to overcome the stigma faced by people with disabilities. ASSETS '21: Proceedings of the 23rd International ACM SIGACCESS Conference on Computers and Accessibility Cite Share Read Abstract Visit publisher Abstract What difference does tech make? Conceptualizations of Disability and Assistive Technology among Kenyan Youth: Conceptualizations of Disability and AT Most research which investigates stigma towards with people with disabilities and the use of Assistive Technology (AT) are based in the Global North and focus on the experiences of people with disabilities and the consequences that stigma has on choices surrounding AT. However, stigma is a societal construct rooted in the attitude and beliefs that people without disabilities hold on disability and AT. Furthermore, the portrayal of people with disabilities and AT is dependent on the social context. In this paper, we examine how young Kenyans without disabilities view people with disabilities and AT users. Findings show that while the portrayal of disability is often shaped by negative emotion, participants felt that many of the barriers affecting people with disabilities were created by society. Perceptions of AT differed –devices were not only seen as a mark of disability but also as a sign of access to resources. Therefore, what we see is an emergent picture where social barriers can be reinforced by poverty, and where poverty reinforces social barriers faced by people with disabilities. We conclude that access to appropriate technology alongside societal interventions tackling incorrect beliefs about disability can help to overcome the stigma faced by people with disabilities. Cite What difference does tech make? Conceptualizations of Disability and Assistive Technology among Kenyan Youth: Conceptualizations of Disability and AT Giulia Barbareschi, Norah Shitawa Kopi, Ben Oldfrey, and Catherine Holloway. 2021. What difference does tech make? Conceptualizations of Disability and Assistive Technology among Kenyan Youth: Conceptualizations of Disability and AT. In The 23rd International ACM SIGACCESS Conference on Computers and Accessibility ( ASSETS '21 ). Association for Computing Machinery, New York, NY, USA, Article 18, 1–13. DOI: https://doi.org/10.1145/3441852.3471226 Share What difference does tech make? Conceptualizations of Disability and Assistive Technology among Kenyan Youth: Conceptualizations of Disability and AT Type Editorial Themes Assistive & Accessible Technology A right to the frivolous? Renegotiating a wellbeing agenda for AT research Giulia Barbareschi & Tom Shakespeare Assistive products (APs) are broadly defined as “ any product (including devices, equipment, instruments, and software), either specially designed and produced or generally available, whose primary purpose is to maintain or improve an individual’s functioning and independence and thereby promote their wellbeing ” (Khasnabis et al., 2015 ). Although the concept of wellbeing is extremely slippery and researchers have yet to agree on a single definition for it, as individuals we instinctively develop mental models about what does, and does not, promote our happiness and wellbeing. Considerations about values, wellbeing and happiness are extremely personal and are shaped by a variety of factors ranging from our age and socio-cultural background to our life experiences (Schwartz & Bardi, 2001 ). RESNA Cite Share Read Abstract Visit publisher Abstract A right to the frivolous? Renegotiating a wellbeing agenda for AT research Assistive products (APs) are broadly defined as “ any product (including devices, equipment, instruments, and software), either specially designed and produced or generally available, whose primary purpose is to maintain or improve an individual’s functioning and independence and thereby promote their wellbeing ” (Khasnabis et al., 2015 ). Although the concept of wellbeing is extremely slippery and researchers have yet to agree on a single definition for it, as individuals we instinctively develop mental models about what does, and does not, promote our happiness and wellbeing. Considerations about values, wellbeing and happiness are extremely personal and are shaped by a variety of factors ranging from our age and socio-cultural background to our life experiences (Schwartz & Bardi, 2001 ). However, when it comes to assistive technology (AT) research, our focus seems to be primarily geared toward values and activities in the domains of education, employment, transport or health, often framed according to an outcome driven perspective that is heavily influenced by what is seen as useful (often what is measurable), vs what is frivolous (less tangible social or emotional aspects). This disparity parallels the priorities of the disability rights movement and disability studies research that have helped to shape the research agenda around disability and AT. Often influenced by labor movement politics, or feminism, there appears to have been more concern with public and practical aspects of social life as opposed to the more private and sensitive ones (Shakespeare, 2014 ). The focus on the public utilitarian function of AT becomes even more evident when we consider AT research carried out in the Global South. In this context the success of an intervention is usually assessed using measures of outcome and impact which can be somehow linked to economic improvement (Alkire, 2016 ). In this editorial, we are not suggesting that enabling people with disabilities to gain a good education, obtain a fulfilling job or be able to vote are not important goals for the APs we develop and research. But are those the only worthwhile goals? Should we not also enquire whether existing and future APs could help people with disabilities to develop meaningful friendships, enjoy fulfilling sex lives with their partners of choice, cook sociable dinners, or engage in their favorite hobbies? Although sporadic publications focus on the role of APs in the context of personal relationships, sexuality, or fun and play for people with disabilities do exist, these are rare, and often framed around utilitarian goals. For example, research around AT and play is largely focused on children and often examined in connection to learning outcomes. Similarly, sex and sexuality are often explored solely in connection to dysfunction, abuse or sexual health (Shakespeare & Richardson, 2018 ). These unbalanced narratives show how the AT research agenda is dictated by a set of universal priorities that are largely focused on global measurable goals that do not necessarily match the everyday values of people with disabilities. We invite researchers and practitioners to consider ways to find a better balance between public and private aspects of life, and between utilitarian and emotional values. Both approaches have a significant impact on the lives of people with disabilities. Ultimately, as AT researchers we need to actively engage with people with disabilities to uncover their priorities, understand what different people with disabilities most value in life, and identify how current and future APs might help to make a positive impact on wellbeing. Aspects of life such as friendship, socialization, sexuality, love and play might indeed be more frivolous than practical ones such as education, health, employment and civil rights, but they are inherent to our shared humanity and fundamental to our happiness. Cite A right to the frivolous? Renegotiating a wellbeing agenda for AT research Giulia Barbareschi & Tom Shakespeare (2021) A right to the frivolous? Renegotiating a wellbeing agenda for AT research, Assistive Technology, 33:5, 237, DOI: 10.1080/10400435.2021.1984112 Share A right to the frivolous? Renegotiating a wellbeing agenda for AT research Type Conference Paper Themes Assistive & Accessible Technology Inclusive Educational Technology Transforming a Monolithic Sheet of Nitinol into a Passive Reconfigurable Tactile Pixel Array Display at Braille Resolution Tigmanshu Bhatnagar , Nicolai Marquardt, Mark Miodownik, Catherine Holloway Shape changing materials create a unique opportunity to design reconfigurable tactile display actuators. In this paper, we present a method that transforms a single thin monolithic sheet of Nitinol into a passive reconfigurable tactile pixel array at Braille resolution. We have designed a 27x27 tactile pixel array in which each pixel can be selectively actuated with an external source of heat. The pixels rise 0.4mm vertically with a peak blocked force of 0.28kg and have an average blocked force of 0.23kg at room temperature. After cooling, the pixels can be mechanically reconfigured back to their flat state for repeatable actuation. We demonstrate this actuator’s interactive capabilities through a novel erasable tactile drawing interface. IEEE World Haptics Conference; 2021 Cite Share Read Abstract Abstract Transforming a Monolithic Sheet of Nitinol into a Passive Reconfigurable Tactile Pixel Array Display at Braille Resolution Shape changing materials create a unique opportunity to design reconfigurable tactile display actuators. In this paper, we present a method that transforms a single thin monolithic sheet of Nitinol into a passive reconfigurable tactile pixel array at Braille resolution. We have designed a 27x27 tactile pixel array in which each pixel can be selectively actuated with an external source of heat. The pixels rise 0.4mm vertically with a peak blocked force of 0.28kg and have an average blocked force of 0.23kg at room temperature. After cooling, the pixels can be mechanically reconfigured back to their flat state for repeatable actuation. We demonstrate this actuator’s interactive capabilities through a novel erasable tactile drawing interface. Cite Transforming a Monolithic Sheet of Nitinol into a Passive Reconfigurable Tactile Pixel Array Display at Braille Resolution T. Bhatnagar, N. Marquardt, M. Miodownik and C. Holloway, "Transforming a Monolithic Sheet of Nitinol into a Passive Reconfigurable Tactile Pixel Array Display at Braille Resolution," 2021 IEEE World Haptics Conference (WHC) , 2021, pp. 409-414, doi: 10.1109/WHC49131.2021.9517239. 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F.H. Paschen, S.N. Nielsen & Assocs., LLC v. Se. Commercial Masonry, Inc., CIVIL ACTION No. 12-2799 SECTION "E" - Federal Cases - Case Law - VLEX 888076147 0: [object Object]. 1: [object Object]. 2: [object Object]. 3: [object Object]. 4: [object Object] Federal Cases F.H. Paschen, S.N. Nielsen & Assocs., LLC v. Se. Commercial Masonry, Inc., CIVIL ACTION No. 12-2799 SECTION "E" Court United States District Courts. 5th Circuit. United States District Court (Eastern District of Louisiana) Writing for the Court SUSIE MORGAN UNITED STATES DISTRICT JUDGE Parties F.H. PASCHEN, S.N. NIELSEN &amp; ASSOCIATES, LLC, Plaintiff v. SOUTHEASTERN COMMERCIAL MASONRY, INC., Defendant Decision Date 10 November 2015 Docket Number CIVIL ACTION No. 12-2799 SECTION "E" F.H. PASCHEN, S.N. NIELSEN & ASSOCIATES, LLC, Plaintiff v. SOUTHEASTERN COMMERCIAL MASONRY, INC., Defendant CIVIL ACTION No. 12-2799 SECTION "E" UNITED STATES DISTRICT COURT EASTERN DISTRICT OF LOUISIANA November 10, 2015 FINDINGS OF FACT AND CONCLUSIONS OF LAW This matter was tried before the Court, sitting without a jury, over two days 1 on the claims of Paschen, S.N. Nielsen & Associates, LLC ("Paschen") against Defendant Southeastern Commercial Masonry, Inc. ("SECM") for breaches of contract for masonry work on two school projects and improperly filing statements of claim and privilege on two public works projects. 2 SECM filed a counterclaim against Paschen for breach of contract, breach of oral contract, and enforcement of statutory liens. 3 Plaintiff Paschen is a limited liability company organized under the laws of Illinois. 4 The members of Paschen are citizens of Indiana, Illinois, Wisconsin, Michigan, Florida, and New Jersey. 5 Defendant SECM is a corporation organized under the laws of Alabama with its principal place of business in Alabama. 6 This Court has jurisdiction pursuant to 28 U.S.C. § 1332 . Page 2 Paschen was the general contractor on two public works projects: the Mildred Osborne School ("Osborne project"), and the Charles J. Colton School ("Colton project"). Paschen entered into two subcontracts with SECM, one to perform masonry work on the Osborne project and the other to perform masonry work on the Colton project. The subcontracts on the Osborne and Colton projects were fixed-price agreements, whereby SECM agreed to perform all of the work within its scope of work under the subcontracts for a set price. 7 Both were fast-track projects. 8 Schedule A to each subcontract describes the work to be done (the "work"). 9 Paschen terminated both contracts with SECM. 10 The Court heard testimony from Larry Van Zuidam, Mark Waller, John Wilkes, Chris Hase, Rupert Perez, Jeffery Posey, Justin Allen Posey, and admitted into evidence the deposition of Adam Lusk. 11 With respect to the Osborne project, the Court rules that Paschen is not entitled to recover for its breach of subcontract claim insofar as it is based on SECM's failure to perform and failure to perform in a timely manner. Nor is Paschen entitled to recover the cost of removing the statement of claim filed by SECM in the public record. However, Paschen is entitled to recover the amount it paid to SECM's sub-subcontractor, Tailored Foam, and attorney's fees and costs related to the prosecution of this portion of its claim. Further, the Court rules that SECM is entitled to recover on its breach of subcontract claim Page 3 for the amounts it is owed under Change Order 24 but not for other change order requests or its request for overtime pay and extra crew. Further, the Court rules that SECM is not entitled to recover on its breach of oral agreement claim for its time and material tickets or its claim for attorney's fees. With respect to the Colton project, the Court rules that Paschen is not entitled to recover for its breach of subcontract claim insofar as it is based on SECM's failure to perform and failure to perform in a timely manner. Nor is Paschen entitled to recover the cost of removing the statement of claim filed by SECM in the public record or its attorney's fees. Further, the Court rules that SECM is entitled to recover the amounts due under Pay Application 17 and to recover its retainage due under the subcontract. SECM is not entitled to recover on Pay Application 18 for back charges related to additional scaffolding costs; Change Orders Change Orders 2, 3, 4, 5, 6, 7, 11, 12, 13, 20 (credit to Paschen) and 22; lost profits on the subcontract; or its attorney's fees. To the extent any finding of fact may be construed as a conclusion of law, the Court adopts it as such. To the extent any conclusion of law may be construed as a finding of fact, the Court adopts it as such. STANDARD OF LAW Written contracts are the law between the parties, and courts are bound to enforce contracts as written. Quinn-L Corp. v. Elkins , 519 So. 2d 1164 (La.App. 1 Cir. 1987). The essential elements of a breach of contract claim are (1) the obligor's undertaking of an obligation to perform, (2) the obligor's failure to perform the obligation (the breach), and (3) the breach results in damages to the obligee. Favrot v. Favrot , 68 So. 3d 1099 , 1109 (La. Page 4 App. 4 Cir. 2011). The breach of a contractual duty cannot be assumed. Morgavi v. Mumme , 270 So. 2d 540 (La. 1972). The burden of proof in an action for breach of contract is on the party claiming rights under the contract. Vignette Publications , Inc . v. Harborview Enterprises , Inc . , 799 So. 2d 531 , 534 (La.App. 4 Cir. 2001). Thus, Paschen has the burden of proof on its breach of contract claims, and SECM has the burden of proof on its breach of contract counterclaims. Paschen and SECM must establish the elements of their claims essential to recovery by a preponderance of the evidence. Bond v. Allemand 632 So. 2d 326 (La.App. 1 Cir. 1993). "A preponderance of the evidence simply means evidence that persuades [the Court] that the plaintiff's claim is more likely true than not true."5th Cir. Pattern Civil Jury Instruction 2.20 (West 1998); see also Layrisson v . H. S. S. Vending Distrib. , No. 97-1440, 1998 WL 355461, at *2 (E.D. La.June 26, 1998). Under Louisiana law, if an individual does not complete the work he has contracted to do or fails to execute it in the manner agreed upon, he is liable for the losses that ensue from his non-compliance.La. Civ. Code art. 2769. To establish a subcontractor's liability due to defective workmanship, the general contractor must prove the existence and nature of the defects, that the defects are due to faulty materials or workmanship, and the cost of repairing the defects. Cascio v. Carpet , 968 So. 2d 844 , 850 (La.App. 2 Cir. 2007). For a breach of contract claim under Louisiana Civil Code article 2769, the appropriate measure of damages is the cost of repairing any defects or the cost of completing the work. Mount Mariah Baptist Church , Inc . v. Pannell's Associated Electric , Inc . , 835 So. 2d 880 , 888 (La.App. 2 Cir. 2002). A plaintiff bringing a claim under Page 5 Louisiana Civil Code article 2769 must prove the costs incurred are reasonably related to the repair. Regions Bank v. Ark-La-Tex Water Gardens , LLC 997 So. 2d 734 , 739-40 (La.App. 2 Cir. 2008). The burden of proof is upon the subcontractor to show that it is entitled to the amount requested in a change order request. Powerhouse Wholesale Electrical Supply v . Spartan Building Corporation , 525 So. 2d 1216 , 1220 (La.App. 1 Cir. 1988). A written construction contract may be modified by an oral contract and the conduct of the parties, even when the written contract contains a provision that change orders must be in writing. Modification of a written agreement can be presumed by silence, inaction, or implication. Aqua Pool Renovations v . Paradise Manor Community , 880 So. 2d 875 , (La.App. 5 Cir. 2004). Whether oral agreements were confected that modified a written contract is a question of fact. Pelican Electrical Contractors v . Neumeyer , 419 So. 2d 1 , 5 (La.App. 4 Cir.) , writ denied , 423 So. 2d 1150 (La. 1982). The party asserting a modification of an obligation must prove by a preponderance of the evidence facts or acts giving rise to the modification.La. Civ. Code art. 1831; Amitech v . Nottingham Const. , 57 So. 3d 1043 (La.App. 1 Cir. 2011). A contract clause providing the architect or engineer shall be the final arbiter of disputes is binding upon the parties to a construction contract, unless the architect or engineer's decision is manifestly erroneous or rendered in bad faith. Where, therefore, the parties have agreed to abide by the decision of an architect, the courts will hesitate, in the interpretation of the contract, to set aside the architect's ruling, unless manifestly arbitrary, or it is shown to have been rendered in bad faith. Delta S. Co., Inc. v. La. & Ark. Ry. Co., Page 6 394 So. 2d 1299 , 1301 (La.App. 1 Cir. 1981). See also Sabine Const . Co., Inc. v. Cameron Sewerage Dist . , 298 So. 2d 319 , 325 (La.App. 3 Cir. 1974); Baker v. Keller Const. Co. , 219 So. 2d 569 , 571 (La.App. 4 Cir. 1969); J. H. Jenkins Contractor , Inc . v. City of Denham Springs , 216 So. 2d 549 , 553 (La.App. 1 Cir. 1968); see also Iteld v . Four Corners Const., L. P. , 157 So. 3d 702 , 715 (La.App. 4 Cir. 2013). "Where the promisee makes performance impossible, it is unimaginable that any civilized system of law would allow that promisee to recover damages for the promisor's failure to perform under the contract. It is a long established principle of law that he who prevents a thing may not avail himself of the non-performance he has occasioned. The principle is founded upon the premise that one should not be able to take advantage of his own wrongful act." Lake Forest, Inc. v. Katz & Besthoff No . 9 , 391 So. 2d 1286 , 1289 (La.App. 4 Cir. 1980) (quoting Cox v . Dep't of Highways , 209 So. 2d 9 , 11 (La. 1968)). As a general rule, an independent contractor maintains the right to control and direct the scope of its work while in progress. See, e. g., Villaronga v. Gelpi P'ship No. 3 , 536 So. 2d 1307 , 1311 (La.App. 5 Cir. 1988). It is within the purview of the subcontractor to determine how and by what means it performs the work it was contracted to complete. See id. Unless stated otherwise in the contract between the parties, the general contractor is unable to exercise any direction or control over the performance of the subcontractor's work. See Trapani v. Jefferson Parish , 180 So. 2d 850 , 852-53 (La.App. 4 Cir. 1965). Contractors who control or direct the means, methods, and operations of a subcontractor may be held liable for the actions of that subcontractor. See, e. g., Sims v. Cefolia , 890 So. 2d 626 , 631 (La.App. 5 Cir. 2004); Migliori v. Willows Apartments , 727 Page 7 So. 2d 1258, 1261 (La. App. 4 Cir. 1999);...
https://case-law.vlex.com/vid/f-h-paschen-s-888076147
STINSON v. STATE | 344 S.W.2d 369 (1961) | sw2d3691705 | Leagle.com SWEPSTON Justice. On February 16 1960 plaintiff in error Donald Verner Stinson hereinafter referred to as defendant...sw2d3691705 STINSON v. STATE View Case Cited Cases Citing Case 344 S.W.2d 369 (1961) Donald Verner STINSON, Plaintiff in Error, v. STATE, Defendant in Error. Supreme Court of Tennessee. https://leagle.com/images/logo.png March 10, 1961. March 10, 1961. Attorney(s) appearing for the Case Ed. R. Davies, Nashville, Olen C. Batchelor, Jr., Memphis, for plaintiff in error. Thomas E. Fox, Assistant Attorney General, for the State. Supreme Court of Tennessee. SWEPSTON, Justice. On February 16, 1960, plaintiff in error Donald Verner Stinson, hereinafter referred to as defendant, was convicted under indictment No. A-84607 charging robbery and being an habitual criminal and was sentenced to life imprisonment. This appeal results from that trial and conviction and the gist of the appeal is that said conviction was void and that he can not be again tried for the alleged offense. Chronologically the steps leading up to the present problem are as follows: February 18, 1954, indictment No. A-67587 was returned in Shelby County charging defendant and another with robbery which was alleged to have occurred on the 13th day of February, 1954, in said County. Included therein was a second count charging this defendant and the co-defendant, not necessary to be further mentioned herein, with being habitual criminals. April 6, 1954, following a trial under said indictment, the jury returned a verdict as follows: "We the jury find the defendant Mac Burton Montgomery, guilty of robbery and fix his punishment at not more than 15 years in the State Penitentiary. We the jury find the defendant, Donald Verner Stinson, is an habitual criminal and guilty as charged in the indictment." May 7, 1954, following the overruling of Stinson's motion for a new trial, sentence was passed as follows: "* * * that he is guilty of being an habitual criminal and that he * * * be confined at hard labor for life; * * *". July 15, 1959, while a prisoner in the State Penitentiary defendant filed a petition for a writ of habeas corpus in the Criminal Court of Davidson County, Tennessee. In this petition defendant contended that the above sentence had been solely for being an habitual criminal which is not a substantive criminal offense (but only a status) and that he was thus suffering involuntary servitude for something not constituting a crime and, therefore, in violation of Amendment 13 to the Federal Constitution and [344 S.W.2d 371] art. I, Sec. 33 of the Tennessee Constitution. As a result of the hearing before Hon. Homer B. Weimar his conviction was held on August 4, 1959, to be void and he was ordered returned to the custody of the District Attorney General of Shelby County for disposition. It will be noted that there was no appeal taken by the State from this judgment of Judge Weimar in the habeas corpus matter. Following two unsuccessful petitions for a writ of habeas corpus in Shelby County, one on October 14, 1959, before Judge Perry Sellers, and the other on December 15, 1959, before Judge W. Preston Battle, defendant was remanded to the custody of the Sheriff of said County for trial under the indictment A-67587, supra. January 15, 1960, defendant was re-indicted or again indicted under No. 84607 by the grand jury of Shelby County for the same offenses alleged in said prior indictment, supra. February 12, 1960, on motion of the District Attorney General indictment A-67587, supra, was quashed by Judge Sellers. On the same date, defendant's motion to quash the second indictment No. 84607 was denied. February 15, 1960, Stinson's plea of double jeopardy was overruled. On the same date and on February 16 Stinson was tried under indictment No. 84607, found guilty of robbery and of being an habitual criminal and sentenced to life imprisonment. His motion for a new trial having been overruled, the within appeal resulted. The first assignment of error is that the Criminal Court of Shelby County committed error by refusing to grant defendant's motion to quash indictment No. 84607, which is the one on which the second trial was had. Under this assignment defendant's brief advances three propositions of law. The first is that where a subsequent penal statute changes a punishment, the former mode is thereby repealed. Counsel then quotes Section 10803 of Williams' 1932 Code which fixed the punishment for the crime of robbery at not less than 5 nor more than 15 years in the penitentiary. Counsel has apparently overlooked the amendment, Ch. 66, Sec. 1, Public Acts of 1953, in which this section was amended to change the penalty to not less than 5 nor more than 25 years; however, this oversight does not affect the result in any way. That was the penalty prescribed and in existence at the time the alleged crime was committed in 1954. Anyway, subsequently by Ch. 72, Public Acts of 1955, said above Code Section 10803 was again amended to fix the punishment for robbery at "not less than 5 nor more than 15 years; provided, that if the robbery is accomplished by the use of a deadly weapon, the punishment shall be death by electrocution, or the jury may commute the punishment to imprisonment for life or for any period of time not less than 10 years." T.C.A. § 39-3901. Defendant's brief cites ample authority to support this proposition and we need refer only to a few cases. In Haley v. State, 156 Tenn. 85, 299 S.W. 799, 800, among other things, the Court quoted from 25 R.C.L., 930, as follows: In discussing criminal statutes it is said: `Thus where a later statute defines an offense that is described in an earlier statute, the earlier statute is repealed; and the same result follows where the new statute changes the penalty, as where punishment by fine of imprisonment is changed to fine and imprisonment.' The principle is further illustrated by a line of cases where there are two statutes prescribing different degrees of punishment as in State v. Lewis, 198 Tenn. 91,278 S.W.2d 81. A repeal by implication occurs even though the subsequent act be an amendment rather than a separate and distinct act on [344 S.W.2d 372] the same subject matter. Cole Manufacturing Co. v. Falls, 92 Tenn. 607, 22 S.W. 856; and Poe v. State, 85 Tenn. 495, 3 S.W. 658. See. also, 1 Sutherland Statutory Construction, Sec. 1932. The second proposition of law under this assignment is that the repeal of a penal statute operates as a pardon of all offenses committed before the repeal and prohibits prosecution, unless the right to prosecute is saved by a provision in the repealing act or by separate legislation. This rule is supported by ample authority as follows: Yeaton v. United States, 1809, 5 Cranch 281,9 U.S. 281; Roberts v. State, 1815, 2 Tenn. 423; Wharton v. State, 1867, 45 Tenn. 1; also numerous cases from other jurisdictions. Counsel for the State concedes the correctness of the two above propositions of law but relies upon T.C.A. § 1-301 which provides: The repeal of a statute does not affect any right which accrued, any duty imposed, any penalty incurred, nor any proceeding commenced, under or by virtue of the statute repealed. This same language appears as Sec. 12 of Williams' 1932 Code, Sec. 61 of Shannon's Compilation and Sec. 49 of the Code of 1858. Of course, so long as the original indictment A-67587 was pending, it was a proceeding commenced within the meaning of the above section; and it was, therefore, proper for Judge Weimar to remand the defendant to the District Attorney General of Shelby County for further proceedings. It seems rather obvious, however, that when that original indictment was quashed, there was no longer any proceedings commenced or pending as of a date prior to the change in the statute with regard to punishment; and no penalty had been incurred because Judge Weimar had declared the conviction void with no appeal therefrom; nor is there anything in the amending act to save the right to prosecute under the former law. Therefore, the attempted indictment of the defendant in January, 1960, under indictment 84607 under the former existing law was void because the right to prosecute under the former law was not saved by Sec. 12 of the Williams' Tennessee Code of 1932 nor by any statutory provision in the amending act. Therefore, it follows that the defendant's third proposition of law is applicable, if this second indictment be treated as an attempt to indict, try, convict and punish defendant under the law as amended, because it would be ex post factoas to him. The State urges that the defendant was not prosecuted under an indictment charging the greater offense under the law as it stood in 1960 and, therefore, was not ex post factoas to him. However in Lindsey v. State of Washington, 1937,301 U.S. 397, 57 S.Ct. 797, 81 L.Ed. 1182, it was held in effect that the prohibition against ex post factolaws looks to the standard of punishment prescribed by a statute, rather than to the sentence actually imposed. An increase in the possible penalty is ex post factoregardless of the length of the sentence actually imposed on a particular defendant, since the measure of punishment prescribed by the later statute is more severe than that of the earlier. Obviously, a statute that increases the penalty for robbery from a maximum of 25 years, as it existed under the amendment of 1953, supra, to a maximum of death by electrocution, should the robbery be accomplished by the use of a deadly weapon, is a statute which inflicts a greater punishment than was capable of being imposed before the 1955 amendment and hence the latter amendment is ex post factoas to this defendant. Ample authority will be found on the question of ex post facto laws under the above circumstances in numerous cases including [344 S.W.2d 373] the following: Lindzey v. State, 1888, 65 Miss. 542, 5 So. 99; People v. Lowell, 1930, 250 Mich. 349, 230 N.W. 202; State v. Ingersoll, 1864, 17 Wis. 631; Hirschburg v. People, 1881, 6 Colo. 145. Now to backtrack somewhat, the State insists that the judgment of conviction in 1954 under the first indictment was not void and that Judge Weimar's action in so holding was itself void, because a writ of habeas corpus cannot be used to serve the purpose of a writ of error or an appeal in the nature of a writ of error, citing Lynch et al. v. State ex rel. Killebrew, 179 Tenn. 339, 166 S.W.2d 397, and State ex rel. Grandstaff v. Gore, 182 Tenn. 94, 184 S.W.2d 366, that there was no appeal from that judgment and that whatever error there appears on the face of the record may be corrected at any time under T.C.A. § 20-1513. The answer to that insistence is that when a court has jurisdiction of the person and of the subject matter its judgments are binding, even though erroneous, until reversed by appeal or writ of error; the Criminal Court of Davidson County had jurisdiction of the writ of habeas corpus petition filed by the defendant. T.C.A. § 23-1803, which provides: The writ may be granted by any judge of the circuit or criminal courts * * *. In Aladdin Industries, Inc. v. Associated Transport, Inc., 1958,323 S.W.2d 222, 229, it is said: The test of the jurisdiction of a court is whether or not it had the power to enter upon the inquiry; not whether its conclusion in the course of it was right or wrong. In Carver v. Anthony, 35 Tenn.App. 306,245 S.W.2d 422, 424, it is said: Jurisdiction carries with it power to determine every issue or question properly arising in the case. In 1 Freeman on Judgments, 5th Ed., Sec. 357, the general rule is stated and we quote only this deduction from the rule: Obviously the power to decide includes the power to decide wrong, and an erroneous decision is as binding as one that is correct until set aside or corrected in a manner provided by law. For the same rule see Reinhardt v. Nealis, 101 Tenn. 169, 46 S.W. 446; Greenlaw v. Kernahan, 1857, 36 Tenn. 371. A recent expression of this Court is found in Bomar v. State ex rel. Stewart, 201 Tenn. 480, 488,300 S.W.2d 885, to the same effect. When the State failed to appeal from the judgment of the Criminal Court of Davidson County, the same became final. There lies the difference between that case and the Lynch and Grandstaff cases, supra, in both of which there was an appeal. Also, the State acquiesced further by quashing the first indictment. Finally, the original judgment of conviction cannot stand for two reasons: (1) because it has been declared void by a court of competent jurisdiction with no appeal therefrom; and a void judgment cannot be corrected; (2) even if said judgment had not been held void and that adjudication become final, no such judgment remains because the indictment which was the foundation for said prosecution and eventual judgment has been quashed. The defendant's second assignment of error need not be considered, therefore, because the disposition heretofore made of the first assignment disposes of the case. The second assignment complains of the failure of the Criminal Court of Shelby County to sustain defendant's plea of former jeopardy. The judgment herein appealed from is accordingly reversed and the defendant is ordered released from custody. All concur. Listed below are the cases that are cited in this Featured Case. Click the citation to see the full text of the cited case. Citations are also linked in the body of the Featured Case.
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(PDF) An Iranian Bomb And The Stink Of American Intervention PDF | On Oct 24, 2022, Shanzey Rashid published An Iranian Bomb And The Stink Of American Intervention | Find, read and cite all the research you need on ResearchGate An Iranian Bomb And The Stink Of American Intervention October 2022 DOI: 10.47611/harp.227 License CC BY-NC-ND 4.0 Authors: <here is a image f2f62089ad6ff61c-d19572ff1996375a> Shanzey Rashid How to Keep the Bomb from Iran Article Full-text available Sep 2006 FOREIGN AFF <here is a image 0c3b4d5d9e7898a4-a49f1d5eebf404b6> Scott Sagan The debate over how to deal with Iran's nuclear program is clouded by historical amnesia. Nuclear proliferation has been stopped before, and it can and should be stopped in this case as well. Unfortunately, with Tehran --as with some of its predecessors --the price for Washington will be relinquishing the threat of regime change by force. The ongoing crisis with Tehran is not the first time Washington has had to face a hostile government attempting to develop nuclear weapons. Nor is it likely to be the last. Yet the reasoning of U.S. officials now struggling to deal with Iran's nuclear ambitions is clouded by a kind of historical amnesia, which leads to both creeping fatalism about the United States' ability to keep Iran from getting the bomb and excessive optimism about the United States' ability to contain Iran if it does become a nuclear power. Proliferation fatalism and deterrence optimism reinforce each other in a disturbing way. As nuclear proliferation comes to be seen as inevitable, wishful thinking can make its consequences seem less severe, and if faith in deterrence grows, incentives to combat proliferation diminish. A U.S. official in the executive branch anonymously told The New York Times in March 2006, "The reality is that most of us think the Iranians are probably going to get a weapon, or the technology to make one, sooner or later." Such proliferation fatalists argue that over the long term, it may be impossible to stop Iran --or other states for that matter --from getting the bomb. Given the spread of nuclear technology and know-how, and the right of parties to the Nuclear Nonproliferation Treaty (NPT) to enrich uranium and separate plutonium, the argument goes, any foreign government determined to acquire nuclear weapons will eventually do so. Moreover, the 1981 Israeli attack on the Osirak nuclear reactor in Iraq may have delayed Iraq's progress, but similar air strikes are unlikely to disable Iran's capacities, since its uranium-enrichment facilities can be hidden underground or widely dispersed. Imposing economic sanctions through the UN Security Council is clearly a preferable option. But as Washington learned with India and Pakistan in the 1980s and 1990s, sanctions only increase the costs of going nuclear; they do not reduce the ability of a determined government to get the bomb. Hezbollah and the Axis of Refusal: Hamas, Iran and Syria Article Full-text available Jul 2010 THIRD WORLD Q <here is a image 58072f3b6d7311fe-e2b8e092190be463> Rola El-Husseini Hezbollah has acquired a dual and contradictory reputation: as a legitimate political actor in Lebanon and as a terrorist organisation in the USA and Israel. This duality can be explained if we understand that Hezbollah is a nationalist entity that defines itself primarily within the Lebanese polity, as well as an anti-imperialist party intent on countering the regional hegemony of Israel and the USA. Forming alliances with Hamas, Iran and Syria, Hezbollah has become part of a ‘rejectionist’ axis that seeks to oppose perceived imperialism in the Middle East; this stance has become increasingly entrenched in the wake of the 2003 US-led invasion of Iraq. Characterisations that focus on Hezbollah as a military opponent confirm the organisation's perceived need for a rejectionist stance. International acceptance of Hezbollah as a legitimate political actor within the Lebanese polity, on the other hand, would help to bring the basis of the rejectionist axis into question. The Dangers of a Nuclear Iran The Limits of Containment Article Jan 2011 FOREIGN AFF Eric S. Edelman <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Andrew Krepinevich Evan Braden Montgomery Iran's acquisition of a bomb would upend the Middle East. It is unclear how a nuclear-armed Iran would weigh the costs, benefits, and risks of brinkmanship and escalation and therefore unclear how easily Tehran could be deterred from attacking the United States' interests or partners in the Middle East. Why Iran Should Get the Bomb Nuclear Balancing Would Mean Stability Article Jul 2012 FOREIGN AFF Kenneth N. Waltz U.S. and Israeli officials have declared that a nuclear-armed Iran is a uniquely terrifying prospect, even an existential threat. In fact, it is the best possible outcome of the West's current standoff with the Islamic Republic. By creating a more durable balance of military power in the Middle East, a nuclear Iran would yield more stability, not less. After Iran Gets the Bomb: Containment and Its Complications Article May 2010 FOREIGN AFF James M. Lindsay Ray Takeyh Despite international pressure, Tehran is continuing its march toward getting a nuclear bomb (or the ability to assemble one quickly). If it succeeds—as seems increasingly likely—the Middle East could become even more unstable. But Washington would still be able to contain and mitigate the consequences of Iran's nuclear defiance, keeping an abhorrent outcome from becoming a catastrophic one. Japan's Nuclear Choice Article Sep 1974 Monte R. Bullard Born in the usa, how america created iran's nuclear program Jan 2015 Steve Inskeep Steve Inskeep. Born in the usa, how america created iran's nuclear program. NPR, 2015. What is hezbollah? Council on Foreign Relations Jan 2020 Robinson Kali Robinson Kali. What is hezbollah? Council on Foreign Relations, 2020. Iran's islamist proxies in the middle east 2021
https://www.researchgate.net/publication/364701560_An_Iranian_Bomb_And_The_Stink_Of_American_Intervention
CPD 12 2012: Professional indemnity insurance for architects | Features | Building Design In a litigious society in which design responsibility extends beyond retirement, architects need to be well versed in the complexities of professional indemnity insurance. This CPD module is sponsored by Building Design Insurance Bureau CPD CPD 12 2012: Professional indemnity insurance for architects In a litigious society in which design responsibility extends beyond retirement, architects need to be well versed in the complexities of professional indemnity insurance. This CPD module is sponsored by Building Design Insurance Bureau How to take this module To take this module read the technical article below and click through to a multiple-choice questionnaire, once taken you will receive your results and if you successfully pass you will be issued automatically with a certificate to print for your records. Insurance is often seen as a necessary evil, but there can be no question of the value of professional indemnity cover. It is a requirement laid down by Arb’s Code of Conduct that to maintain your registration as an architect you must hold “adequate and appropriate cover”, but architects are well advised to ensure they have good cover in place to protect themselves. The principle of PIWith society becoming increasingly litigious, there is a greater chance that a professional person could be faced with a court action to defend themselves against an allegation of poor advice or negligence. The potential consequences can be disastrous — the legal costs along with any award of damages could prove devastating to an architectural practice. Professional indemnity cover will indemnify the insured for damages and legal costs incurred for claims arising out of the provision of professional services, along with access via your insurer to the legal personnel needed to defend you. Key issues Claim notifications It is easy to simply renew a professional indemnity policy and then put it back in the drawer for next year without any further thought. But for the cover to be effective, it is important to comply with the general conditions of the policy. Perhaps most notably and easily missed is the requirement for the insured to notify insurers at the earliest possible point of a potential claim. Source: Ben Sutherland Figures from the Technology&Construction Court show a steep rise in litigation against architects since the recession began. This is often overlooked — an architect will, entirely in good faith, often deal with a client question or minor complaint themselves. More often than not, this action will resolve any dispute, but there is a danger that if it does escalate, your insurers will not accept the claim due to a late notification. Insurers will want to be aware from the outset, so that they can advise their insured accordingly and become involved at the most pertinent time. This ensures that they can mitigate the risk as far as possible and the insured receives the benefit of being “hand held” through the process. It can be difficult to identify when a situation warrants notification. Essentially any direct or indirect criticism, justified or not, written or verbal, should be advised to the insurer or broker. An architect should err on the side of caution and, if in doubt, the insurer should be advised of even matters that seem minor. A notification itself will not prove detrimental to future terms of cover, so there is nothing to lose in notifying the insurer at the earliest opportunity. In this context, it is important to note that a professional indemnity policy will be provided on a “claims made” basis. This means that any claim will be dealt with under the policy that is in force at the time of the complaint, rather than the one that applied at the time of the act that triggered the dispute. This is of course assuming that you have held PI cover continuously through your career and that no retroactive date is applied to your policy. Equally, you should retain cover if you intend to carry out small or occasional projects — the duty of care to your clients will still exist, even if you do not charge fees for your service and/or only give verbal advice. Indemnity limit Arb requires architects to have “adequate and appropriate” cover with a minimum indemnity level of £250,000. It can be difficult to pinpoint an appropriate level of cover because it will depend on the nature of the work and contracts you perform, and ultimately the extent of the potential loss if you make an error on a project. Some contracts may stipulate the level of PI cover required, and this may even be a pre-requirement within the tender process. The £250,000 level may sound high to small practices or sole practitioners, but legal costs can quickly mount up, particularly if a dispute escalates and you must fight a lengthy court battle to clear your name. Disputes over the Clissold Leisure Centre in north London were eventually settled out of court, after Hackney council pursued the architect and cost consultant in a £7 million legal case. Apart from legal costs, you also need to take into account any damages that could be awarded against you, and the cost of remedial works. The level of indemnity will obviously affect the premiums paid. When you submit a new, or renewal, proposal you will be able to obtain quotations for different levels of indemnity which will help you determine anappropriate level of cover. Architects will require their limit of indemnity to be written on an “any one claim” basis (as opposed to “in the aggregate”). This means that the full limit of indemnity applies for each claim that occurs. “Costs in addition” is also beneficial, whereby legal costs are payable in addition to the limit of indemnity, rather than included in the total. Collateral warrantiesArchitects will often be required to commit to collateral warranties as a condition of a contract. A collateral warranty effectively extends their duty of care to other interested parties in addition to the main contractor — the purchaser of the building, for example, or a funder or tenant. It may also extend the period of liability, typically up to 12 years from the point of handover. From an insurance point of view, this does extend the possibility of action being taken against the architect. However, if the wordings of such agreements are sensible and do not exceed the limit of indemnity or go beyond the terms of a professional indemnity wording, a collateral warranty will not necessarily adversely affect the stance of your insurers. Source: Morley von Sternberg The £45 million Thermae Bath Spa complex was the subject of legal claims between the council, contractor and architect. Standard template wordings have been created and are available through professional bodies, which are normally acceptable to professional indemnity insurers. It is, though, important to check your insurer’s stance on collateral warranties before committing to them — some insurers will offer to check a collateral warranty as part of their normal service, whereas others may accept them within certain limits laid down within the policy. Again, if in doubt, check with your insurer. Risk managementInsurers will take a favourable view on practices that adopt procedures that reduce the risk of claims for professional negligence and make it easier to defend against such claims. These might include: Working to a professional code of practice (eg RIBA, RICS, CIOB); Ensuring all works carried out are subject to written contract conditions; Following written guidelines or processes where appropriate; Keeping full records (eg contracts, instructions received, contract amendments, correspondence and phone conversations); Holding evidence that any subcontractors used are reputable and hold their own insurance (including PI). Postscript Privacy policy Information you supply to UBM Information Ltd may be used for publication and also to provide you with information about our products or services in the form of direct marketing by email, telephone, fax or post. Information may also be made available to third parties. “UBM Information Ltd” may send updates about BD CPD and other relevant UBM products and services. By providing your email address you consent to being contacted by email by “UBM Information Ltd” or other third parties. If at any time you no longer wish to receive anything from UBM Information Ltd or to have your data made available to third parties, please write to the Data Protection Coordinator, UBM Information Ltd, FREEPOST LON 15637, Tonbridge, TN9 1BR, Freephone 0800 279 0357 or email [email protected]. Topics CPD
https://www.bdonline.co.uk/cpd/cpd-12-2012-professional-indemnity-insurance-for-architects/5043641.article
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Sustainability | Free Full-Text | Managerial Dilemmas and Entrepreneurial Challenges in the Ambidexterity of SMEs: A Systematic Review for Execution System According to the organizational learning theory, there are two types of corporate activities, exploitation and exploration, for enhancing and improving corporate performance. However, organizations are continually faced with choosing between these two conflicting activities that require different organizational structures, strategies, and environments, respectively. This study& rsquo;s objective is to use a systematic review methodology to investigate how implementing organizational ambidexterity affects managerial performance in small- and medium-sized enterprises (SMEs). Although there is a general consensus about the relationship between ambidexterity and firm performance, few studies have probed into the mechanism of how it is applied to management process and what antecedents affect the implementation of OA in SMEs. The qualitative method was conducted to investigate the influence of the ambidexterity strategy of SMEs on firm performance. According to the findings, organizational ambidexterity in SMEs has a positive impact on the firm& rsquo;s managerial performance. SMEs must make decisions that consider environmental factors. Making practical decisions based on accurate formation, considering organizational human resources for implementing ambidexterity, and sharing specific performance goals are all important considerations. This study is also important for SMEs& rsquo; top management teams to make proper decisions for the firm& rsquo;s sustainable growth via OA, and shed new light on the literature of organization theory that operates in a more turbulent environment. Managerial Dilemmas and Entrepreneurial Challenges in the Ambidexterity of SMEs: A Systematic Review for Execution System by Gayoung Kim 1 , Woo Jin Lee 2 and Hoshik Shim 1,* College of Business Administration, Kookmin University, Seoul 02707, Republic of Korea Graduate School of Global Entrepreneurship, Kookmin University, Seoul 02707, Republic of Korea Sustainability 2022 , 14 (24), 16550; https://doi.org/10.3390/su142416550 Received: 28 October 2022 / Revised: 6 December 2022 / Accepted: 6 December 2022 / Published: 9 December 2022 Abstract : According to the organizational learning theory, there are two types of corporate activities, exploitation and exploration, for enhancing and improving corporate performance. However, organizations are continually faced with choosing between these two conflicting activities that require different organizational structures, strategies, and environments, respectively. This study’s objective is to use a systematic review methodology to investigate how implementing organizational ambidexterity affects managerial performance in small- and medium-sized enterprises (SMEs). Although there is a general consensus about the relationship between ambidexterity and firm performance, few studies have probed into the mechanism of how it is applied to management process and what antecedents affect the implementation of OA in SMEs. The qualitative method was conducted to investigate the influence of the ambidexterity strategy of SMEs on firm performance. According to the findings, organizational ambidexterity in SMEs has a positive impact on the firm’s managerial performance. SMEs must make decisions that consider environmental factors. Making practical decisions based on accurate formation, considering organizational human resources for implementing ambidexterity, and sharing specific performance goals are all important considerations. This study is also important for SMEs’ top management teams to make proper decisions for the firm’s sustainable growth via OA, and shed new light on the literature of organization theory that operates in a more turbulent environment. Keywords: SMEs ; organizational ambidexterity ; organizational learning theory ; systematic review 1. Introduction The company maximizes corporate operation efficiency by maximizing the exploitation of accumulated resources through management. However, in today’s market environment of high market uncertainty, businesses must explore new opportunities. Exploration activities at a company can capitalize on opportunities for new products, services, and innovative technologies. So, in today’s companies, exploitation should be performed simultaneously with exploration. Companies must establish a process that balances exploitation and exploration [ 1 2 ]. Various studies suggest approaches for carrying out these two activities. Organizational ambidexterity refers to an organization’s ability to pursue and balance these two activities at the same time. Recently, SMEs and ventures have also adopted an ambidexterity strategy that simultaneously operates exploitation and exploration for performance and survival [ 3 , 4 ]. This research looked at the ambidexterity strategies of SMEs that are growing with limited resources. Various methods of implementing ambidexterity have been studied according to the environment and situation of the enterprise. Due to a lack of resources and management skills, SMEs always face greater challenges when seeking ambivalence [ 5 ]. This is especially likely for SMEs in transitional and high-growth industries, where top management teams are confronted with and must choose from a plethora of future business opportunities. Many previous studies have discussed OA in SMEs, but there is no integrated research and, therefore, no clear implications that SMEs could apply to their business. The goal of this study is to expand on previous research on organizational ambidexterity in SMEs by looking into the factors that influence the relationship between OA and SME performance. Although many scholars have studied the relationship between ambidexterity and firm performance, few studies have looked into how it is applied to management processes and what factors influence OA implementation in SMEs. The research questions of this study are as follows: (1) What factors influence the implementation of organizational ambidexterity in SMEs, and how do different types of organizational ambidexterity affect SMEs’ performance? (2) How should SMEs that have been through the effectuation process develop an ambidexterity strategy? Some of the additional research questions that could flow from this main question are: Do SMEs that were developed on the basis of the effectuation process after startup choose organizational ambidexterity for their firm’s future growth? Can SMEs expect the same effect as large firms through the implementation of organizational ambidexterity? Although scholars have studied this emerging topic for more than 15 years, there has been limited research conducted in the field of SMEs. This study is also important for SMEs’ top management teams to make proper decisions for the firm’s sustainable growth via OA. Undertaking a careful analysis of the mechanism of organizational ambidexterity in SMEs, this study may shed new light on the literature of organization theory that operates in a more turbulent environment. 2. Literature Review 2.1. The Concept of Exploitation and Exploration March (1991) [ 2 ] published a key paper on exploitation and exploration in organizational learning, which clearly stated the notion of the activities required by the firm. Exploitation implies an organization’s activities, such as efficiency, selection, execution, production, as well as firms learning to enhance their existing capabilities and competencies, using existing knowledge, focusing on current activities, mitigating risks, and predicting outcomes through exploitation in their existing business [ 3 , 6 , 7 ]. Organizational activities associated with exploration include variation, new knowledge, experimentation, flexibility, long-term needs, risk-taking, entrepreneurship, and innovation [ 8 , 9 , 10 ]. Exploration, in other words, refers to the development of new organizational routines, as well as the discovery of new technologies, products, business opportunities, and processes [ 9 , 11 , 12 ]. Based on the conceptual understanding of exploitation and exploration, previous studies have identified what each activity produces as an outcome within the organization. Juni et al. (2013) [ 3 ] found that exploratory activity was primarily related to the firm’s long-term growth in their meta-analysis. While the firm’s exploration activities may not impact immediate profit, they eventually positively impact growth [ 13 ]. In contrast, firms pursuing productivity efficiency rather than innovation were the focus of exploitation activity [ 3 , 14 ]. That is, the firm’s exploitative activities mainly relate to the firm’s current profits but do not closely relate to growth [ 3 ]. Organizations may abandon a promising and seemingly attractive business opportunity because stakeholders perceive the opportunity as overly disruptive. [ 15 ]. Because it is hard to choose just one of the two strategies, previous research on ambidexterity has argued that firms must balance exploitation and exploration [ 16 ]. The ability to aim and apply exploration and exploitation has been suggested as essential for the long-term performance and survival of organizations [ 3 , 4 ]. Furthermore, according to Schumpeterian theory, innovative organizations outperform noninnovative ones, and ambidextrous organizations outperform businesses that focus solely on one strategy, such as exploitation or exploration [ 17 ]. However, organizational ambidexterity is recognized as a paradoxical characteristic in the sense of pursuing two different activities at the same time as evidenced by the use of various terminologies in various studies. Scholars, for example, assert that causation and effectuation are not mutually exclusive but rather interactive relationships [ 18 , 19 ] and that these two strategies can be viewed as distinct types of exploitation and exploration [ 2 , 20 , 21 ], cost leadership and differentiation [ 22 ], competition and collaboration [ 23 ], and efficiency and flexibility [ 24 , 25 ]. 2.2. Characteristics of SMEs SMEs face greater difficulties than large corporations when pursuing an ambidexterity strategy. The majority of previous studies on ambidexterity have concentrated on large corporations. However, in recent years, there has been a growing body of literature studying the practice of ambidexterity at the scope of SMEs, such as ventures, high-tech startups, and entrepreneurial firms [ 26 ]. Many SMEs face managerial quandaries regarding their growth, such as whether to pursue differentiation or low cost as a strategy, adopt a mechanistic or flexible structure, or prioritize control or autonomy [ 27 ]. SMEs may require a new logic to effectively manage their resources and introduce entrepreneurial bricolage, which is defined as “making do by applying combinations of the resources at hand to new problems and opportunities” [ 28 ]. SMEs’ core competencies and management skills are to overcome scarce resources and operate ambidextrous organizations. This study helps to broaden the recognition and integration of organizational ambidexterity in SMEs, as well as the practical difficulties and factors that affect their ability to engage in two different activities related to SMEs’ performance. 2.3. Features of Organizational Ambidexterity Firms can use organizational ambidexterity to solve conflict and the dilemma of paradoxes by employing a few typologies. In previous studies, two ambidextrous methods, contextual and structural ambidexterity, were most representatively presented. Structural ambidexterity is defined as the separation of individuals or groups based on the action plan of an organization [ 29 , 30 , 31 ]. To address the conflict and dilemma created by the paradoxes of balancing exploration and exploitation, firms establish separate units that respond to environmental changes and communicate with external stakeholders. On the other hand, contextual ambidexterity is defined as performing both two strategies at an individual level in the organizational unit [ 30 ]. Individuals focus on the organization’s regular activities while also undertaking new activities [ 30 ]. According to this HRM viewpoint, an ambidextrous structure enables an organization to better take advantage of business opportunities while holding onto its current market share. However, when implementing contextual ambidexterity, an important question about who can manage an individual arises [ 5 , 32 ]. Previous literature suggests another pathway to achieve organizational ambidexterity for firms; sequential ambidexterity [ 31 , 33 ]. Sequential ambidexterity refers to an organization’s focus on one of the competing objectives in turn. Firms achieve different structural alternatives, such as structural or contextual separation, to resolve the organizational paradox. While earlier studies argued that firms should build separate organizational units to gain the benefits of adaptability and alignment at the same time [ 16 , 34 , 35 ]. However, the separated units may not be effective for SMEs due to their small size and limited resources. In reality, these structures hinder the sharing of knowledge and capabilities with the mainstream units. Thus, Duncan (1976) [ 36 ] suggests that organizations should implement a dual structure that allows them to structurally respond to their environment while pursuing both exploration and exploitation. As a result, the focus of this research has been on the factors that enable organizations to create dual structures, as well as the systems and processes that facilitate ambidexterity for SME performance. 2.4. Performance in the SME Organizations Empirical studies have already indicated that ambidextrous organizations have a positive effect on the firm’s performance [ 4 , 5 , 33 , 37 , 38 , 39 , 40 , 41 ]. Many studies have proposed that organizational ambidexterity is related to a longer period of survival [ 42 ], better financial performance [ 43 , 44 , 45 ], and improved learning and innovation [ 46 , 47 ], whether directly related to the firm’s performance or not. However, scholars still have arguments that pursuing such organizational ambidexterity can be either beneficial or detrimental to firms [ 48 , 49 , 50 ]. The lack of empirical tests of the ambidexterity-performance relationship has been criticized by Raisch and Birkinshaw (2008) [ 31 ] and Andriopoulos and Lewis (2009) [ 51 ]. Few studies have provided empirical support for the hypothesis of ambidexterity and performance. For example, Bierly and Daly (2001) [ 52 ] investigated the impact of ambidexterity on firm performance in a sample of 98 manufacturing firms but found no significant results. Katila and Ahuja (2002) [ 53 ] discovered a positive relationship between the proclivity to cite different patents and the proclivity to cite specific patents repeatedly on new product development, but did not test the impact on firm performance [ 54 ]. These ambiguous findings encourage further investigation into whether ambidexterity has a significant impact on the performance and survival of SMEs. However, it is a challenge to capture when and how ambidexterity is implemented and results are created due to the nature of SMEs that operate firms with scarce resources. Therefore, this study focuses on SMEs that are thriving with scarce resources, and analyzes the evidence of the relationship between organizational ambidexterity and performance. SME organizational performance indicators, such as SME innovation, financial gains, product innovation, sales, and investment scales, must be defined, as well as any qualitative outcomes presented in the literature. Simultaneously, the factors affecting SMEs’ performance need to be studied. Scholars have discovered that organizational culture is one of the factors influencing firm performance [ 55 , 56 , 57 , 58 ]. Additionally, manager performance is regarded as the degree to which the manager meets the requirements of his/her general work context toward the firm’s performance [ 59 , 60 ]. Thus, by investigating the factors influencing the firm’s performance, this study will determine the relationship between SMEs’ ambidexterity and performance and under what conditions. 3. Theoretical Framework 3.1. Organizational Learning Theory Organizational adaptation capabilities are a core concept of organizational behavior theory, suggesting that exploitation and exploration activities are needed as a rational system for organizational sustainability. Organizational learning refers to the distribution, acquisition, storage, and interpretation of new knowledge, which are vital success factors of firms [ 61 , 62 , 63 ]. This study employs organizational learning theory from the perspective of adaptation to employ the ambidexterity strategy to overcome the company’s uncertain environment. March (1991) [ 2 ] stated that activities to improve corporate performance in terms of organizational learning can be divided into exploitation and exploration. Organizations are forced to concentrate on exploitation and exploration activities even though those activities are in conflict [ 30 ]. Therefore, companies must find a compromise to balance these two activities. It is also necessary to consider a resource-based perspective (RBV), as companies will eventually be forced to respond to an uncertain environment based on the resources they own. RBV is a strategic position that governs how a company interacts with its tangible and intangible resources [ 64 ]. Many studies suggest that the concept of RBV is more suitable for exploitation than exploration. However, understanding how to apply the concept of RBV in an organization’s activities is required to maintain an appropriate balance between exploration and exploitation. In most cases, businesses will focus and act on either exploration or exploitation. When a company focuses solely on one activity, path-dependent tendencies can be significant, increasing organizational inertia. This poses a risk to the organization in the long run. Based on organizational learning theory, this study explains how companies adapt to new activities that they have never engaged in before. 3.2. Conceptual Framework Figure 1 shows the activities focused on exploitation and exploration based on large companies and SMEs (startups and ventures) [ 65 ]. Quadrant 4 (Q4) represents the activity of existing market participants. Q1 now represents startups entering the market and exploring new businesses. SMEs can exist in both of these areas. However, the premise that SMEs are close to startups and ventures was presented earlier in this study. Q1 and Q4 both choose a path toward Q2, completing an ambidexterity strategy by reinforcing an activity they were not focused on. Ferrary (2011) [ 66 ] described changes in an organization’s internal processes toward Q2 after a large company acquisitioned and merged a startup. Startups that need to investigate stable businesses in the market focus mainly on exploration activities. However, most startups that are acquired by a larger company and primarily carry out the exploitation process are primarily engaged in exploitation activities. Ferrary (2011) [ 66 ] explains that it is not easy to implement an ambidexterity strategy unless companies are willing to do both. Based on the theory of the resource-based view, the merged firm has comparatively fewer resources, causing it to rely on the larger firm’s resources following the M&A. According to organizational learning theory, SMEs have internal resources that can be used to quantify benchmarking and respond flexibly to environmental changes in a flexible manner. SMEs belonging to Q4 might be in the growing or mature stage of the firm where the SMEs already have exploitative capability and intention to adopt explorative activities. In contrast, SMEs in Q1 may be in the early stages of development, where the SMEs remain at the startup level and intend to increase the firm’s efficiency level. According to Kollmann, Kuckertz, and Stöckmann (2009) [ 67 ], entrepreneurial growth companies that have just survived the birth stage still have exploratory behavior—and have entered the phase of rapid growth in which the venture is transferred into a managed firm [ 68 , 69 , 70 , 71 ]. Furthermore, traditional technological life cycle theory suggests that exploration may have the highest payoff in the early stage due to radical product innovation and competing product designs, whereas exploitation may have a higher payoff in the later stage due to cost savings in incremental process innovation [ 67 ]. Thus, exploration is a prerequisite for exploitation, but the advantage of exploration is also dependent on the knowledge gained through exploitation [ 72 ]. Previous research on organizational ambidexterity has been conducted mainly on large firms. The purpose of this research is to look at SMEs that are implementing organizational ambidexterity and analyze the factors that influence their ambidexterity and performance. Thus, as illustrated in Figure 2 , a conceptual framework was constructed for this research. 4. Methods This research employs systematic review (SR) methodology, which employs a structured process to identify trends and meaningful themes in a large body of literature on specific subjects and research questions. This SR methodology is part of the evidence-based management (EBMgt) movement. Evidence-based research synthesis is a valuable method for assessing, summarizing, and disseminating the findings of a large amount of data and scholarship, which is available in print and online databases [ 73 ]. Popay et al. (2006) [ 73 ] assert that the evidenced-based research synthesis is an invaluable method of assessing, recapping, and sharing the findings of a large amount of data and scholarship, which is available in print and online databases. Another strength of this method, as posited by Gough, Thomas and Oliver (2012) [ 74 ] is that the evidenced-based research synthesis is to demonstrate a transparent, thorough, and reliable process for evidence review. Evidence-based synthesis can be a useful tool to help transform contemporary management practice into evidence-based management (EBM). In addition, EBM can bridge the gap between the business and academic worlds by utilizing systematic reviews as the methodology for the decision-making process. The evidenced-based research synthesis has the potential to deliver the synthesis of many different situations by highlighting how certain mechanisms work in particular contexts [ 74 ]. SR is appropriate for this study because it allows us to examine a wide range of empirical studies on organizational ambidextrous approaches in SMEs and their performance. As a result, the SR approach enables us to examine the state of the research question in a short time. Finally, we can use sophisticated and well-structured search and synthesis techniques to draw meaningful conclusions about ambidexterity approaches in a variety of ways. According to Steven (2001) [ 75 ], an SR process should include formulating a clear question, locating all relevant research, and carefully evaluating the quality of each study to meet the rigor required for clinical decisions or, in the case of this review, management decisions (p. 532). The following research questions will be addressed through a synthesis of existing management theory and primary research studies. As previously stated, the methodology will be thematic synthesis. Relevant research will be found by employing carefully chosen inclusion/exclusion criteria, key terms, search strings, and the most applicable date ranges. The following is the methodological approach taken in this study. Identifying the question: this dissertation study’s research question was to determine the antecedents to organizational ambidexterity in SMEs as an intervention within the entrepreneurial and managerial processes of organizational systems to achieve innovation and efficiency. Clarifying the purpose of the review: determining whether ambidexterity in SMEs will improve firm performance, allowing SMEs to seize new opportunities and increase efficiency. Articulating theories: because the implementation of ambidexterity involves numerous challenges and knowledge exchanges, the theory chosen is the basic principle that drives this mechanism. Search for the evidence: the nature and approach of the bibliographic search chosen to answer, obtain and identify bibliographic search engines containing appropriate scientific literature, subject matter experts, databases, and gray materials. Appraise the evidence: an appraised piece of evidence for trustworthiness, validity, and alignment to the research question. Extract the results: review cumulative findings from the literature and combine all the knowledge, from the evidence-based literature appraised and instructional strategies. Synthesize findings: evaluate the decision’s effectiveness and efficiency, as well as its relevance in answering the research question and solving the business problem while making any necessary adjustments. Conclude and make recommendations: highlight gaps in the synthesis of the findings that need to be addressed in the future to develop a set of recommendations and document the implications for managers in SMEs. To illustrate the entire process of selecting evidence and establishing the final sample set for this SR, a preferred reporting items for SRs and meta-analysis (Prisma) diagram is used. As shown in Figure 3 , prisma is a preferred reporting chart for studies that were included and excluded from the SR. As stated by Gough et al. (2012) [ 74 ], Prisma is an essential component of the SR methodology because it allows the reader to follow the rigorous process of reviewing the evidence and establishing the final sample size. 5. Analysis and Findings 5.1. Description of the Data Set For this study, evidence from the scholarly literature was selected from a wide range of contexts, including studies of firms of different SME sizes, industries, geographic locations (different countries), growth stages, and lifespan. The companies examined in the included scholarly studies were from three continents. Given that the studies included in this study drew from firms in North and South America (35%, 13 studies), Europe (24%, 9 studies), and Asia (27%, 10 studies), the common themes extracted for this study may have cross-cultural applications, such as for firms from different geographical locations. Only studies published after the year 2000 were considered, which was one of the key inclusion criteria. Given the relatively new and rapidly evolving theory development of organizational ambidexterity in SMEs, this criterion was used to review the most recent literature on ambidexterity-related topics. The organizational level of analysis of this study was SMEs. Figure 4 also shows that there was insufficient research on OA-SMEs related to the research question in the early 2000s, with an increase in articles occurring in recent years. This rise could be attributed to changes in the market environment and a recognition of the importance of SMEs as a driver of economic growth. The distribution of the sample sizes was 37 studies. There were multiple studies for each of the sample groupings (interview, review, 0-10 samples, etc.). This distribution chart implies that the conclusions drawn from the evidence assessed in this SR of the literature might have broad application given the varying number of SMEs reviewed in the aggregate data. In addition, the type of research methodology for the 37 studies included in this SR of the literature is shown next to the sample size chart. Table A2 and Table A3 in Appendix B contain more specific information, such as journal names, study context, the sample size for each article, and the main theory employed in the study. The citations of a study represent the ripple effect of a certain research domain. The total number of citations for all studies examined in this study was 9290 with an average of 251 citations across 37 articles. However, we excluded four studies that had quite high citation numbers at the end of the process of article selection. Those studies with a high citation count were cited numerous times in recent studies chosen through library research, so there was a strong possibility that they would be redundant to the others. Articles for analysis were gathered with the most recent and influential articles in mind to draw meaningful conclusions. Table A2 and Table A3 in Appendix B provides citation numbers for each study. 5.2. Antecedents of Ambidexterity in SMEs Eighteen studies (49% of total articles) examined the causes of organizational ambidexterity or how specific factors influenced ambidexterity implementation in SMEs. Among these 18 studies, 14 provided evidence in the results section of the article based on various experiments conducted by each study, while four only provided antecedents in the literature review section of the study. The four studies that did not speak to the results were excluded, and only the factors from the study results of the 14 articles were aggregated. Table 1 shows how the antecedents were divided into eight categories. According to the literature uncovered for this SR, the most supportive mode to implement organizational ambidexterity in SMEs is a cooperative organizational tendency. Four of the studies support cooperation as an antecedent, including intra-firm knowledge exchange, inter-organizational coordination, cross-functional organization, and unit interdependence [ 27 , 66 , 77 , 82 , 85 , 86 ]. However, the authors who presented the cooperation antecedent also discovered preparation and support antecedents in their study. These findings are in line with previous scholars who focused their research on the antecedents of organizational ambidexterity [ 5 , 30 , 31 , 32 ]. While earlier studies (e.g., [ 87 , 88 ]) provided empirical evidence of the importance of an organizational atmosphere based on employee and manager cooperation, the relationship between organizational support and new product development performance was not statistically significant [ 58 , 83 ]. The resources, care, and autonomy provided to employees were referred to as organizational support [ 89 ]. Although all eight antecedents identified in the body of evidence contribute to the implementation of AMB for SMEs, cooperation may be the most fundamental antecedent, in that it must be initiated before the other antecedents, such as leadership commitment, readiness for changes, connectedness, etc. can be realized. Cooperation is especially important in the pursuit of AMB in SMEs because knowledge utilization and sharing in organizations must be actively performed to overcome a lack of slack resources, which is common in SMEs. 5.3. Organizational Structure and Features of Ambidexterity in SMEs For the second theme, almost all the studies chosen for the SR mentioned either structural or contextual ambidexterity in SMEs, however, only nine of the 37 studies provided evidence for the type of ambidexterity in the study’s results and conclusions. After analysis, eight of the nine studies concluded that contextual ambidexterity should be implemented in SMEs. Although Ferrary (2011) [ 66 ] discussed the negative aspects of contextual ambidexterity in the organization, there was only one study that concluded that structural ambidexterity should be implemented in SMEs [ 89 ]. These findings demonstrate that for many scholars contextual design for ambidexterity is assumed to contribute to more valid results for SMEs than structural ambidexterity. In creative industries, SMEs lacked the human and financial resources required to conduct two types of activity to achieve an ambidextrous structure. As a result, Parmentier and Picq (2016) [ 82 ] argued that contextual ambidexterity models are better suited to SMEs than other models, particularly in the creative industries. Table 2 provides more information on the different types of structures and their components. Chang et al. (2009) [ 90 ], Patel et al. (2013) [ 77 ], De Clercq et al. (2014) [ 85 ], and Du and Chen (2018) [ 78 ] discussed the importance of human resources in contextual ambidexterity, and Du and Chen (2018) [ 78 ] emphasized integrated-employee behavior as an advantage of contextual ambidexterity. According to this viewpoint, contextual ambidexterity is more likely to emerge from a distinct human resources base than from a set of practices. More specifically, ambidexterity is realized through the flexibility with which SMEs’ human resources allocate their time and attention to exploration and exploitation. Previous research has increasingly argued for evidence for the positive impact of contextual ambidexterity [ 38 ]. According to the findings of this study’s SR of the literature, contextual ambidexterity in an organization required practices that work to improve resource flexibility in their human base so that employees have the discretion and motivation to devote their energy to activities associated with both exploitation and exploration. Exploitation, for example, is seen as a result of having clear performance standards and goals, rapid and open feedback systems, and consistency in how employees are managed. Exploration, on the other hand, refers to an organizational context in which employees actively and voluntarily push their standards and goals to higher levels. Therefore, the HR system in SMEs is highly important to produce these contextual elements. Finally, developing contextual ambidexterity within the HR system improves employees’ practical activity in demonstrating exploitation and exploration across an entire business unit. HRM practices can help SMEs create a behavioral environment that encourages employees to explore and exploit. In pursuing contextual ambidexterity, SMEs need to provide an appropriate environment for employees by offering social support and setting aggressive performance targets. That is, SMEs must provide employees with the appropriate set of HR practices for the development of both efficiency-related competencies and innovation-related competencies [ 77 ]. SMEs must ensure that their HR practices encourage cooperative behavior and mitigate internal rivalry because increasing internal rivalry among employees creates inefficiency in organizations because they compete for knowledge, information, and other types of resources [ 85 ]. 5.4. Performance of SMEs There were four operational factors influencing the performance of SMEs found in the synthesis of the literature: preparation, human resources, resources, and structure. Preparation was defined as readiness for change, goal setting, behavioral integration of the top management team, and a combination of exploitation and exploration that enabled SMEs to improve their firm’s performance [ 5 , 21 , 79 , 84 , 91 ]. In addition to preparation, human resources are also emphasized as being a fundamental factor for performance in SMEs [ 54 , 77 , 92 ]. Human resources appear to be a major attribute of organizational ambidexterity because it has been identified as one of the most important subthemes for ambidexterity antecedents and it contributes to SME performance. The results of analyzing the operational factors affecting performance in more detail are as follows. Patel et al. (2013) [ 77 ] concluded that HPWS affect SME performance and, more specifically, growth by producing an ambidextrous workforce in SMEs. In this study, the results provided robust evidence for the relationship between HPWS in SMEs and firm performance. Firms can expect the dynamic processes of knowledge exploration and exploitation as a key source of a firm’s sustainable competitive edge by increasing the abilities of employees through the system [ 93 ]. De Clercq et al. (2014) [ 85 ] demonstrated a negative relationship between internal rivalry and firm performance and discovered that internal battles over a firm’s resources can impede internal knowledge transfer. Employees must collaborate and interact with others to effectively meet the demands the firm faces rather than compete inside the firm [ 92 ]. Other studies [ 13 , 21 , 85 , 92 ] demonstrated the performance of SMEs in terms of the environment and government policy. Businesses should consider and capitalize on the direction of government policy. Combining exploitation and exploration can serve as a portfolio diversification function and, depending on the environment, SMEs should balance the contradictory activities. In a less uncertain environment, for example, SMEs should prioritize exploitation, while in a more uncertain environment, they should combine exploitation and exploration [ 21 ]. The performance literature was fairly homogeneous in terms of its assessment and value for ambidexterity in SMEs. SMEs that implement a combination of exploitation and exploration perform better overall, but younger or early-stage SME firms should prioritize one activity first to achieve higher performance [ 91 ]. Finally, Lubatkin et al. (2006) [ 5 ] proposed that behavioral integration of the top management team is critical for achieving an ambidextrous orientation that affects performance in SMEs. In addition to investigating operational factors for performance in SMEs, it is also necessary to carefully explore the practical meanings of performance that operational factors affect. As we previously discussed, many other researchers have focused on the outcomes and impact of ambidexterity on performance. Among these studies, contextual ambidexterity appropriate for SMEs contributes to both financial and nonfinancial performance [ 94 , 95 ]. In the same vein, almost all the studies selected for the SR defined the word performance in each study. Revenue, revenue growth, sales growth, profit or profitability, and return on investment were all used to define performance (ROI). It was also defined in nonfinancial terms, such as perceived performance in comparison to competitors, user increases, innovation, firm growth, fulfillment of requirements in the firm, customer relationship, and commercialization of a firm’s intellectual properties. Surprisingly, nonfinancial performance measures were more common in this SR than financial performance measures. This is most likely due to nonfinancial performance measures being more easily accessible through survey sampling than profitability estimates. Table 3 summarizes the financial and nonfinancial performance measures identified in this SR. 5.5. Organizational Resources and Dilemmas in SMEs Recall that studies indicated that there are often internal fights for a firm’s resources in ambidextrous organizations [ 85 ]. March (1991) [ 2 ] previously assumed that simultaneously implementing exploitation and exploration in an organization resulted in a zero-sum game in which both approaches competed for scarce organizational resources. Exploitation and exploration generate tensions with a fundamentally different logic and compete for scarce resources, so the firm must weigh the two [ 38 ]. As a result, this situation leads to dilemmas or difficulties for SMEs, even with the implementation of ambidexterity. As previously discussed in this study, dilemmas of the availability of resources, such as financial support, human resources, knowledge, and skills exist in the firm. Gedajlovic et al. (2012) [ 65 ] insisted that firms with better performance typically possess more slack resources to support exploitative and exploratory activities. Larger firms may have more slack resources than SMEs. Larger firms may engage more in strategic planning (due to their size) and are more likely to be ambidextrous due to resource constraints. However, the size of the firm is not an omniscient factor that always results in having the ability to better implement ambidexterity. According to Lillegraven et al. (2016) [ 84 ], firm size does not affect strategic planning and/or being ambidextrous. Larger established firms are also frequently slower to respond to opportunity than SMEs because their entrepreneurship ability deteriorates over time as their internal structures become increasingly laden with rules, procedures, and systems [ 5 ]. However, in most organizations, key resources appear to be predetermined and housed in core units. Most entrepreneurial or new venture units lack the core resources or the infrastructure required to transform an early-stage venture project into an established viable business [ 76 ]. These resources are typically housed within core business units. 6. Conclusions and Implication This study’s main goal was to determine whether ambidexterity, which has been described as a strategy for large corporations, can be applied to SMEs, and if so, what precedents there are for doing so and what effect these strategies would have on the performance of SMEs. The research question, “what are the determinants of ambidexterity, and what is the effect of organizational ambidexterity on corporate performance in SMEs?” can be answered in part by this study’s findings. An SR methodology was used in this study. An SR is an effective way to check the direction of previous studies on a research question. The SR of 37 studies has demonstrated that the original conceptual model should be revised. Figure 5 depicts the relationships discovered during the SR. According to the review, the organizational ambidexterity of SMEs is a key organizational component that affects the performance of businesses. Additionally, entrepreneurial orientation, where exploration is stronger than exploitation, creates a cooperative culture in the firm, which tends to form contextual ambidexterity in SMEs. Structural ambidexterity influences cooperative organizational culture and knowledge transfer. Additionally, firm performance was not supported by this study however. That is, depending on the firm’s given situation, contextual or structural ambidexterity should be chosen, but most of the studies analyzed in this dissertation study supported contextual ambidexterity. The initial conceptual model put forth the idea that organizational learning helps SMEs develop their ambidexterity. The key finding of the synthesis was that organizational learning not only improves contextual ambidexterity but also offers an experience that informs the decision-making process improvement, as well as creativity and innovation know-how to seize future opportunities and maintain current profit. The mechanism of the conceptual model is very crucial for SME organizations as this provides an opportunity to modify and adapt to a quickly changing environment. For SMEs, organizational ambidexterity can be invaluable in orchestrating changes to the organization’s structure and how it handles potential future opportunities in the VUCA environment. This conceptual model as shown in Figure 5 can serve as a mechanism for the top management teams to implement ambidexterity in SMEs. A total of 37 carefully chosen scholarly studies supported the aforementioned research question. In particular, corporate performance is more important than anything else, and ambidexterity has been shown to have a significant correlation with the performance improvement of SMEs. The company’s resources, organizational structure, organizational goals, and vision are significant factors in implementing ambidexterity. The relevance to performance and the factors of execution provide an important foundation for the company’s working manpower to establish a strategy. In the still underdeveloped field of SMEs, achieving successful results through an efficient blending of related elements can be good practice for ambidexterity. An important organizational decision is how a company will implement an ambidextrous strategy. Decisions made by business executives must take into account the organization’s resource level and various environments. The SR methodology used in this study gave management practitioners who implement organizational ambidexterity in their SMEs invaluable insight. We offer managers a framework for modifying organizational ambidexterity to shape overall innovation management and efficiency. First, we discovered a strong correlation between organizational structure design and performance. The organizational structure should take into account the company’s resources, core competencies, and environments because these choices have an impact on the company’s sustainability. Since the ambidexterity structure requires a balance between exploitation and exploration as an organizational behavior, organizations must support their members to perform both types of activity because the ambidexterity structure necessitates a balance between exploitation and exploration as an organizational behavior. In this vein, temporal separation is considered for a manager to control organizational changes sequentially between phases of exploration and exploitation [ 96 ]. In this type of contextual ambidexterity model, organizations alternate between decentralized periods to foster innovations and centralized periods to increase efficiency. Thus, as a result of this dissertation study, this sequential approach is recommended for practitioners in SMEs. Second, this study implies that contextual ambidextrous SMEs should pay attention to internal competition. Internal conflicts over a firm’s resources may obstruct the transfer of internal knowledge according to De Clercq et al.’s (2014) [ 85 ] research, which established a negative correlation between internal rivalry and firm performance. Practitioners should lessen internal competition because employees need to work together and interact with others to effectively meet the demands the firm faces [ 92 ]. A reward system for sharing knowledge and skills could be suggested. Third, this study shows the need for SMEs to increase knowledge exchange. From the organizational learning perspective, organizations learn to improve their capabilities, apply knowledge, and enhance competencies in their business [ 3 , 6 , 7 ]. To allow employees to share and learn about the other aspects of their work, firms hold regular project meetings or seminars. Fourth, the systematic review suggests that the three activities should be used to further HRM. First of all, foster talents internally in the long term rather than recruit from outside. Establish precise criteria for hiring outside talent as well. Lastly, provide hands-on training programs and career development opportunities for employees. 7. Limitations and Future Research This study has several limitations. First, it is possible that the systematic review methodology used in this dissertation study to extract constructs only adequately captured a subset of the distinction between exploitation and exploration. Future research needs to examine the usefulness of additional measures. Second, as market and technological dynamism change, the successful balance between exploration and exploitation may change significantly. Due to the selected articles’ limitations, this study was only able to analyze specific industries and certain growing stages of firms. To provide more precise controls for industry and growing stage environmental factors, and to investigate how the ideal balance between exploration and exploitation may be dependent on such environmental factors, future research should bring together diverse SME samples. Third, due to sample limitations, this dissertation study could not investigate the impact of explorative and exploitative innovation on long-term performance; 10 years or more. This amount of time is required if we are to examine entrepreneurial orientation businesses in a VUCA setting. To address this issue, future research needs to assemble articles studying longitudinal data over a sufficiently long period. Author Contributions As main contributors, H.S. outlined and performed literature review, and conducted analysis; G.K. and W.J.L. reorganized the manuscript; conducted and additional literature review; conceptualized the work, research design, and discussion; and completed a reference check. W.J.L. and H.S.; Methodology, W.J.L. and H.S.; Investigation, G.K.; Data curation, G.K.; Writing—original draft, G.K., W.J.L. and H.S.; Visualization, W.J.L. All authors have read and agreed to the published version of the manuscript. Funding This research received no external funding. Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement Not applicable. Conflicts of Interest The authors declare no conflict of interest. Appendix A Table A1. Quality Assessment Using Weight of Evidence. Table A1. Quality Assessment Using Weight of Evidence. # Authors WoE-A WoE-B WoE-C WoE-D Decision 1 Felício et al. (2019) [ 89 ] 2 3 3 8 H 2 Yu et al. (2018) [ 97 ] 2 3 3 8 H 3 Sussan et al. (2017) [ 13 ] 2 3 3 8 H 4 Gedajlovic et al. (2012) [ 65 ] 3 2 3 8 H 5 Patel et al. (2013) [ 77 ] 3 3 3 9 H 6 Clercq et al. (2014) [ 86 ] 3 2 3 8 H 7 Lillegraven et al. (2016) [ 84 ] 2 2 2 6 M 8 Ikhsan et al. (2017) [ 27 ] 2 2 2 6 M 9 Parmentier and Picq (2016) [ 82 ] 3 2 2 7 M 10 Ferrary (2011) [ 66 ] 3 2 2 7 M 11 Martínez-Climent et al. (2019) [ 98 ] 2 2 1 5 M 12 Ren and Jackson (2020) [ 99 ] 1 1 1 3 L 13 Chang et al. (2009) [ 90 ] 3 2 3 8 H 14 Soares et al. (2018) [ 17 ] 2 3 2 7 M 15 Mom et al. (2015) [ 92 ] 3 3 3 9 H 16 Du and Chen (2018) [ 78 ] 2 3 3 8 H 17 Chen and Kannan-Narasimhan (2014) [ 76 ] 3 3 3 9 H 18 Kusumastuti et al. (2018) [ 80 ] 2 2 1 5 M 19 Selcer and Decker (2012) [ 79 ] 2 2 2 6 M 20 Han and Celly (2008) [ 54 ] 3 3 3 9 H 21 Joharianzadeh et al. (2015) [ 100 ] 2 2 1 5 M 22 Kollmann et al. (2009) [ 67 ] 2 3 2 7 M 23 Chebbi et al. (2015) [ 81 ] 3 3 2 8 H 24 Heavey et al. (2015) [ 86 ] 3 3 3 9 H 25 He and Wong (2004) [ 38 ] 3 3 3 9 H 26 Cegarra-Navarro and Dewhurst (2007) [ 93 ] 2 2 3 7 M 27 Burpitt and Valle (2010) [ 72 ] 2 3 3 8 H 28 Park and Kim (2015) [ 101 ] 2 3 2 7 M 29 Liu, Wang, and Li (2019) [ 102 ] 2 3 3 8 H 30 Battaglia et al. (2018) [ 91 ] 2 3 3 8 H 31 Günsel et al. (2018) [ 83 ] 2 3 3 8 H 32 Soto-Acosta et al. (2018) [ 103 ] 3 2 2 7 M 33 Venugopal et al. (2018) [ 104 ] 2 2 2 6 M 34 Voss and Voss (2013) [ 105 ] 3 2 3 8 H 35 Chang et al. (2011) [ 106 ] 3 2 2 7 M 36 Chang and Hughes (2012) [ 107 ] 3 2 2 7 M 37 Lubatkin et al. (2006) [ 5 ] 3 2 3 8 H 38 Jansen et al. (2005) [ 96 ] 3 1 2 6 M 39 Cao et al. (2009) [ 20 ] 3 1 1 5 M 40 Tiwana (2008) [ 108 ] 3 1 1 5 M 41 O’Reilly and Tushman (2008) [ 109 ] 3 2 2 7 M Note. Appraisal criteria: 3 = high quality (strong); 2 = medium (moderate); 1 = low quality (weak). Appendix B Table A2. Basic Description of Included Articles. Table A2. Basic Description of Included Articles. # Database Published Year Cited Authors Journals 1 OneSearch 2019 0 Felício et al. Journal of Business Research 2 2018 9 Yu et al. Technological Forecasting and Social Change 3 2017 2 Sussan et al. JOURNAL OF THE ASIA PACIFIC ECONOMY 4 2012 87 Gedajlovic et al. Journal of Business Venturing 5 2013 310 PATEL et al. Academy of Management Journal 6 2014 48 Clercq et al. Small Bus Econ 7 2016 1 Lillegraven et al. Nordicom Review 8 2017 3 Ikhsan et al. International Journal of Business and Society 9 2016 12 Parmentier and Picq Human Resources Management 10 2011 147 Ferrary European Management Journal 11 2019 3 Martínez-Climent et al. Sustainability 12 2009 165 Chang et al. Research Policy 13 2018 0 Soares et al. Journal of Technology Management and Innovation 14 2015 93 MOM et al. Human Resource Management 15 2018 5 Du and Chen International Journal of Innovation Studies 16 2014 23 Chen and Kannan-Narasimhan R&D Management 17 2018 1 Kusumastuti et al. Policy and Governance Review 18 2012 12 Selcer and Decker The International Journal of Organization Innovation 19 2008 118 Han and Celly Canadian Journal of Administrative Sciences 20 2015 1 Joharianzadeh et al. International Journal of Management, Accounting, and Economics 21 2009 30 KOLLMANN et al. Journal of Enterprising Culture 22 2015 33 CHEBBI et al. Human Resource Management 23 2015 42 HEAVEY et al. Human Resource Management 24 2004 3579 He and Wong Organization Science 25 2007 106 Cegarra-Navarro and Dewhurst The International Journal of Human Resource Management 26 ABI/INFORM 2010 12 Burpitt and Valle Journal of Small Business Strategy 27 2015 19 Park and Kim Asia Pacific Journal of Management 28 SCOPUS 2019 1 Liu, Wang, and Li Frontiers of Business Research in China 29 2018 5 Battaglia et al. Management Decision 30 2018 7 Günsel et al. Kybernetes 31 2018 32 Acosta et al. Journal of Knowledge Management 32 2017 5 Venugopal et al. Management Decision 33 2013 228 Voss and Voss Organization Science 34 2011 153 Chang et al. Management Decision 35 2012 219 Chang and Hughes European Management Journal 36 Snowballing 2006 1743 Lubatkin et al. Journal of Management (from article #4) 37 2008 2036 O’Reilly and Tushman Research in Organizational Behavior (from article #4) Note. Cited: from an article published year until 3 November 2019. Table A3. Sample, Methodology, and Theory Descriptions of Included Articles. Table A3. Sample, Methodology, and Theory Descriptions of Included Articles. # Authors Study Context Methodology (Sample Size) Main Theory 1 Felício et al. (2019) [ 89 ] Portugal SMEs Quantitative (202 respondents) Organizational learning theory, Behavioral theory 2 Yu et al. (2018) [ 97 ] China software firms Quantitative (312 firms) Causation and Effectuation 3 Sussan et al. (2017) [ 13 ] Korea high-tech firms Quantitative (2800 firms) Traditional strategy 4 Gedajlovic et al. (2012) [ 65 ] China high-tech firms Quantitative (122 firms) Agency theory 5 Patel et al. (2013) [ 77 ] US high-tech manufacturing SMEs Quantitative (215 firms) Behavioral theory 6 Clercq et al. (2014) [ 85 ] Canadian SMEs Quantitative (146 firms) Contingency perspective 7 Lillegraven et al. (2016) [ 84 ] US newspaper SMEs Quantitative (143 firms) Strategic management theory 8 Ikhsan et al. (2017) [ 27 ] Indonesia SMEs Quantitative (133 firms) Organizational learning theory 9 Parmentier and Picq (2016) [ 82 ] France’s creative industry SMEs Qualitative (11 firms) Ambidexterity 10 Ferrary (2011) [ 66 ] US corporations Qualitative (2 Corp.–case study) Open innovation 11 Martínez-Climent et al. (2019) [ 98 ] (N/A) Qualitative (review) Resource-based view, theory of dynamic capabilities 12 Chang et al. (2009) [ 90 ] Taiwan universities Quantitative (229 respondents) Institutional theory 13 Soares et al. (2018) [ 17 ] Brazil’s higher education institutions Quantitative (79 respondents) Institutional theory 14 Mom et al. (2015) [ 92 ] Global 500 (service and manufacturing) firms Quantitative (337 respondents) Maturity degree of organizational ambidexterity 15 Du and Chen (2018) [ 78 ] China high-tech SMEs Qualitative (2 firms–case study) Human resource management 16 Chen and Kannan-Narasimhan (2015) [ 76 ] US Silicon Valley firms Qualitative (51 interviewees) (N/A) 17 Kusumastuti et al. (2018) [ 80 ] Indonesia business group Quantitative (450 respondents) Formal integration mechanisms (OT) 18 Selcer and Decker (2012) [ 79 ] US large oil and gas company Qualitative (31 interviewees) Resource-based view 19 Han and Celly (2008) [ 54 ] Canada’s international new venture firms Quantitative (70 firms) Structuration theory (loose-tight coupling) 20 Joharianzadeh et al. (2015) [ 100 ] (N/A) Qualitative (Propositions) Theory of dynamic capability 21 Kollmann et al. (2009) [ 67 ] (N/A) Qualitative (Propositions) (N/A) 22 Chebbi et al. (2015) [ 81 ] France telecommunication market Qualitative (interview) (N/A) 23 Heavey et al. (2015) [ 86 ] US high-tech SMEs Quantitative (99 firms) Structural configurations theory 24 He and Wong (2004) [ 38 ] US manufacturing firms Quantitative (206 firms) Social capital theory 25 Cegarra-Navarro and Dewhurst (2007) [ 93 ] Spain optometry and telecommunication SMEs Quantitative (269 firms) Organization theory 26 Burpitt and Valle (2010) [ 72 ] US furniture industry SMEs Quantitative (94 firms) Organizational learning theory 27 Park and Kim (2015) [ 101 ] Korean government-sponsored companies Quantitative (467 firms) Behavioral theory, Resource-based view 28 Liu, Wang, and Li (2019) [ 102 ] China SMEs Qualitative (63 firms) (N/A) 29 Battaglia et al. (2018) [ 91 ] Italy’s high and medium-tech industries Quantitative (221 firms) (N/A) 30 Günsel et al. (2018) [ 83 ] Turkey SMEs Quantitative (105 firms) The emerging view of domain ambidexterity 31 Soto-Acosta et al. (2018) [ 103 ] Spain manufacturing SMEs Quantitative (429 firms) Strategic management 32 Venugopal et al. (2018) [ 104 ] India IT, electronics, biotech SMEs Quantitative (78 firms) Knowledge-based view 33 Voss and Voss (2013) [ 105 ] US nonprofit theater industry SMEs Quantitative (107 firms) Behavioral integration 34 Chang et al. (2011) [ 106 ] Scotland manufacturing and service SMEs Quantitative (265 firms) Strategic combinations 35 Chang and Hughes (2012) [ 107 ] Scotland manufacturing and service SMEs Quantitative (243 firms) (N/A) 36 Lubatkin et al. (2006) [ 5 ] US SMEs Quantitative (139 firms) (N/A) 37 O’Reilly and Tushman (2008) [ 109 ] (N/A) Qualitative (Propositions) Echelon theory Appendix C Table A4. Contribution of Each Article in the Systematic Review. Table A4. Contribution of Each Article in the Systematic Review. # Authors A S P M 1 Felício et al. (2019) [ 89 ] O 2 Yu et al. (2018) [ 97 ] O O 3 Sussan et al. (2017) [ 13 ] O 4 Gedajlovic et al. (2012) [ 65 ] O O 5 Patel et al. (2013) [ 77 ] O O O 6 Clercq et al. (2014) [ 86 ] O O O O 7 Lillegraven et al. (2016) [ 84 ] O O 8 Ikhsan et al. (2017) [ 27 ] O O O 9 Parmentier and Picq (2016) [ 82 ] O O O 10 Ferrary (2011) [ 66 ] O O 11 Martínez-Climent et al. (2019) [ 98 ] O 12 Chang et al. (2009) [ 90 ] O O 13 Soares et al. (2018) [ 17 ] O 14 Mom et al. (2015) [ 92 ] O 15 Du and Chen (2018) [ 78 ] O O 16 Chen and Kannan-Narasimhan (2014) [ 76 ] O 17 Kusumastuti et al. (2018) [ 80 ] O 18 Selcer and Decker (2012) [ 79 ] O O 19 Han and Celly (2008) [ 54 ] O 20 Joharianzadeh et al. (2015) [ 100 ] O O O 21 Kollmann et al. (2009) [ 67 ] O 22 Chebbi et al. (2015) [ 81 ] O 23 Heavey et al. (2015) [ 86 ] O O 24 He and Wong (2004) [ 38 ] O 25 Cegarra-Navarro and Dewhurst (2007) [ 93 ] O 26 Burpitt and Valle (2010) [ 72 ] O 27 Park and Kim (2015) [ 101 ] O 28 Liu, Wang and Li (2019) [ 102 ] O 29 Battaglia et al. (2018) [ 91 ] O 30 Günsel et al. (2017) [ 83 ] O O 31 Soto-Acosta et al. (2018) [ 103 ] O 32 Venugopal et al. (2017) [ 104 ] O 33 Voss and Voss (2013) [ 105 ] O O 34 Chang et al. 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Theoretical framework (Modified from the work of Gedajlovic et al., 2012 [ 65 ]). Note. Path (a) suggests increasing exploration-related activities and path (b) implies increasing exploitation-related activities in firms. Figure 1. Theoretical framework (Modified from the work of Gedajlovic et al., 2012 [ 65 ]). Note. Path (a) suggests increasing exploration-related activities and path (b) implies increasing exploitation-related activities in firms. Figure 2. Conceptual framework. Source: author’s elaboration. Figure 2. Conceptual framework. Source: author’s elaboration. Figure 3. Prisma diagram of preferred reporting for systematic reviews. Figure 3. Prisma diagram of preferred reporting for systematic reviews. Figure 4. Number of studies by publication year (n = 37). Figure 4. Number of studies by publication year (n = 37). Figure 5. Postsynthesis conceptual model of the organizational ambidexterity in SMEs and its influence on firm performance. Figure 5. Postsynthesis conceptual model of the organizational ambidexterity in SMEs and its influence on firm performance. Table 1. Key antecedents of SMEs ambidexterity as found in the systematic review. Concept Category Antecedents Authors Culture organizational culture (bottom-up approach) Ikhsan et al. (2017) [ 27 ] Operation leadership ambidexterity, centralization, connectedness Chen and Kannan-Narasimhan (2015) [ 76 ] HRM HRM system, HRM practices, manager’s fit, enhanced human resource capacity Patel et al. (2013); Du and Chen (2018); Selcer and Decker (2012) [ 77 , 78 , 79 ] Structure (legal) top-management shareholdings, advisory boards, private companies Gedajlovic et al. (2012) [ 65 ]; Kusumastuti (2018); Chebbi et al. (2015) [ 80 , 81 ] Competency creativity, long term consideration and entrepreneur’s experience, entrepreneurial bricolage Parmentier and Picq (2016) [ 82 ]; Chebbi et al. (2015) [ 81 ]; Günsel et al. (2018) [ 83 ] Preparation readiness for change, firm life cycle stage Lillegraven et al. (2016) [ 84 ]; Günsel et al. (2018) [ 83 ] Cooperation Intra-firm knowledge exchange, inter-organizational coordination, cross-functional organization, unit inter-dependence De Clercq et al. (2014) [ 85 ]; Ferrary (2011) [ 66 ]; Heavey et al. (2015) [ 86 ] Support leaders’ commitment and support, senior team (rewards, social relationships) Soares et al. (2018) [ 17 ]; Heavey et al. (2015) [ 86 ] Table 2. Types and common theme of SMEs ambidexterity resulted in the literature reviewed. Table 2. Types and common theme of SMEs ambidexterity resulted in the literature reviewed. AMB Type Common Theme Components Selected Study Structural Structure Need to separate the structures Felício et al. (2019) [ 89 ] Contextual HR The proper set of HR practices Patel et al. (2013) [ 77 ] Negative interaction with internal rivalry De Clercq et al. (2014) [ 85 ] Contextual is more critical for employees Chang et al. (2009) [ 90 ] Make integrated behavior of employees Du and Chen (2018) [ 78 ] Culture The learning process (bottom-up culture) Ikhsan et al. (2017) [ 27 ] Structure No internal separation for AMB Heavey et al. (2015) [ 86 ] Industry Suite in the creative industries Parmentier and Picq (2016) [ 82 ] Environment The disadvantage in changing environment Ferrary (2011) [ 66 ] Table 3. Financial and nonfinancial measures of performance in the SR. Table 3. Financial and nonfinancial measures of performance in the SR. Attribute Performance Measure Selected Study Financial performance Revenue Revenue growth Sales growth Profit or profitability Return on investment (ROI) Battaglia et al. (2018); [ 91 ] Lillegraven et al. (2016); [ 84 ] Lubatkin et al. (2006); [ 5 ] Han and Celly (2008); [ 54 ] De Clercq et al. (2014); [ 85 ] Nonfinancial performance Perceived performance compared to competitors User increases Innovation Growth of the firm Fulfillment of the requirement in the firm Relationship with customers Commercialization of the firm’s intellectual properties Yu et al. (2014); [ 21 ] Patel et al. (2013); [ 77 ] Lillegraven et al. (2016); [ 84 ] Chang et al. (2009); [ 90 ] Mom et al. (2015); [ 92 ] Selcer and Decker (2012); [ 79 ] Han and Celly (2008); [ 54 ] Cegarra-Navarro and Dewhurst (2007) [ 93 ] AMA Style Kim G, Lee WJ, Shim H. Managerial Dilemmas and Entrepreneurial Challenges in the Ambidexterity of SMEs: A Systematic Review for Execution System. Sustainability. 2022; 14(24):16550. https://doi.org/10.3390/su142416550 Chicago/Turabian Style Kim, Gayoung, Woo Jin Lee, and Hoshik Shim. 2022. "Managerial Dilemmas and Entrepreneurial Challenges in the Ambidexterity of SMEs: A Systematic Review for Execution System" Sustainability14, no. 24: 16550. https://doi.org/10.3390/su142416550 Article Metrics MDPI and ACS Style Kim, G.; Lee, W.J.; Shim, H. Managerial Dilemmas and Entrepreneurial Challenges in the Ambidexterity of SMEs: A Systematic Review for Execution System. Sustainability 2022, 14, 16550. https://doi.org/10.3390/su142416550 AMA Style Kim G, Lee WJ, Shim H. Managerial Dilemmas and Entrepreneurial Challenges in the Ambidexterity of SMEs: A Systematic Review for Execution System. Sustainability. 2022; 14(24):16550. https://doi.org/10.3390/su142416550 Chicago/Turabian Style
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Q& M DENTAL: Losses and gains from spin-off of China subsidiary Joomla! - Open Source Content Management Q&M DENTAL: Losses and gains from spin-off of China subsidiary Excerpts from analyst's report Phillip Securities analyst: Soh Lin Sin Loss and Gain of Aidite Spin-off Listing What to lose? (a) Material dilution of the Group’s equity interest in Aidite . To be eligible for listing on the New Third Board, Aidite will need to be converted into a company limited by shares. Post-restructuring exercise, Q&M Dental’s equity interest in Aidite will be diluted from 100% to 51%. Despite the material dilution, it does not have a significant impact on the Group’s current structure, as the Group has always recognised only 51% equity interest in Aidite in its financial results in view of the options granted to the two founders and directors of Aidite. There is a risk where the eventual post spin-off ownership of Aidite could be less than 51%. However, the Group intends to maintain substantial holdings of no less than 30%, such that Aidite will at least still remain as an associated company of the Group. (b) Changes to the Non-Compete and potential loss of the Profit Guarantee. If and only upon successful listing of Aidite on the New Third Board, (i) the Non-Compete undertaking will be restructured directly to Aidite instead of the Group; and (ii) the Profit Guarantee will be discharged. Aidite contributed c.37% of the Group’s profit before tax in FY15, up from that of c.25% in FY14. Notwithstanding its superior growth (profit guarantee is expected to grow at 15% y-y vs Singapore’s 5-10%), if successfully listed in FY16, the remaining Profit Guarantee for the next ten years, which amounts to RMB142.86 mn (equivalent to c.S$29.84 mn @ CNY/SGD 4.787), will be forfeited. Nonetheless, the managements from both Aidite and Q&M are still in the midst of finalizing the terms and conditions. Q&M Dental's COO, Dr Raymond Ang, presenting at a recent Financial PR event for investors. Photo: Ngo Yit Sung What to gain? (a) Unlocks value and a more focused expansion for Aidite as well as Q&M. The potential listing on the New Third Board will offer Aidite new opportunities to accelerate its growth and enhance its core business. The New Third Board mainly serves innovation-oriented, entrepreneurial and growth medium, small and micro enterprises. Given its nature as a national over-the-counter stock exchange, the New Third Board is less accessible as compared to China’s other markets, thus dominated by professional fund managers instead of retail investors. Q&M Dental CEO Dr Ng Chin Siau. Photo: Leong Chan Teik Therefore, it offers new channel for companies to access capital markets and gain greater exposure to the investment community, but less susceptible to erratic trades. On the other hand, Q&M could free up its capital to invest into other areas which could bring higher returns on investments for its shareholders as compared to its manufacturing business. (b) Potential incentives and compelling offers by the local authorities to attract companies to list in the New Third Board. In addition to the lower cost of listing, companies could also enjoy policy incentives and government subsidies. The lack of red tape in the New Third Board could also be a plus for Aidite. There is no requirement for companies to be profitable prior to listing. There are no limits on the amount that shares can move in one day. (c) Potential special dividend from the likely cash accretive restructuring exercise and investment gain (spin-off proceeds less initial acquisition and Aidite’s shares purchase costs). Aidite was acquired in Aug-14 at 9.7x implied PER (RMB39.5 mn cash upfront with further capital injection of RMB35 mn). A value-buy compared to the group’s average historical PER at 42.1x. Taking into consideration of: (i) Higher valuation in China markets Average forward PERs of SGX- and HKex-listed medical equipment & devices manufacturers at 16x and 19x, respectively, compared to that of 62x in China markets. (ii) Pure dental manufacturing peers trading at 15-29x forward PER (iii) Market liquidity risk premium for Aidite to be listed on the New Third Board. It is highly likely that Aidite could fetch a higher valuation in its bourse at home as compared to Q&M’s acquisition PER multiple of 9.7x. Taking guidance from the Aidite’s Profit Guarantee for the year is RMB19.84 mn, and assuming Q&M intends to maintain equity interest in Aidite at 51%, (i) if Aidite is listed at 15x FY16F PER, Q&M would have a net gain of RMB71 mn (or S$15 mn); (ii) if Aidite is listed at 30x FY16F PER, Q&M would have a net gain of RMB217 mn (or S$45 mn); (iii) if Aidite is listed at 60x FY16F PER, Q&M would have a net gain of RMB509 mn (or S$106 mn). On the other hand, Q&M could also issue new shares to Aidite and retain all the proceeds to fund its own expansion. ♦ Target price 70 cents on 38X FY16F earnings Soh Lin Sin, Phillip Securities analyst. Valuation Q&M currently trades at a 43.1x FY15 PER, which is c.56% premium to its Singapore healthcare services peers. As we rollover the balances into a new financial year, we have (i) adjusted the number of clinics to reflect the latest acquisitions, (ii) revised downward our FY16F earnings by 40% to S$15 mn to reflect the challenging business environment in the countries where the Group operates in, and (iii) reset the PER multiple to a 38.2x FY16F PER (a slight premium compare to its Asian peers but 1 std. dev. lower from its 4-year historical PER). In view of the above and with the change of analyst, we downgraded to “Neutral” rating with a lower TP of S$0.70 from S$0.96.
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Agronomy | Free Full-Text | Development of an Occurrence Prediction Model for Cucumber Downy Mildew in Solar Greenhouses Based on Long Short-Term Memory Neural Network The occurrence of cucumber downy mildew in solar greenhouses directly affects the yield and quality of cucumber. Chemical control methods may cause excessive pesticide residues, endanger food quality and safety, pollute the ecological environment, etc. Therefore, it is very important to predict the disease before its occurrence. To provide farmers with better and effective guidance for the prevention and control work, minimize the loss of disease damage, this article took cucumber ‘Lyujingling No. 2′ as the experimental material and acquired greenhouse environmental factors data by wireless sensors, including Temp (Temperature), RH (Relative Humidity), ST (Soil Temperature) and SR (Solar Radiation). LSTM (Long Short-Term Memory) neural network structure was constructed based on Keras deep learning framework to develop a prediction model with time-series environmental factors. Combined with the occurrence of downy mildew from manual investigation and statistics, through debugging the parameters, this article developed an occurrence prediction model for cucumber downy mildew and compared it with KNN (K-Nearest Neighbors Classification) and ANN (Artificial Neural Network). In the prediction model, the forecasted results of the four environmental factors were consistent with the true value distributions, and R2 (R-Squared) were all above 0.95. Among them, the ST variable predicted the best results, e.g., R2 = 0.9982, RMSE (Root Mean Square Error) = 0.08 °C, and MAE (Mean Absolute Error) = 0.05 °C. In the disease occurrence prediction model, the training accuracy was 95.99%, the Loss value was 0.0159, the disease occurrence prediction Accuracy was 90%, Precision was 94%, Recall was 89%, F1-score was 91%, the AUC (Area Under Curve) value was 90.15%, and Kappa coefficient was 0.80. It also had obvious advantages over other different models. In summary, the model had a high classification accuracy and performance, and it can provide a reference for the occurrence prediction of cucumber downy mildew in actual production. by Kaige Liu 1,2 , Chunhao Zhang 1,2 , Xinting Yang 1,2 , Ming Diao 1 , Huiying Liu 1,* and Ming Li 1,2,* 1 Key Laboratory of Special Fruits and Vegetables Cultivation Physiology and Germplasm Resources Utilization of Xinjiang Production and Construction Corps, Department of Horticulture, Agricultural College of Shihezi University, Shihezi 832003, China 2 National Engineering Laboratory for Agri-Product Quality Traceability, Information Technology Research Center, National Engineering Research Center for Information Technology in Agriculture, Meteorological Service Center for Urban Agriculture, Beijing Academy of Agriculture and Forestry Sciences, China Meteorological Administration-Ministry of Agriculture and Rural Affairs, Beijing 100097, China * Authors to whom correspondence should be addressed. Agronomy 2022 , 12 (2), 442; https://doi.org/10.3390/agronomy12020442 Received: 31 December 2021 / Revised: 5 February 2022 / Accepted: 7 February 2022 / Published: 10 February 2022 (This article belongs to the Special Issue Comparison of Sustainable Approaches in Conservation and Protected Agriculture: Asia, Latin America and Europe ) Abstract : The occurrence of cucumber downy mildew in solar greenhouses directly affects the yield and quality of cucumber. Chemical control methods may cause excessive pesticide residues, endanger food quality and safety, pollute the ecological environment, etc. Therefore, it is very important to predict the disease before its occurrence. To provide farmers with better and effective guidance for the prevention and control work, minimize the loss of disease damage, this article took cucumber ‘Lyujingling No. 2′ as the experimental material and acquired greenhouse environmental factors data by wireless sensors, including Temp (Temperature), RH (Relative Humidity), ST (Soil Temperature) and SR (Solar Radiation). LSTM (Long Short-Term Memory) neural network structure was constructed based on Keras deep learning framework to develop a prediction model with time-series environmental factors. Combined with the occurrence of downy mildew from manual investigation and statistics, through debugging the parameters, this article developed an occurrence prediction model for cucumber downy mildew and compared it with KNN (K-Nearest Neighbors Classification) and ANN (Artificial Neural Network). In the prediction model, the forecasted results of the four environmental factors were consistent with the true value distributions, and R 2 (R-Squared) were all above 0.95. Among them, the ST variable predicted the best results, e.g., R 2 RMSE (Root Mean Square Error) = 0.08 °C, and MAE (Mean Absolute Error) = 0.05 °C. In the disease occurrence prediction model, the training accuracy was 95.99%, the Loss value was 0.0159, the disease occurrence prediction Accuracy was 90%, Precision was 94%, Recall was 89%, F 1 - score was 91%, the AUC (Area Under Curve) value was 90.15%, and Kappa coefficient was 0.80. It also had obvious advantages over other different models. In summary, the model had a high classification accuracy and performance, and it can provide a reference for the occurrence prediction of cucumber downy mildew in actual production. Keywords: Pseudoperonospora cubensis ; greenhouse ; fruit cucumber ; forecast model ; deep learning 1. Introduction Cucumber downy mildew is a devastating leaf disease caused by the oomycete Pseudoperonospora cubensis (Berk. & Curt.) Rostov., the pathogenic processes and epidemiology are closely related to environmental conditions [ 1 ]. P. cubensis is spread via wind-borne sporangia, which can be transported long distances and still maintain strong activity. The climate environment in solar greenhouses is conducive to the dispersal of pathogens and sporangia infection, leading to the serious occurrence and rapid spread of cucumber downy mildew [ 2 , 3 ]. If it is not controlled in time, it will cause major production and economic losses [ 4 ]. At present, chemical agents are mainly used in production to prevent and control cucumber downy mildew, which not only contradicts the concept of green development, but also causes excessive pesticide residues, endangers food quality and safety, and pollutes the ecological environment. Therefore, accurate and effective disease prediction is of great significance to the meticulous management, intelligent decision-making of cucumbers, and sustainable development of the agro-ecosystem. In the past, disease prediction usually adopted the method of field investigation, sampling analysis, and relied on experts’ experience to predict. However, this method had disadvantages such as the labor intensity being high, the accuracy being low, and the time-consuming being long, which might delay the best period of prevention and control [ 5 , 6 ]. To solve these problems, scholars respectively proposed the following predicting methods. Pouzeshimiyab et al. [ 7 ] evaluated the sporangia concentration in the air and used climate variable factors as the predictors of the downy mildew linear regression model to reduce the risk of disease infestation in northwestern Iran. In the research of indoor cucumber downy mildew, Neufeld et al. [ 8 ] took the hours of daily temperature and relative humidity ≥80% as the input, developed a cucumber downy mildew infection risk prediction model to predict the risk of squash, and cantaloupe infestation within 24 and 48 h. The authors [ 9 , 10 ] used threshold data such as temperature and humidity, developed an early warning model and early warning system to predict the infection and occurrence of unheated greenhouses cucumber downy mildew in China. The above methods together show that it is feasible and effective to predict cucumber downy mildew through environmental factors. However, they are the main form of logic-based learning, which all belong to inductive logic programming into methods in principle. It is worth mentioning that this method is more complicated, and if used incorrectly, it will reduce the credibility and accuracy of disease prediction. On the other hand, because the changes of environmental factors in greenhouses are affected by many factors, each change is different and has no fixed rate, which is nonlinear [ 11 ]. The increase in data categories and scale will affect the definition of model variables and modeling efficiency. With the development of machine learning, the Internet of Things, big data technology, and high-performance computing provides higher accuracy and application range for the prediction of agricultural diseases [ 12 ]. Jia [ 13 ] determined the input factors of the model by reading and analyzing a large number of documents, and used the support vector machine and decision tree algorithms to develop a greenhouse cucumber downy mildew prediction model. Bhatia et al. [ 14 ] realized the prediction of tomato powdery mildew with the extreme learning machine algorithm based on various meteorological parameters such as solar radiation, wind speed, humidity, temperature, and leaf humidity acquired in real-time by sensors. Xu et al. [ 15 ] established a crop disease prediction framework based on ensemble learning and spatio-temporal recurrent neural network (STRNN). Hsieh et al. [ 16 ] built a rice blast prediction model based on Auto-Sklearn and neural network algorithms combined with the weather data and rice blast disease (RBD) data. The above methods are part of the classic algorithm of machine learning and have a good prediction effect. However, they have poor ability to extract long-term sequence data, that is, they cannot be well correlated with previous data features information during prediction. Due to the lack of memory ability, the robustness of these models will be limited when predicting data based on the learning process. Long Short-Term Memory (LSTM) is a neural network model proposed to solve the long-term dependency problem and is commonly used for the prediction of time-series data [ 17 ]. It optimizes the gradient disappearance and gradient explosion problems in the iterative process of RNN by changing the internal structure and has been widely used in trajectory prediction [ 18 ], air pollution prediction [ 19 ], electricity load forecasting [ 20 ], traffic flows prediction [ 21 ], stock market prediction [ 22 ], and other fields, and has achieved good results. Poornima et al. [ 23 ] developed a drought index prediction model based on LSTM to predict standardized precipitation index, standardized precipitation evapotranspiration index, and severity. Shin et al. [ 24 ] used LSTM to analyze the impact of natural disasters on agricultural products prices, used rice, onions, spring onions, spinach, and zucchini as the target agricultural products, developed a model for predicting agricultural products prices. Cao et al. [ 25 ] used satellite data, climate data, and soil properties to build three statistical-based methods included LASSO, RF, and LSTM for rice yield prediction. Kim et al. [ 26 ] proposed a prediction model of rice blast based on artificial intelligence, and long-term memory networks (LSTMs) were used to predict the incidence of rice blast one year in advance. Xiao et al. [ 27 ] used LSTM to develop a pest occurrence prediction model based on cotton disease, insect pest data, and weather factor change data in India. To our knowledge, the application of LSTM to cucumber disease prediction in solar greenhouses has not been reported yet. This article used IoT sensors to acquire time-series environmental data during the growth of cucumbers in the solar greenhouse. The LSTM neural network structure was constructed based on the Keras deep learning framework. Then, we developed an environmental factors prediction model to assess the predictive ability of the model. Combined with the occurrence of downy mildew from manual investigation and statistics, through debugging the parameters, we developed an occurrence prediction model for cucumber downy mildew. The performance of the model was evaluated. The development of the disease prediction model can provide farmers with better and effective guidance for the prevention and control work, minimize the loss of disease damage, and provide a reference for the prediction research of cucumber downy mildew in solar greenhouses. 2. Materials and Methods 2.1. Cucumber Cultivation Experiment and Data Acquisition The experiment was carried out at the No. 16 greenhouse of Beijing Xiaotangshan National Experiment Station for Precision Agriculture, in Changping District, Beijing, PR China (40.18° N, 116.47° E) from March to July 2021. The greenhouse type was a single-roof solar greenhouse, which faced south from the north and extended from east to west. The specification was 38 × 7 m and covered with polyethylene films, without heating devices. The cucumber variety was ‘Lyujingling No. 2′, purchased from the Vegetable Research Center of Beijing Academy of Agriculture and Forestry Sciences. The cucumber seedlings were transplanted on 4 March 2021, and were disinfected by spraying chlorothalonil before transplanting. The ridge width was 80 cm, the ridge spacing was 80 cm, and the row spacing was 40 × 40 cm. The irrigation method was drip irrigation under the films, and the agricultural operations were carried out following the requirements of pollution-free production. The production process was recorded with field management measures such as ventilation, irrigation, and fertilization. The harvest season was ended on 7 July 2021. The indoor environmental monitoring nodes (EnviroMonitor Node, Davis Instruments, Hayward, CA, USA) were placed at a height of 1.5 m. The wireless temperature and humidity sensors were at a height of 2.5 m, and the soil temperature and water potential sensors were buried in the soil layer of 0.15–0.2 m below the second node in each column ( Figure 1 and Figure 2 a). The weather station Davis Vantage Pro2 (Davis Instruments, Hayward, CA, USA) was located in an open space near the southeast boundary of the greenhouse, and it could automatically communicate with monitoring nodes in the greenhouse under the wireless LAN connection to realize the upload and storage of data ( Figure 1 and Figure 2 b). The data acquisition interval was 15 min, and the data was downloaded from the server once a month. Meanwhile, it could acquire data on various outside environmental factors such as wind speed, rainfall, atmospheric pressure, etc. Taking the occurrence of cucumber downy mildew in the solar greenhouse as the research object, we conducted weekly surveys and observations until the early symptoms of cucumber downy mildew (light yellow water-stained polygonal disease spots on the leaves) appear, determined the center of the disease occurrence, and recorded the time of the first onset. After that, the cycle was changed to a 3~4 d survey interval. According to the Pesticide-Guidelines for the Field Efficacy Trials (I )—Fungicides Against Downy Mildew of Cucumber (GB/T 17980.26-2000) [ 28 ], the diagonal five-point sampling method was adopted for the fixed-point plant investigation. 2.2. Dataset Construction 2.2.1. Model Variables Selection According to the law of cucumber downy mildew occurrence and spread, it can be known that the air temperature and relative humidity are the important factors affecting the occurrence of the disease. In addition, the wet leaves will accelerate the infection of pathogens [ 1 , 2 , 10 , 29 , 30 ] when the relative humidity is too high. The solar radiation [ 2 , 30 ] will affect the activity of sporangia, and cause the soil temperature change. The pathogens that are dormant in the soil begin to disperse, causing the primary infection of the disease. Through reading and comparing a large number of references and combining them with the actual situation, we selected the temperature, relative humidity, soil temperature, solar radiation, and the situation of leaf wetness as the input independent variables of the model. The situation of disease occurrence was used as the output dependent variable of the model. Among them, the situation of leaf wetness was converted from the relative humidity at 2.5 m through the threshold, and 89% was selected as the relative humidity threshold [ 31 ], that is, if the relative humidity was greater than or equal to 89%, the leaves were defined as wet, and less than 89% was defined as the leaves were not wet. Model variables setting, units or descriptions, and symbols definition are shown in Table 1 . 2.2.2. Data Pre-Processing We used PyCharm 2019.3 and Python 3.7.11 to perform mean value calculation, variables name definition, and data format processing on the original environmental data. For missing data caused by equipment aging, damage, etc., linear interpolation was used to process the missing values. The equation used was the following: ( X − X 0 ) . (1) where X 0 , Y 0 , X 1 , Y 1 are known sample data. X is the data between X 0 and X 1 . Y is the missing data corresponding to X to be interpolated. The processing of missing values through linear interpolation was a crucial step in data pre-processing, which not only ensured the completeness of the data, but also reduced the errors that may be caused by missing data. After threshold conversion of the relative humidity, the disease occurrence data was added, and the characteristic variables were divided and the labels were set as shown in Table 1 . As these environmental data had different dimensional units and the same category data difference was small and the distribution was close, the Min-Max normalization method was adopted. The normalization equation is the following: X * = X i − X m i n X m a x − X m i n . (2) where X i is all sample data ( i = 1, 2, 3, …, n). X min is the minimum value among all sample data. X max is the maximum value among all sample data. X * is the normalized results. The data was transformed into supervised data through normalization processing, and the dimension data was transformed into dimensionless data between [0, 1], thereby eliminating the influence between data dimensions and the inter-indices comparability, to reduce the amount of calculation, increase the speed of calculation, and improve the accuracy and performance of the model. Among them, LW was the 0/1 classification feature of whether the leaves were wet or not, and Disease was the 0/1 classification label of whether the Disease occurred or not. The data had been in the range [0, 1], so normalization was not required. After normalization, the model dataset was obtained. A total of 70% of the total data was divided into the model training set (8279 pieces) for the model to learn the information in the data, and the remaining 30% was the model test set (3548 pieces), used to test the effectiveness of the validation model on data learning and made classification predictions. 2.3. Disease Occurrence Prediction Model Development Deep learning is the process of continuously adjusting the network and enabling the model to perform various nonlinear transformations on the input variables to effectively fit the output. The influence of different parameters on the gradient descent speed of the model and the results may also be different, so it is necessary to continuously test the network, and choose the best optimizer and learning rate to optimize and improve the model [ 32 , 33 ]. The Keras deep learning framework is an advanced neural network Application Programming Interface (API) written by Python, which included neural network layers, loss functions, optimizers, activation functions, and other modules for model construction, training, debugging, and evaluation. It was used for the rapid construction of the model framework. KNN [ 34 ] (K-Nearest Neighbors Classification) is a commonly used classification algorithm in data mining, it represents the data to be classified by its nearest K neighbors values, and realizes the division of classification results. ANN [ 35 ] (Artificial Neural Network) is a traditional neural network algorithm, and it is the simplest neural network structure, with only a single hidden layer. This experiment was carried out in a GPU environment. The Keras deep learning framework (TensorFlow as the backend) was used to complete the construction of the model and debug the learning process, and compare it with the KNN classification algorithm and the ANN algorithm. The model training environment and parameters configuration are shown in Table 2 shown. This model consisted of two LSTM layers, a Dropout layer, and a Dense layer. Among them, LSTM defined the three-dimensional shape (None, 1, 5) of the input dataset and conducted preliminary learning on a large amount of input data by increasing the number of neuron nodes (None, 1, 128). None (None, 1, 5) represents the number of every time input data, 1 represents a label category (the situation of disease occurrence), and 5 represents the number of five features (five independent variables we selected). Here, 128 represents the number of defined network units. The dropout layer was a regularization operation on the network, whose contained useless information network units will be randomly hidden or discarded during the training process to prevent the model from overfitting. The LSTM_1 had the same scale as the LSTM layer after regularization. It stored, memorized, and classified information related to the features and labels of the training dataset and saved the remaining network units for data dimensionality reduction (None, 64). The Dense layer was a fully connected layer, which could map the feature classification results (None, 1) of the upper network through nonlinear changes to the output space, and then improve the classification accuracy of the model. The structure diagram of the disease occurrence prediction model is shown in Figure 3 . According to the learning effect of the training set, the above model used the test set features to predict the situation of disease occurrence (Not Occurrence: 0; Occurrence: 1), compared the predicted label with the actual label, and calculated the evaluation indicators of the corresponding prediction model. 2.4. Model Evaluation Indicators The prediction model of time-series environmental factors used RMSE (Root Mean Square Error) and MAE (Mean Absolute Error) as evaluation indicators to describe the error between the true value and the predicted value. The disease occurrence prediction model used Accuracy , Precision , Recall , F 1 - score and ROC (Receiver Operating Characteristic) curve, AUC (Area Under Curve) value, confusion matrix, and k value (Kappa coefficient) as performance evaluation indicators. The calculated equation used were the following: R M S E = ∑ i = 1 n ( O i − Y i ) 2 n , (3) M A E = ∑ i = 1 n O i − Y i n . (4) where O i is the true value. Y i is the predicted value. n is the total number of samples. Accuracy represents the proportion of the samples that are correctly predicted in the total sample. Precision represents the proportion of the samples that are predicted to be correct in the sample. Recall represents the proportion of the samples that predicted the disease in the actual disease sample F 1 - score is a comprehensive evaluation indicator combined with Precision and Recall . The calculated equation used were the following: A c c u r a c y = T P + T N T P + F N + F P + T N , (5) P r e c i s i o n = T P T P + F P , (6) R e c a l l = T P T P + F N , (7) F 1 -score = 2 ∗ P r e c i s i o n ∗ R e c a l l P r e c i s i o n + R e c a l l . (8) ROC curve is a graph obtained by using FPR (False Positive Rate) as the abscissa and TPR (True Positive Rate) as the ordinate to show the classification effect of the model. The AUC value is the area under the ROC curve. The closer its value is to 1, the higher the classification performance of the model. The calculated equation used were the following: F P R = F P T N + F P , (9) T P R = T P T P + F N . (10) The confusion matrix is a visual evaluation indicator that displays the model classification results through a matrix of n rows × n columns. The k value is a consistency check method, and the calculation result is usually between 0 and 1, which is calculated through the numerical calculation of each matrix to measure the classification prediction accuracy. The k value consistency classification criteria are shown in Table 3 . The calculated equation used are the following: k = p 0 − p e 1 − p e , (11) p 0 = T P + T N + F N + F P + T N , (12) p e = ( T N + F P ) ∗ ( ( (13) In the above Equations (5)–(13), TP means True Positive, which refers to samples that are actually positive and predicted to be positive. FP means False Positive, refers to samples that are actually negative and predicted to be positive. TN means True Negative, refers to samples that are actually negative and predicted to be negative. FN means False Negative, refers to samples that are actually positive and predicted to be negative. P 0 means the observation consistency, P e means the chance consistency. 3. Results 3.1. Time-Series Environmental Factors Prediction Results According to the time-series environmental factors data acquired by the sensors, the missing data was processed through linear interpolation, and the four model independent variables were predicted including the temperature (Temp), relative humidity (RH), soil temperature (ST), and solar radiation (SR) in the greenhouse. The results are shown in Figure 4 . The results in Figure 4 and Table 4 shows that the forecasted results of the four environmental factors were consistent with the true value distributions, and R 2 (R-Squared) were all above 0.95. Among them, the ST variable predicted the best results, e.g., R 2 = 0.9982, RMSE MAE = 0.05 °C, and within acceptable error range. The results and error level reflected that the model was reliable in predicting time-series environmental factors in the solar greenhouse, and verifying that the model had high accuracy. The disease occurrence prediction model could be further developed through model debugging. 3.2. Model Debugging Results After threshold conversion of relative humidity, disease occurrence data was added and normalized the data. In order to make the model have the best performance, we selected four good performance and commonly used optimizers for debugging the parameters, when the learning rate was the default value of 0.001, selected the optimizer with the best results. Then for this best performing optimizer, we set different learning rates for it to compare which is optimal, as shown in Table 5 . It could be seen that the training set and test set accuracy of the Adam optimizer with a learning rate of 0.001 were the highest among the four optimizers, with a training set accuracy of 95.99% and a test set accuracy of 89.91%. According to the debugging results, this model chose Adam (LR = 0.001) as the optimizer. During the training process, the training set accuracy and loss value rise and fall with epochs are shown in Figure 5 . Since the two represent the quality of the data learning and the error in the model convergence process, the results showed that the training set accuracy and Loss value change were stable and had good results. The Loss value was 0.0159, which indicated that the model had high robustness. 3.3. Disease Occurrence Prediction Results for Different Models By drawing the ROC curve and confusion matrix, calculating the AUC value and Kappa coefficient, the classification situation and prediction results were evaluated, as shown in Figure 6 . From the figure, AUC = 0.9015, indicated that the model classification effect was better; according to the confusion matrix, the ordinate and abscissa were actual disease not occurrence (0) and disease occurrence (1) and predicted disease not occurrence (0) and disease occurrence (1), respectively. The total number in the four matrices was the number of test set 3548 pieces (where TN = 1320, TP = 1872, FN = 228, FP = 128). According to Equations (11)–(13), the k value was 0.80. The result obtained from the k value consistency classification criteria in Table 3 was that the prediction accuracy had substantial consistency, which showed that the accuracy of the prediction of the model was at a high level. As shown in Table 6 , by comparing the evaluation indicators of the LSTM model selected in this article with the KNN classification algorithm and the ANN algorithm model evaluation indicators established based on Keras, the LSTM model predicted the disease occurrence Accuracy , Precision , Recall , and F 1 - score of 90, 94, 89, and 91%, respectively. It could be seen that these indicators were significantly higher than the indicators of the KNN model and the ANN model, indicating that the LSTM method had obvious advantages over the KNN and ANN methods. The model predicted the occurrence of disease in the verification data better and had a high classification accuracy, indicating that the model had high performance. 4. Discussion This article developed a cucumber downy mildew prediction model based on the data of environmental factors in the solar greenhouse. However, this was obtained under two assumptions. The first assumption was that there had been pathogens in the greenhouse. Infection of pathogens is the root cause of cucumber downy mildew. They may be via wind-borne sporangia from outside into the greenhouse [ 1 , 2 ] or maybe always left in the greenhouse on plant residues or soil. As the model was the two-class prediction of whether the disease occurred, this article did not trace the pathogens’ source and did not study the different pathogenic mechanisms presented by different sporangia concentrations. Obviously, in the process of disease investigation, the occurrence of cucumber downy mildew confirmed this assumption. In addition, the cucumber variety we selected was susceptible to disease in previous years, and thus meets the condition that the hosts can be infected. That is, the existence of pathogens, the climate environment suitable [ 9 , 10 , 29 ] for the dispersal of pathogens [ 1 , 2 , 30 ] in the greenhouse, and the sensitive host plant tissues together led to the disease epidemic. The second assumption was to ignore the impact on cucumber growth caused by manual management. Because if human factors cause drastic changes in the greenhouse climate environment, data acquisition, and environmental factors prediction results will be unavailable and will affect disease progression [ 36 ] and disease prediction accuracy. Of course, we will ensure that the opening and closing time of greenhouse vents and field management operations are consistent and orderly every day, except for sudden changes in external weather that require separate management measures. This article started from the time of onset of the disease symptoms, divided the growing season into pre-onset and post-onset, constructed an LSTM neural network structure based on the Keras deep learning framework, and developed a prediction model for the temperature, relative humidity, soil temperature, and solar radiation in the solar greenhouse. Based on the evaluation results of the environmental factors prediction model ( Figure 4 ), we can see that LSTM has achieved good results in the processing of time-series data, this is similar to Liu’s [ 11 ] research. Therefore, through parameter adjustment, model debugging, and adding the situation of leaf wetness and the situation of disease occurrence data, it can be used to develop the disease occurrence prediction model. Compared with the existing prediction models [ 7 , 8 , 9 , 10 , 13 ] for cucumber downy mildew, this model is more advantageous in analyzing time-series data closely related to the occurrence of the disease, with higher accuracy and wider applicability. The LSTM was the first time to be applied in the prediction of cucumber downy mildew in solar greenhouses, and it has some shortcomings in this study. Since each piece of data in this experiment represents the data acquired by sensors every 15 min, the error in the prediction ( Figure 6 ) may be because since the features between the data within 15 min were too detailed or small, and the model was not easy learning and distinguishing results in the inability, resulting in classification errors. However, it was precisely because of the small data acquisition interval that the total number of classification errors was also accumulated in units of 15 min, which greatly improved the precise range of disease occurrence time and facilitates farmers to take management and prevention measures in advance [ 1 , 3 , 29 , 31 , 36 ]. At the same time, model classification performance can be improved through model regularization, parameter optimization, and learning rate adjustment [ 32 , 33 ]. This is also the reason for the adjustment of the parameters and the concrete manifestation of the result obtained after the adjustment. In future work, the pathogenic sporangia growth curve, incidence rate, disease index, and other data can be used as the basis and distinguishing standard of disease occurrence level [ 2 ] to explore their changes and connections. At the same time, combined with the prediction model of environmental factors in the greenhouse [ 11 ], realize the short-term environmental factors in the future using the data acquired from these predictions. Then, develop a disease prediction system, through the data of future short-term environmental factors, the disease occurrence prediction model is used to predict the future occurrence of disease, and the two-classification problem of predicting the occurrence of the disease is extended to a multi-classification problem of predicting the severity of disease occurrence, to better help farmers to take prevention or control measures in advance. We can also place the disease occurrence prediction model on the platform [ 37 ], which can automatically call and analyze data to realize the visual path of the dynamic spread [ 38 ] of the disease for users’ reference. At the same time, we will increase the verification experiments in different greenhouses, different seasons and different varieties to expand the scope of application of the model and improve the research on the prediction of cucumber diseases in solar greenhouses. Author Contributions Conceptualization, H.L. and M.L.; Methodology, K.L., H.L. and M.L.; Software, K.L.; Validation, K.L.; Formal analysis, K.L.; Investigation, K.L. and C.Z.; Resources, H.L. and M.L.; Data curation, K.L. and C.Z.; Writing—original draft preparation, K.L.; Writing—review and editing, K.L.; Visualization, K.L.; Manuscript revising, H.L. and M.L.; Study design, X.Y., M.D. and M.L.; Supervision, X.Y., M.D., H.L. and M.L.; Project administration, X.Y., M.D., H.L. and M.L.; Funding acquisition, M.L. All authors have read and agreed to the published version of the manuscript. Funding This work was funded by the Science and Technology Innovation Capacity Building Project of Beijing Academy of Agriculture and Forestry Sciences (No. KJCX20211002); Youth Program of National Natural Science Foundation of China (31401683); National Key R&D Program of China (SQ2020YFF0418305), and the FP7 Framework Program (PIRSES-GA-2013-612659). 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The schematic diagram of the experiment sensors equipment installation. represents the 1.5 m high environmental monitoring nodes, ⃞ represents the 2.5 m high wireless temperature and humidity sensors, ⃤ represents the soil temperature and water potential sensors in the soil layer of 0.15–0.2 m, represents the weather station; N means north. Figure 1. The schematic diagram of the experiment sensors equipment installation. ⃝ represents the 1.5 m high environmental monitoring nodes, ⃞ represents the 2.5 m high wireless temperature and humidity sensors, ⃤ represents the soil temperature and water potential sensors in the soil layer of 0.15–0.2 m, ♢ represents the weather station; N means north. Figure 2. Photos of equipment installation. ( a ) Photo of the indoor sensors. ( b ) Photo of the weather station. Figure 2. Photos of equipment installation. ( a ) Photo of the indoor sensors. ( b ) Photo of the weather station. Figure 3. The structure diagram of disease occurrence prediction model. Figure 3. The structure diagram of disease occurrence prediction model. Figure 4. The solar greenhouse internal environmental factors prediction results. ( a ) Temp, ( b ) RH, ( c ) ST, ( d ) SR. Figure 4. The solar greenhouse internal environmental factors prediction results. ( a ) Temp, ( b ) RH, ( c ) ST, ( d ) SR. Figure 5. Variation diagram of the training set accuracy and Loss value. Figure 5. Variation diagram of the training set accuracy and Loss value. Figure 6. Disease occurrence prediction model classification indicators. ( a ) ROC curve. ( b ) confusion matrix. Figure 6. Disease occurrence prediction model classification indicators. ( a ) ROC curve. ( b ) confusion matrix. Table 1. Model variables setting, units or descriptions, and symbols definition. Table 1. Model variables setting, units or descriptions, and symbols definition. Variables Units or Descriptions Symbols Temperature °C 1 Temp Relative Humidity % 1 RH Soil Temperature °C 2 ST Solar Radiation W/m 2 1 SR The Situation of Leaf Wetness Not Wet: 0(RH’ < 89%); Wet: 1(RH’ ≥ 89%) 3 LW The Situation of Disease Occurrence Not Occurrence: 0; Occurrence: 1 Disease 1 The average value of environmental monitoring nodes at 1.5 m each 15 min. 2 The average value of soil temperature sensors each 15 min. 3 The average value of the temperature and humidity sensors at 2.5 m (RH’) each 15 min. Table 2. The model training environment and parameters configuration. Table 2. The model training environment and parameters configuration. Table 3. The k value consistency classification criteria. Table 3. The k value consistency classification criteria. k Value Consistency Criteria 0~0.20 slight 0.21~0.40 fair 0.41~0.60 moderate 0.61~0.80 substantial 0.81~1 almost perfect Table 4. Error evaluation indicators of environmental factors prediction results. Table 4. Error evaluation indicators of environmental factors prediction results. Variables R 2 RMSE MAE Temp 0.9929 0.48 °C 0.33 °C RH 0.9875 2.16% 1.39% ST 0.9982 0.08 °C 0.05 °C SR 0.9581 36.19 W/m 2 18.21 W/m 2 Table 5. Different optimizers and learning rates debugging results. Table 5. Different optimizers and learning rates debugging results. Optimizers Learning Rates Training Set Accuracy (%) Test Set Accuracy (%) Nadam 0.001 95.69 89.37 Adamax 0.001 93.36 89.40 RMSprop 0.001 95.07 89.12 Adam 0.001 95.99 89.91 Adam 0.0001 89.35 85.65 Adam 0.01 90.55 85.29 Table 6. Comparison of LSTM, KNN, and ANN model evaluation indicators. Table 6. Comparison of LSTM, KNN, and ANN model evaluation indicators. Classes Classification Results Accuracy (%) Precision (%) Recall (%) F 1 - Score (%) LSTM KNN ANN LSTM KNN ANN LSTM KNN ANN LSTM KNN ANN 0 90 87 74 85 83 65 91 85 76 88 84 70 1 94 90 82 89 88 73 91 89 77
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Symmetry | Free Full-Text | Study of Decision Framework of Shopping Mall Photovoltaic Plan Selection Based on DEMATEL and ELECTRE III with Symmetry under Neutrosophic Set Environment Rooftop distributed photovoltaic projects have been quickly proposed in China because of policy promotion. Before, the rooftops of the shopping mall had not been occupied, and it was urged to have a decision-making framework to select suitable shopping mall photovoltaic plans. However, a traditional multi-criteria decision-making (MCDM) method failed to solve this issue at the same time, due to the following three defects: the interactions problems between the criteria, the loss of evaluation information in the conversion process, and the compensation problems between diverse criteria. In this paper, an integrated MCDM framework was proposed to address these problems. First of all, the compositive evaluation index was constructed, and the application of decision-making trial and evaluation laboratory (DEMATEL) method helped analyze the internal influence and connection behind each criterion. Then, the interval-valued neutrosophic set was utilized to express the imperfect knowledge of experts group and avoid the information loss. Next, an extended elimination et choice translation reality (ELECTRE) III method was applied, and it succeed in avoiding the compensation problem and obtaining the scientific result. The integrated method used maintained symmetry in the solar photovoltaic (PV) investment. Last but not least, a comparative analysis using Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) method and VIKOR method was carried out, and alternative plan X1 ranks first at the same. The outcome certified the correctness and rationality of the results obtained in this study. Background: Study of Decision Framework of Shopping Mall Photovoltaic Plan Selection Based on DEMATEL and ELECTRE III with Symmetry under Neutrosophic Set Environment by Jiangbo Feng 1,* , Min Li 2 and Yansong Li 1 1 School of Electrical and Electronic Engineering, North China Electric Power University, Beijing 102206, China 2 Sinopec Nanjing Eegineering and Construction Inc., Nanjing 210000, China * Author to whom correspondence should be addressed. Symmetry 2018 , 10 (5), 150; https://doi.org/10.3390/sym10050150 Received: 23 April 2018 / Revised: 2 May 2018 / Accepted: 3 May 2018 / Published: 9 May 2018 (This article belongs to the Special Issue Algebraic Structures of Neutrosophic Triplets, Neutrosophic Duplets, or Neutrosophic Multisets ) Abstract 1. Introduction The frequent occurrence of fog or haze and other negative types of climate change in recent decades is the grave reality that the whole world is experiencing. The pivotal reason behind these environmental problems is atmospheric pollutants and greenhouse gas emissions, mainly produced by fossil fuel consumption. Fossil fuel supplies approximately 80% of the world’s energy, and it is drying up with the rapid increase of the world energy demand [ 1 ]. To face this situation, many countries have endorsed policies to submit fossil fuel utilization with renewable energy generation. Among diverse types of alternative energy, solar photovoltaic (PV hereinafter) energy is recognized as promising, since sunlight is unlimited and widespread and the converting efficiencies of photovoltaic are getting higher and higher while the manufacturing costs are becoming lower and lower [ 2 ]. The past five years has witnessed the astonishing increase in installed cumulative globe solar PV capacity, which nearly quintupled from 70 GW in 2011, to 275 GW in 2016. China is following the worldwide trend with solar PV rapid development and gained the number one cumulative PV capacity of 65.57 GW in 2016. It is worth noting that the large-scale ground PV power station, newly installed, had 28.45 GW capacity this year, and grew by 75% compared to the last year, accounting for 89% of all new PV power plants in 2016, while the distributed PV, newly installed, with 3.66 GW capacity this year, increased by 45% in comparison to last year, and accounted for 11% of capacity of new installations in 2016. The scale of distributed PV development is significantly lower than that of the large-scale ground PV. Under these circumstances, the China authorities have launched the feed in tariff adjustment. The feed in tariff of ground solar PV generation will decrease to some extent, but in contrast to that of distributed PV, will not decrease at all. As shown in Figure 1 , according to the 13th five-year (2016–2020) solar energy planning objectives of China, the goal is to build a total installed capacity of 150 GW solar PV, in which more than 40% of the new installed capacity will be from distributed PV, and to build 100 distributed PV demonstration areas. In fact, China is a country with high potential of solar radiation, and of generous policy subsidies to promote achieving the ambitious plan. Obviously, in China, distributed solar PV generation is government encouraged, well-resourced, environmentally friendly, and closely following the world trend. It is worth considering investment in such a promising project. Figure 1. Chinese photovoltaic power structure, 2012–2016. Numerous vacant roofs of building or structures in the cities provide the best-fitting location for distributed solar PV, and farsighted investors have been preempting outstanding roof resources. There are various types of buildings, such as government building, hospitals, schools, coliseums, or residential and industrial buildings. Among all these types, the shopping centers possesses plenty of advantages, superior to the other types of buildings, and are one of the most promising places worth preempting for PV installation. First of all, previous construction characters of shopping centers facilitate the rooftop PV installation. According to literature [ 3 ], the availability rate of roof space is between 60% and 65% in shopping malls, but just 22% and 50% in residential buildings. That is to say, double or triple PV capacity can be installed in the former roofs, compared to the latter one. Secondly, the shopping malls need a large amount of electricity consumption daily, the most generation can feed the themselves-consumption. Besides, it is usually cited in downtown areas and populated areas. On the one hand, there have a so complete transmission and distribution network that the surplus generation can efficiently feed local electricity consumption. On the other hand, brand advertisement and promotion of the PV manufacturer and the rising level of awareness of the citizen towards sustainable efforts can be greatly obtained for the large visitors there. Last but not least, facing the non-manageable feature through electricity generation in PV facilities, technical management measures need to be taken for protecting distribution system [ 4 ]. Fortunately, the shopping malls equipped professional staff and equipment for energy supply, security, air conditioning, and so on. So, the previous staff in shopping malls can condemn the whole new challenge to reduce the extra expenditure in PV management. It is desirable to adopt a proper methodology for evaluating the shopping mall PV plan in order to demonstrate the optimal possible selections for an investment. Since the following three problems existed in this issue, which are the interaction problems between the criteria, the loss of evaluation information in the conversion process, and the compensation problems between diverse criteria. There is no doubt that traditional multi-criteria decision-making (MCDM) method failed to solve the three problems at the same time. Nevertheless, the decision-making trial and evaluation laboratory (DEMATEL) method can help analyze the internal influence and connection behind each criterion, and the interval-valued neutrosophic set is accomplished in expressing the imperfect knowledge of experts group. Besides, an extended ELECTRE III method as an outstanding outranking method can succeed in avoiding the compensation problem, and the integrated method used maintained symmetry in the solar PV investment. Therefore, in this context, the integrated DEMATEL method and extended ELECTRE III method under interval-valued neutrosophic set environment for searching the optimal shopping mall solar PV plan has been devised. 2. Literature Review MCDM (multi-criteria decision-making) has been successfully applied in energy planning problems. For example, a review of MCDM methods towards renewable energy development identified MCDM methods as one of the most suitable tools to finding optimal results concerned with energy planning progress in complex scenarios, including various indicators, and conflicting objectives and criteria [ 5 ]. For example, Fausto Cavallaro et al. use an intuitionistic fuzzy multi-criteria approach combined with fuzzy entropy to rank different solar-hybrid power plants successfully [ 6 ]. In a real case, it is different for decision makers to express preferences when facing inaccurate, uncertain, or incomplete information. Although the fuzz set, intuitionistic fuzzy sets, interval-valued intuitionistic fuzzy sets, and hesitant fuzzy sets can address the situation. However, when being asked the evaluation on a certain statement, the experts can use the interval-valued neutrosophic set (IVNNS) expressing the probability that the statement is true, false, and the degree of uncertainty can be accurately described, respectively [ 7 ]. The IVNNS, combined with outrank methods, has addressed many MCDM problems successfully [ 8 ]. For example, the IVNNS combined with VIKOR was applied to solve selection of location for a logistic terminal problem [ 9 ]. Hong-yu Zhang et al. developed two interval neutrosophic number aggregation operators and applied them to explore multi-criteria decision-making problems [ 10 ]. The independence of criteria remains in most of the MCDM methodologies. In recent years, lots of methods appeared to solve the problem, and the DEMATEL method is popularly used. According to the statistic censused in article [ 11 ], of the use of MCDM methods in hybrid MCDM methods, the top five methods are Analytical Network Process (ANP), DEMANTEL, Analytic Hierarchy Process(AHP), TOPSIS, and VIKOR. The DEMATEL methodology has been acknowledged as a proper tool for drawing the relationships concerning interdependencies and the intensity of interdependence between complex criteria in an evaluation index system [ 12 , 13 ]. As a powerful tool to describe the effect relationship, it help evaluate the enablers in solar power developments [ 11 ] and evaluate factors which influencing industries’ electric consumption [ 14 ]. The application of DEMATEL contributed to determining the weight coefficient of the evaluation criteria, and successfully helped identify the suitable locations for installation of wind farms. It is the DEMATEL method that helped the investors improve their decisions when there are many interrelated criteria. Thus, the connection relationship of the climate and economy criteria that exists in this study is of great need of the application of DEMATEL method. The commonly used outrank models are TOPSIS, AHP, ANP, preference ranking organization method for enrichment evaluations(PROMETHE), and ELECTRE, of which ELECTRE methods are preferred by decision makers in energy planning progress. Among the ELECTRE methods, ELECTRE III method conveys much more information than the ELECTRE I and ELECTRE II methods [ 15 ]. In the literature [ 16 ], economics of investment in the field of PV, an inclusive decision-making structure using ELECTRE III that would help photo voltaic (PV) system owners, bureaucrats, and the business communities to decide on PV technologies, financial support systems and business strategies were featured. ELECTRE III was used to structure a multi-criteria framework to evaluate the impact of different financial support policies on their attractiveness for domestic PV system deployment on a multinational level [ 17 ]. Due to the compensation problem in information processing, incomplete utilization of decision information, and information loss, ELECTRE III was chosen to build a framework for offshore wind farm site selection decision in the intuitionistic fuzzy environment. These literature studies improve the application of ELECTRE III method in the energy planning process, and terrify the effectiveness of evaluation in decision making progress [ 18 ]. In conclusion, based on the mentioned evolvement, the shopping mall PV plan evaluation result will be more scientific and reasonable than before. 3. Decision Framework of SMPV Plan Selection The evaluation criteria are basic to the entire evaluation, so that they are of great importance to the shopping mall photovoltaic plan selection. In view of the special characteristics of photovoltaic plan and the shopping malls, six factors were taken into consideration, namely architectural elements, climate, photovoltaic array, economy, risk, contribution. Table 1 shows six criteria and twenty-one subcriteria. Table 1. Analysis of evaluation attributes of shopping centers photovoltaic plan selection. 3.1. Architectural Elements Not all the shopping malls are suitable to allocate the photovoltaics, and architectural elements are the primary intrinsic limitations. Steep roof pitch and wrong orientation will increase the difficulty of allocation and maintenance. In addition, building obstructions, and vegetation shading part of the space are not able to allow for the allocation of PV equipment, which can be measured by the covering ratio estimated by Equation (2). Last but not least, the photovoltaic roof space needed to be calculated by the Equation (1). Colmenar-Santos, Antonio et al. [ 15 ] assessed the photovoltaic potential in shopping malls by calculating the photovoltaic roof space. We decided to refer to this research method. R S P V = R S × α (1) R S P V is PV roof space, R S stand for roof space, α is availability ratio C R = L / ( a + b ) = tan φ tan ( α s ) α sin φ tan ( α s ) α + sin φ tan φ sin ( γ s ) a (2) C R is covering ratio. ( α s ) α solar altitude angle ( γ s ) a φ solar azimuth angle. The value is at nine o’clock on the winter solstice in each location. 3.2. Climate Not all the locations of the shopping malls have the optimal climate for solar power generation. It is undoubted that the solar resource depends on local climate. Thus, the annual average solar radiation, land surface temperature, and annual sunshine utilization hours, are the four typical criteria to judge whether the local solar energy resource is in abundance. 3.3. Photovoltaic Array It is well known that the performance of photovoltaic arrays will impact the electricity generation reliability and stability. The dust in the photovoltaic cell panel will reduce the solar energy conversion efficiency, meanwhile, since the photovoltaic cell panel damage and faults are directly related to the electricity supply reliability, the repair and clean rate should be pondered. In addition, it is worth concerning whether the specified type of the photovoltaic panel is absolutely suitable to the local solar regime. The total PV area affects the electricity generated which is calculated by Equation (3). PV generation (yearly electricity generation) is estimated by Equation (4). A panel = R S P V × C R (3) E = H × A panel × ε × κ (4) H is the total yearly solar irradiation. A panel is the total area of PV panel. ε is the efficiency of the panel. κ is the comprehensive facility performance efficiency, which is 0.8 [ 19 ], and 0.28 is the empirical conversion coefficient of the PV module area to the horizontal area. 3.4. Economy It is beyond doubt that the economy of the shopping mall photovoltaic plans ought to be taken into account by the decision makers. There are plenty of studies to assess the financial aspects of the photovoltaic projects. Indrajit Das et al. [ 23 ] presented an investor-oriented planning model for optimum selection of solar PV investment decisions. Rodrigues Sandy et al. [ 24 ] conducted economic analysis of photovoltaic systems under China’s new regulation. The economic assessment methods there are so suitable and scientific that they are worth referring to in this paper. The significant economic attributes we considered are pay pack period, total investment, total profit, and annual rate of return, which are calculated by Equations (5)–(7). I = C × A panel × p panel a panel (5) I is the total investment, C is the average cost of building per W roof PV projects. p panel is the max power pin (W) under STC situation of the solar panel, a panel is the area of per photovoltaic panels. B = P E × t L C + P S × t S − I × t L C − O × t L C (6) B is the total profit, P E is the electricity price buying from the power supply company, P S is the electricity price subsidy, t L C is the time of PV projects life cycle, t S is the time subsidy lasting, O is the cost for operation and maintenance. R O I = B I × t L C (7) R O I is the annual rate of return. T P B = I P E + P S − I − O (8) T P B is the pay pack year. 3.5. Contribution Although the environmental and social contributions the SMPV projects made may not be calculated explicitly as economic profit, there is no denying that these benefits result in increase in local economy and employment, and environment protection and publicity effects are worth the focus of attention. Particularly, the shopping mall holds a great number of visitors. On the one hand, it obtains, easily, the brand advertisement and promotion when PV equipment of a particular company occupies the rooftop of a large commercial building. On the other hand, it is effective to raise the level of awareness of the citizen towards renewable energy and sustainable efforts. 3.6. Risk Expect that for the above attributes, the risk faced cannot be neglected. First of all, the government subsides policy is likely to change, and the impartiality, sufficiency, stability, and constancy of the subsidy is unable to be ensured. Secondly, the generating capacity is influenced by the climate heavily, so the profits will reduce when facing consecutive rainy days. Thirdly, the rooftop usage needs the allowance from all the owners, however, the rooftop ownership and occupancy disputes are a very common risk. Last but not least, the connected photovoltaic grid is unable to bring any benefits to the grid enterprise because of the intermittent power output. Thus, how long the support to photovoltaic grid connected from the grid enterprise can exist is uncertain. All in all, the SCPV plan alternatives ought to be appraised from architectural elements, climate, photovoltaic array performance, economy, risk, contribution attributes. The unique custom-made framework of criteria and subcriteria is set up in view of the actual SMPV plans and national conditions. 4. Research Methodology A decision framework of SMPV selection has been proposed in this section, and there are four phases in this framework, as shown in Figure 2 . The research framework is described in the following subsections. Figure 2. The flowchart of the research methodology. DEMATEL: decision-making trial and evaluation laboratory. 4.1. Preliminary Knowledge in the Neutrosophic Set Environment Due to the existence of many uncertainties in real decision-making problems, such as indeterminate and inconsistent, the neutrosophic set (NS) is used in the MCDM method, and definition of NS is introduced in this section. Definition 1 [ 25 ] . Let X be a space of objects with a generic element in X denoted by x . A NS A in X is defined using three functions: truth-membership function T A ( x ) , indeterminacy-membership function I A ( x ) and falsity-membership function F A ( x ) . These functions are real standard or nonstandard subsets of ] 0 − , 1 + [ , that is, T A ( x ) : X → ] 0 − , 1 + [ , I A ( x ) : X → ] 0 − , 1 + [ and F A ( x ) : X → ] 0 − , 1 + [ . And that the sum of T A ( x ) , I A ( x ) and F A ( x ) satisfies the condition 0 − ≤ sup T A ( x ) + sup I A ( x ) + sup F A ( x ) ≤ 3 + . Since the non-standard unit interval ] 0 − , 1 + [ is hard to apply in practice, and the degree of truth, falsity, and indeterminacy about a certain statement could not be described precisely in the practical evaluation, the interval-valued neutrosophic set (IVNNS) of standard intervals has been proposed by Wang [ 26 ], and a few definitions and operations of IVNNS are introduced in the GPP technology selection MCDM problem. Definition 2 [ 26 ] . Let X be a space of objects with a generic element in X denoted by x . An IVNNS A can be defined as A = { 〈 x , T A ( x ) , I A ( x ) , F A ( x ) 〉 : x ∈ X } (9) where T A ( x ) : X → [ 0 , 1 ] , I A ( x ) : X → [ 0 , 1 ] , F A ( x ) : X → [ 0 , 1 ] . For each element x in X , these functions can be expressed as T A ( x ) = [ inf T A ( x ) , sup T A ( x ) ] ⊆ [ 0 , 1 ] , I A ( x ) = [ inf I A ( x ) , sup I A ( x ) ] ⊆ [ 0 , 1 ] , F A ( x ) = [ inf F A ( x ) , sup F A ( x ) ] ⊆ [ 0 , 1 ] and 0 ≤ sup T A ( x ) + sup I A ( x ) + sup F A ( x ) ≤ 3 , x ∈ X . For convenience, the interval-valued neutrosophic number (IVNN) can be expressed as a ˜ = 〈 [ T a ˜ L , T a ˜ U ] , [ I a ˜ L , I a ˜ U ] , [ F a ˜ L , F a ˜ U ] 〉 , and L , U represent the inferiors and superiors of IVNN respectively. Definition 3 [ 10 ] . Let a ˜ = 〈 [ T a ˜ L , T a ˜ U ] , [ I a ˜ L , I a ˜ U ] , [ F a ˜ L , F a ˜ U ] 〉 and b ˜ = 〈 [ T b ˜ L , T b ˜ U ] , [ I b ˜ L , I b ˜ U ] , [ F b ˜ L , F b ˜ U ] 〉 be two IVNNs, and λ is a real number for not less than 0. Which operational rules can be expressed as follows a ˜ ⊕ b ˜ = 〈 [ T a ˜ L + T b ˜ L − T a ˜ L · T b ˜ L , T a ˜ U + T b ˜ U − T a ˜ U · T b ˜ U ] , [ I a ˜ L · I b ˜ L , I a ˜ U · I b ˜ U ] , [ F a ˜ L · F b ˜ L , F a ˜ U · F b ˜ U ] 〉 (10) a ˜ ⊗ b ˜ = 〈 [ T a ˜ L · T b ˜ L , T a ˜ U · T b ˜ U ] , [ I a ˜ L + I b ˜ L − I a ˜ L · I b ˜ L , I a ˜ U + I b ˜ U − I a ˜ U · I b ˜ U ] , [ F a ˜ L + F b ˜ L − F a ˜ L · F b ˜ L , F a ˜ U + F b ˜ U − F a ˜ U · F b ˜ U ] 〉 (11) λ a ˜ = 〈 [ 1 − ( 1 − T a ˜ L ) λ , 1 − ( 1 − T a ˜ U ) λ ] , [ ( I a ˜ L ) λ , ( I a ˜ U ) λ ] , [ ( F a ˜ L ) λ , ( F a ˜ U ) λ ] 〉 (12) a ˜ λ = 〈 [ ( T a ˜ L ) λ , ( T a ˜ U ) λ ] , [ 1 − ( 1 − I a ˜ L ) λ , 1 − ( 1 − I a ˜ U ) λ ] , [ 1 − ( 1 − F a ˜ L ) λ , 1 − ( 1 − F a ˜ U ) λ ] 〉 (13) The original data of selection of SPPV are collected and processed in this phase. The alternative plans of the GPP project are evaluated by the experts, firstly according to the local technical condition data and practical experience. Then, the decision matrices are expressed in the form of IVNNs, which can handle incomplete and indeterminate information. Finally, a comprehensive decision matrix is formed based on interval-valued neutrosophic number weighted geometric operator (IVNNWG) operator. Let A i denote the technology alternatives ( i = 1 , 2 , ⋯ m ), and C j denote the criteria ( j = 1 , 2 , ⋯ n ). It is assumed that a ˜ i j k can be used to represent the evaluation value of attribute of alternative from every expert E k ( k = 1 , 2 , ⋯ h ) . Definition 4 [ 27 ] . Let A ˜ i j k = ( a ˜ i j k ) m × n be the IVNN-decision matrix of the k -th DM, k = 1 , 2 , ⋯ h , and a ˜ i j k = 〈 [ T a ˜ i j k L , T a ˜ i j k U ] , [ I a ˜ i j k L , I a ˜ i j k U ] , [ F a ˜ i j k L , F a ˜ i j k U ] 〉 . An IVNNWG operator is a mapping: I V N N n → I V N N , such that I V N N W G ω ( a ˜ i j 1 , a ˜ i j 2 , ⋯ , a ˜ i j h ) = ∏ k = 1 k = h ( a ˜ i j k ) ω k = 〈 [ ∏ k = 1 k = h ( T a ˜ i j k L ) ω k , ∏ k = 1 k = h ( T a ˜ i j k U ) ω k ] , [ 1 − ∏ k = 1 k = h ( 1 − I a ˜ i j k L ) ω k , 1 − ∏ k = 1 k = h ( 1 − I a ˜ i j k U ) ω k ] , [ 1 − ∏ k = 1 k = h ( 1 − F a ˜ i j k L ) ω k , 1 − ∏ k = 1 k = h ( 1 − F a ˜ i j k U ) ω k ] 〉 (14) where ω = ( ω 1 , ω 2 , ⋯ , ω h ) T represents the weight vector of DMs, satisfying Σ k = 1 h ω k = 1 , ω k ∈ [ 0 , 1 ] . 4.2. Phase I Identification of Alternative SMPV Plans At this stage, a group of experts consisting of several doctorate engineers will be constituted by the investor. All the experts possess abundant working experience in solar energy investment field, and are specialized in solar photovoltaic and power grid technologies. More than twenty famous influential large-scale shopping malls located in those cities with both abundant sunshine and general policy subsidies need to be collected, and based on that information, less than ten alternative plans roughly screened out, based on the plentitude of documents and investigation. After that, the investigation will be carried out by the experts group, and involve meeting the Development and Reform Commission, the Meteorological Bureau, and the local power supply companies, in order to gather information about solar resources, city planning and construction, local solar subsidy policies, distributed solar power planning, economic assessment, and approved shopping mall rooftops for construction. Lastly, there will be less than five of the most potential alternative places presented for the next evaluation. 4.3. Phase II Determination of the Weights of Criteria Based on DEMATEL Method The importance of the criteria on GPP technology selection is different, so the DEMATEL method is used to decide the weight of criteria in this phase. The direct and indirect causal relations among criteria are considered in the DEMATEL method, and the subjective judgment of DMs is also considered. The steps of determining the weights based on the DEMATEL method are shown as follows [ 28 ]: Step 1. Determine the influence factors in the system The influence factors of GPP technology selection system are determined based on expert opinions and literature reviews, which is called the criteria, as shown in Table 1 . Step 2. Construct the direct-relation matrix among the criteria The direct-relation matrix X = ( x p q ) n × n is constructed in stages, where x p q is used to represent the degree of direct influence of p th criterion on q th criterion which is evaluated by the experts, and n is the number of criteria. Step 3. Normalize the direct-relation matrix The direct-relation matrix X = ( x p q ) n × n is normalized into Y = ( y p q ) n × n . A normalization factor [ 29 ] s is applied in the normalized calculation, and the normalized direct-relation matrix Y is calculated by using Equations (1) and (2). Y = s · X (15) s = Min ( 1 Max 1 ≤ p ≤ n ( ∑ q = 1 n x p q ) , 1 Max 1 ≤ q ≤ n ( ∑ p = 1 n x p q ) ) (16) Step 4. Calculate the comprehensive-relation matrix. The comprehensive-relation matrix T is obtained by using Equation (3). T = ∑ λ = 1 ∞ Y λ = Y ( I − Y ) − 1 (17) where T = ( t p q ) n × n , p , q = 1 , 2 , ⋯ n , and t p q is used to represent the degree of total influence of p th criterion on q th criterion. I represents for the identity matrix. Step 5. Determine the influence relation among criteria The influence degree and influenced degree of the criteria is determined after obtaining the comprehensive-relation matrix T . The sum of the row and column values of matrix T can be obtained by the Equations (4) and (5). The sum of row values of T , denoted by D , which represents the overall influence of a given criterion on other criteria. The sum of column values of T , denoted by R , which implies the overall influence of other criteria on a given criterion. D = ( d p ) n × 1 = ∑ q = 1 n t p q (18) R = ( r q ) 1 × n = ∑ p = 1 n t p q (19) The causal diagram is obtained based on the D + R and D − R values. The D + R value indicates the importance of indicator in the SMPV plan selection system, the greater the D + R value, the more important the corresponding indicator is. On the other hand, the D − R value indicates the influence between a certain indicator and the other indicators, which can be separated into cause and effect groups. The indicator, which has positive values of D − R , belongs to the cause group, and dispatches effects to the other indicators. Otherwise, the indicator, which has negative values of D − R , belongs to the effect group, and receives effects to the other indicators. Step 6. Determine the weight of criteria The criteria are represented by j , and satisfying j = 1 , ⋯ p , ⋯ q , ⋯ n , then the weights of criteria are determined based on the following Equations (6) and (7) [ 30 ]. w j ′ = [ ( d j + r j ) 2 + ( d j − r j ) 2 ] 1 / 2 (20) w j = w j ′ ∑ j = 1 n w j ′ (21) where w j ′ denotes the relative importance of the indicators, and w j denotes the weights of the indicators in SMPV technology selection. 4.4. Phase III Calculation IVNNs Performance Score ELECTRE is a family of methods used for choosing, sorting and ranking, multi-criteria problems. ELECTRE III was developed by Roy in 1978m, which is valued outranking relation. A = { a 1 , a 2 , … , a n } is the finite set of alternatives, Y = { y 1 , y 2 , … , y m } is the finite set of criteria, y j ( a ) represents the performance of alternative a on criterion y j ∈ Y . Assume that all the criteria are of the gain type, which means the greater the value, the better. q j is the indifference threshold, which represents two alternatives in terms of their evaluations on criterion y j . In general, q j is a function of attribute value q j ( a i ) , which can be denoted as q j ( y j ( a i ) ) ; p j ( y j ( a i ) ) is preference threshold, which indicates that there is a clear strict preference of one alternative over the other in terms of their evaluations on criterion y j . In addition, v j ( y j ( a i ) ) is a veto threshold that indicates that the attribute value y j ( a i ) of scheme a i is lower than the attribute value y j ( a k ) of scheme a k , and when it reaches or exceeds v j ( y j ( a i ) ) , it is not recognized that the a i is preferred to the a k . y j ( a i ) − y j ( a k ) which indicates the situation of preference of a i over a k for criterion C j . A weight w j expresses the relative importance of criterion y j , as it can be interpreted as the voting power of each criterion to the outranking relation. Where y j ( a i ) and y j ( a k ) are expressed in the form of IVNNs in the paper, that is, y j ( a i ) = 〈 [ T i L , T i U ] , [ I i L , I i U ] , [ F i L , F i U ] 〉 , y j ( a k ) = 〈 [ T k L , T k U ] , [ I k L , I k U ] , [ F k L , F k U ] 〉 . In the calculation of Equation (8), let y j ( a i ) = ( T i L + T i U ) − ( I i L + I i U ) − ( F i L + F i U ) (22) y j ( a k ) = ( T k L + T k U ) − ( I k L + I k U ) − ( F k L + F k U ) (23) and so y j ( a i ) − y j ( a k ) = ( T i L + T i U − T k L − T k U ) + ( I i L + I i U − I k L − I k U ) + ( F i L + F i U − F k L − F k U ) (24) T i j = { δ i a i j a i max ( i ∈ θ B ) λ i a i min a i j ( i ∈ θ C , a i min ≠ 0 ) λ i ( 1 − a i j a i max ) ( i ∈ θ C , a i min ≠ 0 ) I i j = { ε i a i j a i max ( i ∈ θ B ) μ i a i min a i j ( i ∈ θ C , a i min ≠ 0 ) a n d μ i ( 1 − a i j a i max ) ( i ∈ θ C , a i min ≠ 0 ) F i j { F i j U = 1 − T i j L − I i j L F i j L = 1 − T i j U − I i j U (25) The δ , λ refer to the certainty parameters of the benefit criteria and cost criteria, respectively [ 23 ], while the ε , μ stand for the uncertainty parameters of the benefit criteria and cost criteria respectively, and they obey rule 0 < δ i + ε i ≤ 1 , 0 < λ i + μ i ≤ 1 . 4.5. Phase IV Calculation of Outranking Relation of IVNNs Based on Extended ELECTRE-III Step 1. Define the concordance index The concordance index c ( a i , a k ) that measures the strength of the coalition of criteria the support the hypothesis “is at least as good as”, c ( a i , a k ) is computed for each ordered pair a i , a k ∈ A as follows: c ( a i , a k ) = ∑ j = 1 n w j c j ( a i , a k ) / ∑ i = 1 n w j (26) and the partial concordance index c ( a i , a k ) is defined as c j ( a i , a k ) = { 0 ( y j ( a i ) − y j ( a k ) ≤ q j [ y j ( a i ) ] ) 1 ( y j ( a i ) − y j ( a k ) ≤ q j [ y j ( a i ) ] ) y j ( a i ) − y j ( a k ) − q j [ y j ( a i ) ] p j [ y j ( a i ) ] − q j [ y j ( a i ) ] ( o t h e r s ) (27) Step 2. Define the discordance index The discordance index d j ( a i , a k ) is defined as follows: d j ( a i , a k ) = { 0 ( y j ( a k ) − y j ( a i ) ≤ − q j [ y j ( a i ) ] ) 1 ( y j ( a k ) − y j ( a i ) ≥ v j [ y j ( a i ) ] ) y j ( a k ) − y j ( a i ) + q j [ y j ( a i ) ] v j [ y j ( a i ) ] + q j [ y j ( a i ) ] ( o t h e r s ) (28) Step 3. Define the degree of credibility of the outranking relation The overall concordance and partial discordance indices are combined to obtain a valued outranking relation with credibility s ( a i , a k ) ∈ [ 0 , 1 ] defined by: s ( a i , a k ) = { c ( a i , a k ) ( ∀ j , d j ( a i , a k ) ≤ c ( a i , a k ) ) c ( a i , a k ) ∏ j ∈ J ( a i , a j ) 1 − d j ( a i , a k ) 1 − c ( a i , a k ) ( o t h e r s ) (29) where j ( a i , a k ) is the set of criteria for which d j ( a i , a k ) > c ( a i , a k ) . Step 4. Define the ranking of the alternatives ∑ s ( a i ≻ a k ) means the sum degree of credibility that alternative a i outranks all the other alternatives, and ∑ s ( a k ≻ a i ) means the sum degree of credibility that all the other alternatives outrank alternative a i . Thus, Δ S ( a i ) represents the ranking of the alternative a i , and the higher the Δ S ( a i ) value is, the more superior the outranking order is. Δ S ( a i ) = ∑ s ( a i ≻ a k ) − ∑ s ( a k ≻ a i ) ( k = 1 , 2 … n ) (30) 5. A Real Case Study A Chinese renewable energy investment company wants to build a shopping center rooftop photovoltaic power project. In order to seek the optimal shopping mall for rooftop photovoltaic power plants, furthermore, one must judge the weight and the influence network of the criteria. A group of experts consisting of three doctorate engineers (referred to as E1, E2, E3) was constituted by the company. All three experts possess more than 15 years’ working experience in solar energy investment field, and are specialized in solar photovoltaic and power grid technologies. The collaboration of the all the experts was needed, thus, a pseudo-delphi method was applied in which each expert has no interaction. Considering the development target and the investment capacity of the company, the famous influential large-scale shopping malls located in those cities, with both abundant sunshine and general policy subsidies, have been roughly screened out based on the plentitude of documents and investigation. The investigation involved several potential shopping malls located in Beijing, Shanghai, Guangzhou, Chengdu, Hangzhou, and Nanjing. The experts group met the Development and Reform Commission, the Meteorological Bureau, and the local power supply companies, in order to gather information about solar resources, city planning and construction, local solar subsidy policies, distributed solar power planning, economic assessment, and approved shopping mall rooftops for construction. There are four potential shopping malls picked out after the first filter, and they are the Golden Resources shopping mall in Beijing, Super Brand Mall in Shanghai, Deji Plaza in Nanjing, Jiangsu province, The Mixc shopping mall in Shenzhen, Guangdong province (hereafter referred to as X 1 , X 2 , X 3 , X 4 ), as shown in Figure 3 . Figure 3. The alternative shopping malls geography distribution. Firstly, based on the evaluation criteria, the influence of each criteria to the other one criteria was accessed by the experts. Then, the three experts discussed with each other and obtained a consensus about the influence of each criteria, as shown in Table 2 . According to the DEMANTEL method, the weight of criteria and subcriteria was calculated based on Equations (15)–(21), and shown in Table 2 . For the intuitive and simple understanding and analysis of the criteria and subcriteria, Figure 4 and Figure 5 were drawn. As shown in Figure 4 , the horizontal axis represents the importance of a criteria, while the vertical axis indicates the influence between the criteria, and the arrow is from the sender of this influence to the receiver. As we can see, the (b) economy (0.286) obtained the most importance, but was vulnerable to other criteria. The (a) architectural element and (c) climate (0.88) seemed not particularly important, however, they had significant direct impacts to the other four criteria. The (f) risk (0.188), (d) photovoltaic array (0.162), and (e) contribution (0.151) were considered of medium importance, and among them, (f) and (d) had more of an impact, while (e) received more impact. Horizontal histogram clearly and intuitively shows the weight of each subcriteria in Figure 5 . It is obvious that the (b1) Total investment, (b2) Total profit, and (b3). Annual rate of return acquired the highest weight, in addition to the (f4) Government subsidies reduction, (e2) Publicity effects and (d2). PV area was considered to be less but also very important. Therefore, it can be imagined that the SMPV plan alternatives which obtained high scores in these criteria are more likely to win the competition. Figure 4. The weights of subcriteria. Figure 5. Influential network relationship map within systems. Table 2. The score of influence among each subcriteria. Secondly, there are two types of criteria, one is quantitative, and the other is qualitative. On one hand, for the quantitative subcriteria, searching from the NASA atmospheric science data center, the data for c1, c2, c3 were obtained. Through using the Google earth map, the roof space data were obtained. Then, according to Equations (1)–(8), the data for a3, b1–b4, d2, d3 were estimated. Because the Equations (1)–(8) are just for rough estimate, these data were not highly accurate. Considering the uncertainty and fuzziness of the data, Equation (25) was used to turn the numerical value into an IVNN value. The performance scores of the quantitative subcriteria are shown in Table 3 . On the other hand, for the qualitative subcriteria, the experts group devoted their efforts to investigate the alternative plans and evaluate the performance score for the subcriteria a1, a2, d1, d4, e1–e3, f1–f4. The performance scores of the qualitative subcriteria were shown in Table 4 . In addition, the subcriteria were divided into positive and negative. The score of positive criteria higher and negative criteria lower means the alternative better. In this paper, subcriteria b1, d4, f1, f3, f4 are negative and the others are positive. Table 3. IVNN performance scores of alternative SMPV plans on the quantitative subcriteria. Table 4. IVNN performance scores of alternative SMPV plans on the qualitative subcriteria. Thirdly, based on the weight of the sub-criteria and the IVNN scores of each alternative on each subcriteria, the final composite scores were calculated by improved ELECTRIC III method. After being told that q j is the indifference threshold, p j is the preference threshold and v j is the veto threshold, the experts group suggested that ∑ s ( a i , a k ) − ∑ s ( a k , a i ) ( k = 1 , 2 … n ) , respectively. The concordance index c ( X i , X k ) and the partial concordance index c j ( X i , X k ) were calculated by Equations (26) and (27), as shown in Table 5 . The discordance index d j ( X i , X k ) was achieved by Equation (28), as shown in Table 6 . Then, overall concordance and partial discordance indices was obtained by Equation (29) as shown in Table 7 . Finally, the degree of credibility of the outranking relation was calculated by Equation (30), and the rankings of alternative X1, X2, X3, X4 was shown in Table 8 . Table 5. The concordance index and the partial concordance index for each pair of SMPV plans. Table 6. The discordance index for each pair of SMPV plans. Table 7. The overall concordance and partial discordance indices for each pair of SMPV plans. Table 8. Final composite scores and rankings of alternative SMPV plans. From Table 8 , the SMPV plan X1 of the Golden Resources shopping mall in Beijing is the optimal selection. The alternative X1 is particularly superior to other alternative plans in terms of the economy, photovoltaic array, and contribution criteria, while these three criteria weighed more than a half of the entire criteria weights, so there is no doubt that plan X1 obtained the best position. However, plan X1 performs badly in the risk and architectural elements criteria. Respectively, Plan X2 have strength on the economy, but are weak on photovoltaic criteria. Yet, plan X2 is much better than plan X3 and X4, so that it can be the stand-by choice. The ranking order using ELECTRI III is X1 > X2 > X3 > X4. In order to check the validity of the results, TOPSIS and VIKOR methods were used to reorder the alternative SMPV plans as shown in Table 9 . The result obtained by TOPSIS method is X1 > X4 > X3 > X2, while the result achieved by VIKOR method is X1 > X4 > X3 > X2. from these three rankings, alternative plan X1 is the optimal selection, no matter what method was used. That is to say, the alternative X1 is much better than the remaining alternatives, and there is no doubt in choosing X1 first. However, the rankings for X2, X3, and X4 are different between these three methods. There is the veto threshold, which indicates when the value of alternative Xi is lower than the value of alternative Xj, and the lower value exceeds the veto threshold, and it is not recognized that Xi is preferred to the Xj in general. However, it is the other term in TOPSIS method and VIKOR method, and some really bad performance in a certain criterion can be tolerated and remedied by other good performances in other criteria. In that case, an alternative with some fatal defect in a certain criterion of an alternative may be neglected, which leads to an unsatisfactory selection. When an alternative is vetoed better than the other alternative in ELECTRE III, it can still come out in front in the TOPSIS and VIKOR methods. That why the X2, X3, X4 ranked differently in TOPSIS and VIKOR methods. Table 9. The rankings of SMPV plans using TOPSIS and VIKOR. 6. Conclusions The selection of SMPV plan is crucial to the entire life of SMPV project. Although there has been some research on this issue, several questions still need addressing. Firstly, the interaction of the criteria lay in the evaluation criteria. Secondly, the loss of evaluation information exited in the information conversion process. Thirdly, the compensation problem between best and worst performance in diverse criteria was not easily to avoided. In this paper, an integrated MCDM framework was proposed to address the SMPV plan selection problem. First of all, the compositive evaluation index was constructed, and the application of DEMATEL method helped analyze the internal influence and connection behind each criterion. From the influential network-relationship map, we discovered that the criteria (b) economy obtained the most importance but was vulnerable to other criteria as well as the (a) architectural element and (c) climate had significant direct impacts to the other four criteria. These three criteria should be the first for the decision maker to consider when selecting the SMPV plan. Then, the interval-valued neutrosophic set is utilized to express the imperfect knowledge of experts group. Since the application of IVNNS, the experts can clearly express their evaluation information, including their certainty, uncertainty, as well as hesitation attitude. Following this, an extended ELECTRE III method as an outstanding outranking method was applied, and it succeed in avoiding the compensation problem and obtaining the scientific result. In the case of China, the integrated method has been successfully applied to select the SMPV plan X1 as the optimal selection which is particularly superior to other alternative plans in terms of the economy, photovoltaic array, and contribution criteria. Also, the integrated method used maintained symmetry in the solar PV investment. Last but not least, a comparative analysis using TOPSIS method and VIKOR method was carried out, and alternative plan X1 ranks first at the same. The outcome certified the correctness and rationality of the results obtained from this paper. Therefore, this study has not only served to evaluate the SMPV plans, it has also demonstrated how it is possible to combine IVNNS, DEMATEL method, and ELECTRE III method for application in handling MCDM problems in the field of solar energy. Author Contributions M.L. designed the decision framework of shopping mall photovoltaic plan selection, and studied the proposed method. 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Criteria Subcriteria Resources (a) Architectural elements a1 Roof pitch and orientation [ 2 ] a2 Covering ratio [ 2 ] a3 PV roof space [ 2 ] (b) Economy b1 Total investment [ 19 ] b2 Total profit [ 19 ] b3 Annual rate of return [ 20 ] b4 Payback year [ 20 ] (c) Climate c1 Annual average solar radiation (kwh/m 2 /year) [ 19 , 21 ] c2 Land surface temperature (°C) [ 19 , 21 ] c3 Annual sunshine utilization hours (h) [ 19 , 21 ] (d) Photovoltaic array d1 Suitability of the local solar regime [ 22 ] d2 PV area [ 2 ] d3 PV generation (yearly electricity generation) MWh/year [ 2 , 19 ] d4 Repair and clean rate [ 20 ] (e) Contribution e1 Increase in local economy and employment [ 22 ] e2 Publicity effects Own e3 Environment protection [ 23 ] (f) Risk f1 Grid connection risk [ 19 ] f2 Rooftop ownership and occupancy disputes Own f3 Bad climate [ 22 ] f4 Government subsidies reduction Own Table 2. The score of influence among each subcriteria.
https://www.mdpi.com/2073-8994/10/5/150/xml
Topical versus systemic antibiotics for chronic suppurative otitis media - Chong, L-Y - 2021 | Cochrane Library Administration, Topical; Aminoglycosides [administration & dosage]; Amoxicillin-Potassium Clavulanate Combination [administration & dosage]; Anti-Bacterial Agents [*administration & dosage]; Bias; Chronic Disease; Ofloxacin [administration & dosage]; Otitis Media, Suppurative [*drug therapy]; Quinolones [administration & dosage]; Randomized Controlled Trials as Topic; Time Factors Topical versus systemic antibiotics for chronic suppurative otitis media References References to studies included in this review Jump to: excluded studies de Miguel 1999 {published data only} De Miguel Martinez I, Vasallo Morillas JR, Ramos Macias A. Antimicrobial therapy in chronic suppurative otitis media [Terapeutica antimicrobiana en otitis media cronica supurada]. Acta Otorrinolaringologica Espanola 1999 ; 50 (1):15-9. 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Double-blind comparative trial of trimethoprim-polymyxin B and trimethoprim-sulphacetamide-polymyxin B ear drops in the treatment of otorrhoea [Etude comparative a double insu sur les solutions otiques de trimethoprime - polymyxine B et de trimethoprime - sulfacetamide - polymyxine B dans le traitement de l'otorrhee]. Annales d'Oto-laryngologie et de Chirurgie Cervico Faciale 1981 ; 98 (1-2):37-40. [CENTRAL: CN-00026056] CENTRAL [EMBASE: 1982037351] [PMID: 6269476] PubMed Gyde 1982 {published data only} Gyde MC, Norris D, Kavalec EC. The weeping ear: clinical re-evaluation of treatment . Journal of International Medical Research 1982 ; 10 (5):333-40. [CENTRAL: CN-00029419] CENTRAL [PMID: 6754505] Hemlin 1997 {published data only} Hemlin C, Carenfelt C, Papatziamos G. Single dose of betamethasone in combined medical treatment of secretory otitis media . Annals of Otology, Rhinology, and Laryngology 1997 ; 106 (5):359-63. 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Among Aboriginal children (2 months of age and up to 17 years of age) with chronic suppurative otitis media, is 4 months of povidone-iodine ear wash and/or oral cotrimoxazole in addition to standard treatment (cleaning and dry mopping with tissue spears plus topical ciprofloxacin) superior to standard treatment alone for resolving ear discharge? A 2x2 factorial randomised controlled trial . www.anzctr.org.au (first received 25 March 2014). CENTRAL [ACTRN12614000234617] Wigger C, Leach AJ, Beissbarth J, Oguoma V, Lennox R, Nelson S, et al. Povidone-iodine ear wash and oral cotrimoxazole for chronic suppurative otitis media in Australian aboriginal children: study protocol for factorial design randomised controlled trial . BMC Pharmacology & Toxicology 2019 ; 20 (1):46. [CENTRAL: CN-01954293] CENTRAL [PMID: 31351491] IRCT20130427013136N6 {published data only} IRCT20130427013136N6. 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Effectiveness of sulfamethoxazole-trimethoprim in the treatment of chronic otitis media . https://clinicaltrials.gov/show/nct00189098 (first received 16 September 2005). [CENTRAL: CN-01039521] van der Veen EL, Rovers MM, Albers FW, Sanders EA, Schilder AG. Effectiveness of trimethoprim/sulfamethoxazole for children with chronic active otitis media: a randomized, placebo-controlled trial . Pediatrics 2007 ; 119 (5):897-904. [CENTRAL: CN-00588516] [PMID: 17473089] Link to article van der Veen EL, Schilder AG, Timmers TK, Rovers MM, Fluit AC, Bonten MJ, et al. Effect of long-term trimethoprim/sulfamethoxazole treatment on resistance and integron prevalence in the intestinal flora: a randomized, double-blind, placebo-controlled trial in children . Journal of Antimicrobial Chemotherapy 2009 ; 63 (5):1011-6. [CENTRAL: CN-00697186] [PMID: 19297377] Verhoeff M, Rovers MM, Sanders EAM, Schilder AGM. The COCO-study: a randomized clinical trial of the efficacy of trimethoprim-sulfamethoxazole (co-trimoxazole) in children with chronic suppurative otitis media . Clinical Otolaryngology and Allied Sciences 2004 ; 29 (4):460. [CENTRAL: CN-00874123] CENTRAL van Dongen 2014 {published data only} NTR1481. Comparison of ototopical antibiotic-steroid drops or oral antibiotics versus watchful waiting in children with acute tympanostomy tube otorrhea [Comparison of Bacicoline-B eardrops or oral Augmentin versus watchful waiting in children with acute tympanostomy tube otorrhea]. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1481 (first received 6 October 2008). [CENTRAL: CN-00974948] van Dongen TMA, van der Heijden GJMG, Venekamp RP, Rovers MM, Schilder AGM. A trial of treatment for acute otorrhea in children with tympanostomy tubes . New England Journal of Medicine 2014 ; 370 (8):723-33. [CENTRAL: CN-00982484] [EMBASE: 2014119997] [PMID: 24552319] van Hasselt 1997 {published data only} van Hasselt P, van Kregten E. Treatment of chronic suppurative otitis media with ofloxacin in hydroxypropyl methylcellulose ear drops: a clinical/bacteriological study in a rural area of Malawi . International Journal of Pediatric Otorhinolaryngology 2002 ; 63 (1):49-56. [CENTRAL: CN-00519676] van Hasselt P. Pilot trial of treatment of chronic suppurative otitis media (CSOM) with several types of ear drops in Nkota Kota District, Malawi . Internal Report of the Christian Blind Mission International 1997 . [CENTRAL: CN-00519675] van Hasselt 1998a {published data only} van Hasselt P, van Kregten E. Treatment of chronic suppurative otitis media with ofloxacin in hydroxypropyl methylcellulose ear drops: a clinical/bacteriological study in a rural area of Malawi . International Journal of Pediatric Otorhinolaryngology 2002 ; 63 (1):49-56. [CENTRAL: CN-00519676] van Hasselt P. A controlled trial of the treatment of CSOM in rural Malawi . In: Conference of the Pan-African Federation of Otorhinolaryngological Societies (PAFOS); 1998; Nairobi. Nairobi, 1998 . [CENTRAL: CN-00519673] Vishwakarma 2015 {published data only} Vishwakarma K, Khan FA, Nizamuddin S, Signh P, Yadav L. Role of topical acetic acid in comparison to gentamicin for the management of chronic suppurative otitis media . International Archives of Biomedical and Clinical Research 2015 ; 1 (1):13-6. [CENTRAL: CN-01601165] CENTRAL Google Scholar Wintermeyer 1997 {published data only} Wintermeyer SM, Hart MC, Nahata MC. Efficacy of ototopical ciprofloxacin in pediatric patients with otorrhea . Otolaryngology - Head & Neck Surgery 1997 ; 116 (4):450-3. Mehboob 2019 {published data only} Mehboob S, Rafi ST, Ahmed N, Mehjabeen. Association of hearing loss with depression, anxiety and stress in patients suffering from chronic suppurative otitis media . Pakistan Journal of Medical Sciences 2019 ; 35 (2):510-4. [PMID: 31086542] PubMed Samarei 2014 {published data only} Samarei R. Comparison of local and systemic ciprofloxacin ototoxicity in the treatment of chronic media otitis . Global Journal of Health Science 2014 ; 6 (7 Spec No):144-9. Additional references Jump to: Baumann 2011 Baumann I, Gerendas B, Plinkert PK, Praetorius M. General and disease-specific quality of life in patients with chronic suppurative otitis media--a prospective study . Health and Quality of Life Outcomes 2011 ; 9 :48. [DOI: 10.1186/1477-7525-9-48 ] Bhutta 2011 Bhutta MF, Williamson IG, Sudhoff HH. Cholesteatoma . BMJ 2011 ; 342 :d1088. [DOI: 10.1136/bmj.d1088 ] Bhutta 2016 Bhutta MF. Evolution and otitis media: a review, and a model to explain high prevalence in indigenous populations . Human Biology 2016 ; 87 (2):92-108. Bhutta 2020 Bhutta MF, Head K, Chong LY, Daw J, Schilder AGM, Burton MJ, Brennan-Jones CG. Aural toilet (ear cleaning) for chronic suppurative otitis media . Cochrane Database of Systematic Reviews 2020 , Issue 9. Art. No: CD013057. [DOI: 10.1002/14651858.CD013057.pub2 ] Brennan‐Jones 2020a Brennan-Jones CG, Head K, Chong LY, Tu N, Burton MJ, Schilder AGM, et al. Topical antibiotics for chronic suppurative otitis media . Cochrane Database of Systematic Reviews 2020 , Issue 1. Art. No: CD013051. [DOI: 10.1002/14651858.CD013051.pub2 Brennan‐Jones 2020b Brennan-Jones CG, Chong LY, Head K, Burton MJ, Schilder AGM, Bhutta MF. Topical antibiotics with steroids for chronic suppurative otitis media . Cochrane Database of Systematic Reviews 2020 , Issue 9. Art. No: CD013054. [DOI: 10.1002/14651858.CD013054.pub2 ] Chong 2021 Chong L-Y, Head K, Webster KE, Daw J, Richmond P, Snelling T, Bhutta MF, et al. Systemic antibiotics for chronic suppurative otitis media . Cochrane Database of Systematic Reviews 2021 , Issue 1. Art. No: CD013052. [DOI: 10.1002/14651858.CD013052.pub2 ] Dubey 2007 Dubey SP, Larawin V. Complications of chronic suppurative otitis media and their management . Laryngoscope 2007 ; 117 (2):264-7. Egger 1997 Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test . BMJ 1997 ; 315 (7109):629-34. Elbourne 2002 Elbourne DR, Altman DG, Higgins JP, Curtin F, Worthington HV, Vail A. Meta-analyses involving cross-over trials: methodological issues . International Journal of Epidemiology 2002 ; 31 (1):140-9. Elemraid 2010 Elemraid MA, Brabin BJ, Fraser WD, Harper G, Faragher B, Atef Z, et al. Characteristics of hearing impairment in Yemeni children with chronic suppurative otitis media: a case-control study . International Journal of Pediatric Otorhinolaryngology 2010 ; 74 (3):283-6. Google Scholar Gates 2002 Gates GA, Klein JO, Lim DJ, Mogi G, Ogra PL, Pararella MM, et al. Recent advances in otitis media. 1. Definitions, terminology, and classification of otitis media . Annals of Otology, Rhinology & Laryngology. Supplement 2002 ; 188 :8-18. Google Scholar Gilbert 2007 Gilbert JG, Dawes PJ, Mahadevan M, Baber WJ, Hall F. Use of ototoxic eardrops: a position statement from the New Zealand Society of Otolaryngology Head and Neck Surgery . New Zealand Medical Journal 2007 ; 120 (1258):84-93. Google Scholar Handbook 2011 Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011 . Available from www.cochrane-handbook.org. Head 2020a Head K, Chong LY, Bhutta MF, Morris PS, Vijayasekaran S, Burton MJ, et al. Topical antiseptics for chronic suppurative otitis media . Cochrane Database of Systematic Reviews 2020 , Issue 1. Art. No: CD013055. [DOI: 10.1002/14651858.CD013055.pub2 Head 2020b Head K, Chong LY, Bhutta MF, Morris PS, Vijayasekaran S, Burton MJ, et al. Antibiotics versus topical antiseptics for chronic suppurative otitis media . Cochrane Database of Systematic Reviews 2020 , Issue 1. Art. No: CD013056. [DOI: 10.1002/14651858.CD013056.pub2 Jensen 2013 Jensen RG, Koch A, Homøe P. The risk of hearing loss in a population with a high prevalence of chronic suppurative otitis media . (9):1530-5. [DOI: Mahadevan M, Navarro-Locsin G, Tan HK, Yamanaka N, Sonsuwan N, Wang PC, et al. A review of the burden of disease due to otitis media in the Asia-Pacific International Journal of Pediatric Otorhinolaryngology (5):623-35. [DOI: Mittal R, Lisi CV, Gerring R, Mittal J, Mathee K, Narasimhan G, et al. Current concepts in the pathogenesis and treatment of chronic suppurative otitis media . Journal of Medical Microbiology 2015 64 (10):1103-16. [DOI: 10.1099/jmm.0.000155 Monasta L, Ronfani L, Marchetti F, Montico M, Vecchi Brumatti L, Bavcar A, et al. Burden of disease caused by otitis media: systematic review and global estimates Nadol JB Jr, Staecker H, Gliklich RE. Outcomes assessment for chronic otitis media: the Chronic Ear Survey . Laryngoscope 2000 110 (3 Pt 3):32-5. [DOI: 10.1097/00005537-200003002-00009 Olatoke 2008 Olatoke F, Ologe FE, Nwawolo CC, Saka MJ. The prevalence of hearing loss among schoolchildren with chronic suppurative otitis media in Nigeria, and its effect on academic performance . Ear, Nose, & Throat Journal 2006 ; 132 (10):1115-8. [DOI: 10.1001/archotol.132.10.1115 Journal of International Advanced Otology (3):248-52. [DOI: 10.5152/iao.2015.1701 Verhoeff 2006 Yorgancılar E, Yildirim M, Gun R, Bakir S, Tekin R, Gocmez C, et al. Complications of chronic suppurative otitis media: a retrospective review European Archives of Oto-rhino-laryngology 2013 270 (1):69-76. [DOI: 10.1007/s00405-012-1924-8 Chong 2018b Chong LY, Head K, Richmond P, Snelling T, Schilder AGM, Burton MJ, et al. 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[DOI: 10.1002/14651858.CD013053 ] Characteristics of studies Characteristics of included studies [ordered by study ID] awaiting classification de Miguel 1999 Study characteristics Methods5‐arm, non‐blinded, parallel‐group RCT, with 7 days duration of treatment and 15 days duration of follow‐up Participants Location:Canary Islands, Spain Setting of recruitment and treatment:general hospital, published in 1999 Sample size:125 Number randomised:25 in group A, 25 in group B, 25 in group C, 25 in group D, 25 in group E Number completed:25 in group A, 25 in group B, 25 in group C, 25 in group D, 25 in group E Participant (baseline) characteristics: Age (mean, range): 39.6 years, 6 to 83, but 17/125 of participants were children Gender (F/M): 56 (44.8%)/69 (55.2%) Main diagnosis: chronic otitis media, which comprised the following groups: Simple chronic otitis media ‐ no osteitic changes, tympanosclerosis or cholesteatoma (n = 45) Osteitic chronic otitis media ‐ with changes to the ossicular chain and some permanent alterations in the mucosa (tympanosclerosis or chronic granulomatosis) (n = 32) Cholesteatomatous chronic otitis media (n = 17) Post‐surgery cases (n = 31) High‐risk population: Cleft palate (or other craniofacial malformation): not reported Down syndrome: not reported Indigenous groups (Australian Aboriginals/Greenland natives): not reported Immunocompromised: not reported Diagnosis method: Confirmation of perforated tympanic membrane: all patients had otoscopy under microscopy at entry. 51.2% had "non‐marginal tympanic perforation" .The involvement of the ossicular chain in the otological microscopic examination was found in 43.2% of the patients. Presence of mucopurulent discharge: 113/125 (90.4%), 89/125 (71.2%) with odorous discharge Duration of symptoms (discharge): not reported Other important effect modifiers Alternative diagnosis of ear discharge: cholesteatoma (n = 17) Patients with discharge after operation: unclear type/reason for operations (n = 31) Number who have previously had grommets inserted: not reported Number who have had previous ear surgery: at least 31/125 (24.8%), reasons and type of surgery not reported Number who had previous antibiotic treatment for CSOM: 79/125 (63.2%) Inclusion criteria: Patients (adults and children) with chronic otitis media, presenting with chronic otorrhoea as major symptom. Diagnostic criteria not reported. Exclusion criteria:not reported Interventions Group A (n = 25):oral ciprofloxacin, 500 mg/12 hours for 7 days Group B (n = 25):topical ciprofloxacin 0.2%, 3 ear drops/8 hours for 7 days Group C (n = 25):topical ciprofloxacin 0.5%, 3 ear drops/8 hours for 7 days Group D (n = 25):topical ciprofloxacin 0.2%, 3 ear drops/8 hours for 7 days and oral ciprofloxacin, 500 mg/12 hours for 7 days simultaneously Group E (n = 25):topical polymixin B + neomycin + hydrocortisone, 3 ear drops/8 hours for 7 days Concurrent treatment:all patients had aspiration and cleaning of ear secretions before beginning treatment; analgesics and antipyretics OutcomesOutcomes of interest in the review: Primary outcome:Resolution of ear discharge at 1 to 2 weeks. Unclear if otoscopically confirmed. Secondary outcomes:Hearing: hearing tests at time of diagnosis, at 8 days and at 15 daysSuspected ototoxicity Funding sourcesNo information provided Declarations of interestNo information provided Notes Unit of randomisation:person Methods for including patients with bilateral disease:not reported Risk of bias Bias Authors' judgement Support for judgement Random sequence generation (selection bias) Unclear risk Quote: "125 patients were analysed for two years attending to health system with chronic otorrhea as the mean symptom" Comment: insufficient information about the sequence generation process to permit judgement Allocation concealment (selection bias)Unclear riskQuote: "Patients were randomized to five therapeutic groups"Comment: insufficient information about allocation concealment method provided Blinding of participants and personnel (performance bias)All outcomesHigh riskComment: no information provided about blinding method or use of placebo. The treatment arms involved different dosage forms (oral versus ear drops) – blinding of these interventions impossible without use of placebo. Blinding of outcome assessment (detection bias)All outcomes High risk Comment: no information provided regarding to who assessed the outcomes. For subjective outcomes (otoscopy examinations, hearing test or adverse events) it is probable that the knowledge of treatment group has influenced the results. Incomplete outcome data (attrition bias)All outcomesUnclear riskComment: no dropouts or missing data reported; no statements about missing data Selective reporting (reporting bias)Unclear riskComment: insufficient information to permit judgement of 'low risk' or 'high risk'; protocol for trial not available Esposito 1990 Study characteristics Methods3‐arm, non‐blinded, parallel‐group RCT, with 5 to 10 days of treatment and 24 hours and 14 days follow‐up after end of treatment Participants Location:Naples, Italy, 1 site Setting of recruitment and treatment:Clinic of Infectious Diseases and Otolaryngology, University of Naples Sample size: Number randomised: 20 in each intervention Number completed: 20 in each intervention Participant (baseline) characteristics: Age: mean 38 years Gender (F/M): 29 (48%)/31 (52%) Main diagnosis: mild or moderate CSOM in the acute stage High‐risk population: no Cleft palate (or other craniofacial malformation): not reported Down syndrome: not reported Indigenous groups (Australian Aboriginals/Greenland natives): not reported Immunocompromised: "no patients had diabetes or any other comorbidities" Diagnosis method: Confirmation of perforated tympanic membrane: not reported Presence of mucopurulent discharge: not reported Duration of symptoms (discharge): not specified Other important effect modifiers: Alternative diagnosis of ear discharge: not reported Number who have previously had grommets inserted: not reported Number who have had previous ear surgery: not reported Number who had previous antibiotic treatment for CSOM: 38/60 (63%) had at least 5 days of antibiotics and did not respond Inclusion criteria: Mild to moderate chronic otitis media in acute stage without cholesteatoma or mastoiditis Exclusion criteria: Younger than 18 years old Cholesteatoma Mastoiditis Interventions Topical plus systemic ciprofloxacin (n = 20):3 drops topical ciprofloxacin 250 µg/mL in saline solution locally twice a day PLUS oral ciprofloxacin 250 mg twice a day until cure or up to 10 days Topical ciprofloxacin (n = 20):3 drops topical ciprofloxacin 250 µg/mL in saline solution locally twice a day until cure or up to 10 days Oral ciprofloxacin (n = 20):oral ciprofloxacin 250 mg twice a day until cure or up to 10 daysAll interventions given for at least 5 days; those not cured at 5 days carried on up to 10 days Concurrent treatment:not reported Outcomes Outcomes of interest in the review: Primary outcomes: Resolution of ear discharge at 1 week (5 to 11 days) and 2 to 4 weeks (19 to 24 days). Unclear if otoscopically confirmed. Secondary outcomes: Suspected ototoxicity (audiometric and vestibular function) Serious complications, including intracranial complications (such as otitic meningitis, lateral sinus thrombosis, and cerebellar abscess) and extracranial complications (such as mastoid abscess, postauricular fistula and facial palsy) and death Adverse effects from treatment Funding sources"The ciprofloxacin tablets and powder used in this study were kindly provided by Bayer Italia Spa, Milan, Italy." Declarations of interestNo information provided Notes Unit of randomisation:person Methods for including patients with bilateral disease:not reported Risk of bias Bias Authors' judgement Support for judgement Random sequence generation (selection bias) High risk Quote: "Ciprofloxacin was randomly administered according to the following schedules" Comment: randomisation method not clearly specified. 38/60 patients were previously unsuccessfully treated with at least 5 days of antibiotics – unclear how this was distributed across groups. 12/20 in the oral ciprofloxacin only group had Pseudomonasversus 8/20 in other groups. Allocation concealment (selection bias)Unclear riskComment: there is no information regarding the method of allocation concealment Blinding of participants and personnel (performance bias)All outcomes High risk Quote: "group A (20 patients), 250mg orally twice a day; group (20 patients), 3 drops containing 250ug/mL of ciprofloxacin in saline solution locally twice a day; and group C (20 patients), both the previous treatments twice a day" Comment: participants are most likely not to be blinded as the routes of administration (oral versus topical) are different among groups and there is no mention of the use of a placebo Blinding of outcome assessment (detection bias)All outcomes High risk Quote: "Patients were clinically examined before, during (every 2‐3 days) and after the therapy". Comment: not specified who assessed the outcomes or that the assessment method was standardised. The use of "cure", "improvement" and "failure" seemed to be more of a subjective judgement. Incomplete outcome data (attrition bias)All outcomesLow riskComment: no dropout cases were reported. All of the patients randomised are presented in the results of the study. Selective reporting (reporting bias) High risk Comment: there is no protocol for the trial on clinicaltrials.gov or in the EU register of clinical trials. Some of the results mentioned in the methods section are not fully presented in the results section (e.g. hearing assessment). A "cure" or resolution of discharge is only reported at one time point (most likely 14 days after end of treatment). The other time point, 24 hours after the end of treatment (i.e. 6 to 11 days), was not reported. Esposito 1992 Study characteristics Methods2‐arm, non‐blinded, parallel‐group RCT, with 5 to 10 days of treatment and follow‐up at 12 hours, 14 days and 21 days after interruption of treatment Participants Location:Naples, Italy, 1 site Setting of recruitment and treatment:Institutes of Infectious Diseases and Otolaryngology, University of Naples Sample size: Number randomised:30 in intervention, 30 in comparison Number completed:30 in intervention, 30 in comparison Participant (baseline) characteristics: Age: adults, mean 39 (range 18 to 65) Gender (F/M): 33 (55%)/27 (45%) Main diagnosis: mild to moderate chronic otitis media in acute stage with perforation of tympanic membrane High‐risk population: Cleft palate (or other craniofacial malformation): not reported Down syndrome: not reported Indigenous groups (Australian Aboriginals/Greenland natives): not reported Immunocompromised: not reported Diagnosis method: Confirmation of perforated tympanic membrane: otoscopy assessment before, during and after the therapy Presence of mucopurulent discharge: 60/60 (100%) Duration of symptoms (discharge): ≥ 15days Other important effect modifiers Alternative diagnosis of ear discharge: not reported Number who have previously had grommets inserted: not reported Number who have had previous ear surgery: not reported Number who had previous antibiotic treatment for CSOM: 40/60 (67%) Inclusion criteria: "The otitis media had lasted at least 3 years, purulent otorrhea had recurred at least once annually, and recurrent episodes of purulent otorrhea had been constant for at least 15 days" Exclusion criteria: Pregnant women Previous allergy to quinolone or aminoglycosides Younger than 18 years old Cholesteatoma or mastoiditis Interventions Intervention (n = 30):topical ciprofloxacin hydrochloride 250 mg/mL, 12‐hourly for 5 to 10 days Comparator group (n = 30):intramuscular gentamicin sulphate 80 mg 12‐hourly for 5 to 10 days Concurrent treatment:aural toileting not mentioned OutcomesOutcomes of interest in the review: Primary outcomes:Clinical and bacteriological resolution 12 hours, 14 days and 21 days after treatment Secondary outcomes:Ototoxicity Funding sourcesNo information provided Declarations of interestCiprofloxacin powder was provided by Bayer Italia Spa, Milan, Italy; gentamicin by Schering Plough, Milan Notes Unit of randomisation:not reported Methods for including patients with bilateral disease:not reported Risk of bias Bias Authors' judgement Support for judgement Random sequence generation (selection bias)Unclear riskQuote: "Ciprofloxacin was randomly given according to the following schedules"Comment: method of selection was not specific Allocation concealment (selection bias)Unclear riskComment: no specific information given Blinding of participants and personnel (performance bias)All outcomesHigh riskComment: both treatments are by different routes of administration and given that no placebo was used, masking the intervention arms would not be achievable Blinding of outcome assessment (detection bias)All outcomesHigh riskComment: no indication that outcomes assessors were blinded Incomplete outcome data (attrition bias)All outcomesUnclear riskComment: no dropouts reported Selective reporting (reporting bias) High risk Quote: "the clinical and bacteriological evaluation was stated 12 hours and 14 and 21 days (follow‐up) after the interruption of treatment" Comment: study protocol not available for assessment. Although the methods section indicates that 3 time points were measured, only one time point (unclear which one) was reported. The other 2 time points were not reported. Povedano 1995 Study characteristics Methods2‐arm, non‐blinded, parallel‐group RCT, with 10 days duration of treatment and follow‐up Participants Location:Spain, unclear how many sites Setting:otolaryngology department, general hospital, Spain, 1994 Sample size: Number randomised:30 in group A, 30 in group B Number completed:30 in group A, 30 in group B Participant (baseline) characteristics: Age: mean 45 ± 2 years, range 18 to 65 Gender (F/M): 35 (58%)/25 (42%) Main diagnosis: active phase of chronic otorrhoea High‐risk population: not reported Cleft palate (or other craniofacial malformation): not reported Down syndrome: not reported Indigenous groups (Australian Aboriginals/Greenland natives): not reported Immunocompromised: not reported Diagnosis method: Confirmation of perforated tympanic membrane: unclear Presence of mucopurulent discharge: 60/60 (100%) Duration of symptoms (discharge): not reported Other important effect modifiers Alternative diagnosis of ear discharge: not reported Number who have previously had grommets inserted: not reported Number who have had previous ear surgery: not reported Number who had previous antibiotic treatment for CSOM: not reported Inclusion criteria: Patients with chronic active otorrhoea in the active phase (diagnostic criteria used not reported) Exclusion criteria: Age < 18 years Allergy to fluoroquinolones Medical comorbidities (diabetes mellitus, cardiomyopathy, etc.) Interventions Group A (n = 30):oral ciprofloxacin, 500 mg/12 hours, for 10 days Group B (n = 30): topical ciprofloxacin 250 µg/mL, 5 ear drops/12 hours, for 10 days Concurrent treatment:not reported OutcomesOutcomes of interest in the review: Primary outcomes:Resolution of ear discharge ("dry ear"), measured at between 1 to 2 weeks. Unclear if otoscopically confirmed. Funding sourcesNo information provided Declarations of interestNo information provided Notes Unit of randomisation:not reported Methods for including patients with bilateral disease:not reported Risk of bias Bias Authors' judgement Support for judgement Random sequence generation (selection bias)Unclear riskQuote: patients were "allocated randomly"Comment: insufficient information about the sequence generation process Allocation concealment (selection bias)Unclear riskQuote: "Ciprofloxacin was randomly administered to two groups"Comment: no information was provided to determine adequate allocation concealment Blinding of participants and personnel (performance bias)All outcomesHigh riskComment: no indication of use of placebo; different methods of administration Blinding of outcome assessment (detection bias)All outcomesHigh riskComment: no indication of blinding of outcomes assessors Incomplete outcome data (attrition bias)All outcomesLow riskQuote: "All patients finished the study, without reporting of attrition during follow‐up" Selective reporting (reporting bias)Unclear riskComment: insufficient information to permit judgement of 'low risk' or 'high risk' (no protocol available or pre‐specified outcomes) Ramos 2003 Study characteristics Methods6‐arm, open‐label, parallel‐group RCT, with 7‐day duration of treatment and 10 days of follow‐up; follow‐up to 3 days after finishing the treatment Participants Location:Spain Setting of recruitment and treatment:3 ENT departments of 3 tertiary hospitals Sample size:300 patients Number randomised:50 in each group Number completed:50 in each group Participant (baseline) characteristics: Age (mean, range): 5 to 73, n = 36 (12%) were children (< 14 years) Gender (F/M): 134 (44.7%)/166 (55.3%) Main diagnosis: chronic ear discharge, which comprised the following groups: Simple chronic otitis media (n = 128): no lesions of the ossicular chain, erosion of the tympanic frame, absence of tympanosclerosis and no evidence of cholesteatoma Chronic otitis media with osteolysis (OMCO) (n = 57): osteolytic lesions and alterations of the mucosa of medium type, types of pansclerosis, granulomatous lesions, atelectasis or marginal perforation, without signs of cholesteatoma Chronic cholesteatoma (n = 42): signs of infection of middle cholesteatoma Chronic otorrhoea in operated ears (n = 73): radical mastoidectomy (n = 40), tympanoplasty infection (n = 21), transtympanic grommets (n = 12) High‐risk population: Cleft palate (or other craniofacial malformation): not reported Down syndrome: not reported Indigenous groups (Australian Aboriginals/Greenland natives): not reported Immunocompromised: not reported Diagnosis method: Confirmation of perforated tympanic membrane :all had otoscopic examination at baseline; 62.3% had perforation confirmed (marginal perforation: 1.43% non‐marginal perforation: 42% attical perforation) Presence of mucopurulent discharge: otoscopic examination Duration of symptoms (discharge): "for more than 6 weeks or sporadically with 3 or more episodes in the last year" Other important effect modifiers Alternative diagnosis of ear discharge: cholesteatoma (n = 42) Number who have previously had grommets inserted: 12 Number who have had previous ear surgery: 73 Number who had previous antibiotic treatment for CSOM: 65.6% (n = 197) Inclusion criteria: Chronic otorrhoea, meaning that those cases presenting permanent, unilateral or bilateral, otorrhoea for more than 6 weeks, or sporadically, as long as it has manifested 3 or more episodes in the last year, regardless of the origin and morphological changes Exclusion criteria: Pregnant women Patients with renal and/or hepatic impairment patients who had undergone topical or systemic antibiotic treatment during the 48 hours prior to the start of the study Patients with mycotic infections Patients who had concomitant treatment with theophylline or antacids, which include magnesium hydroxide or aluminium hydroxide in the formulation Interventions Group A (n = 50):oral ciprofloxacin 500 mg 12‐hourly PLUS topical ciprofloxacin 0.2% 0.5 mL, 8‐hourly for 7 days Group B (n = 50):topical ciprofloxacin 0.3% PLUS fluocinolone 0.5 mL, 8‐hourly for 7 days Group C (n = 50):topical ciprofloxacin 0.5%, 0.5 mL, 8‐hourly for 7 days Group D (n = 50):topical ciprofloxacin 0.2%, 0.5 mL, 8‐hourly for 7 days Group E (n = 50):topical polymyxin 10,000 IU, neomycin 0.0035 g, hydrocortisone 0.00025 g, 8‐hourly for 7 days Group F (n = 50):oral ciprofloxacin 500 mg, 12‐hourly for 7 days Concurrent treatment:not reported Outcomes Outcomes of interest in the review: Primary outcome: Resolution of ear discharge ("dry ear"), unclear whether otoscopically confirmed, at 1 to 2 weeks Secondary outcomes: Hearing: hearing tests at time of diagnosis, at 8 days and at 15 days Suspected ototoxicity Suspected ototoxicity: diagnosed with audiogram (specific definition not stated, but study reports 0/125 patients had ototoxicity from treatment) Balance problems/dizziness/vertigo: not reported Tinnitus: not reported Funding sourcesNo information provided Declarations of interestNo information provided Notes Unit of randomisation:person Methods for including patients with bilateral disease:not reported Risk of bias Bias Authors' judgement Support for judgement Random sequence generation (selection bias) Unclear risk Quote: "patients were randomly allocated into 6 groups" Comment: insufficient information about the sequence generation. In addition, the study stated that children were not randomised to oral ciprofloxacin: unclear how this was done. Allocation concealment (selection bias) Unclear risk Quote: "patients were randomly allocated into 6 groups" Comment: insufficient information about allocation concealment. There is no information about how they maintained allocation concealment but did not randomise children to ciprofloxacin. Blinding of participants and personnel (performance bias)All outcomesHigh riskComment: no information provided about blinding method or use of placebo. The treatment arms involved different dosage forms (oral versus ear drops) – blinding of these interventions is impossible without the use of placebo. Blinding of outcome assessment (detection bias)All outcomesHigh riskComment: no information provided regarding who assessed the outcomes. For subjective outcomes (otoscopy examinations) the knowledge of treatment group may influence the results. Incomplete outcome data (attrition bias)All outcomes Low risk Comment: 2 patients on oral treatment were reported as withdrawn due to gastrointestinal adverse events. Unclear from which group this was and whether these patients were counted in the percentages reported. The percentage of withdrawal is small. Selective reporting (reporting bias)Unclear riskComment: audiogram was performed at baseline and end of treatment, but not reported Yuen 1994 Study characteristics MethodsNon‐blinded, parallel‐group RCT, with 1 week of treatment and a total of 2 weeks follow‐up Participants Location:Hong Kong, 1 site Setting of recruitment and treatment:outpatient clinic of the Otorhinolaryngology Unit, the University of Hong Kong, Queen Mary Hospital between October 1991 and February 1993 Sample size:60 Number randomised:30 in ofloxacin group, 30 in amoxicillin‐clavulanic acid group Number completed:29 in ofloxacin group, 27 in amoxicillin‐clavulanic acid group Participant (baseline) characteristics: Age: 18 to 70 years with a median of 35 years Gender (F/M): 33 (55%)/23 (45%) Main diagnosis: active chronic suppurative otitis media with central perforation High‐risk population: Cleft palate (or other craniofacial malformation): not reported Down syndrome: not reported Indigenous groups (Australian Aboriginals/Greenland natives): not reported Immunocompromised: not reported Diagnosis method: Confirmation of perforated tympanic membrane: size of perforation documented Presence of mucopurulent discharge: 39/60 Duration of symptoms (discharge): not reported Other important effect modifiers: Alternative diagnosis of ear discharge: none Number who have previously had grommets inserted: none Number who have had previous ear surgery: not reported Number who had previous antibiotic treatment for CSOM: not reported Inclusion criteria: Active chronic suppurative otitis media with central perforation Exclusion criteria: Cholesteatoma Discharging mastoid cavity Large aural polyp Acute traumatic perforation Acute otitis media Presence of a grommet History of radiotherapy of temporal bone and otomycosis All patients had no prior antibiotic treatment for at least 1 week before commencement of treatment Interventions Intervention (n = 30):0.3% ofloxacin ear drops 3 times daily for 1 week Comparator group (n = 30): oral amoxicillin‐clavulanic acid (375 mg) 3 times daily for 1 week Concurrent treatment:suction clearance of aural pus under microscopy (conducted after obtaining microbiology sample at baseline) Outcomes Outcomes of interest in the review: Primary outcomes: Complete resolution of ear discharge, measured at between 1 to 2 weeks Pain (otalgia) Secondary outcomes: Hearing loss (pure‐tone audiograms were carried out before commencement and after completion of treatment) Suspected ototoxicity (tinnitus, hearing loss, dizziness) Funding sources"This study was supported in part by a grant (No. 335/048/0040) from the committee on research and conference grants of the University of Hong Kong." Declarations of interestNo information provided Notes Unit of randomisation:person Methods for including patients with bilateral disease:not reported Risk of bias Bias Authors' judgement Support for judgement Random sequence generation (selection bias)Low riskQuote: "patients were randomized to two groups by drawing concealed envelopes."Comment: adequate randomisation sequence generation. Allocation concealment (selection bias)Low riskQuote: "patients were randomized to two groups by drawing concealed envelopes."Comment: no further information about how the allocation was concealed (e.g. opaque envelope) but should be adequate Blinding of participants and personnel (performance bias)All outcomesHigh riskComment: no blinding or placebo mentioned – should be unblinded study Blinding of outcome assessment (detection bias)All outcomes Low risk Quote: "The patients were instructed for the documentation of the degree of severity (graded into mild, moderate, and severe) of symptoms of otalgia, tinnitus, hearing loss, dizziness, and aural discharge daily for 2 weeks on a card…" Comment: patients were the main assessors of outcomes – not blinded and most outcomes were subjective Incomplete outcome data (attrition bias)All outcomes Low risk Comment: 1/30 (3%) in the ofloxacin group and 2/30 (7%) in the amoxicillin‐clavulanic acid group defaulted visits. One patient in the amoxicillin‐clavulanic acid group stopped treatment early due to adverse effects. The attrition percentage was small and clearly documented. Selective reporting (reporting bias)Unclear riskComment: no published protocol was found. Some of the outcomes described as collected in the methods section were not fully reported, e.g. otalgia, degree of severity. CSOM: chronic suppurative otitis media; F: female; M: male; RCT: randomised controlled trial; WHO: World Health Organization Characteristics of excluded studies [ordered by study ID] Jump to: included studies awaiting classification StudyReason for exclusion Abbott 2016POPULATION: not CSOM (acute otitis media without perforation) Adler 2000POPULATION: acute otitis media with effusion for less than a week; patients with chronic or subchronic otitis media, or acute exacerbation of otitis media were specifically excluded Agro 1998STUDY DESIGN: not a RCT (current practice versus history control) Arguedas 1993STUDY DESIGN: not a RCT (all patients had the same intervention) Aslan 1998STUDY DESIGN: no description of randomisationINTERVENTION: low‐dose versus high‐dose topical antibiotics Asmatullah 2014COMPARISON: variety of topical antibiotics (see CSOM‐1) Baba 1980INTERVENTION: comparison of antibiotics within same class and spectrum of activity (cefraxadine versus cephalexin); cefraxadine a withdrawn drugDURATION: only 6 days of follow‐up Baba 1982bPOPULATION: acute suppurative otitis media, including acute otitis media Baba 1983POPULATION: acute suppurative otitis media Baba 1983bPOPULATION: acute suppurative otitis media Baba 1983cPOPULATION: acute suppurative otitis media Baba 1986STUDY DESIGN: not a RCT (all patients received the same treatment, aztreonam) Baba 1987POPULATION: acute suppurative otitis media Baba 2008STUDY DESIGN: not a RCT (all patients received the same intervention) Baba 2008aSTUDY DESIGN: not a RCT (all patients received the same intervention) Bakir 2013STUDY DESIGN: not a RCT (prospective case‐control study) Berman 1990POPULATION: middle ear effusion, not CSOM Block 2000POPULATION: not CSOM (acute otitis media without perforation of tympanic membrane) Bogomil'skii 1999POPULATION: less than half were COM. Not able to distinguish COM patients from other types of diagnosis ‐ data not reported separately Brook 1979STUDY DESIGN: not a RCT ‐ (alternative treatment) aminoglycosides only added when Gram‐negative organisms present in large numbers Brook 1980STUDY DESIGN: not a RCT (all patients received the same intervention, additional intervention only added based on bacteriological findings) Bross Soriano 1996POPULATION: AOM; patients with CSOM were excluded Browning 1983INTERVENTION: standard antibiotics were not given, the choice was dependent on cultures Browning 1983bINTERVENTION: culture sensitivity‐based prescribing versus empirical treatment with metronidazole Browning 1984STUDY DESIGN: not a RCT Clayton 1990POPULATION: less than 20% had otorrhoea with "central perforation"; others were patients with otitis externa and mastoid cavity problems Connolly 1997INTERVENTION: compared method of administration i.e. delivery system (spray versus drops) of neomycin‐dexamethasone CTRI/2019/09/021197INTERVENTION: ayurvedic preparation is not an intervention under investigation Deguchi 1985STUDY DESIGN: not a RCT Deguchi 1986STUDY DESIGN: not a RCT Deitmer 2002STUDY DESIGN: not a RCT Dellamonica 1995INTERVENTION: within‐class comparison (cephalosporin) Eason 1986COMPARISON: systemic antibiotics versus none (see CSOM‐2), topical steroids versus none (see CSOM‐4), antiseptics versus none (see CSOM‐5), and aural toilet versus none (see CSOM‐7) Esposito 2000STUDY DESIGN: not a RCT (all patients had the same intervention ‐ ceftazidime) Fliss 1990COMPARISON: variety of systemic antibiotics (see CSOM‐2) Fombeur 1994STUDY DESIGN: not a RCT (no mention of randomisation)INTERVENTION: high‐dose versus low‐dose ciprofloxacin Fradis 1997COMAPRISON: variety of topical antibiotics (see CSOM‐1) and topical antiseptic versus none (see CSOM‐6) Garcia‐Rodriguez 1993POPULATION: mixture of patients, less than half had CSOM; patients were not stratified by diagnosis Gehanno 1997STUDY DESIGN: not a RCT (all patients had the same intervention) Ghosh 2012COMPARISON: variety of systemic antibiotics (see CSOM‐2) Granath 2007POPULATION: not CSOM (patients with recurrent acute otitis media with discharge through tympanostomy tube) Gupta 2015COMPARISON: antibiotic versus antiseptic (see CSOM‐6) Gyde 1978COMPARISON: variety of topical antibiotics (see CSOM‐1) Gyde 1981POPULATION: less than 50% (27/68) had CSOM Gyde 1982POPULATION: less than 50% had CSOM Hemlin 1997POPULATION: unilateral or bilateral secretory otitis media (COME)INTERVENTION: systemic corticosteroids Hwang 2015STUDY DESIGN: not a RCT (case‐control study) I‐HEAR‐BETACOMPARISON: systemic antibiotic versus none (see CSOM‐2), topical antiseptic versus none (see CSOM‐5), topical antiseptic versus topical antibiotic (see CSOM‐6) IRCT20130427013136N6POPULATION: patients had otitis externa IRCT2016082313136N4POPULATION: patients had otomycosis ISRCTN12149720INTERVENTION: antimicrobial peptide OP145 ISRCTN84220089INTERVENTION: antimicrobial peptide OP145 Jahn 1984STUDY DESIGN: not a RCT Jamallulah 2016COMPARISON: variety of topical antibiotics (see CSOM‐1) Jang 2004STUDY DESIGN: not a RCT (mentioned use of a "control group", no mention of randomisation) Jaya 2003COMPARISON: topical antibiotic versus topical antiseptic (see CSOM‐6) Jiang 2016INTERVENTION: comparison of two agents of the same class of antibiotics (erythromycin versus azithromycin) used in addition to a Traditional Chinese Medicine product Kadar 2003STUDY DESIGN: not a RCT Kasemsuwan 1997COMPARISON: topical antibiotic versus none (see CSOM‐1) Kashiwamura 2004STUDY DESIGN: cohort (no comparison group)POPULATION: less than 50% with CSOM Kaygusuz 2002COMPARISON: topical antibiotics versus none (see CSOM‐1) and variety of topical antibiotics plus steroids (see CSOM‐4) Kenna 1986STUDY DESIGN: not a RCT; cohort study (no comparison group) Khanna 2000INTERVENTION: culture sensitivity‐based prescribing Khon 2012POPULATION: not CSOM ‐ either diffuse otitis externa or acute otitis externaSTUDY DESIGN: no evidence of randomisation Kothari 1969STUDY DESIGN: not a RCT (no comparison) Kovacic 1999STUDY DESIGN: not a RCT (compared ofloxacin in patients who had previous ear surgery versus no previous ear surgery) Kurilin 1976STUDY DESIGN: not a RCT (no mention of RCT design or control group included for comparison) Lancaster 1999STUDY DESIGN: not a RCT (cross‐sectional survey) Lancaster 2003STUDY DESIGN: not a RCT (compared compliance) Lang 1992STUDY DESIGN: not a RCT (case series) Lautala 1983STUDY DESIGN: not a RCT (case series) Legent 1994COMPARSION: variety of systemic antibiotics (see CSOM‐2) Li 2004INTERVENTION: not an intervention of interest to the review (self‐prepared Chinese herbal medicine ear drops) Liu 1990STUDY DESIGN: not a RCT Liu 2003COMPARISON: variety of topical antibiotics (see CSOM‐1) Loock 2012COMPARISON: variety of topical antiseptics (see CSOM‐5) and topical antibiotic versus topical antiseptic (see CSOM‐6) Lorente 1995COMPARISON: variety of topical antibiotics (see CSOM‐1) Macfadyen 2005COMPARISON: topical antibiotic versus topical antiseptic (see CSOM‐6) Merifield 1993STUDY DESIGN: not a RCT (case series) Mesure 1973POPULATION: in clinical trial part of study (part 2) only one case of chronic otitis media Minja 2006COMPARISON: systemic antibiotic versus none (see CSOM‐2) and topical antiseptic versus none (see CSOM‐5) Mira 1993COMPARISON: adding topical antibiotic to systemic antibiotic (see CSOM‐1) Morgon 1976STUDY DESIGN: single arm study Nawasreh 2001COMPARISON: variety of topical antibiotics (see CSOM‐1) Nwokoye 2015COMPARISON: variety of systemic antibiotics (see CSOM‐2) Onali 2018COMPARISON: systemic antibiotic versus none (see CSOM‐2) Papastavros 1989COMPARISON: topical antiseptic versus none (see CSOM‐5) Poliakova 1991STUDY DESIGN: not a RCT Principi 1995POPULATION: acute and recurrent otitis media Quick 1973POPULATION: not CSOM (included acute tonsillitis, acute pharyngitis, acute sinusitis, acute otitis media, chronic sinusitis and peritonsillar abscess) Quick 1975POPULATION: not CSOM (only 6/145 patients had otitis media) Renuknanada 2014COMPARISON: systemic antibiotics added to topical antibiotics (see CSOM‐2) Roberts 2004POPULATION: acute suppurative otitis media (duration of discharge less than 2 weeks) Rotimi 1990COMPARISON: variety of systemic antibiotics (see CSOM‐2) Saez‐Llorens 2005POPULATION: AOM Sanchez Gonzales 2001COMPARISON: variety of systemic antibiotics (see CSOM‐2) Siddique 2016COMPARISON: variety topical antibiotics (see CSOM‐1) Singhal 1992STUDY DESIGN: not a RCT (no comparison group) Somekh 2000COMPARISON: variety of systemic antibiotics (see CSOM‐2) Stenstrom 1991POPULATION: acute otitis media; not CSOM Sugiyama 1981STUDY DESIGN: not a RCT (no indication of randomisation) Sultan 2017STUDY DESIGN: not a RCT ‐ single intervention (oral levofloxacin) studied Sumitsawan 1995STUDY DESIGN: not a RCT ‐ single intervention (ofloxacin drops) studied Supiyaphun 1995STUDY DESIGN: not a RCT (cohort ‐ all patients received same treatment) Tachibana 1986STUDY DESIGN: not a RCT (all patients received same treatment) Thomsen 1976STUDY DESIGN: not a RCTPOPULATION: acute suppurative otitis media Tong 1996COMPARISON: steroids added to topical antibiotics (see CSOM‐4) Tutkun 1995COMPARISON: variety of topical antibiotics (see CSOM‐1) Van de Heyning 1986STUDY DESIGN: not a RCT (cohort ‐ all patients received same treatment) van der Veen 2007COMPARISON: systemic antibiotics versus none (see CSOM‐2) van Dongen 2014POPULATION: 1) inclusion of minimum 2 weeks (review defined exclusion of 6 weeks perioperatively); 2) maximum duration of otorrhoea was 1 week van Hasselt 1997COMPARISON: variety of topical antibiotics (see CSOM‐1) and topical antibiotics versus topical antiseptics (see CSOM‐6) van Hasselt 1998aCOMPARISON: variety of topical antibiotics (see CSOM‐1) Vishwakarma 2015COMPARISON: topical antiseptic versus topical antibiotic (see CSOM‐6) Wintermeyer 1997STUDY DESIGN: not a RCT (cohort) AOM: acute otitis media; COM: chronic otitis media; CSOM: chronic suppurative otitis media; OME: otitis media with effusion; RCT: randomised controlled trial For CSOM‐1 to ‐7 Cochrane Reviews seeTable 1. Characteristics of studies awaiting classification [ordered by study ID] Jump to: included studies excluded studies Mehboob 2019 Methods3‐arm, unclear blinding, single‐centre, parallel‐group, unclear if RCT, with unclear duration of treatment and unclear duration of follow‐up Participants Location:Pakistan, 1 site Setting of recruitment and treatment:ENT department of tertiary health care hospital in Karachi, May to September 2018 Sample size:120 participants (120 ears) Number randomised:40 treated with ciprofloxacin, 40 treated with amoxicillin‐clavulanic acid, 40 untreated (control) Number completed:not reported Participant (baseline) characteristics: Age: range 18 to 75 years (inclusion criteria) Gender (F/M): 60 female (50%)/60 male (50%) Main diagnosis: unilateral ear presentation of chronic suppurative otitis media High‐risk population: Cleft palate (or other craniofacial malformation): not reported Down syndrome: not reported Indigenous groups (Australian Aboriginals/Greenland natives): not reported Immunocompromised: not reported Diagnosis method: Confirmation of perforated tympanic membrane: not reported, otoscopically confirmed Presence of mucopurulent discharge: without fluid discharge at time of pure‐tone audiometry Duration of symptoms (discharge): not reported Other important effect modifiers: Alternative diagnosis of ear discharge: not reported Number who have previously had grommets inserted: not reported Number who have had previous ear surgery: not reported Number who had previous antibiotic treatment for CSOM: not reported Inclusion criteria: Patients aged between 18 to 75 years Both the genders Unilateral ear presentation of CSOM without fluid discharge at the time of pure‐tone audiometry Exclusion criteria: Paediatric population Patients over 75 years History of neurological disorder or profound psychological distress, cardiac arrest, family history of sensorineural hearing loss or using hearing aid Interventions Intervention (n = 40 participants):ciprofloxacin, method of administration not reported, dosage not reported, duration of treatment not reported Intervention (n = 40 participants):amoxicillin‐clavulanic acid, method of administration not reported, dosage not reported, duration of treatment not reported Comparator group (n = 40 participants):untreated Concurrent treatment:not reported Outcomes Outcomes of interest in the review: Primary outcomes: Not reported Secondary outcomes Hearing: pure‐tone audiometry was examined at different frequencies using an audiometer with aural headphones to measure hearing thresholds Notes Funding sources:"University Research funding committee of JSMU" Unit of randomisation:person Methods for reporting outcomes of patients with bilateral disease:not reported, only included unilateral presentation of CSOMHearing thresholds divided into 7 categories as normal (25 dB), mild (26 to 34 dB) hearing loss (HL), moderate (50 to 64 dB) HL, severe (65 to 79 dB) HL, profound (80 to 94 dB) HL and deafObjective: to study the correlation of hearing loss with depression, anxiety and stress in patients suffering from chronic suppurative otitis media in local population of PakistanDepression, anxiety and stress were scored taking depression, anxiety and stress scale (DASS) as tool and Likert scale was taken for scoringAwaiting author reply regarding randomisation Samarei 2014 Methods2‐arm, non‐blinded, single‐centre, parallel‐group "RCT", with 10 to 17 days duration of treatment and 30 days duration of follow‐up Participants Location:Iran, 1 site Setting of recruitment and treatment:not reported Sample size: Number randomised:unclear – it appears some patients may have been excluded from the study Number completed:40 in topical ciprofloxacin, 32 in systemic ciprofloxacin Participant (baseline) characteristics: Age: not reported Gender (F/M): not reported Main diagnosis: purulent active otorrhoea and perforated tympanic membrane for more than 3 months High‐risk population: unclear Cleft palate (or other craniofacial malformation): not reported Down syndrome: not reported Indigenous groups (Australian Aboriginals/Greenland natives): not reported Immunocompromised: not reported Diagnosis method: Confirmation of perforated tympanic membrane: unclear (no method described but inclusion criteria implies all patients had perforated membrane) Presence of mucopurulent discharge: unclear (no method described but inclusion criteria implies all patients had purulent discharge) Duration of symptoms (discharge): 3 months (inclusion criteria) Other important effect modifiers: Alternative diagnosis of ear discharge: 0% Number who have previously had grommets inserted: not reported Number who have had previous ear surgery: not reported Number who had previous antibiotic treatment for CSOM: not reported Inclusion criteria: Purulent active otorrhoea and perforated tympanic membrane for more than 3 months Exclusion criteria: Age less than 18 years Pregnancy Breastfeeding Recent local drug "Proposals for viral infections" Sensitivity to the fluoroquinolone drug group Use of systemic medications that are ototoxic Concurrent infection of the middle and external fungal Interventions Intervention (n = 40):ciprofloxacin ear drops, unclear concentration, 2 drops twice daily, 10 days treatment and additional 7 days if ear not dry at 10 days Comparator group (n = 32): ciprofloxacin orally 500 mg, 1 tablet twice daily, 10 days treatment and additional 7 days if ear not dry at 10 days Concurrent treatment:"regular suction for outer middle ear washings." No other concurrent treatment mentioned. Outcomes Outcomes of interest in the review: Primary outcomes: Adverse effects (reported as measured in the methods but no results given) Secondary outcomes: Hearing loss (measured as change in hearing threshold from baseline or at endpoint) Adverse effects from treatment (reported as measured in the methods but no results given) Notes Unit of randomisation:person Methods for including patients with bilateral disease:not reportedAwaiting author reply regarding randomisation CSOM: chronic suppurative otitis media; F: female; M: male; RCT: randomised controlled trial Data and analyses Open in table viewer Comparison 1. Topical quinolone versus oral quinolone Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size 1.1 Resolution of ear discharge Show forest plot4Risk Ratio (M‐H, Fixed, 95% CI)Subtotals only Analysis 1.1 Comparison 1: Topical quinolone versus oral quinolone, Outcome 1: Resolution of ear discharge 1.1.1 1 to 2 weeks3285Risk Ratio (M‐H, Fixed, 95% CI)1.48 [1.24, 1.76] 1.1.2 2 to 4 weeks140Risk Ratio (M‐H, Fixed, 95% CI)2.12 [1.20, 3.75] Comparison 2. Topical quinolone versus intramuscular gentamicin Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size2.1 Resolution of ear discharge Show forest plot1Risk Ratio (M‐H, Fixed, 95% CI)Subtotals only Open in figure viewer Analysis 2.1Comparison 2: Topical quinolone versus intramuscular gentamicin, Outcome 1: Resolution of ear discharge2.1.1 2 to 4 weeks160Risk Ratio (M‐H, Fixed, 95% CI)1.92 [1.24, 2.98] Comparison 3. Topical quinolone versus oral amoxicillin‐clavulanic acid Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size 3.1 Resolution of ear discharge Show forest plot1Risk Ratio (M‐H, Fixed, 95% CI)Subtotals only Analysis 3.1 Comparison 3: Topical quinolone versus oral amoxicillin‐clavulanic acid, Outcome 1: Resolution of ear discharge 3.1.1 1 to 2 weeks156Risk Ratio (M‐H, Fixed, 95% CI)2.93 [1.50, 5.72] 3.2 Resolution of ear discharge ‐ sensitivity analysis, re‐including excluded case Show forest plot1Risk Ratio (M‐H, Fixed, 95% CI)Subtotals only Analysis 3.2 Comparison 3: Topical quinolone versus oral amoxicillin‐clavulanic acid, Outcome 2: Resolution of ear discharge ‐ sensitivity analysis, re‐including excluded case 3.2.1 1 to 2 weeks157Risk Ratio (M‐H, Fixed, 95% CI)3.03 [1.55, 5.95] Figures and Tables - Figure 1 Study flow diagram. Figures and Tables - Figure 2 'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies. Figures and Tables - Figure 3 'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study. Figures and Tables - Figure 4 Forest plot of comparison: 1 Topical quinolone versus oral quinolone, outcome: 1.1 Resolution of ear discharge. Figures and Tables - Figure 5 Forest plot of comparison: 3 Topical quinolone versus intramuscular (IM) gentamicin, outcome: 3.1 Resolution of ear discharge. Figures and Tables - Figure 6 Forest plot of comparison: 2 Topical quinolone versus oral amoxicillin‐clavulanic acid, outcome: 2.1 Resolution of ear discharge. Navigate to figure in Review Print figure Open in new tab Figures and Tables - Analysis 1.1 Comparison 1: Topical quinolone versus oral quinolone, Outcome 1: Resolution of ear discharge Figures and Tables - Analysis 2.1 Comparison 2: Topical quinolone versus intramuscular gentamicin, Outcome 1: Resolution of ear discharge Navigate to figure in Review Print figure Open in new tab Figures and Tables - Analysis 3.1 Comparison 3: Topical quinolone versus oral amoxicillin‐clavulanic acid, Outcome 1: Resolution of ear discharge Navigate to figure in Review Print figure Open in new tab Figures and Tables - Analysis 3.2 Comparison 3: Topical quinolone versus oral amoxicillin‐clavulanic acid, Outcome 2: Resolution of ear discharge ‐ sensitivity analysis, re‐including excluded case Summary of findings 1. Topical quinolone compared to oral quinolone for chronic suppurative otitis media Topical quinolone compared to oral quinolone for chronic suppurative otitis media Patient or population:people (of any age) with CSOM Setting:various; general hospital in Spain (de Miguel 1999;Povedano 1995), three tertiary hospitals in Spain (Ramos 2003) and university clinic in Italy (Esposito 1990) Intervention:topical quinolone Comparison:oral quinolone Outcomes Relative effect (95% CI) Number of participants (studies) Anticipated absolute effects * (95% CI) Certainty of the evidence (GRADE) What happens Without topical (ear drops) With topical (ear drops) DifferenceResolution of ear discharge ‐ 1 to 2 weeksAssessed with: 2 studies otoscopically confirmed, 2 studies unclear methodFollow‐up: 1 to 2 weeksRR 1.48(1.24 to 1.76)285(3 RCTs)Study population⊕⊕⊝⊝ low 1,2Topical antibiotics (quinolones) may slightly increase the resolution of ear discharge at 1 to 2 weeks.57.1%84.6%(70.9 to 100)27.5% more(13.8% more to 42.9% more)Resolution of ear discharge ‐ after 4 weeksNo study reported this outcome.Health‐related quality of lifeNo study reported this outcome.Ear pain (otalgia) or discomfort or local irritationNo study reported this outcome.HearingNo study reported results for this outcome, despite three studies mentioning it as an outcome of interest.Serious complicationsNo studies reported this outcome.Suspected ototoxicityAssessed with: unclear methodFollow‐up: 10 to 15 days—265(3 RCTs)Three studies reported that they did not suspect ototoxicity in any participants, but it is unclear how this was measured (de Miguel 1999;Esposito 1990;Ramos 2003).⊕⊝⊝⊝ very low 3,4It is unclear if there is a difference in ototoxicity between topical and systemic quinolones.* The risk in the intervention group(and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effectof the intervention (and its 95% CI). CI:confidence interval; RCT:randomised controlled trial; RR:risk ratio GRADE Working Group grades of evidence High certainty:We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty:We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty:Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty:We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect 1Downgraded to low certainty: downgraded by one level for risk of bias (study limitations) as all studies had no blinding of participants and did not provide any descriptions of randomisation and allocation concealment methods. Outcomes were not well‐defined and were subjective. 2Downgraded to low certainty: downgraded by one level due to imprecision as they were very small studies, with a small total sample size. 3Downgraded by two levels for risk of bias (study limitations) as the studies did not blind participants and did not provide any descriptions of randomisation and allocation concealment methods. It was also unclear whether the outcome was assessed appropriately as insufficient information was provided. 4Downgraded by one level due to imprecision as numeric results were not reported. Figures and Tables - Summary of findings 1. Topical quinolone compared to oral quinolone for chronic suppurative otitis media Navigate to table in Review Summary of findings 2. Topical quinolone compared to intramuscular gentamicin for chronic suppurative otitis media Topical quinolone compared to intramuscular gentamicin for chronic suppurative otitis media Patient or population:adults with CSOM Setting:university clinic, Italy Intervention:topical quinolone Comparison:intramuscular gentamicin Outcomes Relative effect (95% CI) Number of participants (studies) Anticipated absolute effects * (95% CI) Certainty of the evidence (GRADE) What happens Without topical quinolone With topical quinolone DifferenceResolution of ear discharge at 1 to 2 weeksThis study did not report this outcome.Resolution of ear discharge after 4 weeksThe study did not report this outcome.Health‐related quality of lifeThe study did not report this outcome.Ear pain (otalgia) or discomfort or local irritationAssessed with: self‐reportedFollow‐up: 21 days—60(1 RCT)The authors of the study reported that "no side effect was recorded in any patient", but it is not clear whether ear pain was included as a side effect.⊕⊝⊝⊝ very low 1,2It is unclear if there is a difference between topical quinolone compared with intramuscular gentamicin with regards to ear pain.HearingAssessed with: audiometryFollow‐up: 21 days—60(1 RCT)One study indicated that audiometry was performed after treatment, but only reported that "no worsening of the audiometric function related to local or parenteral therapy was observed".⊕⊝⊝⊝ very low 1,2It is unclear if there is a difference between topical quinolone compared with intramuscular gentamicin with regards to hearing.Serious complicationsAssessed with: self‐reportedFollow‐up: 21 days—60(1 RCT)The authors of the study reported that "no side effect was recorded in any patient".⊕⊝⊝⊝ very low 1,2It is unclear if there is a difference between topical quinolone compared with intramuscular gentamicin with regards to serious complications.Suspected ototoxicityAssessed with: audiometric and vestibular testsFollow‐up: 21 days—60(1 RCT)Audiometric measurement and vestibular tests were performed before and 24 hours after the end of the therapy, the authors stating that "no side effect was recorded".⊕⊝⊝⊝ very low 1,3,4It is unclear if there is a difference between topical quinolone compared with intramuscular gentamicin with regards to suspected ototoxicity.* The risk in the intervention group(and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effectof the intervention (and its 95% CI). CI:confidence interval; RCT:randomised controlled trial; RR:risk ratio GRADE Working Group grades of evidence High certainty:We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty:We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty:Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty:We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect 1Downgraded by two levels for imprecision as it was a single study, with very small sample size (60). Results were only provided as a narrative description. 2Downgraded by two levels for risk of bias (study limitations) as the study had no blinding of participants and did not provide any descriptions of randomisation and allocation concealment methods, and it was unclear whether the outcome was measured appropriately. 3Downgraded by one level for risk of bias as the study had no blinding of participants and did not provide any descriptions of randomisation and allocation concealment methods. 4Downgraded by one level for indirectness as it was unclear whether the outcome was assessed appropriately ‐ no information was provided regarding assessment of tinnitus, or whether bone conduction studies were used. Figures and Tables - Summary of findings 2. Topical quinolone compared to intramuscular gentamicin for chronic suppurative otitis media Summary of findings 3. Topical quinolone compared to oral amoxicillin‐clavulanic acid combination for chronic suppurative otitis media Topical quinolone compared to oral amoxicillin‐clavulanic acid combination for chronic suppurative otitis media Patient or population:adults with CSOM Setting:otorhinolaryngology outpatient clinic of a university hospital, Hong Kong Intervention:topical quinolone Comparison:oral amoxicillin‐clavulanic acid combination Outcomes Relative effect (95% CI) Number of participants (studies) Anticipated absolute effects * (95% CI) Certainty of the evidence (GRADE) What happens Without topical quinolone (ear drops) With topical quinolone (ear drops) DifferenceResolution of ear discharge ‐ 1 to 2 weeksAssessed with: unclear if otoscopically confirmedFollow‐up: 1 to 2 weeksRR 2.93(1.50 to 5.72)56(1 RCT)Study population⊕⊝⊝⊝ very low 1,2It is uncertain if there is a difference between topical quinolone (ear drops) and oral combination of amoxicillin‐clavulanic acid in resolution of ear discharge at 1 to 2 weeks.25.9%76.0%(38.9 to 100)50.0% more(13 more to 122.4 more)Resolution of ear discharge after 4 weeksThe study did not report this outcome.Health‐related quality of lifeThe study did not report this outcome.Ear pain (otalgia) or discomfort or local irritationAssessed with: self‐reportedFollow‐up: 2 weeks—56(1 RCT)The study reported that "no patient of the ofloxacin‐treated group complained of adverse side effects. There was no hypersensitivity reaction to the topical ofloxacin". It is not clear whether ear pain was specifically assessed.⊕⊝⊝⊝ very low 1,3It is unclear if there is a difference between topical quinolone compared with oral amoxicillin‐clavulanic acid with regards to ear pain.HearingAssessed with: bone conductionFollow‐up: 2 weeks—56(1 RCT)The study reported that "there were no significant differences between the pre‐treatment and post‐treatment audiograms of bone conduction thresholds at frequencies of 0.5, 1, 2 and 4KHz".⊕⊝⊝⊝ very low 1,3It is unclear if there is a difference between topical quinolone compared with oral amoxicillin‐clavulanic acid with regards to hearing.Serious complicationsThe study did not report this outcome.Suspected ototoxicityAssessed with: bone conductionFollow‐up: 2 weeks—56(1 RCT)Bone conduction studies were completed and the study authors reported that "there were no significant differences between the pre‐treatment and post‐treatment pure‐tone audiograms of bone conduction thresholds at frequencies of 0.5, 1, 2, and 4kHz". No further details were provided for the results of patient diaries on dizziness or tinnitus.⊕⊝⊝⊝ very low 1,3It is unclear if there is a difference between topical quinolone compared with oral amoxicillin‐clavulanic acid with regards to ototoxicity.* The risk in the intervention group(and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effectof the intervention (and its 95% CI). CI:confidence interval; RCT:randomised controlled trial; RR:risk ratio GRADE Working Group grades of evidence High certainty:We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty:We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty:Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty:We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect 1Downgraded by one level for risk of bias (study limitations) as there was no blinding of participants (although outcome assessors were blinded). 2Downgraded by two levels for imprecision as there was only one study with a very small sample size (56 participants). 3Downgraded by two levels due to imprecision as this was a single study with only 56 participants and the data were only reported narratively. Figures and Tables - Summary of findings 3. Topical quinolone compared to oral amoxicillin‐clavulanic acid combination for chronic suppurative otitis media Navigate to table in Review Table 1. Table of Cochrane Reviews Topical antibiotics with steroids Topical antibiotics Systemic antibiotics Topical antiseptics Aural toileting (ear cleaning)Topical antibiotics with steroidsReview CSOM‐4Topical antibioticsReview CSOM‐4Review CSOM‐1Systemic antibioticsReview CSOM‐4Review CSOM‐3Review CSOM‐2Topical antisepticsReview CSOM‐4Review CSOM‐6Review CSOM‐6Review CSOM‐5Aural toiletingReview CSOM‐4Not reviewedNot reviewedNot reviewedReview CSOM‐7Placebo (or no intervention)Review CSOM‐4Review CSOM‐1Review CSOM‐2Review CSOM‐5Review CSOM‐7CSOM‐1: Topical antibiotics for chronic suppurative otitis media (Brennan‐Jones 2020a).CSOM‐2: Systemic antibiotics for chronic suppurative otitis media (Chong 2021).CSOM‐3: Topical versus systemic antibiotics for chronic suppurative otitis media (Chong 2018b).CSOM‐4: Topical antibiotics with steroids for chronic suppurative otitis media (Brennan‐Jones 2020b).CSOM‐5: Topical antiseptics for chronic suppurative otitis media (Head 2020a).CSOM‐6: Antibiotics versus topical antiseptics for chronic suppurative otitis media (Head 2020b).CSOM‐7: Aural toilet (ear cleaning) for chronic suppurative otitis media (Bhutta 2020). Figures and Tables - Table 1. Table of Cochrane Reviews Table 2. Examples of antibiotics classes and agents with anti‐Pseudomonas activity Class of antibiotics Examples Route of administrationQuinolonesCiprofloxacin, ofloxacin, levofloxacinOral, intravenous, topicalAminoglycosidesGentamicin, tobramycinTopical or parenteralNeomycin/framycetinOnly topicalCephalosporinsCeftazidimeParenteralPenicillinsTicarcillin plus clavulanic acidParenteralMonobactamsAztreonamParenteral Figures and Tables - Table 2. Examples of antibiotics classes and agents with anti‐Pseudomonas activity Table 3. Summary of included studies Ref ID (no. participants) Setting Population Intervention 1 Intervention 2 Treatment duration Follow‐up Background Treatment Notes 1. Topical quinolone versus oral quinolonesde Miguel 1999(n = 75)Spain, general hospitalChronic otitis mediaMean age 39.6 yearsTopical ciprofloxacin 0.2%/0.5%, 3 drops/8 hoursOral ciprofloxacin, 500 mg/12 hours7 days15 daysAll patients had aspiration and cleaning of ear secretions before beginning treatmentAnalgesics and antipyreticsPart of a 5‐arm trialEsposito 1990(n = 40)Italy, university clinicMild or moderate CSOM in the acute stageMean age 38 yearsTopical ciprofloxacin 250 µg/mL in saline solution, 3 drops twice dailyOral ciprofloxacin 250 mg twice daily5 days, up to 10 days if not cured14 daysNonePart of 3‐arm trialPovedano 1995(n = 60)Spain, general hospitalActive phase of chronic otorrhoeaMean age 45 yearsTopical ciprofloxacin 250 µg/mL, 5 ear drops/12 hoursOral ciprofloxacin, 500 mg/12 hours10 days10 daysNone—Ramos 2003Ramos 2003(n = 150)Spain, ENT department of 3 tertiary hospitalsSimple chronic otitis media (42.7%), chronic otitis media with osteolysis (19%), chronic cholesteatoma (14%), chronic otorrhoea in operated ears 24.3%)Age range 5 to 73, 12% were children < 14 yearsTopical ciprofloxacin 0.2%/0.5%, 0.5 mL/8 hoursOral ciprofloxacin 500 mg, 12‐hourly7 days10 daysNonePart of 6‐arm trial 2. Topical quinolone versus intramuscular gentamicinEsposito 1992(n = 60)Italy, university clinicMild to moderate otitis media in acute stage with perforation of tympanic membraneAdults > 18 years oldTopical ciprofloxacin hydrochloride, 250 mg/mL, 12‐hourlyIntramuscular gentamicin sulphate, 80 mg, 12‐hourly5 to 10 days21 days after interruption of treatmentNone— 3. Topical quinolone versus oral systemic beta‐lactamsYuen 1994(n = 60)Hong Kong, university otorhinolaryngology outpatient clinicActive chronic suppurative otitis media with central perforationAge range 18 to 70, median 35Topical ofloxacin 0.3%, 3 times dailyOral amoxicillin‐clavulanic acid 375 mg, 3 times daily1 week2 weeksSuction clearance of aural pus under microscopy conducted after obtaining microbiology sample at baseline—CSOM: chronic suppurative otitis media
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(PDF) 121: Mesenchymal stem cells for treatment of steroid-resistant graft-versus-host disease PDF | On Feb 1, 2007, S.-J. Ho and others published 121: Mesenchymal stem cells for treatment of steroid-resistant graft-versus-host disease | Find, read and cite all the research you need on ResearchGate 121: Mesenchymal stem cells for treatment of steroid-resistant graft-versus-host disease February 2007 Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation13(2):46-47 DOI: 10.1016/j.bbmt.2006.12.125 License CC BY-NC-ND 4.0 Authors: <here is a image a6186a5c26e9c4b4-b4f34799df86e3da> Shir-Jing Ho St George Hospital <here is a image 1937ee36a50dd27a-fa33d150fae83bfe> Pamela Dyson SA Pathology <here is a image f2f62089ad6ff61c-d19572ff1996375a> T. Rawling T. Rawling <here is a image f2f62089ad6ff61c-d19572ff1996375a> J. Stevens J. Stevens Figures <here is a image a4f9cd17579f7750-ff3ad9d068380cb9> Patient characteristics and summary of results … Figures - available via license: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International to39.5%ofeligiblecontrols.Threepatientsdied,(1relapse,2 infection)comparedto17controls(9relapse,5infection,3 GvHD).Longerfollow-upandimmunerecoverydataarecontinu- ing. MSCuseisfeasibleandsafewithoutinfusionaltoxicitiesand,as ourstudyseemstosuggest,stabilizeengraftment.Basedonour findings,wheregraftdysfunction,delayedhematological(immune) recoverycompromisethesuccessofstemcelltransplantoutcome, clinicalrandomizedstudiesofMSCsarewarranted. Table1 Patientcharacteristicsandsummaryofresults PATIENTS (n ⴝ10) CONTROLS (n ⴝ48) Male:Female6(60%):4(40%)29(60%):19(40%) Age(range)8years(2–15)8years(6mo–18) Malignant7(70%)34(70%) Immune2(25%)6(13%) Benign1(13%)8(17%) DonorMale:Female5:324:24 CD34infused31.8(SD3.1)20(SD6.8).NS CD3infused0.3(SD0.30)0.68(SD0.7).NS Overallsurvival 7/10(70%) FU3-48mo 31/48(64%) FU2-6y DaystoLeukocyte > 1.0 ⴛ109/l12(SD1.9)18(SD3.3)p ⴝ 0.0005 DaystoNeutrophil > 0.5 ⴛ109/l13(SD1.5)15(SD3.6)p ⴝ 0.14 DaystoPlatelets > 20 ⴛ109/l13(SD2.7)21(SD14.7)p ⴝ 0.08 DaystoReticulocytes > 2015(SD4.9)35(SD14.9)p ⴝ 0.04 119 CO-TRANSPLANTATIONOFMESENCHYMALSTEMCELLSANDHEMA- TOPOIETICSTEMCELLS LeBlanc,K. 1,2 ,Sundberg,B. 1 ,Lonnies,H. 1 ,Aschan,J. 2,3 , Barkholt,L. 1,2 ,Gustafsson,B. 4 ,Ringden,O. 1,21 DivisionofClinical Immunology,F79,KarolinskaUniversityHospitalHuddinge,Karolin- skaInstitutet,Stockholm,Sweden; 2 CenterforAllogeneicStemCell Transplantation,HuddingeUniversityHospital,Stockholm,Sweden; 3 DivisionofHematology,M54,KarolinskaUniversityHospitalHud - dinge,KarolinskaInstitutet,Stockholm,Sweden; 4 DepartmentofPedi - atrics,KarolinskaUniversityHospitalHuddinge,Stockholm,Sweden. Sevenpatients,3leukemics,2patientswithsevereaplasticane- mia(SAA)and2SCIDpatients,underwentco-transplantation withmesenchymalstemcells(MSC)andhematopoieticstemcells (HSC).MSCweregiveninapilotstudyto4patientsandforgraft failureandretransplantationto3patients.HSCTdonorswere3 HLA-identicalsiblingsand4unrelated(2matchedand1major mismatchedunrelatedand1mismatchedunrelatedcordblood). Conditioningwasmyeloablativein4patientsandRICin3pa- tients.MSCdonorswereHLA-identicalsiblingsin3casesand haploidenticalin4cases.Passage2-3MSCweregivenatadoseof 1 ⫻10 6 /kgpatientweightwithin4hoursoftheHSCTgraft. ANC ⬎ 0.5 ⫻10 9 /Lwasreachedinamedianof12(range10-28) days.Platelets ⬎ 30 ⫻10 9 /Lwasachievedinamedianof12(8-36) days.Allpatientshad100%donorchimerismforCD3,CD19and CD33within100days.AcuteGvHDgrade0-Iwasseenin5 patients,twopatientshadgradeIIoneproceededtochronic GvHD.Onepatientdiedofaspergillosis,theotherpatientsare aliveandwell. OnepatientwithSAAwasonCyclosporinforHenoch-Scho¨nlein purpurasincemanyyears.Thisandgraftfailureresolvedafter retransplantationofMSC ⫹HSC. Conclusion: MSCco-transplantationresultedinfastengraft- mentofANCandplateletsand100%donorchimerism,evenin3 patientsregraftedforgraftfailure/rejection. 120 LONGTERMENGRAFTMENTAFTERALLOGENEICTRANSPLANTATION FORBETA-THALASSEMIAMAJOR:EVIDENCEFORAROLEOFCD3 CELLSEARLYAFTERTRANSPLANTATION Nuernberger,W.A. 1 ,Thiele,B. 2 ,Kraut,L. 1 ,Fauser,A.A. 11 Clinicfor BMTandHematology/Oncology,Idar-Oberstein,Germany; 2 Institute forImmunologyandGenetics,Kaiserslautern,Germany. Bonemarroworbloodstemcelltransplantationistheonlycure for ␤-thalassemiamajor,however,despitemyeloablativecondi- tioningregimens,thebasicdifficultyisa15-30%graftfailurerate inthesepatients.OurhypothesisisthattheremaybeaT-cell dependentgraft-versus-myeloneffectthatestablishesandstabilizes theengraftmentofallogeneicbloodstemcellsinpatientswith thalassemiamajor. Inafirstattempt,weassessedtheCD3chimerismearlyafter transplantationinapediatriccaseseriesofsixtransplantations(2 related,4unrelateddonors)transplantedfrom2001to2004witha minimumfollow-upperiodof2yearsaftertransplantation.The donorswerefullymatchedatHLA-DRB1(highresolution)and HLA-Aand-B(lowresolution).PeripheralbloodCD3chimerism wasdeterminedatday ⫹30(median).Chimerismofunfractionated WBCwasdeterminedpatientsbeginningday ⫹13(median)and repeateduntilastableengraftmentorgraftfailurewasachieved. Patients(n ⫽4)withaCD3donorchimerismof ⬎80%estab- lishedalongtermengraftmentandremainedfreeoferythrocyte transfusions(days ⫹ 133, ⫹775, ⫹815, ⫹2033).Twoofthese patientsdevelopedalowtotalchimerism(minimum42%onday ⫹ 93,and45%onday⫹ 42,resp.)afterthatahighertotaldonor chimerismhadbeenachieved(90%onday ⫹17and92%onday ⫹ 20,resp.).Westoppedtheimmunosuppressivetherapyinboth patientsassoonastheresultoftheCD3chimerismwasavailable. Bothpatientsincreasedtheirtotalchimerismupto98%;one developedGvHDII°oftheskinthatresolvedaftersteroidtherapy withoutimpairmentofthetotalchimerism. TwopatientswithaCD3donorchimerism ⬍10%losttheirgraft completely,despitethefact,thatonepatientshowedahightotal chimerismof89%onday ⫹6.Onepatientisagainontheeryth- rocytetransfusionprogramme,theotherengraftedafterre-trans- plantfromanunrelateddonor. WeconcludethatearlydeterminationoftheCD3chimerism maybehelpfulforpatientmanagement.Inaddition,monitoringof theCD3chimerismshouldbeincludedintransplantprotocolsfor beta-thalassemiamajor. 121 MESENCHYMALSTEMCELLSFORTREATMENTOFSTEROID-RESISTANT GRAFT-VERSUS-HOSTDISEASE Ho,S.-J. 1 ,Dyson,P. 2 ,Rawling,T. 2 ,Stevens,J. 2 ,Patton,N. 1,2 , To,L.B. 1,2 ,Lewis,I. 1,21 RoyalAdelaideHospital,Adelaide,South Australia,Australia; 2 InstituteofMedicalandVeterinaryScience,Ad - elaide,SouthAustralia,Australia. Background Allogeneichematopoieticstemcelltransplantationisawelles- tablishedtreatmentforhematologicalmalignanciesandothercon- ditionswhichcanbeassociatedwithsignificantmorbidityand mortality,particularlythedevelopmentofsevereacutegraft-ver- sus-hostdisease(GVHD).Severesteroid-refractoryacuteGVHD continuestobeassociatedwithan80-90%mortalitydespitethe useofmanyimmunosuppressiveagentswithdifferingmodesof action.Mesenchymalstemcells(MSC)arerare,non-hemopoietic cellsfoundinthebonemarrow,capableofdifferentiationinto bone,cartilage,muscleandfatcells.Inadditiontotheirpotential roleintissuerepair,MSChaveuniqueimmunomodulatoryprop- erties.Invitrostudiesdemonstratetheyarebothnon-immuno- genicandimmunosuppressive.Thesepropertyhavebeenexploited inthetreatmentofsevereaGVHD.LeBlancetalreportedthefirst caseofthesuccessfultreatmentofsteroid-refractoryGVHDwith MSCin2004andinarecentlyreportedEBMTstudyanoverall responserateof69%wasseenin28patientswithsteroidrefractory aGVHD.WereportourexperiencewiththeuseofMSCfor GVHDin3patientsoverthelast7months. PosterSessionI 46 6 st nd recipient(31yoM)receivedMSCs onday ⫹ 39andday ⫹47forprogressivegradeIII-IVskin,gutand liverGVHD.ATGandetanerceptwerealsogivenonday ⫹42.He succumbedonday ⫹54.The3 MSCsonday ⫹42forgradeII-IIIskinGVHDwithanencour- PreliminarystudiesdemonstrateMSCinfusionisfeasibleinthe timingandtrueresponserate. 1 ... Il s'agit d'une maladie médiée par les lymphocytes T, CD4, stimulés par les cellules présentatrices de l'antigène du receveur. D'autres études menées chez les patients adultes ont confirmé ces résultats (Fang et al., 2007; Ho et al., 2007; Kebriaei et al., 2009;von Bonin et al., 2009). ... Activité immunosuppressive des cellules stromales mésenchymateuses dérivées de cellules souches pluripotentes induites humaines : induction de lymphocytes T régulateurs in vitro et in vivo et expression de PD-L1 La grande originalité de mon projet réside dans la génération de cellules stromales mésenchymateuses (MSCs) à partir de cellules souches pluripotentes induites humaines (iPS). Je rappellerai les propriétés phénotypiques, de multipotence et immunosuppressives des MSCs et m’attarderai sur leurs différents mécanismes immunomodulateurs. Cependant, leur nombre limité et leur isolation difficile limitent leur utilisation thérapeutique nécessitant une autre source de cellules.Mon travail a donc été de générer et de caractériser des MSCs issues d’iPS (huiPS-MSCs). L'avantage des huiPS-MSCs réside dans leur plus grande disponibilité et la possibilité d'en avoir à volonté. Encore faut-il valider l’intérêt thérapeutique potentiel de ces huiPS-MSCs. Premièrement, mes résultats in vitro montrent que les huiPS-MSCs présentent une activité immunosuppressive sur les lymphocytes T (LT) activés conduisant à une induction de LT régulateurs FoxP3+ fonctionnels. Deuxièmement, dans une approche plus axée sur la thérapie, j’ai analysé in vivo l’activité́ immunosuppressive des huiPS-MSCs dans un modèle de réaction xénogénique de greffon contre l'hôte (souris immunodéficientes NSG injectées avec des LT humains). Je montre clairement, après traitement avec les huiPS-MSCs, une réduction de la proportion de LT humains producteurs de cytokines inflammatoires (IFNγ et TNFα) typiques de la pathologie et l’apparition concomitante de LT présentant un phénotype régulateur (production d’IL10 et expression de FoxP3). La fin de mon travail a été de caractériser moléculairement la régulation de l’expression de PD-L1, une molécule immuno-régulatrice puissante, entre les MSCs issues de la moelle osseuse (BM-MSCs) de donneurs sains et nos huiPS- MSCs. Les huiPS-MSCs ont une expression constitutive de PD-L1, qui est absente sur les BM-MSCs. J’ai analysé les microARNs susceptibles de limiter l’expression de PD-L1, j’ai pu en identifier plusieurs. En mesurant leur expression dans les différentes MSCs à notre disposition, je montre que cette expression est inverse par rapport à celle de PD-L1. J’ai ainsi pu démontrer l’activité immunosuppressive de nos huiPS-MSCs in vitro et in vivo avec une perspective d’induction de tolérance immune, et caractériser la régulation de l’expression de PD-L1, molécule immunosuppressive exprimée par les huiPS-MSCs. ... Children tended to have a better response at 68% compared with 43% (p = 0.07) in adults [110]. Several other studies have been undertaken looking at MSC source, dosage and different serum for MSC expansion [111] [112] [113][114][115][116]. Consistently, MSCs were shown to provide complete or partial response in the majority of patients. ... Stromal cell-based immunotherapy in transplantation Organs are composed of parenchymal cells that characterize organ function and nonparenchymal cells that are composed of cells in transit, as well as tissue connective tissue, also referred to as tissue stromal cells. It was originally thought that these tissue stromal cells provided only structural and functional support for parenchymal cells and were relatively inert. However, we have come to realize that tissue stromal cells, not restricted to in the thymus and lymphoid organs, also play an active role in modulating the immune system and its response to antigens. The recognition of these elements and the elucidation of their mechanisms of action have provided valuable insight into peripheral immune regulation. Extrapolation of these principles may allow us to utilize their potential for clinical application. In this article, we will summarize a number of tissue stromal elements/cell types that have been shown to induce hyporesponsiveness to transplants. We will also discuss the mechanisms by which these stromal cells create a tolerogenic environment, which in turn results in long-term allograft survival. Heparinization of cell surfaces with short peptide-conjugated PEG-lipid regulates thromboinflammation in transplantation of human MSCs and hepatocytes Statement of signigficance: We present a promising approach to enhance the biocompatibility of therapeutic cells. Here we used short peptide-conjugated PEG-lipid for cell surface modification and heparin conjugates for the coating of human hepatocytes and MSCs. We screened the short peptides to find higher affinity for heparinization of cell surface and performed hemocompatibility assay of heparinized human hepatocytes and human MSCs in human whole blood. Using heparin-binding peptide with higher affinity, not only coagulation activation but also complement activation was significantly suppressed. Thus, it was possible to protect human hepatocytes and human MSCs from the attack of thromboinflammatory activation, which can contribute to the improvement graft survival. Mesenchymal Stem Cells for Treatment and Prevention of Graft-Versus-Host Disease and Graft Failure After Hematopoietic Stem Cell Transplantation and Future Challenges <here is a image bcd70958986d32b0-dc60eddc6c7619c5> Olle Ringdén Graft-versus-host disease (GVHD) is a cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The rationale to use mesenchymal stem cells (MSCs) to prevent and treat GVHD and graft failure is due to the ability of MSCs to suppress alloantigen-induced T-cells in vitro. This effect was seen despite HLA-incompatibility between MSC and stimulatory or alloreactive cells in vitro, enabling the potential use of third party MSCs in the clinic. Because MSCs home to target organs of tissue toxicity and have low immunogenicity, they may be important in regenerative medicine, for instance in the treatment of acute GVHD. Clinically, MSCs were found to completely reverse severe acute GVHD in approximately 50% of the patients with steroid-refractory GVHD. In addition, MSCs interfere with coagulation and were found to have a positive effect on hemorrhagic cystitis and were able to stop major hemorrhages in HSCT patients. MSCs produce hematopoietic growth factors and have been used clinically to support hematopoiesis and to treat graft failure. Future related areas of research include prospective randomized clinical trials, determining optimum cell source and dose, identifying the best route of infusion and defining the appropriate number of passages for the MSCs to be used for therapeutic applications. Mesenchymal stem cells for treatment of acute and chronic graft-versus-host disease, tissue toxicity and hemorrhages <here is a image bcd70958986d32b0-dc60eddc6c7619c5> Olle Ringdén Mesenchymal stem cells (MSCs) have immunomodulatory effects and low immunogenicity. MSCs inhibit T-cell alloreactivity in vitro. Immune inhibition is caused by soluble factors. MSCs affect almost all cells of the immune system. They are safe to infuse in humans with no acute toxicity and no ectopic tissue formation. We treated patients with life-threatening acute graft-versus-host disease (GVHD) not responding to conventional immunosuppressive therapy with MSCs. Approximately half of the patients responded. HLA-identical or third party MSCs were equally effective. Children tended to have a better response compared to adults. MSCs have also been used for chronic GVHD with positive effects. MSCs also reversed tissue toxicity such as hemorrhagic cystitis, pneumomediastinum and colon perforation with peritonitis. A patient with extensive hemorrhages was successfully treated with repeated doses of MSCs pooled from two donors. This may indicate that MSCs apart from wound healing may stimulate clotting and vasoconstriction. To conclude, MSCs is a novel treatment that may be used for GVHD, tissue toxicity and hemorrhages because of its immune inhibitory and anti-inflammatory effects. The expansion of human cells to produce cell therapeutic products for the treatment of disease is, with few exceptions, an experimental therapy. Because cell therapies involve a biological product, often with some genetic or other modification, they require extensive pre-clinical research and development. Cell therapy production processes and premises require licensing by the Therapeutic Goods Administration. In this review, timed to coincide with the international meetings of the ISCT and ISSCR in Australia, we describe some promising cell therapies currently under development.
https://www.researchgate.net/publication/279419317_121_Mesenchymal_stem_cells_for_treatment_of_steroid-resistant_graft-versus-host_disease
REMINGTON PG6030 All In One Grooming Kit Instruction Manual Learn how to use your new Remington PG6030 All In One Grooming Kit with this user manual. Features include a groomer, wide and detail trimmers, nose and ear trimmer, and more. Get started with charging and attaching guide combs for the perfect trim every time. REMINGTON PG6030 All In One Grooming Kit Instruction Manual Contents hide 1 REMINGTON PG6030 All In One Grooming Kit 2 KEY FEATURES 3 GETTING STARTED 4 HOW TO USE 4.1 Attaching and removing the trimmer attachments 5 CARE FOR YOUR GROOMER 6 IMPORTANT SAFETY INSTRUCTIONS 7 BATTERY REMOVAL 8 ENVIRONMENTAL PROTECTION 9 SERVICE AND GUARANTEE 10 Documents / Resources 10.1 References 11 Related Posts REMINGTON PG6030 All In One Grooming Kit Thank you for buying your new Remington® product. Before use, please read these instructions carefully and keep them safe. Remove all packaging before use. CAUTION Use this appliance only for its intended use as described in this manual. Do not use attachments not recommended by Remington® Do not use this product if it is not working correctly, if it has been dropped or damaged, or dropped in water. KEY FEATURES On/off switch Groomer Wide trimmer Detail trimmer Miniscreen shaver Nose, ear, eyebrow trimmer 2 attachment guide combs Charging Indicator Stand Adaptor 3-year guarantee GETTING STARTED Charging your groomer Before using your groomer for the first time, charge for 14-16 hours. Make sure the product is turned off Place your groomer into the stand, connect the adaptor to the product and then to the mains. The charging indicator will light up. Your appliance cannot be overcharged. However if the product is not going to be used for an extended period of time (2-3 months), unplug it from the mains and store. Fully recharge your appliance when you would like to use it again. To preserve battery life, let them run out every 6 months then recharge for 14-16 hours. HOW TO USE Attaching and removing guide combs With the trimmer blade facing away from you, slide the guide comb over the back of the trimmer blade and click into position. With the trimmer blade facing away from you, carefully push the guide comb away from the wide-head trimmer. Before you begin Comb facial hair with a fine comb before you start trimming. Hairs should be dry and without any waxes or lotions before using the groomer To thin and taper beards or moustaches Attach the wide trimmer blade. Place the hair length attachment on the trimmer blade, select the desired length and switch on. Start trimming under the chin, following the jawbone line. Work toward the ear and upper beard line using an upward motion. To trim edge of beard or moustache Attach the detail trimmer blade. Hold groomer with cutting blade facing you. Start with edge of beard/moustache line, and with the cutting blades resting lightly against your skin, use slow movements to create a beard/moustache line. To trim sideburns Hold groomer with cutting blade facing you. Use a small comb to lift the hairs. Hold the comb at the desired beard or moustache length. Move the groomer along the comb to cut the hairs. Use light pressure and well-controlled movements to trim hair. Trimming the nape of your neck Attach the wide trimmer blade. Use your fingers to lift the hair at the base of your head up off the neck. Your index finger should be covering the roots of the hairs you are lifting to prevent accidental removal by a groomer. Using your other hand, hold the groomer to the base of your neck with the cutting unit facing up, and move the groomer up the length of the neck until the unit touches your finger covering the hair roots at the base of your head. Move the unit slowly when performing this operation and to keep the hair roots at the base of your head out of the way of the groomer. To remove hair from nose and ear Attach nose, ear & eyebrow attachment. Insert groomer’s cutting unit gently into the nostril or ear. Gently move the groomer in and out of the nostril or ear and at the same time rotate the groomer. Avoid inserting the cutting unit more than 6mm into your nostril or ear. To remove hair from eyebrows Attach nose, ear, eyebrow attachment. Gently guide cutting unit to stray, unwanted hairs along the eyebrow line or protruding from the eyebrow itself. To remove the hairs completely lower onto the skin and move over desired area. Use slow and well-controlled movements. Tips for best results Comb your hair in the direction that it grows so that the hairs are at their maximum height and facing in the same direction. After trimming, lightly go over the trimmed areas with the foil to get a smooth clean finish. Since all hairs do not grow in the same direction, you may want to try different trimming positions (i.e. upwards, downwards or across) for better results. Attaching and removing the trimmer attachments Note: Always ensure the groomer is switched off before changing any attachments. To remove, hold the groomer with one hand and turn the trimmer head anti-clockwise with the other. To attach, hold the groomer with on hand and turn the trimmer head clockwise with the other. Using the detailed trimmer Hold the groomer with the surface (back side) of the blade guiding against the skin. Use motions similar to using a wet blade to provide the closest trim. Note: This attachment provides a dual-purpose solution for stubble or close results without irritation. Using your miniscreen shaver Hold the groomer so the MiniScreen gently touches your face. Use short, and well-controlled movements to shave around your beard/moustache. Use your free hand to stretch your skin. This encourages the hair to stand upright, making it easier to shave. Note: The MiniScreen shaver was designed to shave the detail areas around your beard moustache/sideburns. It was not designed to shave your entire face. For a close comfortable shave, guaranteed, use one of Remington’s electric shavers. CARE FOR YOUR GROOMER Care for your product to ensure long-lasting performance. We recommend that you clean your groomer after each use. The easiest and the most hygienic way to clean the groomer is by rinsing the product head after use with warm water. Always keep the protective cap on the shaving head and keep the trimmer in the “off” position when the shaver is not in use. After each use Rinse the accumulated hair from the cutters and shake off excess water. Alternatively, use a brush. Gently tap on a flat surface to remove hair particles, and brush the remaining hairs away. Place one or two drops of cutter oil or sewing machine oil on the blades. Turn the clipper on to distribute the oil evenly, wipe off any excess oil. Wipe the main unit with a damp cloth and dry it immediately. Note: Ensure that the groomer is turned off when applying the oil or rinsing under the tap. IMPORTANT SAFETY INSTRUCTIONS Warning: To reduce the risks of burns, electrocution,fire or injury to persons: An appliance should never be left unattended when plugged in to a power outlet, except when charging. Keep the power plug and cord away from heated surfaces. Make sure the power plug and cord do not get wet. Do not plug or unplug the appliance with wet hands. Do not use the product with a damaged cord. A replacement can be obtained via our International Service Centres. Do not twist or kink the cable, and don’t wrap it around the appliance. Store the product at a temperature between 15°C and 35°C. Only use the parts supplied with the appliance. The appliance, including its cord, must not be used, played with, cleaned or maintained by persons under eight years old and should at all times be kept out of their reach. Use, cleaning or maintenance of the appliance by children over eight or by anyone with a lack of knowledge, experience or with reduced physical, sensory or mental capabilities should only be undertaken after receiving appropriate instruction and under the adequate supervision of a responsible adult to ensure that they do so safely and that the hazards involved are understood and avoided. Always remember to turn on the groomer before you insert it into your nose or ear to avoid injury. Don’t put the appliance in liquid, don’t use it near water in a bath-tub, basin or any other vessel, and don’t use it outdoors. BATTERY REMOVAL The battery must be removed from the appliance before it is scrapped. The appliance must be disconnected from the supply mains when removing the battery. Unplug groomer from the outlet to avoid risk of electrical shock. Pry the upper housing from the product with a flat head screwdriver. This will expose the batteries. With wire cutters, clip the wires leading to the batteries. Remove the batteries from the product. Contact your local authorities for proper disposal. The battery is to be disposed of safely. ENVIRONMENTAL PROTECTION To avoid environmental and health problems due to hazardous substances in electrical and electronic goods, appliances marked with this symbol must not be of with unsorted municipal waste, but recovered, reused or recycled. SERVICE AND GUARANTEE This product has been checked and is free of defects. We guarantee this product against any defects that are due to faulty material or workmanship for the guarantee period from the original date of consumer purchase. If the product should become defective within the guarantee period, we will repair any such defect or elect to replace the product or any part of it without charge, provided there is proof of purchase. This does not mean an extension of the guarantee period. In the case of a guarantee simply call the Service Centre in your region. This guarantee is offered over and above your normal statutory rights. The guarantee shall apply in all countries in which our product was sold via an authorised dealer. This guarantee does not include damage to the product by accident or misuse, abuse, alteration to the product or use inconsistent with the technical and/or safety instructions required. This guarantee shall not apply if the product has been dismantled or repaired by a person not authorised by us. If you call the Service Centre, please have the Model No. to hand, as we won’t be able to help you without it. Its on the rating plate which can be found on the appliance. Remington® is a Registered Trade Mark of Spectrum Brands, Inc., or one of its subsidiaries ADDRESS: VARTA Consumer Batteries GmbH & Co. KGaA, Alfred-Krupp-Str. 9, 73479 Ellwangen, Germany www.rermington-europe.com Documents / Resources REMINGTON PG6030 All In One Grooming Kit [pdf] Instruction Manual PG6030, All In One Grooming Kit, PG6030 All In One Grooming Kit, Grooming Kit References Europe - Travel and Destinations Miller Distributors Malta | Miller Distributors Limited Remington - EST. NEW YORK 1937 | Haircare & Personal Care Appliances for Men & Women Remington, UK | Haircare & Personal Care Appliances for Men & Women Remington remington.hu THULE 187014 Fixpoint Kit This kit is only for vehicles with fixpoint mounting. Kit Warning Mounting Thule Sweden…
https://manuals.plus/remington/pg6030-all-in-one-grooming-kit-manual
An Official American Thoracic Society/European Respiratory Society Statement: Key Concepts and Advances in Pulmonary Rehabilitation | American Journal of Respiratory and Critical Care Medicine Background: Pulmonary rehabilitation is recognized as a core component of the management of individuals with chronic respiratory disease. Since the 2006 American Thoracic Society (ATS)/European Res... Abstract Section:ChooseTop of pageAbstract <<Executive SummaryContentsOverviewIntroductionMethodsDefinition and ConceptExercise TrainingPulmonary Rehabilitation ...Behavior Change and Colla...Body Composition Abnormal...Physical ActivityTiming of Pulmonary Rehab...Patient-centered OutcomesProgram OrganizationHealth Care UseMoving ForwardReferencesCITING ARTICLES Background: Pulmonary rehabilitation is recognized as a core component of the management of individuals with chronic respiratory disease. Since the 2006 American Thoracic Society (ATS)/European Respiratory Society (ERS) Statement on Pulmonary Rehabilitation, there has been considerable growth in our knowledge of its efficacy and scope. Purpose: The purpose of this Statement is to update the 2006 document, including a new definition of pulmonary rehabilitation and highlighting key concepts and major advances in the field. Methods: A multidisciplinary committee of experts representing the ATS Pulmonary Rehabilitation Assembly and the ERS Scientific Group 01.02, “Rehabilitation and Chronic Care,” determined the overall scope of this update through group consensus. Focused literature reviews in key topic areas were conducted by committee members with relevant clinical and scientific expertise. The final content of this Statement was agreed on by all members. Results: An updated definition of pulmonary rehabilitation is proposed. New data are presented on the science and application of pulmonary rehabilitation, including its effectiveness in acutely ill individuals with chronic obstructive pulmonary disease, and in individuals with other chronic respiratory diseases. The important role of pulmonary rehabilitation in chronic disease management is highlighted. In addition, the role of health behavior change in optimizing and maintaining benefits is discussed. Conclusions: The considerable growth in the science and application of pulmonary rehabilitation since 2006 adds further support for its efficacy in a wide range of individuals with chronic respiratory disease. Keywords:COPD;pulmonary rehabilitation;exacerbation;behavior;outcomes Executive Summary Section:ChooseTop of pageAbstractExecutive Summary <<ContentsOverviewIntroductionMethodsDefinition and ConceptExercise TrainingPulmonary Rehabilitation ...Behavior Change and Colla...Body Composition Abnormal...Physical ActivityTiming of Pulmonary Rehab...Patient-centered OutcomesProgram OrganizationHealth Care UseMoving ForwardReferencesCITING ARTICLES Download Executive Summary of this ATS/ERS Statement Contents Section:ChooseTop of pageAbstractExecutive SummaryContents <<OverviewIntroductionMethodsDefinition and ConceptExercise TrainingPulmonary Rehabilitation ...Behavior Change and Colla...Body Composition Abnormal...Physical ActivityTiming of Pulmonary Rehab...Patient-centered OutcomesProgram OrganizationHealth Care UseMoving ForwardReferencesCITING ARTICLES Overview Introduction Methods Definition and Concept Exercise Training  Introduction  Physiology of Exercise Limitation   Ventilatory limitation   Gas exchange limitation   Cardiac limitation   Limitation due to lower limb muscle dysfunction   Limitation due to respiratory muscle dysfunction  Exercise Training Principles  Endurance Training  Interval Training  Resistance/Strength Training  Upper Limb Training  Flexibility Training  Neuromuscular Electrical Stimulation  Inspiratory Muscle Training  Maximizing the Effects of Exercise Training   Pharmacotherapy    Bronchodilators    Anabolic hormonal supplementation   Oxygen and helium–hyperoxic gas mixtures   Noninvasive ventilation   Breathing strategies   Walking aids Pulmonary Rehabilitation in Conditions Other Than COPD  Interstitial Lung Disease  Cystic Fibrosis  Bronchiectasis  Neuromuscular Disease  Asthma  Pulmonary Arterial Hypertension  Lung Cancer  Lung Volume Reduction Surgery  Lung Transplantation Behavior Change and Collaborative Self-Management  Introduction  Behavior Change   Operant conditioning   Changing cognitions   Enhancement of self-efficacy   Addressing motivational issues  Collaborative Self-Management  Advance Care Planning Body Composition Abnormalities and Interventions  Introduction  Interventions to Treat Body Composition Abnormalities  Special Considerations in Obese Subjects Physical Activity Timing of Pulmonary Rehabilitation  Pulmonary Rehabilitation in Early Disease  Pulmonary Rehabilitation and Exacerbations of COPD  Early Rehabilitation in Acute Respiratory Failure   Physical activity and exercise in the unconscious patient   Physical activity and exercise in the alert patient   Role for rehabilitation in weaning failure Long-Term Maintenance of Benefits from Pulmonary Rehabilitation   Maintenance exercise training programs   Ongoing communication to improve adherence   Repeating pulmonary rehabilitation   Other methods of support Patient-centered Outcomes  Quality-of-Life Measurements  Symptom Evaluation  Depression and Anxiety  Functional Status  Exercise Performance  Physical Activity  Knowledge and Self-Efficacy  Outcomes in Severe Disease  Composite Outcomes Program Organization  Patient Selection  Comorbidities  Rehabilitation Setting   Home-based and community-based exercise training   Technology-assisted exercise training  Program Duration, Structure, and Staffing  Program Enrollment  Program Adherence  Program Audit and Quality Control Health Care Use  Program Costs  Impact on Health Care Use  Impact on Medical Costs  Cost-Effectiveness Moving Forward Overview Section:ChooseTop of pageAbstractExecutive SummaryContentsOverview <<IntroductionMethodsDefinition and ConceptExercise TrainingPulmonary Rehabilitation ...Behavior Change and Colla...Body Composition Abnormal...Physical ActivityTiming of Pulmonary Rehab...Patient-centered OutcomesProgram OrganizationHealth Care UseMoving ForwardReferencesCITING ARTICLES Pulmonary rehabilitation has been clearly demonstrated to reduce dyspnea, increase exercise capacity, and improve quality of life in individuals with chronic obstructive pulmonary disease (COPD) (1). This Statement provides a detailed review of progress in the science and evolution of the concept of pulmonary rehabilitation since the 2006 Statement. It represents the consensus of 46 international experts in the field of pulmonary rehabilitation. On the basis of current insights, the American Thoracic Society (ATS) and the European Respiratory Society (ERS) have adopted the following new definition of pulmonary rehabilitation: “Pulmonary rehabilitation is a comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, education, and behavior change, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health-enhancing behaviors.” Since the previous Statement, we now more fully understand the complex nature of COPD, its multisystem manifestations, and frequent comorbidities. Therefore, integrated care principles are being adopted to optimize the management of these complex patients (2). Pulmonary rehabilitation is now recognized as a core component of this process (Figure 1) (3). Health behavior change is vital to optimization and maintenance of benefits from any intervention in chronic care, and pulmonary rehabilitation has taken a lead in implementing strategies to achieve this goal. Figure 1.A spectrum of support for chronic obstructive pulmonary disease. Reprinted by permission from Reference3. Download Figure|Download Powerpoint[More][Minimize] Noteworthy advances in pulmonary rehabilitation that are discussed in this Statement include the following: • There is increased evidence for use and efficacy of a variety of forms of exercise training as part of pulmonary rehabilitation; these include interval training, strength training, upper limb training, and transcutaneous neuromuscular electrical stimulation. • Pulmonary rehabilitation provided to individuals with chronic respiratory diseases other than COPD (i.e., interstitial lung disease, bronchiectasis, cystic fibrosis, asthma, pulmonary hypertension, lung cancer, lung volume reduction surgery, and lung transplantation) has demonstrated improvements in symptoms, exercise tolerance, and quality of life. • Symptomatic individuals with COPD who have lesser degrees of airflow limitation who participate in pulmonary rehabilitation derive similar improvements in symptoms, exercise tolerance, and quality of life as do those with more severe disease. • Pulmonary rehabilitation initiated shortly after a hospitalization for a COPD exacerbation is clinically effective, safe, and associated with a reduction in subsequent hospital admissions. • Exercise rehabilitation commenced during acute or critical illness reduces the extent of functional decline and hastens recovery. • Appropriately resourced home-based exercise training has proven effective in reducing dyspnea and increasing exercise performance in individuals with COPD. • Technologies are currently being adapted and tested to support exercise training, education, exacerbation management, and physical activity in the context of pulmonary rehabilitation. • The scope of outcomes assessment has broadened, allowing for the evaluation of COPD-related knowledge and self-efficacy, lower and upper limb muscle function, balance, and physical activity. • Symptoms of anxiety and depression are prevalent in individuals referred to pulmonary rehabilitation, may affect outcomes, and can be ameliorated by this intervention. In the future, we see the need to increase the applicability and accessibility of pulmonary rehabilitation; to effect behavior change to optimize and maintain outcomes; and to refine this intervention so that it targets the unique needs of the complex patient. Introduction Section:ChooseTop of pageAbstractExecutive SummaryContentsOverviewIntroduction <<MethodsDefinition and ConceptExercise TrainingPulmonary Rehabilitation ...Behavior Change and Colla...Body Composition Abnormal...Physical ActivityTiming of Pulmonary Rehab...Patient-centered OutcomesProgram OrganizationHealth Care UseMoving ForwardReferencesCITING ARTICLES Since the American Thoracic Society (ATS)/European Respiratory Society (ERS) Statement on Pulmonary Rehabilitation was published in 2006 (
https://www.atsjournals.org/doi/10.1164/rccm.201309-1634ST?rfr_dat=cr_pub%20%200pubmed&rfr_id=ori%3Arid%3Acrossref.org&url_ver=Z39.88-2003
Want to design only a top part of catamaran, looking of plans for hulls 14m, aluminum | Boat Design Net Hi! Got some savings over the years and recently thought to start to build an aluminum solar powered catamaran. It is not tons of money, but from my... Want to design only a top part of catamaran, looking of plans for hulls 14m, aluminum Hi! Got some savings over the years and recently thought to start to build an aluminum solar powered catamaran. It is not tons of money, but from my rough calculations I should be able to afford to build a 14m aluminum solar powered cat. I'm total newbie to building boats so here will be my couple of questions that I'm curious of: 1. Software: what software you find best to design yachts (free or paid, but if paid lets keep it reasonable price)? 2. Would be actually happy to get ready design of hulls, where I could just step in and do design of the top part of boat, any recommendations where I can find such a designs that I could only adapt to my needs (14m, aluminum, ocean crossing)? 3. If it is gonna be a catamaran and will have 2 electric motors that can drive back and forth each separately then do I still need a rudder? 4. What is the minimum speed to maintain in storm conditions on such a boat? 5. What would be recommended clearance between bottom part of deck and water level? 6. Anyone else building an aluminum boat? Will be glad if you drop a line of comment, link or anything else about above questions Welcome to the forum Daniel. Quick simple answers to your questions: 1. Any - which ever YOU find easy to sue. There are many out there but each takes time to learn. So which ever you find most intuitive. 2. Many on this forum (including myself) can provide such. 3. How will you steer without a rudder? 4. A 14m boat in a storm..should be in port and/or safe harbour! 5. If a cat, the wetdeck freeboard should be a minimum of 5% Lwl. 6. Many.. just search this forum. More broadly. For anyone to assist you, you need an SOR - a statement of requirements. So the designer, knows what they are 'aiming' at. Otherwise you could get a box hull or a canoe hull and/or anything in between which may or may not be suitable for you. Thus, define your parameters via the SOR. A successful design - is greater than the sum of its individual parts.... Can you post your rough calculations of the cost of building the boat? Ad Hoc said: ↑ Welcome to the forum Daniel. Quick simple answers to your questions: 1. Any - which ever YOU find easy to sue. There are many out there but each takes time to learn. So which ever you find most intuitive. 2. Many on this forum (including myself) can provide such. 3. How will you steer without a rudder? 4. A 14m boat in a storm..should be in port and/or safe harbour! 5. If a cat, the wetdeck freeboard should be a minimum of 5% Lwl. 6. Many.. just search this forum. More broadly. For anyone to assist you, you need an SOR - a statement of requirements. So the designer, knows what they are 'aiming' at. Otherwise you could get a box hull or a canoe hull and/or anything in between which may or may not be suitable for you. Thus, define your parameters via the SOR. Thanks for your reply!!! Ad1. I feel actually very comfortable with Solvespace, but never thought of it as something I could design a hull with. I'll think of it... Ad2. Do you have like ready ones? And how much would you want for it? (and where are you from? ) Or can you recommend someone, or someones plans? Ad3. As it is gonna be all electric solar powered (no sails or whatsoever) catamaran with electric motor on each of hull I can make one motor even pull and another push at the same time. The question is if that would provide enough maneuverability on 14x8m boat? Ad4. Agree, but crossing Atlantic in a solar powered boat (I assume it is not gonna be a speed daemon) might end up in some rough conditions, thus my question I did already requirements, some basic cad drawings and estimations based on that. gonzo said: ↑ Can you post your rough calculations of the cost of building the boat? All electric, all aluminum, power catamaran, without anything close to fancy interior (woods, etc) - 150K USD That is rough estimation, might be less, might be more. @Daniel Mazurkiewicz I think that your estimate of US$ 150,000 is extremely optimistic. While the cost of labour to build the boat in the Ukraine is probably much less than in Western Europe, you still have to buy the aluminium and the welding materials, not to mention the large battery bank and the electric motors. Can you maybe post some copies of of your CAD drawings on here please? Daniel Mazurkiewicz said: ↑ As it is gonna be all electric solar powered (no sails or whatsoever) catamaran with electric motor on each of hull I can make one motor even pull and another push at the same time. The question is if that would provide enough maneuverability on 14x8m boat? Yes, having the engines so far apart will make the boat very manoeuverable - but you will still need to have rudders, unless you are proposing to use outboard motors (but I don't think that anybody yet makes electric outboard motors big enough for a 14 metre cat). If you do not have rudders, and something happens to one engine, then you will not be able to steer the boat. Software is the least relevant question here. And "ocean crossing 14m cat from aluminum" is not really an SOR. $150k sounds unrealistic for a custom built boat of that size. Add electric powertrain and it is not going to cut it. I also question how sensible choice solar is for ocean crossing. It is ok for many uses but for day in day out (nights too..) it is not simple or affordable choice. Quickly checked price ranges of used 45ft cats. Seems to be $1 million new, $500k for 5 year old and $250k 25 year old. +-20% So how will one make one, with an exotic powertrain, for $150k is beyond me. kerosene said: ↑ Software is the least relevant question here. And "ocean crossing 14m cat from aluminum" is not really an SOR. $150k sounds unrealistic for a custom built boat of that size. Add electric powertrain and it is not going to cut it. I also question how sensible choice solar is for ocean crossing. It is ok for many uses but for day in day out (nights too..) it is not simple or affordable choice. Quickly checked price ranges of used 45ft cats. Seems to be $1 million new, $500k for 5 year old and $250k 25 year old. +-20% So how will one make one, with an exotic powertrain, for $150k is beyond me. Disclaimer: I am a farming game developer not a naval architect or ocean crossing specialist I'm an electrical engineer, so nothing exotic from that side for me (and nothing extraordinarily expensive here). Did estimations for: 20kWh peak solar panels 2 x 10kW BLDC motors 60kWh batteries ~~ 40k USD Don't need speed boat thus thought 2x10kW should be enough to run a boat efficiently, but if I'm wrong, will be happy to hear what is the minimum that I should consider Then question of how much aluminum sheets will I need? I assumed 5000-6000kg, is that right? And then all the rest... bajansailor said: ↑ Can you maybe post some copies of of your CAD drawings on here please? Nothing fancy there, just couple of boxes that did let me quickly and roughly estimate how much aluminum I would need for desired dimmensions bajansailor said: ↑ I see your point. Thanks! Build costs for all electric gonna run about 3-5k usd per foot 45' low end, very low end stuff, no work outsourced; cheap yard time maybe 3k 5k is more practical Daniel, have you had a look at Bruce Roberts' webpage re his aluminium power catamaran designs? https://www.bruceroberts.com/public/HTML/CATS.htm Using the Cat400 as an example - https://www.bruceroberts.com/public/HTML/descriptions/cat39_description.htm They mention that the study plans cost US$95 and that "Each STUDY PLAN contains ALL the construction drawings for each material - ALUMINUM & FIBERGLASS as applicable to the particular boat plan - with up to 25 sheets per plan! Lists of materials - Technical information - Numerous construction drawings are all included." It could be worthwhile investing $95 in a set of plans so that you can get a rough idea of what you will be up against re the design of your vessel. Edit - for general reference, you could also have a look at the aluminium power (and sailing) cats built by GHI Yachts in South Korea. https://www.ghiyachts.com/복제-products But I will again agree with the others above, re how US$150,000 is only going to be a fraction of the cost to build your cat, and that 2 x 10 kw electric motors are not going to be enough power for it to operate effectively. What happens when you have to motor into a 20 knot (or more) head wind and a rough sea? Your vessel is not going to be very seaworthy if it cannot do this, as you might have to motor off a lee shore in anger sometime. I doubt you can find plans for generic hulls to put a superstructure on. Most you can do is buy plans for a similar sailing cat and adapt. I would suggest designing a rough superstructure/interior and making a detailed list of weights (primarily the propulsion unit, but also furniture, etc.), then hire a NA to transform your drawings into a boat. 2x10kW will probably be enough, there are similar size outboard powered sailing cats, altough most will be lighter. It all depends on your desired average speed, as long as 5kn is acceptable, you are good. Battery size is marginal, 60kWh will barely bring you trough the night. Six hours of darkness means a max power of 10kW and no reserve. Unless you are willing to significantly go down with speed at night, upgrade to at least 80kWh. 20kWp of panels is ambitious with your budget. Covering the entire boat with standard panels will have disadvantages, better panels are more expensive. You should aim for a more realistic 12-15kWp. This also has implications on your daylight speed, since you need to recharge the battery. Storms, you have two kinds of: the ones where you have searoom and the ones you don't. The first kind is simple, let out the drogues and run with the wind. The second ones are also simple, either you manage to get to safety with the available battery, or you wreck on a lee shore. You don't have the power or range to do much in a storm, for that you need a diesel (either an additional prop, or genset with additional electric motors). Morale, when in coastal waters follow the weather closely and always have a safe harbour in battery reach. Needed Al weight depends. Thin skin is lighter but more difficult construction. Thick skin is easier to build but heavier. Waste ranges from 20-45%. But generally speaking yes, for an all Al boat (superstructure could be something else if you wish) you will have to buy around 5t (+/-1t) of it in different thicknesses. 2012 Custom Aluminum Catamaran sailboat for sale in Texas https://www.sailboatlistings.com/view/94066 For a build that size and your planned use, I would seriously consider using second hand Nissan Leaf power plants. They are affordable, compact, and powerful with an integrated gearbox and inverter, and there are experts out there offering stand alone control interfaces making them easy to adapt to builds like yours. They are a power plant you can grow into, and as batteries and solar get better, you can operate them at a higher voltage. Regarding using forward and reverse independent thrust of each motor for steering, yes it can be done but as others have pointed out if you lose propulsion from one motor you won’t be able to steer or even keep a course without a rudder. I use this method on my catamaran and keep a rudder onboard that can be center mounted for steering in case of emergency. Also keep in mind using the motor propulsion for steering is great for slow speed maneuverability, but is more inefficient at higher speeds and less responsive than a properly designed rudder. On my boat, I tend to drop the throttle of one motor to allow the opposite to overtake in order to steer in a direction, rather than throttling one up to overtake the other. Either way, your goal should be making the boat as efficient as possible, and a rudder system will allow the boat and its motors to maintain a more constant speed when maneuvering, wasting less energy. Rumars said: ↑ I doubt you can find plans for generic hulls to put a superstructure on. Most you can do is buy plans for a similar sailing cat and adapt. I would suggest designing a rough superstructure/interior and making a detailed list of weights (primarily the propulsion unit, but also furniture, etc.), then hire a NA to transform your drawings into a boat. Getting a friend with a FreeCAD since yesterday, i saw there are even FEM analysis available out of the box. Lets see what I can come up with over coming weekend. Rumars said: ↑ 2x10kW will probably be enough, there are similar size outboard powered sailing cats, altough most will be lighter. It all depends on your desired average speed, as long as 5kn is acceptable, you are good. Battery size is marginal, 60kWh will barely bring you trough the night. Six hours of darkness means a max power of 10kW and no reserve. Unless you are willing to significantly go down with speed at night, upgrade to at least 80kWh. 20kWp of panels is ambitious with your budget. Covering the entire boat with standard panels will have disadvantages, better panels are more expensive. You should aim for a more realistic 12-15kWp. This also has implications on your daylight speed, since you need to recharge the battery. Storms, you have two kinds of: the ones where you have searoom and the ones you don't. The first kind is simple, let out the drogues and run with the wind. The second ones are also simple, either you manage to get to safety with the available battery, or you wreck on a lee shore. You don't have the power or range to do much in a storm, for that you need a diesel (either an additional prop, or genset with additional electric motors). Morale, when in coastal waters follow the weather closely and always have a safe harbour in battery reach. 5kn is not an issue for me, as long as it will let maintain safe speed/maneuverability in rough conditions. Plan to have onboard "emergency" power generator, wouldn't it solve the issue? Needed Al weight depends. Thin skin is lighter but more difficult construction. Thick skin is easier to build but heavier. Waste ranges from 20-45%. But generally speaking yes, for an all Al boat (superstructure could be something else if you wish) you will have to buy around 5t (+/-1t) of it in different thicknesses. Was googling for superstructure in terms of boat design, you mention it second time here and I'm not sure if I get what it means exactly. I find your advice and infos are very valuable, THANKS, will follow them! And before jumping to "deep water", will make sure that can afford what I would like to have
https://www.boatdesign.net/threads/want-to-design-only-a-top-part-of-catamaran-looking-of-plans-for-hulls-14m-aluminum.66529/
The United States in Literature w/Three Long Stories by James E. Miller Jr. | Open Library The United States in Literature by James E. Miller Jr., Carlota Cárdenas de Dwyer, Kerry M. Wood, John Smith, William Bradford, Sarah Kemble Knight, William Byrd II, Cotton Mather, Jonathan Edwards - undifferentiated, Anne Bradstreet, Taylor, Edward, Phillis Wheatley, Philip Morin Freneau, Benjamin Franklin, J. Hector St. John de Crèvecoeur, Thomas Jefferson, Thomas Paine, Washington Irving, James Fenimore Cooper, William Cullen Bryant, Henry Wadsworth Longfellow, Oliver Wendell Holmes, John Greenleaf Whittier, James Russell Lowell, James W. C. Pennington, Francis Wright, W. E. B. Du Bois, Edgar Allan Poe, Edward Rowe Snow, Ralph Waldo Emerson, Henry David Thoreau, Seattle Chief, Margaret Fuller, Harriet Jane Hanson Robinson, Nathaniel Hawthorne, Harriet Beecher Stowe, Louisa May Alcott, Frederick Douglass, Abraham Lincoln, Robert E. Lee, Mollie Dorsey Sanford, Sidney Lanier, Elizabeth Cady Stanton, Walt Whitman, Emily Dickinson, Mark Twain, Satanta, Chief Joseph, Ambrose Bierce, Mary Eleanor Wilkins Freeman, Kate Chopin, Stephen Crane, Paul Laurence Dunbar, Edwin Arlington Robinson, Edgar Lee Masters, James Thurber, Willa Cather, Sherwood Anderson, Katherine Anne Porter, F. Scott Fitzgerald, Ernest Hemingway, William Faulkner, John Steinbeck, Richard Wright, Eudora Welty, Ezra Pound, Amy Lowell, Carl Sandburg, Langston Hughes, Marianne Moore, Archibald MacLeish, Robert Frost, Countee Cullen, Edna St. Vincent Millay, Elinor Wylie, Sara Teasdale, T. S. Eliot, James Weldon Johnson, John Crowe Ransom, Wallace Stevens, Jean Toomer, William Carlos Williams, E. E. Cummings, Phyllis McGinley, Arna Wendell Bontemps, Claude McKay, Margaret Walker, Robinson Jeffers, Louise Bogan, Lewis Thomas, Dorothy Parker, Tennessee Williams, Robert Anderson, Lillian Hellman, Patrick F. McManus, William Least Heat Moon, Richard Rodriguez, Sabine R. Ulibarrí, Lorraine Hansberry, James Baldwin, Ralph Ellison, Mona Van Duyn, Richard Wilbur, Denise Levertov, David Wagoner, Theodore Roethke, Robert Hayden, Karl Jay Shapiro, Adrienne Rich, Richard Eberhart, May Swenson, Mari Evans, Maxine Kumin, Elizabeth Bishop, Howard Nemerov, Robert Lowell, Galway Kinnell, William Stafford, Randall Jarrell, Gwendolyn Brooks, John N. Morris, Sylvia Plath, Imamu Amiri Baraka, Vern Rutsala, N. Scott Momaday, Lawson Fusao Inada, Jim Wayne Miller, James Masao Mitsui, Gary Soto, Leslie Silko, Teresa Palomo Acosta, Isaac Asimov, John Updike, Bernard Malamud, Carson McCullers, Kurt Vonnegut, Flannery O'Connor, Ray Bradbury, Eugenia Collier, Annie Dillard, Henry James Jr., Edith Wharton, 1987, Scott Foresman and Company edition, Hardcover in English - America Reads/Seventh Edition An edition of The United States in Literature (1985) The United States in Literature w/Three Long Stories America Reads/Seventh Edition by James E. Miller Jr. , Carlota Cárdenas de Dwyer , Kerry M. Wood , John Smith , William Bradford , Sarah Kemble Knight , William Byrd II , Cotton Mather , Jonathan Edwards - undifferentiated , Anne Bradstreet , Taylor, Edward , Phillis Wheatley , Philip Morin Freneau , Benjamin Franklin , J. Hector St. John de Crèvecoeur , Thomas Jefferson , Thomas Paine , Washington Irving , James Fenimore Cooper , William Cullen Bryant , Henry Wadsworth Longfellow , Oliver Wendell Holmes , John Greenleaf Whittier , James Russell Lowell , James W. C. Pennington , Francis Wright , W. E. B. Du Bois , Edgar Allan Poe , Edward Rowe Snow , Ralph Waldo Emerson , Henry David Thoreau , Seattle Chief , Margaret Fuller , Harriet Jane Hanson Robinson , Nathaniel Hawthorne , Harriet Beecher Stowe , Louisa May Alcott , Frederick Douglass , Abraham Lincoln , Robert E. Lee , Mollie Dorsey Sanford , Sidney Lanier , Elizabeth Cady Stanton , Walt Whitman , Emily Dickinson , Mark Twain , Satanta , Chief Joseph , Ambrose Bierce , Mary Eleanor Wilkins Freeman , Kate Chopin , Stephen Crane , Paul Laurence Dunbar , Edwin Arlington Robinson , Edgar Lee Masters , James Thurber , Willa Cather , Sherwood Anderson , Katherine Anne Porter , F. Scott Fitzgerald , Ernest Hemingway , William Faulkner , John Steinbeck , Richard Wright , Eudora Welty , Ezra Pound , Amy Lowell , Carl Sandburg , Langston Hughes , Marianne Moore , Archibald MacLeish , Robert Frost , Countee Cullen , Edna St. Vincent Millay , Elinor Wylie , Sara Teasdale , T. S. Eliot , James Weldon Johnson , John Crowe Ransom , Wallace Stevens , Jean Toomer , William Carlos Williams , E. E. Cummings , Phyllis McGinley , Arna Wendell Bontemps , Claude McKay , Margaret Walker , Robinson Jeffers , Louise Bogan , Lewis Thomas , Dorothy Parker , Tennessee Williams , Robert Anderson , Lillian Hellman , Patrick F. McManus , William Least Heat Moon , Richard Rodriguez , Sabine R. Ulibarrí , Lorraine Hansberry , James Baldwin , Ralph Ellison , Mona Van Duyn , Richard Wilbur , Denise Levertov , David Wagoner , Theodore Roethke , Robert Hayden , Karl Jay Shapiro , Adrienne Rich , Richard Eberhart , May Swenson , Mari Evans , Maxine Kumin , Elizabeth Bishop , Howard Nemerov , Robert Lowell , Galway Kinnell , William Stafford , Randall Jarrell , Gwendolyn Brooks , John N. Morris , Sylvia Plath , Imamu Amiri Baraka , Vern Rutsala , N. Scott Momaday , Lawson Fusao Inada , Jim Wayne Miller , James Masao Mitsui , Gary Soto , Leslie Silko , Teresa Palomo Acosta , Isaac Asimov , John Updike , Bernard Malamud , Carson McCullers , Kurt Vonnegut , Flannery O'Connor , Ray Bradbury , Eugenia Collier , Annie Dillard , Henry James Jr. , and Edith Wharton An edition of The United States in Literature (1985) The United States in Literature w/Three Long Stories America Reads/Seventh Edition by James E. Miller Jr. , Carlota Cárdenas de Dwyer , Kerry M. Wood , John Smith , William Bradford , Sarah Kemble Knight , William Byrd II , Cotton Mather , Jonathan Edwards - undifferentiated , Anne Bradstreet , Taylor, Edward , Phillis Wheatley , Philip Morin Freneau , Benjamin Franklin , J. Hector St. John de Crèvecoeur , Thomas Jefferson , Thomas Paine , Washington Irving , James Fenimore Cooper , William Cullen Bryant , Henry Wadsworth Longfellow , Oliver Wendell Holmes , John Greenleaf Whittier , James Russell Lowell , James W. C. Pennington , Francis Wright , W. E. B. Du Bois , Edgar Allan Poe , Edward Rowe Snow , Ralph Waldo Emerson , Henry David Thoreau , Seattle Chief , Margaret Fuller , Harriet Jane Hanson Robinson , Nathaniel Hawthorne , Harriet Beecher Stowe , Louisa May Alcott , Frederick Douglass , Abraham Lincoln , Robert E. Lee , Mollie Dorsey Sanford , Sidney Lanier , Elizabeth Cady Stanton , Walt Whitman , Emily Dickinson , Mark Twain , Satanta , Chief Joseph , Ambrose Bierce , Mary Eleanor Wilkins Freeman , Kate Chopin , Stephen Crane , Paul Laurence Dunbar , Edwin Arlington Robinson , Edgar Lee Masters , James Thurber , Willa Cather , Sherwood Anderson , Katherine Anne Porter , F. Scott Fitzgerald , Ernest Hemingway , William Faulkner , John Steinbeck , Richard Wright , Eudora Welty , Ezra Pound , Amy Lowell , Carl Sandburg , Langston Hughes , Marianne Moore , Archibald MacLeish , Robert Frost , Countee Cullen , Edna St. Vincent Millay , Elinor Wylie , Sara Teasdale , T. S. Eliot , James Weldon Johnson , John Crowe Ransom , Wallace Stevens , Jean Toomer , William Carlos Williams , E. E. Cummings , Phyllis McGinley , Arna Wendell Bontemps , Claude McKay , Margaret Walker , Robinson Jeffers , Louise Bogan , Lewis Thomas , Dorothy Parker , Tennessee Williams , Robert Anderson , Lillian Hellman , Patrick F. McManus , William Least Heat Moon , Richard Rodriguez , Sabine R. Ulibarrí , Lorraine Hansberry , James Baldwin , Ralph Ellison , Mona Van Duyn , Richard Wilbur , Denise Levertov , David Wagoner , Theodore Roethke , Robert Hayden , Karl Jay Shapiro , Adrienne Rich , Richard Eberhart , May Swenson , Mari Evans , Maxine Kumin , Elizabeth Bishop , Howard Nemerov , Robert Lowell , Galway Kinnell , William Stafford , Randall Jarrell , Gwendolyn Brooks , John N. Morris , Sylvia Plath , Imamu Amiri Baraka , Vern Rutsala , N. Scott Momaday , Lawson Fusao Inada , Jim Wayne Miller , James Masao Mitsui , Gary Soto , Leslie Silko , Teresa Palomo Acosta , Isaac Asimov , John Updike , Bernard Malamud , Carson McCullers , Kurt Vonnegut , Flannery O'Connor , Ray Bradbury , Eugenia Collier , Annie Dillard , Henry James Jr. , and Edith Wharton The United States in Literature w/Three Long Stories Publish Date 1987 Publisher Language English Pages 846 Previews available in:English Subjects Children's fiction , Classic Literature , Crime , Detective and mystery stories , Fiction , Horror stories , Juvenile fiction , Revenge , American Horror tales , burial vaults , catalepsy , dragons , gothic fiction , hermitages , heroic romances , horror , horror tales , hysteria , knights , maces , psychogenic death , short stories , tarns , memory plays , autobiographical drama , Family , American drama , Drama , open_syllabus_project , Young men , Human relations , Brothers and sisters , Mothers and sons , Families , Young women with disabilities , Mothers and daughters , domestic drama , Interpersonal relations , Reading Level-Grade 7 , Reading Level-Grade 9 , Reading Level-Grade 8 , Reading Level-Grade 11 , Reading Level-Grade 10 , Reading Level-Grade 12 , impulse , responsibility , short story , American literature , Collections , Study and teaching (Secondary) , Literature , Satanism , Puritans , catechism , History , United States Civil War , hanging , Confederacy , Union , Littérature américaine People Montresor , Fortunato , Luchresi , Lady Fortunato , Roderick Usher , Madeline Usher , Ethelred , Goodman Brown , Faith Brown , Goody Cloyse , Devil , Peyton Farquhar , Mrs. Sommers , Amanda Wingfield , Laura Wingfield , Tom Wingfield , Jim O'Connor Places New England , Salem Village , Massachusetts , United States , Alabama , Owl Creek Bridge , Saint Louis (Mo.) , Saint Louis , Missouri Times 1600s , Civil War , 1861-1865 , American Civil War , 19th century , carnival Showing 1 to 3 of 5 entries Book Details Published in Glenview, Illinois Edition Notes Copyright Date 1987 The Physical Object Format Hardcover Pagination xvii, 846p. Number of pages 846 ID Numbers Open Library OL11081751M Internet Archive 0673270556 ISBN 13 9780673270559 OCLC/WorldCat 23377795 Goodreads 5729334 History Created April 30, 2008
https://openlibrary.org/books/OL11081751M/The_United_States_in_Literature?v=11
Third Brigade Historical Marker Army of the Potomac Second Corps Third Division Third Brigade Colonel George L. Willard Colonel Eliakim Sherrill Lieut. Colonel James M. Bull 39th (4 cos.), 111th, 125th, 126th. (A historical marker located near Gettysburg in Adams County, Pennsylvania.) Cumberland Township near Gettysburg in Adams County, Pennsylvania — The American Northeast (Mid-Atlantic) Third Brigade Third Division - Second Corps — Army of the Potomac — Photographed By Craig Swain, September 17, 2008 1. Third (Willard's) Brigade Tablet The trefoil of the II Corps appears at the tablet's top. Inscription. Third Brigade. Third Division - Second Corps. Army of the Potomac Second Corps Third Division Third Brigade Col. George L. Willard Col. Eliakim Sherrill Lieut. Col. James M. Bull 39th (4 cos.), 111th, 125th, 126th. New York Infantry. July 2 Took position in the morning along Cemetery Ridge at the right of the Angle. Near sunset went to the left to support Third Corps. Charged Brig. Gen. Barksdale's Brigade in the wooded swale at the head of Plum Run forcing it back and capturing many prisoners. The 39th New York recaptured Battery I 5th U.S. from the 21st Miss. Col. Willard was killed and Brig. Gen. Barksdale mortally wounded. At dark the Brigade returned and was held in reserve., July 3 Engaged on the skirmish line with much loss. At 3 p.m. after a terrific cannonade of two hours the Brigade was moved up to the line of the Second Brigade and assisted in repulsing Longstreet's assault in which Col. Sherrill was mortally wounded. A large detail from the Brigade under Capt. Armstrong of the 125th New York and the 8th Ohio on the skirmish line withdrew to the right and poured a deadly fire upon the left of the assaulting lines and then charging captured prisoners and flags., Casualties. Killed 11 officers 126 men. Wounded 26 officers 516 men. Captured or missing 33 men. Total 714. . This historical marker was erected in 1912 by Gettysburg National Military Park Commission. It is in Cumberland Township near Gettysburg in Adams County Pennsylvania Army of the Potomac Second Corps Third Division Third Brigade Col. George L. Willard Col. Eliakim Sherrill Lieut. Col. James M. Bull 39th (4 cos.), 111th, 125th, 126th. New York Infantry July 2 Took position in the morning along Cemetery Ridge at the right of the Angle. Near sunset went to the left to support Third Corps. Charged Brig. Gen. Barksdale's Brigade in the wooded swale at the head of Plum Run forcing it back and capturing many prisoners. The 39th New York recaptured Battery I 5th U.S. from the 21st Miss. Col. Willard was killed and Brig. Gen. Barksdale mortally wounded. At dark the Brigade returned and was held in reserve. July 3 Engaged on the skirmish line with much loss. At 3 p.m. after a terrific cannonade of two hours the Brigade was moved up to the line of the Second Brigade and assisted in repulsing Longstreet's assault in which Col. Sherrill was mortally wounded. A large detail from the Brigade under Capt. Armstrong of the 125th New York and the 8th Ohio on the skirmish line withdrew to the right and poured a deadly fire upon the left of the assaulting lines and then charging captured prisoners and flags. Casualties. Killed 11 officers 126 men. Wounded 26 officers 516 men. Captured or missing 33 men. Total 714. Erected 1912 by Gettysburg National Military Park Commission. Topics. This historical marker is listed in this topic list: War, US Civil . A significant historical date for this entry is July 2, 1863. Location. 39° 48.916′ N, 77° 14.114′ W. Marker is near Gettysburg, Pennsylvania, in Adams County. It is in Cumberland Township. Marker is on Hancock Avenue, on the right when traveling north. Located next to the Brian Farm Buildings on Cemetery Ridge, at Gettysburg National Military Park. Touch for map . Marker is in this post office area: Gettysburg PA 17325, United States of America. Touch for directions. Other nearby markers. At least 8 other markers are within walking distance of this marker. Third Division (a few steps from this marker); 111th New York Infantry (a few steps from this marker); 12th Regiment New Jersey Volunteers (a few steps from this marker); The Brian Farm (a few steps from this marker); 11th Mississippi Infantry Regiment (within shouting distance of this marker); Abraham Brian Farm (within shouting Photographed By Craig Swain, September 17, 2008 2. Third Brigade Tablet from Across the Road distance of this marker); 107th Regiment Pennsylvania Infantry (within shouting distance of this marker); Pettigrew's Charge (within shouting distance of this marker). Touch for a list and map of all markers in Gettysburg. that is related to this marker. To better understand the relationship, study each marker in the order shown. Also see . . . Reports of Lieut. Col. James M. Bull . Lt. Col. Bull, to whom command fell after Col. Sherrill was wounded, wrote the Brigade report. Of the action on July 3, he stated: About 1 p.m. the enemy opened from his batteries planted on the slope of the hill across the flat mentioned, evidently with the intention of silencing our batteries, and a terrific cannonade ensued, which continued about two hours, during which period the regiments remained in the position before stated. Near the close of this severe artillery duel, the regiments were formed on the hill with other regiments of the division, to repel an infantry attack. The enemy, advancing in four lines across the flat, were subjected to a murderous fire of Photographed By Craig Swain 3. Willard's Brigade Repulses the Attack Looking west, from near the Willard Marker (see related markers). In the evening of July 2, the lead two regiments of Willard's Brigade, the 125th and 126th New York, charged on line, led by Willard, directly into Barksdale's Mississippi Brigade which was just then crossing Plum Run (in the bottom land here). Colonel Willard was killed leading this assault. The 111th New York, held in reserve, was soon ordered up to support the right of the Brigade, assisting the 1st Minnesota, which at that time was standing alone against Wilcox's Alabama Brigade. The fourth regiment of Willard's Brigade, the 39th New York, was detailed to recapture a Federal artillery battery to the left of this line. musketry and artillery, and were driven back in confusion, after an engagement of about an hour. (Submitted on December 21, 2008, by Craig Swain of Leesburg, Virginia.) Photographed By Craig Swain, February 21, 2009 4. Third Brigade's Portion of the Line Looking at Cemetery Ridge from the west. The Bryan farm ins in the center frame, with several monuments from the Brigade seen in profile on the ridge line. Col. Sherrell, then in command of the Brigade, posted the 111th New York forward centered at the barn. The 126th New York north of the barn, closer to Ziegler's Grove. The 125th and 39th in reserve. Photographed By Craig Swain, September 17, 2008 5. The Brigade's Second Rank Looking south from the tablet location with the Third Division Tablet in the background. The 39th and 125th New York were posted behind the front line (on the stone wall) on July 3. The position was in and around an orchard just south of the Brian house. When the Confederate infantry advanced, those two regiments moved forward to reinforce the main Federal line. Photographed By Craig Swain, September 17, 2008 6. Flanking Position From Hancock Avenue, looking at the north side of the Brian barn. As the Confederate infantry neared the stone wall, portions of the 108th New York (2nd Brigade, 3rd Division, II Corps) and 125th New York wheeled left across the open ground here. From a line near the modern white rail fence, the New Yorkers poured a destructive fire upon the mixed regiments from Pettigrew's and Tremble's Divisions. Credits. on February 7, 2023. It was originally submitted on December 21, 2008, by Craig Swain of Leesburg, Virginia. This page has been viewed 952 times since then and 7 times this year. Photos: 1, 2. submitted on December 21, 2008, by Craig Swain of Leesburg, Virginia. 3. submitted on March 1, 2009, by Craig Swain of Leesburg, Virginia. 4. submitted on March 29, 2009, by Craig Swain of Leesburg, Virginia. 5. submitted on December 21, 2008, by Craig Swain of Leesburg, Virginia. 6. submitted on March 29, 2009, by Craig Swain of Leesburg, Virginia.
https://www.hmdb.org/m.asp?m=14568
HuTools Keyless Entry Door Lock Deadbolt Installation Guide Installation Guide Read this manual carefully before installing and operating! D F I A E J G C H L K. 7 A ... Quick Set Up READ this before proceeding to programming. ... Please start over. Master Co Installation Guide for HuTools models including: Keyless Entry Door Lock Deadbolt, HT01 Installation Guide Installa on Overview Installation Guide Read this manual carefully before installing and operating! D F I A E J G C H L K. 7 A ... Quick Set Up READ this before proceeding to programming. ... Please start over. Master Code New User Code Enter the New User Code Again 2 B.Add User Code Up to 20 User Codes can be stored. After 10 unsuccessful attempts at entering a ... Browser built in viewer PDF Viewer Universal Document Viewer Google Docs View Google Drive View Download Document [pdf] Download Document [Optimized] Document: Text Not Your Device? Search For Manuals / Datasheets: File Info : application/pdf, 4 Pages, 3.22MB Document B15Ta3dti3S HuTools HT01 Installation Guide Read this manual carefully before installing and operating! STEP 2 Determine backset and adjust the latch Hold the latch in front of the door hole, with the latch face flush against the door edge. Is the slotted hole centered in the door hole? YES NO Rotate and pull the latch as shown to extend latch. 1 Installaon Overview Read this manual carefully before installing and operating! 1 Install the physical lock (Step 1-7) 2 Detect door orientation (Step 8-9) 3 Change the default master code (See Quick Set Up) Slotted hole is centered. No adjustment is required. Proceed to next step. Slotted hole is NOT centered. STEP 3 Install the latch Customize setting (See Quick Set Up) 4 Contents A Latch ×1 B Drive-In Collar ×1 C Strike ×1 D Exterior Assembly ×1 E Mounng Plate ×1 F Interior Assembly ×1 G Baery Cover ×1 H Strike Screws ×2 I Latch Screws ×2 J Mounng Plate Screws ×2 K Interior Assembly Screws ×3 L Key ×1 Is the door edge chiseled? YES NO 1 chiseled not chiseled 3 2 2-3/4" (70mm) 2 4 B (Optional) D A F E J G K I C L H If any parts are missing or damaged, please contact Customer Support. TOOL REQUIRED: USE OF A POWERED SECREWDRIVER IS NOT RECOMMENDED Installation STEP 1 Prepare the door and check dimensions 1-3/8" to 2" 35 mm to 50 mm 2-1/8" 54 mm 1" 25 mm 2-3/8" or 2-3b/4a"ckset 60 or 70 mm Actual Size I ST4*22 Do not overghten screws. B Install latch in door with wood block and hammer. STEP 4 Install strike and test alignment C H IMPORTANT: Make sure hole in door frame is drilled a minimum of 1" (25 mm) deep. 1. With the door closed, use a flat-head screwdriver to test if deadbolt works smoothly. 2. Check alignment between the latch and the strike, making sure when the deadbolt is extended, it is going into the bolt hole and not hing the deadbolt strike or door frame. STEP 5 Install exterior assembly A IMPORTANT: Do not insert the physical key unl lock is completely installed. With the latch fully retracted (in the unlocked posion) , route the cable below the latch. STEP 7C Actual Size K M4*6 Aach Interior Assembly to Mounng Plate and ghten 3 Screws K. unlocked IMPORTANT: Test the thumbturn for smooth rotaon. If thumbturn doesn't rotate, repeat step 7B , making sure the thumbturn in vercal posion. STEP 5B Keep parallel to door Secure the mounng plate with the supplied edge. screws. Do not overghten screws. unlocked J 1/4-28*55 Actual Size STEP Door handing Perform a factory reset to detect le/right door orientaon. IMPORTANT: Always run this step aer installaon. 8A The motor will not operate before compleng the step. unlocked While the door is OPENED and UNLOCKED (latch retracted), load 3 AA baeries into the baery compartment. Vercal NOTE: For best results, use new, non-rechargeable Alkaline baeries only. Do not mix old and new baeries. STEP 6 Remove baery cover IMPORTANT: Do not load baeries unl lock is completely installed. F G STEP 8B Press the Reset buon first and keep holding it while you place the 4th baery. Do not release the reset buon keep holding the reset buon, unl the latch bolt extend. Locate the slot at the boom and use your fingernail or a flat head screwdriver to pry the cover up and pull it off. reset buon STEP STEP 7 7 Install interior A assembly B unlocked Insert the cable connector to the socket. Push the connector in firmly unl it is completed seated. Vercal Horizontal Rotate the thumbturn and keep it in a vercal posion. Make sure the latch is sll fully retracted (unlocked). IMPORTANT: If the latch doesn't extend within 10 seconds, repeat step 7B and 8A, making sure the thumbturn is always vercal and latch always retracted. STEP 9 Test the lock Test with the door open to avoid an accidental lockout. Lock Press and hold any button for 2 seconds. Unlock Enter 12345678 on keypad Programming Instruction How To Use Quick Set Up A.UNLOCK the door from outside Master code Or User code B. LOCK the door from outside Auto Lock Mode The bolt will automacally extend in 30 seconds aer unlocking. You need to enable this feature by programming Manual Mode Press any buon keypad for 2 seconds Programming Basic READ this before proceeding to programming. A.Master Code The default master code is 12345678. This code must be changed prior to programming the lock. The Master Code is used for programming and for feature settings. It will also unlock the lock. B.Code Format Code is 4-10 digits. Both master code and user code do not support the following sequence. a. Forward number sequence 123456789 b. Backward number sequence 9 8 7 65 4 3 2 1 c. Repeat number sequence 2 2 2 22 2 2 2 2 d. Contain exisng code sequence If 5 6 8 3 Then 5 6 8 3 9 1 and 9 1 5 6 8 3 C. Wrong Entry Limit After 10 unsuccessful attempts at entering a valid PIN code, the unit will shut down for 3 minuets. D.Unlock with Fake code User can prevent pin code exposure from strangers by entering random digits before or after pin code. 83618 137192 14710 password Random digits E. Baery Indicator If you hear 10 beeps corresponding with 10 red flashes after pressing any key or lock and unlock the door, that's an indication that the batteries need to be replaced soon. Please replace with 4 new AA alkaline batteries and do not mix old and new batteries. All settings are retained in the memory when the batteries are removed and replaced. F. Key Override Key Override can be used to gain access when the batteries are completely dead or when no valid User Code is known. Important Note: Please keep at least one copy of the backup key in secure location outside of your place. IMPORTANT: Each programming step needs to be completed within 5 seconds. If you hear 5 rapid beeps that indicates entry error or me-out. Please start over. A.Change Master Code The default Master Code is 12345678. It is required that you change it to a code of your own before programming. Master Code 1 New Master Code Enter the New Code Again B. Add User Code Up to 20 User Codes can be stored. Master Code 2 Enter the New User Code Again New User Code C. Delete User Code Master Code 3 Unwanted User Code D.Enable Silent Mode The beep sounds when pressing keypad can be muted. But you will still hear low battery and system alerts. Master Code 42 E. Disable Silent Mode Master Code 41 F. Enable Auto Lock Automatically locks the deadbolt 30 seconds after unlocking. This feature is off by default. Master Code 51 G.Disable Auto Lock Master Code 52 H.Set Auto Lock Time Delay You can set the Auto Lock time delay between 10 and 99 seconds. Master Code 8 Enter New Duration Time(10-99) I. Add One-Time Code This code can only be used once and is automatically deleted when used. Master Code 7 New Master Code Enter the New User Code Again J. Vacation Mode This is a security feature for you when you are leaving your home for vacation or long trip. Enabling vacation mode will restrict all user codes until master code is entered on keypad. If the lock is unlocked by thumb turn, the lock will sound an alarm. Master Code 6 Factory Default Settings Troubleshootingccontinued Sengs Master Code Auto Lock Silent Mode Wrong Code Entry Limit Vacation Mode Factory Defaut 12345678 Disabled Disabled 10 times Disabled How To Reset IMPORTANT: By performing the steps below, you will teach the lock the orientaon of your door and delete all User Codes associated with the lock. Factory reset process is the same as door handing. Step1 Keep the door opened and make sure the latch is retracted and thumbturn vertical. Step2 Press and hold the reset button with one hand and the other hand takes out one battery and places it back. Step3 Do not release the reset button after battery is connected, instead, keep holding it until the latch automatically extends. Safety Warnings Protect your User Codes and Master Code. Restrict access to your lock's interior assembly and routinely check your settings to ensure they have not been altered without your knowledge. Proper cleaning and maintenance of your lock ensures it will continue to work as it should. Do not apply cleaner or detergent directly to any part of the lock. The HuTools meets IP54 water-resistance. It can withstand water splashes ; however, do not let water and liquids get into the lock. Avoid exposure to direct sunlight. Long-term exposure to direct sunlight may damage the lock. The temperature range of the HuTools is between -4°F to 131°F. Troubleshooting 1 Problem: When reseng the lock, the latch does not extend but I can hear the motor is turning. Cause A): The latch and strike are misaligned, causing the latch to bind. Soluon A): a. Adjust the posion of the strike plate. b. Make sure you reset the lock with the door opened. Cause B): Internal electronic components have a residual charge which the lock tries to use, and it is not adequate to allow the lock to funcon when connecng the baeries. Soluon B): Disconnect the baeries. Press and release any key on the keypad and keep the baeries disconnected for at least 5 minutes. If there is residual charge within the lock, this will consume the charge. Cause C): The mounng screws securing the exterior keypad and the latch bolt are over-ghtened. Soluon C): Slightly loosen the screws. 2 Problem: When reseng the lock, the latch does not extend and I can't hear the motor turning. Cause: The lock is not reset properly. Soluon: Repeat step 7B and 8A, make sure that the thumbturn is vercal and the deadbolt latch is retracted (unlocked) when installing and reseng. 3 Problem: The lock does not lock and unlock electronically. Cause: The door handing process was not executed. Soluons: Perform a factory reset to teach the lock the orientaon of your door (Step 8). * If none of the above resolves your issue, please contact us. 4 Problem: Aer installaon, the thumbturn cannot rotate. Cause A): The lock is not installed properly. Soluon A): Remove and re-install the whole lock, making sure that the thumbturn is vercal and the lock is in unlock posion when installing. Do not insert the backup key when installing. Cause B): Internal electronic components have a residual charge which the lock tries to use, and it is not adequate to allow the lock to funcon when baery connected. Soluon B): Disconnect the baeries. Press and release any key on the keypad and keep the baeries disconnected for at least 5 minutes. If there is residual charge within the lock, this will consume the charge. 5 Problem: The lock only funcons electronically when the backup key is in; I cannot pull the key out in the unlocked posion. Cause: The lock is not installed properly. Soluon: aRemove and re-install the whole lock, making sure that the thumbturn is vercal and the lock is in unlocked posion when installing. bDo not insert the physical key before lock is completely install. 6 Problem: The keypad doesn't respond when touched (no lights are visible and no beeping is heard) . Cause: The lock has no power. Soluon: a. Make sure the cable is properly connected. b. Change the baeries with 4 fresh AA standard alkaline baeries. Do not mix old and new baeries. 7 Problem: The baeries run low quickly. Cause: The deadbolt and the strike plate could be misaligned, especially when there's change in temperature and humidity, doors can become `warped'. As a result, there could be strong `fricon' as the deadbolt tries to extend. More fricon means that the motor needs to work harder to lock your door, so your baeries life may be impacted. Soluon: Make sure your door locks and unlocks smoothly. Re-install your lock and make sure the latch and strike are properly aligned. 8 Problem: When aempng to lock the deadbolt electronically, the latch goes in and out for a few mes. Cause: The latch and strike are misaligned. Soluon: aMake sure the bolt hole on the door frame is at least 1 inch deep so the bolt fully extends. b. Check if the door closes properly. Make sure when the dead bolt is extended, it is going into the bolt hole and not hing the deadbolt strike or door frame. c. Check for loose door hinges. 9 Problem: When aempng to unlock the deadbolt electronically, the latch goes in and out for a few mes. Cause: As in the problem with locking the bolt, the bolt may be binding against the strike plate. There may be interference, especially if the door has warped due to a change in the weather. Soluon: aCheck if the door closes properly. Make sure when the deadbolt is extended, it is going into the bolt hole and not hing the deadbolt strike or door frame. b. Check for loose door hinges 10 Problem: I received 5 rapid beeps when programming. Cause: a. Time-out b. Wrong entry Soluon: a. Complete each step within 5 seconds. b. Change the default master code before programming. c. Enter a new code in correct format and within 4 to 10 digits. 11 Problem: I forgot my Master Code. Soluon: Perform a factory reset. Once the reset is completed, all codes and sengs will be erased and the master code will return to the default value ( 12345678) . 12 Problem: I lost all the preset codes aer door handing. Cause: Door handing is the same as factory reset. You lock has restored to factory default. Soluon: Re-program your codes. Adobe PDF library 15.00 Adobe Illustrator CC 22.0 (Windows)
https://manuals.plus/m/d3915c2e1d4b1dd7dfe8aadb4e88402222e06e4228a029b2777c68a68b4b8b26
Adaptive controllability of microscopic chaos generated in chemical reactor system using anti-synchronization strategy 2022, Volume 12 , Issue 3 : 611-620. Doi: 10.3934/naco.2021025 Adaptive controllability of microscopic chaos generated in chemical reactor system using anti-synchronization strategy Taqseer Khan and Harindri Chaudhary , Department of Mathematics, Jamia Millia Islamia, India Corresponding author: [email protected] Received: November 30, 2020 Revised: May 31, 2021 Early access: July 2021 Published: September 2022 Abstract Abstract In this manuscript, we design a methodology to investigate the anti-synchronization scheme in chaotic chemical reactor system using adaptive control method (ACM). Initially, an ACM has been proposed and analysed systematically for controlling the microscopic chaos found in the discussed system which is essentially described by employing Lyapunov stability theory (LST). The required asymptotic stability criterion of the state variables of the discussed system having unknown parameters is derived by designing appropriate control functions and parameter updating laws. In addition, numerical simulation results in MATLAB software are performed to illustrate the effective presentation of the considered strategy. Simulations outcomes correspond that the primal aim of chaos control in the given system have been attained computationally. Keywords: Adaptive control method , Chaotic system , Lyapunov stability analysis , Anti-Synchronization , Chemical reactor system . Mathematics Subject Classification: 34K23, 34K35, 37B25, 37N35. Citation: Full Text(HTML) Figure 1.Phase diagram of 3-D chaotic chemical reactor system in x m 1 − x m 2 − x m 3space Figure 3.Anti-synchronization state trajectories of 3-D chaotic chemical system (A) between x m 1 ( t ) − x s 1 ( t ), (B) between x m 2 ( t ) − x s 2 ( t ), (C) between x m 3 ( t ) − x s 3 ( t ), (D) synchronization error of the system, (E) Parameter estimation Cited by References References [1] K. Bouallegue , A new class of neural networks and its applications, Neurocomputing , 249 (2017), 28-47. [2] M. Chen and Z. Han , Controlling and synchronizing chaotic genesio system via nonlinear feedback control, Chaos, Solitons & Fractals , 17 (2003), 709-716.  doi: 10.1016/S0960-0779(02)00487-3. [3] H. Delavari and M. Mohadeszadeh , Hybrid complex projective synchronization of complex chaotic systems using active control technique with nonlinearity in the control input, Journal of Control Engineering and Applied Informatics , 20 (2018), 67-74. [4] Z. Ding and Y. 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Poincare, Sur le probleme des trois corps et les equations de la dynamique, Acta Mathematica , 13 (1890), A3–A270. [25] A. Provata , P. Katsaloulis and D. A. Verganelakis , Dynamics of chaotic maps for modelling the multifractal spectrum of human brain diffusion tensor images, Chaos, Solitons & Fractals , 45 (2012), 174-180. [26] S. Rasappan and S. Vaidyanathan, Synchronization of hyperchaotic liu system via backstepping control with recursive feedback, In International Conference on Eco-friendly Computing and Communication Systems , Springer, (2012), 212–221. [27] F. P. Russell , P. D. Duben , X. Niu , W. Luk and T. N. Palmer , Exploiting the chaotic behaviour of atmospheric models with reconfigurable architectures, Computer Physics Communications , 221 (2017), 160-173.  doi: 10.1016/j.cpc.2017.08.011. [28] B. Sahoo and S. 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Phase diagram of 3-D chaotic chemical reactor system in x m 1 − x m 2 − x m 3 space Figure 2. Time series of 3-D chaotic chemical reactor system Figure 3. Anti-synchronization state trajectories of 3-D chaotic chemical system (A) between x m 1 ( t ) − x s 1 ( t ) , (B) between x m 2 ( t ) − x s 2 ( t ) , (C) between x m 3 ( t ) − x s 3 ( t ) , (D) synchronization error of the system, (E) Parameter estimation
https://www.aimsciences.org/article/doi/10.3934/naco.2021025?viewType=html
608601 PIN Code Area & City in Tamil Nadu State, India We found a total of 11 post offices linked with the postal code 608601. This PIN Code is associated with Cuddalore district of Tamil Nadu in India. The first digit of ZIP Code 608601 i.e. 6 represents the region Tamil Nadu, the second digit 0 denotes the sub-region Central, Trichirapalli and the third digit 8 indicates the sorting-district Cuddalore. 608601 PIN We found a total of 11 post offices linked with the postal code 608601. This PIN Code is associated with Cuddalore district of Tamil Nadu in India. The first digit of ZIP Code 608601 i.e. 6 ... read more+ represents the region Tamil Nadu, the second digit 0 denotes the sub-region Central, Trichirapalli and the third digit 8 indicates the sorting-district Cuddalore. show less- S.No Post Office PIN Code District State 1. Azhisikudi Branch Post Office Postal Sub-District : Chidambaram Postal Region : Central, Trichirapalli Postal Division : Cuddalore Postal Taluk : Chidambaram 608601 Cuddalore Tamil Nadu 2. B.Odaiyur Branch Post Office Postal Sub-District : Chidambaram Postal Region : Central, Trichirapalli Postal Division : Cuddalore Postal Taluk : Chidambaram 608601 Cuddalore Tamil Nadu 3. Bhuvanagiri Sub Post Office Telephone Number : 04144-240094 Postal Sub-District : Chidambaram Postal Region : Central, Trichirapalli Postal Division : Cuddalore Postal Taluk : Chidambaram 608601 Cuddalore Tamil Nadu 4. Budavarayanpettai Branch Post Office Postal Sub-District : Chidambaram Postal Region : Central, Trichirapalli Postal Division : Cuddalore Postal Taluk : Chidambaram 608601 Cuddalore Tamil Nadu 5. Kothavacheri Branch Post Office Postal Sub-District : Chidambaram Postal Region : Central, Trichirapalli Postal Division : Cuddalore Postal Taluk : Chidambaram 608601 Cuddalore Tamil Nadu 6. Kummidimulai Branch Post Office Postal Sub-District : Chidambaram Postal Region : Central, Trichirapalli Postal Division : Cuddalore Postal Taluk : Chidambaram 608601 Cuddalore Tamil Nadu 7. Manjakollai Branch Post Office Postal Sub-District : Chidambaram Postal Region : Central, Trichirapalli Postal Division : Cuddalore Postal Taluk : Chidambaram 608601 Cuddalore Tamil Nadu 8. Melamanakudi Branch Post Office Postal Sub-District : Chidambaram Postal Region : Central, Trichirapalli Postal Division : Cuddalore Postal Taluk : Chidambaram 608601 Cuddalore Tamil Nadu 9. Miralur Branch Post Office Postal Sub-District : Chidambaram Postal Region : Central, Trichirapalli Postal Division : Cuddalore Postal Taluk : Chidambaram 608601 Cuddalore Tamil Nadu 10. Puvalai Branch Post Office Postal Sub-District : Chidambaram Postal Region : Central, Trichirapalli Postal Division : Cuddalore Postal Taluk : Chidambaram 608601 Cuddalore Tamil Nadu 11. Sathapadi Branch Post Office Postal Sub-District : Chidambaram Postal Region : Central, Trichirapalli Postal Division : Cuddalore Postal Taluk : Chidambaram 608601 Cuddalore Tamil Nadu List of 37 Localities / Villages with 608601 as PIN Code: S.No Village/Locality PIN Code Post Office Sub-District District 1. Budavarayanpettai 608601 Budavarayanpettai B.O Chidambaram Cuddalore 2. Chokkankollai 608601 Sathapadi B.O Chidambaram Cuddalore 3. Melmanakkudi 608601 Melamanakudi B.O Chidambaram Cuddalore 4. Puvalai east 608601 Puvalai B.O Chidambaram Cuddalore 5. Ayikulam 608601 Kummidimulai B.O Chidambaram Cuddalore 6. Erettaikulam 608601 Azhisikudi B.O Chidambaram Cuddalore 7. Kilavadinatham 608601 B.Odaiyur B.O Chidambaram Cuddalore 8. Puvalai 608601 Puvalai B.O Chidambaram Cuddalore 9. Puvalai west 608601 Puvalai B.O Chidambaram Cuddalore 10. Siyappadi 608601 B.Odaiyur B.O Chidambaram Cuddalore 11. Suthukuzhi 608601 Budavarayanpettai B.O Chidambaram Cuddalore 12. Vaiyalamur 608601 Sathapadi B.O Chidambaram Cuddalore 13. Ellaikudi 608601 Kummidimulai B.O Chidambaram Cuddalore 14. Miralur 608601 Miralur B.O Chidambaram Cuddalore 15. Therkuthittai 608601 Melamanakudi B.O Chidambaram Cuddalore 16. Sathapadi 608601 Sathapadi B.O Chidambaram Cuddalore 17. Kothavacheri 608601 Kothavacheri B.O Kurinjipadi Cuddalore 18. Thimmireddipalyam 608601 Budavarayanpettai B.O Chidambaram Cuddalore 19. Vandiyankuppam 608601 Manjakollai B.O Chidambaram Cuddalore 20. B.Udaiyur 608601 B.Odaiyur B.O Chidambaram Cuddalore 21. Manaveli 608601 Budavarayanpettai B.O Chidambaram Cuddalore 22. Nallanthethu 608601 Azhisikudi B.O Chidambaram Cuddalore 23. Sitheri 608601 Melamanakudi B.O Chidambaram Cuddalore 24. Vadakkutittai 608601 Melamanakudi B.O Chidambaram Cuddalore 25. Alamelumangapuram 608601 Puvalai B.O Chidambaram Cuddalore 26. Azhisikudi 608601 Azhisikudi B.O Chidambaram Cuddalore 27. Jayankondam 608601 Kummidimulai B.O Chidambaram Cuddalore 28. Kummidimulai 608601 Kummidimulai B.O Chidambaram Cuddalore 29. Vaduvankulam 608601 Melamanakudi B.O Chidambaram Cuddalore 30. Vandurayanpattu 608601 Azhisikudi B.O Chidambaram Cuddalore 31. B.Odaiyur 608601 B.Odaiyur B.O Chidambaram Cuddalore 32. Bhuvanagiri 608601 Bhuvanagiri S.O Chidambaram Cuddalore 33. Chettikulam 608601 Kothavacheri B.O Kurinjipadi Cuddalore 34. Manjakkollai 608601 Manjakollai B.O Chidambaram Cuddalore 35. Nathamedu 608601 Kothavacheri B.O Kurinjipadi Cuddalore 36. Periyambedu 608601 Azhisikudi B.O Chidambaram Cuddalore 37. Vatharayanthethu 608601 Manjakollai B.O Chidambaram Cuddalore Location of Chidambaram on Map Frequently Asked Questions (FAQs): Ques 1.: What place does the PIN code 608601 belongs to?Ans.: The name of the area with which the PIN Code 608601 belongs to is Chidambaram, Cuddalore in the Tamil Nadu state of India. Ques 2.: How many post offices are linked with the PIN Code 608601?Ans.: There are around 11 post offices in Cuddalore that are linked with the PIN Code 608601. Few of them are: B.Odaiyur, Budavarayanpettai, Bhuvanagiri, Azhisikudi, Kothavacheri and Kummidimulai. Ques 3.: What is the postal code 608601 made up of?Ans.: The 1st digit of the postal code 608601 i.e. 6 represents the region Tamil Nadu, the 2nd digit 0 denotes the sub-region Central, Trichirapalli and the 3rd digit 8 indicates the sorting-district Cuddalore. And the rest of the digits, 601, represent a particular post office. Ques 4.: How many villages have the PIN Code 608601?Ans.: There are around 37 villages in Tamil Nadu which have the PIN code as 608601. Few of them are: Erettaikulam, Siyappadi, Chokkankollai, Puvalai west, Kilavadinatham, Ayikulam, Budavarayanpettai, Puvalai east, Melmanakkudi and Puvalai. Other 70 PIN codes attached to Cuddalore:606103,608703,608602,606111,608302,607003,606103,608201,606106,608701,607301,606111,608702,608601,608002,608502,607109,608401,608703,606110,606108,608401,606104,607303,607102,607005,606304,608303,608002,608201,607303,608102,606003,608704,607801,607105,608704,607303,607102,607802,607802,607401,607004,608602,608702,607106,607301,606106,606303,608305,606104,607804,608601,608102,607105,608702,607101,608305,608001,606108,608302,606108,605007,607102,606303,608701,606103,608701,606302and606003 Other 35 districts in Tamil Nadu:Vellore,Virudhunagar,Kanchipuram,Tiruppur,Madurai,Dharmapuri,Pondicherry,Dindigul,Jhajjar,Thanjavur,Nilgiris,Tuticorin,Karaikal,Kanyakumari,Theni,Namakkal,Tiruchirappalli,Krishnagiri,Villupuram,Erode,Tiruvarur,Ramanathapuram,Tiruvallur,Karur,Nagapattinam,Sivaganga,Tirunelveli,Coimbatore,Tiruvannamalai,Ariyalur,Perambalur,Pudukkottai,Salem,CuddaloreandChennai
https://www.icbse.com/pincodes/608601
Why Iran and Its Proxies Remain Undeterred by the Pandemic - Conflict Zones in the Time of Coronavirus: War and War by Other Means - Carnegie Endowment for International Peace Why Iran and Its Proxies Remain Undeterred by the Pandemic Table of Contents The Pandemic Further Complicates Afghanistan’s Path to Peace Jarrett Blanc How Different Post-Soviet Conflict Zones Have Fared Amid the Pandemic Why Iran and Its Proxies Remain Undeterred by the Pandemic A Beleaguered Iraq Faces Interlocking Pandemic Crises Hafsa Halawa Israelis and Palestinians Struggle With COVID-19 and With Each Other Zaha Hassan , Aaron David Miller The Pandemic’s Ripple Effects Are Among Libya’s Many Miseries North Korea Has Adopted Severe Measures to Stave Off the Coronavirus Kathryn Botto How the Pandemic Has Laid Bare Somalia’s Weak Governing Structures Tihana Bartulac Blanc How the Pandemic Is Amplifying the Impact of Conflict in Syria Maha Yahya The Pandemic Accelerates Venezuela’s Transformation Into a Police State Yemen’s Devastating War Continues Despite an Unchecked Pandemic Table of Contents The Islamic Republic of Iran and its regional proxies have navigated the coronavirus pandemic with a combination of denial, deflection, and determination. They first attempted to conceal the virus’s outbreak, then blamed their adversaries for spreading it, and eventually steeled themselves to continue the path of “resistance,” despite the economic hardship. The net effect is that the power of Iran and its regional proxies appears relatively undiminished, while the living conditions of the citizens under their care have further deteriorated. The pandemic was an opportunity for Iran’s proxies, which style themselves as hybrid actors interested in the delivery of services to their constituents, to mount early public demonstrations of power and mobilize their public health resources. In time, however, the cross-sectarian and transnational nature of the pandemic meant that states, not militias, would have to take the lead in closing borders, conducting national testing, and leading public health and education strategies directed at all citizens, regardless of sect. Years before the pandemic hit, Iran’s outsized influence in four Arab capitals—Baghdad, Beirut, Sanaa, and Damascus—was established largely as a result of the power vacuums created by the 2003 U.S. invasion of Iraq and the 2011 Arab Spring uprisings. The embattled leaders of Iraq, Lebanon, Yemen, and Syria are all either indebted to Iran for its support, reliant on Iran for their survival, fearful of ignoring Iranian demands, or a combination of all three. The economic crises caused by the pandemic have only accentuated this dependency. The Pandemic’s Stark, Underreported Impact on Iran The combination of the pandemic, U.S. sanctions, falling oil prices, mismanagement, and corruption have debilitated Iran’s economy in 2020 but triggered little introspection among Tehran’s ruling elite. Iranian Supreme Leader Ayatollah Ali Khamenei initially alleged the coronavirus was a U.S. bioweapon, which provided him the pretext to appoint a commander from the Islamic Revolutionary Guard Cor ps, rather than a physician, to lead a newly formed Health Command Center. Indeed, despite hopes in Washington that the pandemic might hasten the Islamic Republic’s collapse, the virus has seemingly accelerated Iran’s transition from (elderly) clerical rule to (middle-aged) military rule. Early on, the Shia shrine city of Qom was one of the initial epicenters of coronavirus outbreaks outside China, and in March 2020 it was estimated that90 percentof all coronavirus cases in the Middle East at the time had originated in Iran. Many of these cases were thought to be either Shia pilgrims visiting Iran or Shia fighters training in the country. As of early December, Iran officially had over 1 millioncoronavirus casesand ranked eighth in the world with more than 50,000 deaths. But leaked government data from July 2020 suggested that coronavirus deaths were nearlythree times greaterthan those reported at the time. These leaks reflected the anger of Iranian health ministry officials toward the country’s security and intelligence forces, who have a history of suppressing unflattering news about Iran so as not to embolden Tehran’s adversaries. The Iranian government’s contradictory messaging was further on display when President Hassan Rouhani inexplicably claimed in July that25 million Iraniansmay have been infected with the virus. That stark figure is one hundred times theofficial tallyin December 2020, and it outstripped the number of reported cases at the time (about 270,000) by an even wider margin. The Fallout for Iranian Proxies and Partners In neighboring Iraq—which has many pilgrims and fighters who travel to Iran frequently—COVID-19 cases began toskyrocketin the summer. Like their patrons in the Islamic Revolutionary Guard Corps, Iraqi Shia militias known as the Popular Mobilization Forces (PMF) sought to rehabilitate their tattered image—after overseeingviolent crackdownsagainst peaceful protesters last year—bybuildingtemporary, mobile hospitals to treat coronavirus patients. Yet the economic and political grievances that triggered Iraq’s popular unrest—which included theburningof Iranian consulates—has worsened. Even senior Iraqi officialsadmitthe country’s economy is in crisis and “riddled with corruption.” Lebanese Hezbollah—Iran’s chief regional proxy—also helped violentlyquellpopular protests and was accused of bringing the coronavirus into Lebanon from the early outbreak in Iran. Like the PMF in Iraq, Hezbollahdeployedvolunteers and doctors and created makeshift healthcare facilities in Lebanon. Critics accused them of performingtheatricsmore than offering genuine medical assistance. Any popular goodwill Hezbollah generated beyond its Shia base likely evaporated after the massive August 2020 fire at an ammonium nitrate depot at the Beirut port triggered one of thelargest explosions in human history. Thoughover 200 peoplewere killed, thousands were injured, and huge swathes of the city weredestroyed, Hezbollah—which operated freely in the port and has used ammonium nitrate in past operations—helped thwart an independent investigation. For years, Hezbollah’s lack of a formal role in the Lebanese government allowed the group to wield power without accountability. Given its active role in Lebanese politics today, however, one Lebanese observerassessedthat Hezbollah “got power but they lost the country and the people.” In war-torn Yemen—considered theworld’s greatest humanitarian crisisby the UN—coronavirus cases are presumed to be high but impossible to quantify given the lack of testing and humanitarian access. The leadership of the Iran-backed Houthis, who control most of the country,contendedthe pandemic was an American “biological warfare” plot, accused Saudi Arabia of sending virus-stricken Yemenis back home to spread the virus, and warned its citizens not to wear “COVID-infected” face masks ostensibly airdropped by Saudi airplanes. Yet given Yemen’s graver challenges—including widespread famine and the return of more lethal diseases such as polio and cholera—the coronavirus is not the top crisis on the Yemeni government’s agenda. As for Syria, even before the pandemic began, the country’s lengthy civil war had claimed between400,000and600,000lives and forcedhalf the populationto flee from their homes. The pandemic hasreportedlybeen “out of control” in Syria, but cases remain significantly undercounted. The outbreakreportedlyhit Iranian fighters and Iranian-supported units hardest, and among thecasualtieswas a senior Islamic Revolutionary Guard Corps commander in Syria. While U.S. President Donald Trump and his administration believed the pandemic couldweakenIran’s presence and influence in Syria, so far these predictions have not borne out. The UN World Food Programmeestimatesthat 9.3 million Syrians are unsure where their next meal is coming from, while the number ofSyrians lining up for breadhas visibly increased.Syrian refugeesin neighboring countries have also been hit hard. Aid organizations have expressed concerns about Syrian dictator Bashar al-Assad’srestrictionsof humanitarian access andexpropriationof international financial assistance. Conclusion While the coronavirus pandemic could have provided Tehran, its regional proxies, and Washington an opportunity to cooperate against a common foe, the hostility and mistrust of the Trump era has proved too wide for even a deadly pandemic to bridge. At the same time, economic hardship has made Tehran’s regional proxies more, not less, reliant on Iranian largesse. At some point, popular economic and political frustrations within Iran, and against Tehran’s regional proxies, will once again resurface. But history has shown such backlash is more likely to happen when people’s expectations have been raised and then dashed, rather than during times of financial destitution. Table of Contents The Pandemic Further Complicates Afghanistan’s Path to Peace Jarrett Blanc How Different Post-Soviet Conflict Zones Have Fared Amid the Pandemic Thomas de Waal Why Iran and Its Proxies Remain Undeterred by the Pandemic Karim Sadjadpour A Beleaguered Iraq Faces Interlocking Pandemic Crises Hafsa Halawa Israelis and Palestinians Struggle With COVID-19 and With Each Other Zaha Hassan , Aaron David Miller The Pandemic’s Ripple Effects Are Among Libya’s Many Miseries Frederic Wehrey North Korea Has Adopted Severe Measures to Stave Off the Coronavirus Kathryn Botto How the Pandemic Has Laid Bare Somalia’s Weak Governing Structures Tihana Bartulac Blanc How the Pandemic Is Amplifying the Impact of Conflict in Syria Maha Yahya The Pandemic Accelerates Venezuela’s Transformation Into a Police State Francisco Toro Yemen’s Devastating War Continues Despite an Unchecked Pandemic Ahmed Nagi Carnegie Europe Carnegie India
https://carnegieendowment.org/2020/12/17/why-iran-and-its-proxies-remain-undeterred-by-pandemic-pub-83467
Micromachines | Free Full-Text | Thermal Analysis of Flip-Chip Bonding Designs for GaN Power HEMTs with an On-Chip Heat-Spreading Layer In this work, we demonstrated the thermal analysis of different flip-chip bonding designs for high power GaN HEMT developed for power electronics applications, such as power converters or photonic driver applications, with large gate periphery and chip size, as well as an Au metal heat-spreading layer deposited on top of a planarized dielectric/passivation layer above the active region. The Au bump patterns can be designed with high flexibility to provide more efficient heat dissipation from the large GaN HEMT chips to an AlN package substrate heat sink with no constraint in the alignment between the HEMT cells and the thermal conduction bumps. Steady-state thermal simulations were conducted to study the channel temperatures of GaN HEMTs with various Au bump patterns at different levels of current and voltage loadings, and the results were compared with the conventional face-up GaN die bonding on an AlN package substrate. The simulations were started from a single finger isolated HEMT cell and then extended to multiple fingers HEMT cells (total gate width > 40 mm) to investigate the “thermal cross-talk” effect from neighboring devices. Thermal analysis of the GaN HEMT under pulse operation was also performed to better reflect the actual conditions in power conversion or pulsed laser driver applications. Our analysis provides a combinational assessment of power GaN HEMT dies under a working condition (e.g., 1MHz, 25% duty cycle) with different flip chip packaging schemes. The analysis indicated that the channel temperature rise (∆T) of a HEMT cell in operation can be reduced by 44~46% by changing from face-up die bonding to a flip-chip bonding scheme with an optimized bump pattern design. Background: Thermal Analysis of Flip-Chip Bonding Designs for GaN Power HEMTs with an On-Chip Heat-Spreading Layer by Kuo-Bin Hong 1 , Chun-Yen Peng 1 , Wei-Cheng Lin 2 , Kuan-Lun Chen 3 , Shih-Chen Chen 1 , Hao-Chung Kuo 1 , Edward Yi Chang 2,3 and Chun-Hsiung Lin 2,* 1 Semiconductor Research Center, Hon Hai Research Institute, Taipei 114699, Taiwan 2 International College of Semiconductor Technology, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan 3 Department of Materials Science and Engineering, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan * Author to whom correspondence should be addressed. Micromachines 2023 , 14 (3), 519; https://doi.org/10.3390/mi14030519 Abstract : In this work, we demonstrated the thermal analysis of different flip-chip bonding designs for high power GaN HEMT developed for power electronics applications, such as power converters or photonic driver applications, with large gate periphery and chip size, as well as an Au metal heat-spreading layer deposited on top of a planarized dielectric/passivation layer above the active region. The Au bump patterns can be designed with high flexibility to provide more efficient heat dissipation from the large GaN HEMT chips to an AlN package substrate heat sink with no constraint in the alignment between the HEMT cells and the thermal conduction bumps. Steady-state thermal simulations were conducted to study the channel temperatures of GaN HEMTs with various Au bump patterns at different levels of current and voltage loadings, and the results were compared with the conventional face-up GaN die bonding on an AlN package substrate. The simulations were started from a single finger isolated HEMT cell and then extended to multiple fingers HEMT cells (total gate width > 40 mm) to investigate the “thermal cross-talk” effect from neighboring devices. Thermal analysis of the GaN HEMT under pulse operation was also performed to better reflect the actual conditions in power conversion or pulsed laser driver applications. Our analysis provides a combinational assessment of power GaN HEMT dies under a working condition (e.g., 1MHz, 25% duty cycle) with different flip chip packaging schemes. The analysis indicated that the channel temperature rise (∆T) of a HEMT cell in operation can be reduced by 44~46% by changing from face-up die bonding to a flip-chip bonding scheme with an optimized bump pattern design. Keywords: bonding ; flip-chip device ; high-electron mobility transistor ; thermal analysis 1. Introduction GaN-based HEMTs demonstrate superior performance for applications in power electronics because of their outstanding material properties of a high breakdown electric field (1–3 MV/s), high electron saturated velocity (2.2 × 10 7 cm/s), and high sheet electron density (above 1.0 × 10 13 cm −2 ) [ 1 ]. A radio frequency (RF) GaN HEMT power amplifier with output power density more than 40 W/mm or a GaN HEMT power converter with breakdown voltage higher than 1200 V have been demonstrated [ 1 , 2 ]. More recently, GaN HEMTs have shown their capabilities in the emerging applications of high-power pulsed laser driver for the LiDAR applications [ 3 ]. For the packaging and integration of the GaN HEMT device on a package substrate, face-up die bonding with a wire connection and flip-chip bonding processes are frequently used techniques. Flip-chip technologies offer the major advantage of lower parasitic inductances over the face-up die bonding method by avoiding the wire connections [ 4 ]. Moreover, multiple active and passive devices can be integrated on a single substrate with all components being flip-chip bonded and communicating through the preformed thin/thick film metal conductors on the substrate to increase the compactness [ 5 ]. Connecting multiple active devices in parallel to raise the output current level is also a more effective way to reduce parasitic effects than a single large device [ 6 ]. Although flip-chip technology provides benefits to enhance the performance and to increase the density of integration, the high power GaN HMETs may suffer from self-heating as the power is increased and confined in a small area. Therefore, good thermal management through the packaging designs become a critical issue. For the thermal management of the GaN HEMT packages for power applications including RF power amplifiers or power converters, highly thermal conductive package substrates, such as AlN or metal-coated ceramics, are usually employed as a heat sink [ 7 ]. For conventional face-up attached GaN device dies with the backside mounted on a heat sink, the heat dissipation is greatly affected by the wafer-type (e.g., Si, sapphire, etc.), the package substrate and the die attaching materials (i.e., epoxy, eutectic solder, etc.). By contrast, flip-chip packaging offers the capability to locate the metal bump to directly connect the face-down active region of the device with the heat sink and leads to much better thermal management. A variety of the flip-chip bonding schemes for a GaN HEMT RF power amplifier were reported, and the commonly recognized effective designs usually involved directly connecting the individual drain and source fingers with the AlN heat sink. Different bumps or underfill materials were also studied [ 8 , 9 ]. However, such a bonding scheme had smaller bump dimension and required high resolution in alignment. To date, most of the designs and thermal analyses for the flip-chip package of GaN HEMT that are reported are based on RF power amplifiers (i.e., RF GaN HEMT), the device layout, dimension and operation modes of GaN HEMT for power management (i.e., power GaN HEMT) or photonic device drivers are quite different. First of all, to sustain the much higher operating drain voltages up to several hundred or kilo-volt ranges, the source-drain metal space (L ds ) is much wider. The L ds of a typical RF GaN HEMT is less than 5 µm, while L ds for a power GaN HEMT is usually near 20 µm. That means the metal density of RF GaN HEMT is higher. Secondly, the total gate periphery (W g ) of power GaN HEMT is much longer than RF GaN HEMT in order to handle to up to decades of amperes of current. The total W g of an RF GaN HEMT is typically a few millimeters (mm), with each gate finger width limited within a few hundred micrometers (µm) for multiple gate devices [ 10 ] in order to handle high frequency signals. The total gate width of power HEMT is in the range of several tens up to hundreds of millimeters with a single gate finger width larger than 1mm. The larger gate periphery of power GaN HEMT also leads to a much larger die size. Thirdly, the RF GaN HEMT is operated under continuous DC bias, while power GaN HEMT is operated without DC bias with pulsed drain current conduction at a frequency of kHz to MHz ranges. Previously, conventional face-up double gate fingers GaN HEMTs capped by a diamond heat spreader and a SiN passivation layer for RF application have been accomplished and discussed [ 11 ]. Thermal experiments show that thermal resistance of GaN HEMT with a diamond heat spreader layer is lower than traditional GaN HEMT with a SiN passivation layer by 21.4%. Furthermore, a diamond heat spreader has been applied on the Si hybrid micro-cooler for improving the hotspot’s cooling capability for RF GaN HEMTs [ 12 ]. The experiment and simulation results demonstrated that the estimated maximum temperature of the face-up GaN HEMTs can be reduced by 40.4% with a diamond heat spreader and 27.3% for that with a copper heat spreader, respectively. In this paper, we focused our analysis on GaN HEMT to be used in power converter applications (i.e power GaN HEMT). We propose different flip-chip bump approaches to achieve good thermal performance for power GaN HEMT devices. Different from the direct connection of source-drain finger metal pads with an AlN heat sink using metal bumps for RF GaN HEMT, a metal heat-spreading layer was fabricated on top of the planarized dielectric layer above the active region of the HEMTs. Then, different Au heat-conducting patterns were used to connect the metal heat-spreading layer and the AlN packaging substrate heat sink. The design of the bump pattern was decoupled from the GaN HEMT layout to provide flexibility for designing bumping structures with high thermal efficiency and mechanical robustness. We compared thermal simulations among face-up die bonding and the proposed flip-chip bonding schemes using the finite element software COMSOL. Thermal simulations were conducted step-by-step from a single gate finger HEMT cell, and then extended to multiple fingers HEMTs with various finger amounts to study the “thermal cross-talk” effects [ 13 ]. The channel temperatures of the power HEMTs of various bonding schemes were first accessed based on steady state DC conditions in order to quickly collect the effects of various voltage, current and transistor peripheries. Then, the more time-consuming dynamic analysis based on the pulsed current that is close to the actual operating condition of power GaN HEMT was conducted at selected conditions to provide a comprehensive assessment of a power GaN HEMT dies under a working condition (e.g., 1 MHz, 25% duty cycle) with different packaging schemes [ 14 ]. We have also shown that by using the metal heat-spreading layer, as well as optimized bump design, the improved thermal dissipation allows up to 44~46% reduction in channel temperature rises (∆T) for multiple fingers GaN HEMTs compared with the face-up bonding scheme, and can be achieved for both steady state and pulse operations. 2. Device Structures for Thermal Analysis The AlGaN/GaN HEMT grown on a Si substrate was employed for the study. The heterostructure consists of AlGaN (25 nm), an undoped GaN layer (1.3 µm) and a GaN/AlGaN/AlN buffer layer (4 µm). Figure 1 a depicts the cross-sectional structure of the GaN HEMT device. The HEMT device with gate offset had a gate length of 2.5 µm and a source-to-drain space of 20.5 µm. The ohmic contact to the gate distance were 3 µm and 15 µm for the source and drain, respectively. The layout of the multiple fingers HEMT for simulation is depicted in Figure 1 b. For the simplicity of analysis, the gates were separated equally with a pitch size of 100 µm, and the sizes of the source and drain contact pads were adjusted to achieve the gate offset with a larger gate-to-drain space than gate-to-source space. The drain current–voltage (I–V) performances for the thermal simulation were obtained from a 20-fingers HEMT with a total gate width of 20 mm (i.e., each finger is 1 mm) with a constant gate voltage (e.g., 0 V), as shown in Figure 1 c. The thickness of the Si substrates of the GaN chips were 300 µm. The power density of the heat generated is also labeled in Figure 1 c. The channel temperature of the face-up bonded (FU-0) GaN HEMT device on an AlN heat sink using a Au bonding layer is simulated as the controlled reference to compare with our new flip-chip bonding design. For the flip-chip bonded devices in this study, the schematic drawings are depicted in Figure 2 . The scheme of flip-chip bonding with a heat spreader above the active region is different from most previously reported structures, which have their bumps for heat conduction directly connected between the ohmic contact pads and the AlN heat sink [ 8 ]. We inserted a Au heat spreading metal layer on top of the chip, which was covered by a planarized dielectric/passivation layer, for the Au bumps (i.e., Au rods/gratings) to connect between the chips and the AlN package substrate for heat conduction. A planarized silicon nitride (SiN) layer of 2 µm covered the HEMT as an interlevel dielectric layer and a passivation layer. Then, a heat-spreading metal layer (i.e., Au or Cu) was deposited on top of the SiN layer. The thick metal bump for electric connection or heat dissipation were formed on the 300 µm-thick AlN package substrate heat sink using the standard thick film fabrication processes, which are provided by many commercial suppliers. Then, the GaN device die and the AlN package substrate were bonded face-to-face using metal solders, high temperature hot press or ultrasonic methods. Two major types of metal bump patterns were employed. The first type (FC-1) consisted of circular-shaped Au rods with a diameter of 50 µm with a space between the pillars of 100 µm. The second type (FC-2) consisted of long stripes along the FET finger directions to form a grating structure with a width of 50 µm and pitch of 100 µm. The height of the metal bump was 36 µm. Two heat-spreading layers with a thickness of 2 µm were deposited on the chip and the package substrates, which indicates the total height for heat conducting between the chip and the package substrates was 40 µm. 3. Results and Discussion The analysis of the thermal behavior of the different integration structures employed a three-dimensional (3D) finite element analysis model. The heat generated in the channel region based on the I–V behavior (as shown in Figure 1 c) of the GaN HEMT is taken as the heat source. The heat is assumed to be generated along the channel region and the location of heat generation can be accurately predicted by the use of the two heat source model [ 15 ]. The material properties, including density (ρ), thermal conductivity (κ) and heat capacity (C p ) for the thermal analysis are listed in Table 1 . Typically, the thermal properties of materials are temperature dependent, therefore, the material nonlinear effects [ 16 ] were also included in our analysis and the parameters for the temperature of 300 K used in the simulation are taken from Refs. [ 17 , 18 , 19 , 20 , 21 ]. In addition, recently, the comparison of linear and nonlinear thermal conductivity models for AlGaN/GaN HEMTs has demonstrated that the calculated data of the nonlinear model are in good agreement with the measured data [ 22 ]. The thermal interaction between the individual gate fingers for the parallel-connected multiple gate HEMTs, which is known as the “thermal cross-talk” effect, were also included in our analysis. Such effect is very significant and cannot be neglected for the power GaN HEMT with large gate periphery. As mentioned previously, the W g of power GaN HEMT can be in the range of tens to hundreds of millimeters with tens of HEMT cells connected in parallel (i.e., multi-finger HEMTs). The accumulation of heat transmitted from neighboring parallel HEMT cells of a specific HEMT cell could raise the channel temperature significantly. However, the temperature rise owing to the thermal cross-talk effect would become saturation as the parallel HEMT cell amount (i.e., number of fingers) reached larger numbers due to thermal equilibrium between heat generation and heat dissipation by the whole structure. The saturation of the channel temperature rising with respect to the amounts of parallel HEMT cells may not be observed for smaller RF GaN HEMT dies. Moreover, the thermal analysis based on the steady state can be more straightforward; nevertheless, transient analysis for devices under pulse operation is necessary for reflecting the thermal behavior under many actual use conditions. For GaN HEMT used in power electronics, there is usually no steady state DC bias. Typically, the GaN HEMT is operated in pulsed drain current conduction mode, in which the peak power could be much higher than the average power, while the duty cycle may be low and adjustable, at a frequency of kHz to MHz ranges. The channel temperature rises and falls following the drain current pulses. However, the temperature would not fall back to the original point right away for each cycle, and the time-dependent transient behavior in heating and cooling during an operating cycle need to be well analyzed. The temperature rise in pulse operation is the accumulation of the residual heating from previous cycles. The steady-state thermal simulation would result in an overestimated channel temperature rise. Nevertheless, such steady-state analysis provides an upper bounding situation. Additionally, it can also be used to estimate the pulse current condition after being adjusted to a derated steady state average power. Our thermal analysis was started with steady-state analysis for a single HEMT cell, then we extended the simulation to verify the thermal cross-talk effect of multiple HEMT cells. Thermal simulations of GaN HEMT under pulse bias and current, which mimics the real situation of operation of a converter or pulse laser driving circuit, were also conducted to analyze the channel temperatures of different packaging scheme. Figure 3 a shows the comparison of the channel temperature rise (ΔT = T max − T amb ) of a single gate HEMT cell using different bonding schemes (FU-0, FC-1 and FC-2) under different DC bias conditions, as well as different ambient temperatures, T amb (i.e., 300 K~360 K), where T max indicates the maximum channel temperature. It can be seen that the FU-0 device showed the higher ΔT, with values ranging from 145.9 °C to 171.1 °C for ambient temperature, and ranging from 300 K to 360 K with V DS up to 20 V (i.e., drain current saturated at 0.45 A/mm). The sensitivity to ambient temperature could be to the result of a relatively longer heat transfer distance of the FU-0 scheme and lower thermal conductivity resulting from the effect of nonlinear thermal conductivity. For the FC-1 bonding scheme, the temperature rise can be decreased down to 86.4 °C to 92.6 °C with minor dependence on ambient temperature, while the FC-2 showed a similar temperature rise near 87.8 °C to 94.4 °C. It is very clear that the shorter distance from the heat generating channel to the AlN heat sink of the flip-chip bonding schemes (i.e., bump height) leads to the cooler channel temperature and less sensitivity to ambient temperature than the FU-0 scheme. The slightly difference (<2 °C) in channel temperatures between FC-1 and FC-2 are more likely owing to the different spatial overlapping of the Au bump patterns and GaN HEMT fingers. The bump pattern with Au gratings in the simulation are not deliberately aligned to the multiple fingers of the GaN HEMT devices in our study. If the arrangement of long grating patterns were purposely designed to align with the FET source/drain fingers, FC-2 could probably provide more efficient heat transfer paths than the rod-shaped bumps of FC-1. The inset of Figure 3 a also compares the channel temperatures for the FU-0 with the substrate thickness of 100 µm and 300 µm, and the difference in the channel temperature is around 11.9~18.4 °C for V DS = 20 V under ambient temperatures between 300 K to 360 K. The results suggest that the flip-chip bonding for the GaN HEMT chip with a heat-spreading layer showed superior heat dissipating capability than the FU-0 structures. Figure 3 b demonstrates the channel temperature rises (ΔT) of multiple fingers HEMTs under different drain bias (V DS ) of 6 V, 9 V and 12 V for T amb = 300 K, different from the drain current (i.e., as shown in Figure 1 c) to illustrate the “thermal cross-talk” effects. The channel temperature rises are plotted against different amounts of gate fingers. It can be seen that the both FC-1 and FC-2 flip-chip bonding schemes showed lower ΔT than the FU-0 case. The ΔT increased with the parallel connected gate amounts and gradually became saturated above 21 and 13 HEMT cells stacked for the FU-0 and flip-chip bonding schemes when V DS = 12 V. The saturation shifted to more gate amounts as the drain voltage increased, indicating more lateral heat conduction with a hotter channel. The discrete RF device structures with various gate fingers (≤10 fingers) amounts and different gate pitches between 25 µm to 50 µm were reported previously [ 23 , 24 ]. The typical unit gate width is below 500 µm per gate. In this study, we extend the analysis to GaN HEMTs for power conversion or photonic device driver applications, and the HEMT dimensions are in the range of tens of millimeters. We simulated the device with a unit gate finger width of 1 mm and a gate pitch of 100 um, with amounts of the gate up to 45. It can be seen in our study that the channel temperature rising can increase around 3.2 to 3.7 times for the FU-0 structure when the drain bias raises from 6 V to 12 V by comparing the single gate ΔT value and the saturated multiple gate ΔT values. For example, the channel temperature can increase from 71.6 °C to 268 °C for FU-0 structures biased at 12 V as the gate amounts increase from 1 gate to 45 gates. On the other hand, the channel temperature rise of the flip-chip bonded structures can be limited below 3 times between ΔT of a single gate and saturated ΔT of multiple gate devices. For example, the channel temperature increased from approximately 43.4 °C to 121.9 °C for the FC-1 structure biased at 12 V as the gate amount increased from 1 gate to 45 gates. By utilizing of the FC-1 and FC-2 structures, the saturated ΔT for multiple fingers HEMTs can be dramatically decreased to 45.5% and 46.7% of ΔT of a conventional face-up bonded (FU-0) structure. For RF GaN HEMT, there are several thermal analysis reports published by manufacturers [ 25 , 26 ]. To further compare the thermal performances between our analysis on power GaN HEMT and the reported RF GaN HEMTs, the channel temperature can be compared for face-up mounted dies so as to exclude the effects of flip-chip bump designs. For example, the measured channel temperature rise (ΔT) of 157 °C was reported for a multiple gate finger 14.4 mm gate width (W g ) HEMT with 4 W/mm power dissipation [ 25 ]. The channel temperature rise reported is close to our thermal simulation results of ΔT ~150 °C for 13 fingers HEMT (W g = 13 mm, Figure 3 b), though the substrate and die attaching solder are different. On the other hand, the RF GaN HEMT with a smaller W g of 2 mm exhibiting a lower temperature rise of approximately 70~80 °C was reported [ 26 ], which is near our results for 2 fingers HEMT (W g = 2 mm, Figure 3 b). The lower temperature rise could be attributed to the weaker “thermal cross-talk” effect of the smaller HEMT size. Based on the comparison, we suggest that the thermal performances are similar between the reported RF GaN HEMT and our power GaN HEMT, regardless of the differences in the device layouts (i.e., L ds , L g and gate pitch). The temperature distributions in the x–y and x–z cross-section plots of GaN HEMTs with nine gate fingers operated at V DS = 12 V and T amb = 360 K for three different bonding schemes are depicted in Figure 4 . For the FU-0 scheme, the simulated temperature distribution is shown in Figure 4 a. The heat was generated at the channel, then radially spread from the center of the channel to the heat sink through the Si substrate and bonding metal. For the flip-chip bonding schemes, the heat would be spread to both upward and downward paths. The upward heat flow is dissipated through Si substrate to the air, while the downward heat flow is conducted through the Au metal heat-spreading layer and epoxy/Au bumps to the AlN package substrate heat sink. The relevant temperature profiles are demonstrated in Figure 4 b,c for the FC-1 and FC-2 schemes, respectively. Furthermore, a material with high thermal diffusivity, α = κ/(ρ·C p ) [ 27 ], means that the heat can be rapidly transferred from the hot region to the cold region. The estimated thermal diffusivities are also listed in Table 1 . In spite of containing epoxy, which has worse thermal conductivity and diffusivity properties, the average thermal diffusivities (44.6 mm 2 /s and 58.4 mm 2 /s) of whole flip-chip package bodies including Au heat-spreading layers, epoxy and Au rods/gratings patterns for FC-1 and FC-2 are approximately in a similar magnitude with the thermal diffusivity value of GaN. The thinner package body of flip-chip bonding schemes with Au heat-spreading layers would be beneficial for the quicker relief of the thermal accumulation. For power GaN HEMT, the applications in power conversion or driver for a photonic device (i.e., laser, light-emitting diode) are functioning in pulse mode. Thus, the transient heating effect of GaN HEMT under pulse operation was also analyzed. Figure 5 illustrates the transient temperature responses of GaN HEMTs with five gate fingers (i.e., W g = 5 mm) for the three different bonding schemes. The power GaN HEMTs were simulated under more stringent conditions, e.g., V DS = 20 V and T amb = 360 K, to imitate the real working environment. The dynamic thermal simulation of a GaN HEMT device bonded on an AlN package substrate heat sink can be simplified as an equivalent RC circuit model, which consists of a series thermal resistance R th and a shunt thermal capacitance C th , as shown in the inset of Figure 5 a. The heating pulse was assumed to be a square wave with a pulse-width modulation frequency of 1 MHz (the corresponding time period is 1 µs) and a duty cycle of 25%. Figure 5 a depicts the transient temperature rise of a five-fingers GaN HEMT device with a gate pitch of 100 µm being continuously operated for 100 pulses. Obviously, the calculated temperature ripples for the FU-0, FC-1 and FC-2 structures illustrate a clear difference. The ΔT are 41.1 °C, 23.1 °C and 24 °C for FU-0, FC-1 and FC-2, respectively. Moreover, as shown in Figure 5 b, the ΔT for FU-0, FC-1 and FC-2 are increased from 41.1 °C to 55.4 °C, 23.1 °C to 29.1 °C and 24 °C to 29 °C, respectively, for the case of gate pitch = 50 µm. It is clearly demonstrated that the thermal cross-talk effect is still crucial for power GaN HEMT with multiple fingers operated at a higher modulation frequency. Through the steady-state and transient thermal analysis, it was shown that our proposed flip-chip bonding designs possess excellent capabilities to effectively dissipate the heat. 4. Conclusions We have presented the steady state and transient thermal analysis of GaN HEMT with a Au metal heat-spreading layer flip-chip bonded on an AlN package substrate heat sink. The superior heat dissipating capabilities of the proposed flip-chip bonding schemes for power GaN HEMT were presented and compared with the conventional face-up bonding scheme. Analysis of the thermal cross-talk effect indicated that multiple gate HEMT could show 3.2~3.7 times higher channel temperature rising than single gate HEMT, depending on the various bonding schemes. The transient analysis for the pulse operation of the GaN HEMTs were also provided. The ΔT for FU-0, FC-1 and FC-2 increased 41.1 °C, 23.1 °C and 24 °C, respectively, for the case of gate pitch = 100 µm after continuous operation for 100 cycles with a frequency of 1 MHz and a duty cycle of 25 %. This work offers viable flip-chip bonding designs to provide better thermal management for power GaN HEMT. Author Contributions Conceptualization, K.-B.H., C.-Y.P. and C.-H.L.; methodology, K.-B.H., C.-Y.P., C.-H.L. and W.-C.L.; software, K.-B.H.; validation, K.-B.H., C.-Y.P. and W.-C.L.; writing—original draft preparation, K.-L.C.; writing—review and editing, K.-B.H., K.-L.C. and C.-H.L.; supervision, E.Y.C.; project administration, S.-C.C.; funding acquisition, E.Y.C. and H.-C.K. All authors have read and agreed to the published version of the manuscript. Funding This research was funded by the National Science and Technology Council, Taiwan (NSTC 111-2622-8-A49-021-SB). Data Availability Statement Not applicable. 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In Proceedings of the 2009 IEEE MTT-S International Microwave Symposium Digest, Boston, MA, USA, 7–12 June 2009; pp. 917–920. [ Google Scholar ] [ CrossRef ] Hosch, M.; Pomeroy, J.; Sarua, A.; Kuball, M.; Jung, H.; Schumacher, H. Field dependent self-heating effects in high-power AlGaN/GaN HEMTs. In Proceedings of the International Conference on Compound Semiconductor Manufacturing Technology, CS MANTECH, Tampa, FL, USA, 18–21 May 2009; pp. 32–55. [ Google Scholar ] Jakani, A.; Sommet, R.; Simbélie, F.; Nallatamby, J.C. Understanding the Thermal Time Constants of GaN HEMTs through Model Order Reduction Technique. Electronics 2021 , 10 , 3138. [ Google Scholar ] [ CrossRef ] Figure 1. ( a ) Cross-sectional plot of a single GaN HEMT device. ( b ) The three-dimensional schematic of a multiple gate HEMT device. ( c ) The drain current–voltage curve and corresponding power density of a single GaN HEMT. Figure 1. ( a ) Cross-sectional plot of a single GaN HEMT device. ( b ) The three-dimensional schematic of a multiple gate HEMT device. ( c ) The drain current–voltage curve and corresponding power density of a single GaN HEMT. Figure 2. Cross-sectional view and three-dimensional schematics of the proposed flip-chip bonding designs for high power GaN HEMTs. Figure 2. Cross-sectional view and three-dimensional schematics of the proposed flip-chip bonding designs for high power GaN HEMTs. Figure 3. Calculated channel temperature rises for ( a ) single gate and ( b ) multiple gate GaN HEMTs. The channel temperature rises of FU-0, FC-1 and FC-2 are indicated by the circle, triangle and square, respectively. The blue, red and green lines plotted in Figure ( a ) indicate that the ambient temperatures are set to 300 K, 330 K and 360 K, respectively. Figure 3. Calculated channel temperature rises for ( a ) single gate and ( b ) multiple gate GaN HEMTs. The channel temperature rises of FU-0, FC-1 and FC-2 are indicated by the circle, triangle and square, respectively. The blue, red and green lines plotted in Figure ( a ) indicate that the ambient temperatures are set to 300 K, 330 K and 360 K, respectively. Figure 4. Temperature distributions of GaN HEMTs with nine gate fingers operated at V DS = 12 V and T amb = 360 K for ( a ) FU-0, ( b ) FC-1 and ( c ) FC-2 bonding schemes. The x–z cross-section is cut along the center of the AlGaN channel. Figure 4. Temperature distributions of GaN HEMTs with nine gate fingers operated at V DS = 12 V and T amb = 360 K for ( a ) FU-0, ( b ) FC-1 and ( c ) FC-2 bonding schemes. The x–z cross-section is cut along the center of the AlGaN channel. Figure 5. Transient temperature responses of three different bonding schemes. The GaN HEMTs with five gate fingers operated at a pulse-width modulation frequency of 1 MHz with a duty cycle of 25% for the gate pitch of ( a ) 100 µm and ( b ) 50 µm, respectively. The V DS and T amb are fixed at 20 V and 360 K. The inset of Figure ( a ) shows the effective thermal RC network model. Figure 5. Transient temperature responses of three different bonding schemes. The GaN HEMTs with five gate fingers operated at a pulse-width modulation frequency of 1 MHz with a duty cycle of 25% for the gate pitch of ( a ) 100 µm and ( b ) 50 µm, respectively. The V DS and T amb are fixed at 20 V and 360 K. The inset of Figure ( a ) shows the effective thermal RC network model. Table 1. Material constants used in the simulation for the temperature of 300 K are listed below. Table 1. Material constants used in the simulation for the temperature of 300 K are listed below. Property SiN GaN AlGaN AlN Si Au Epoxy ρ (κγ/μ 3 ) 3100 6150 6282 6810 2330 19,300 2080 κ (W/m·K) 18.5 130 17.2 180 148 310 1.22 C p (J/Kg·K) 709 431 494.4 748 255 137 1010 α (μμ 2 /σ) 8.4 49 5.5 35.3 249.1 123.6 0.58 MDPI and ACS Style Hong, K.-B.; Peng, C.-Y.; Lin, W.-C.; Chen, K.-L.; Chen, S.-C.; Kuo, H.-C.; Chang, E.Y.; Lin, C.-H. Thermal Analysis of Flip-Chip Bonding Designs for GaN Power HEMTs with an On-Chip Heat-Spreading Layer. Micromachines 2023, 14, 519. https://doi.org/10.3390/mi14030519 AMA Style Hong K-B, Peng C-Y, Lin W-C, Chen K-L, Chen S-C, Kuo H-C, Chang EY, Lin C-H. Thermal Analysis of Flip-Chip Bonding Designs for GaN Power HEMTs with an On-Chip Heat-Spreading Layer. Micromachines. 2023; 14(3):519. https://doi.org/10.3390/mi14030519 Chicago/Turabian Style Hong, Kuo-Bin, Chun-Yen Peng, Wei-Cheng Lin, Kuan-Lun Chen, Shih-Chen Chen, Hao-Chung Kuo, Edward Yi Chang, and Chun-Hsiung Lin. 2023. "Thermal Analysis of Flip-Chip Bonding Designs for GaN Power HEMTs with an On-Chip Heat-Spreading Layer" Micromachines14, no. 3: 519. https://doi.org/10.3390/mi14030519 Hong, K.-B.; Peng, C.-Y.; Lin, W.-C.; Chen, K.-L.; Chen, S.-C.; Kuo, H.-C.; Chang, E.Y.; Lin, C.-H. Thermal Analysis of Flip-Chip Bonding Designs for GaN Power HEMTs with an On-Chip Heat-Spreading Layer. Micromachines 2023, 14, 519. https://doi.org/10.3390/mi14030519 AMA Style Hong K-B, Peng C-Y, Lin W-C, Chen K-L, Chen S-C, Kuo H-C, Chang EY, Lin C-H. Thermal Analysis of Flip-Chip Bonding Designs for GaN Power HEMTs with an On-Chip Heat-Spreading Layer. Micromachines. 2023; 14(3):519. https://doi.org/10.3390/mi14030519
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Refworld | U.S. Committee for Refugees World Refugee Survey 1999 - Belarus Refworld is the leading source of information necessary for taking quality decisions on refugee status. Refworld contains a vast collection of reports relating to situations in countries of origin, policy documents and positions, and documents relating to international and national legal frameworks. The information has been carefully selected and compiled from UNHCR's global network of field offices, Governments, international, regional and non-governmental organizations, academic institutions and judicial bodies. U.S. Committee for Refugees World Refugee Survey 1999 - Belarus <table><tbody><tr><td> Publisher</td><td> United States Committee for Refugees and Immigrants</td></tr><tr><td> Publication Date</td><td> 1 January 1999</td></tr><tr><td> Cite as</td><td> United States Committee for Refugees and Immigrants, U.S. Committee for Refugees World Refugee Survey 1999 - Belarus, 1 January 1999, available at: https://www.refworld.org/docid/3ae6a8c02c.html [accessed 23 June 2023]</td></tr><tr><td> Disclaimer</td><td> This is not a UNHCR publication. UNHCR is not responsible for, nor does it necessarily endorse, its content. Any views expressed are solely those of the author or publisher and do not necessarily reflect those of UNHCR, the United Nations or its Member States.</td></tr></tbody></table> At the end of 1998, about 16,500 asylum seekers and refugees in need of protection were living in Belarus. These included 79 individuals granted refugee status by the Belarusan Committee on Migration, 521 asylum seekers who were registered or had cases pending with the regional migration services, 2,785 asylum seekers – mostly from outside the former Soviet Union – who were registered with UNHCR, and about 13,100 former Soviet nationals who had not registered with Belarus's regional migration services, but whom UNHCR considered to be potential asylum seekers. During the year, 421 asylum seekers registered with UNHCR. The largest numbers were from Afghanistan (74 percent), Georgia (11 percent), Tajikistan (4 percent) and Algeria (2.4 percent). Approximately 150 asylum seekers registered with the regional migration services, most of whom were from Afghanistan (56 percent), Georgia (25 percent), and Tajikistan (8.4 percent). Asylum Belarus has not acceded to the UN Refugee Convention or Protocol. Instead, Belarus adopted a domestic law "On Refugees" in February 1995, which mirrors the Refugee Convention in some respects, but includes provisions that restrict access to the vast majority of applicants, particularly those originating from former Soviet states. Barred from access, many bona fide refugees reportedly do not register and live in the country without documentation. Government and UNHCR figures may, therefore, significantly understate the number of individuals in need of protection in Belarus. Estimates of the number of undocumented migrants in, and transiting through, Belarus range from 100,000 to 300,000. Belarus began implementing the law on refugees in 1997, for the first time granting refugee status to 38 Afghans and 12 Ethiopians – most of whom were long-time residents of Belarus. Under the law, asylum seekers register with the regional migration service, which forwards applications to the Committee on Migration for status determinations. The Committee's willingness to accept new applications was largely untested before 1998. The Committee granted refugee status to 29 persons in 1998 – a 42 percent decrease from 1997. During the year, Belarus expanded its ability to accept and process asylum applications. By June, asylum seekers could file applications in any of Belarus's six regional migration services, including one city migration service in Minsk. By December 31, the regional migration services had forwarded 144 of 266 asylum applications to the Committee on Migration. At year's end, the Committee had recognized 79 persons – 63 Afghans and 16 Ethiopians – as refugees. Belarus's new refugee status determination procedure remained irrelevant for the vast majority of asylum seekers in 1998, however. During the year, the regional migration services refused to register approximately 400 asylum applications. Although information on the nationalities of those rejected and the exact reasons for rejection is sparse, UNHCR attributed the rejections (and an even greater number of nonregistrations) largely to a safe third country provision in the law on refugees. Under the provision, Russia – through which almost 90 percent of Belarus's arrivals travel – is considered a safe third country. Consequently, Belarusan migration services refuse to register the asylum claims of persons who transit through Russia. The Committee on Migration also refuses most applications from asylum seekers from other member countries of the Commonwealth of Independent States (CIS). CIS citizens and their descendants who left, or were forcibly deported from, Belarus but can demonstrate permanent residency in Belarus before November 12, 1991 (the date the law on citizenship entered into force) are eligible for citizenship. Others are not considered for citizenship or, in most cases, asylum. At least 13,100 asylum seekers from former Soviet states – most of whom arrived in Belarus years ago – remain unregistered because the government requires them to apply under the restrictive refugee law. In March, Belarus signed the CIS agreement on Cooperation in Combatting Illegal Migration. The agreement does not affect registered refugees and asylum seekers. UNHCR expressed concern, however, that refugees who do not register or whose applications are denied under Belarus's restrictive registration practices will be arrested, detained, and returned to countries where they fear persecution. In December, Belarus's parliament adopted a new immigration law that was unimplemented at year's end. Like the CIS Agreement, the law reportedly will not apply to registered asylum seekers and refugees but contains no exemptions for asylum seekers excluded from the registration process. The Propiska System The age-old Soviet internal registration system ( propiska) remained in full force in Belarus throughout 1998, preventing many recognized refugees from obtaining residence permits, work authorization, housing, health care, and social services. Although the law on refugees provides that recognized refugees should be accorded a residence permit through the propiskasystem, only 21 refugees had received residence permits by year's end. To obtain a propiska, refugees must show that a family or organization will provide them with housing. Given the acute housing shortage in Belarus, such a guarantee was reportedly very difficult to obtain. Bureaucratic difficulties in obtaining even a temporary propiskaforced the majority of asylum seekers to rent apartments illegally. Most, nevertheless, were able to obtain primary education and health care. Political Developments Democratization slid further backward in Belarus during 1998, as President Alexander Lukashenko continued to consolidate his power through authoritarian tactics. Human Rights Watch reported in July that the government's campaign to crush all aspects of civil society by restricting freedom of expression, systematically harassing independent-minded civic organizations, and squelching public protest continued unabated. The political situation led several neighboring countries to grant refugee status to Belarusans crossing the border in search of asylum.
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SCHUMER, GILLIBRAND, SLAUGHTER ANNOUNCE MONROE COMMUNITY COLLEGE SECURES $550,000 TO MAKE COLLEGE A TOP PHOTONICS TRAINING CENTER - New York Photonics New York Photonics has been working on getting this designation for over 10 years. It wasn't until Professor Alexis Vogt, PhD came to MCC that it began to move… SCHUMER, GILLIBRAND, SLAUGHTER ANNOUNCE MONROE COMMUNITY COLLEGE SECURES $550,000 TO MAKE COLLEGE A TOP PHOTONICS TRAINING CENTER In Manufacturing , New York Photonics , New York State Optics , Optics , Workforce Development News Tag NYPhotonics New York Photonics has been working on getting this designation for over 10 years.  It wasn’t until Professor Alexis Vogt, PhD came to MCC that it began to move forward.  Thank you, Alexis! SCHOOL AIMS TO MEET GROWING DEMAND FOR SKILLED WORKERS IN UPSTATE NEW YORK Monroe Community College (MCC), The Only Community College In The Nation Offering An Optics and Photonics Associates Degree, Needed Federal Funds To Expand Facilities, Meet Regional Need For Trained Workers Over $500K from National Science Foundation (NSF) Is First Step Towards Making MCC the Northeast Regional Center for Optics and Photonics; Schumer, Gillibrand, Slaughter Urged Feds To Approve Funds That Would Support New Equipment, Curriculum & Recruitment Schumer, Gillibrand, Slaughter: Critical Fed Funds Will Help Build on MCC’s Proven Success in Optics and Photonics U.S. Senate Minority Leader Charles E. Schumer, Senator Kirsten Gillibrand, and Congresswoman Louise Slaughter (NY25) today announced the National Science Foundation’s (NSF) Advanced Technology Foundation’s Education program has awarded $550,434 for Monroe Community College (MCC). The funding will allow MCC to expand its optics and photonics degree programs, purchase new equipment, as well as develop a new curriculum and expand student outreach.  Optics and photonics involves the science and application of light and are key to many industries including manufacturing, telecommunications and medicine. “MCC is a proven leader in optics and photonics training, and we have an opportunity here to build on that success by creating a top-notch training center that will prepare Upstate New Yorkers for good-paying, middle-class jobs in this burgeoning field,” said Senator Schumer. “This five hundred thousand will enable MCC to expand its optics and photonics degree programs, update its equipment, and put it on track to become the Northeast Regional Center for Optics & Photonics. This grant is the first step in creating a regional center that will ensure all of New York and the entire Northeast has the workforce it needs to attract, build and sustain a strong photonics industry.” “This federal funding is great news for Monroe Community College and for the entire Rochester community,” said Senator Kirsten Gillibrand . “The Rochester area is already at the center of the American optics and photonics industries, and these funds will help secure MCC’s position as a leading training center for students who want good-paying jobs in these fields. I will continue to do everything I can to make sure our students are prepared to take on the good-paying jobs of the future.” “We have fought hard these last few months to ensure the National Science Foundation understood the important impact this federal award could have in helping train the next generation advanced manufacturing workforce.” SaidCongresswoman Louise Slaughter.“It was truly a team effort that would not have been possible without the work of Alexis Vogt and the extraordinary leadership of President Kress. I’m proud to have stood with Monroe Community College in support of their proposal every step of the way. This federal award will help Monroe County continue to lead the world in optics and photonics,” said Slaughter. MCC is currently the only community college in the U.S. with an optics and photonics associate’s degree program, and is looking to become a major training center for this burgeoning field. Schumer, Gillibrand said that MCC hopes to ultimately become the “Northeast Regional Center for Optics & Photonics,” and this federal funding will help start make that expansion possible. L to R: student Mark Smith; Professor Bill Strong; Professor Alexis Vogt, PhD; MCC President Anne Kress; Congresswoman Louise Slaughter Additionally this NSF grant is the first step in MCC reaching that goal of becoming a center for photonics training and, eventually, middle-class job growth in this growing industry. Schumer explained that there are currently over 120 optics, photonics and imaging companies that employ over 24,000 people across the Finger Lakes, Southern Tier and Central New York regions.  Schumer, Gillibrand said this federal funding would help provide training for over 800 area high school and college students through the proposed OPT IN! program. Schumer said that OPT IN! would put Rochester area students in the best possible position to pursue higher education and compete in the job market. Not only would it allow high school students to earn college credits, Schumer argued that OPT IN! would make it easier for non-traditional students, such as veterans, to transfer from MCC to four-year universities and to complete critical student internships. The grant would also allow MCC to develop new and revised curriculum, and expand online education. Finally, Schumer explained that OPT IN ! would broaden industry and community partnerships aimed at recruitment and education about optics and photonics as a career option. Dr. Alexis Vogt, Endowed Chair & Associate Professor of Optics at Monroe Community College said, “We are very appreciative of the Senators’ support to help us win this grant.  We are now on our way to making Monroe Community College the home of the Northeast Regional Center for Photonics & Optics.  This grant to allow MCC to strengthen our region’s optics and photonics workforce and provide students here with employment opportunities in regional high skill, high demand positions.  Ultimately this funding gives us the foundation to begin creating a regional center that will ensure all of New York and the entire Northeast has the workforce it needs to attract, build and sustain a strong photonics industry.” The photonics and optics industry is central to the New York State economy and the Rochester area in particular. According to the Rochester Regional Photonics Cluster (RRPC), these companies generate $3 billion in revenue per year, and support 1-in-14 households in Monroe County. In addition to the one-of-a-kind program at MCC, Rochester is home to the University of Rochester’s Institute of Optics, and the Laboratory for Laser Energetics at Rochester Institute of Technology. Statewide, New York universities educate 60 percent of the nation’s optics Ph.Ds. Schumer, Gillibrand has long championed optics and photonics in the Rochester area. Earlier this year, Schumer, Gillibrand announced that the NSF awarded a $2 million dollar grant to the University of Rochester’s photonics research program. These funds created new opportunities for AIM Photonics Center outreach in the Rochester community. The University of Rochester was able to create K-12 education materials to teach students about photonics and optics. A copy of Senator Schumer’s October 2016 letter to the National Science Foundation Director appears below: Dear Director Cordova, I am pleased to write in strong support of Monroe Community College (MCC) grant application to the National Science Foundation’s (NSF) Advanced Technological Education (ATE) program to enable MCC to expand its optics and photonics education and training program so that MCC can train more students to fill available high skill, high demand positions at local and regional employers.  Currently MCC is the only college in the nation that offers an associate degree program in optics, and yet, in the Rochester region there are now more job openings for these positions than there are graduated students ready to fill these openings.  Thus, MCC’s proposal, named the Optics & Photonics Technology INnovation-OPT IN!, will expand MCC’s work by first expanding and enriching its curriculum to train students for today’s cutting-edge photonics fields, and secondly by linking with secondary schools, universities, and employers to create a seamless pipeline for more students to seek a career in photonics. Currently more than 120 optics, photonics, and imaging companies employ over 24,000 people across the Finger Lakes, Southern Tier and Central New York regions. With an anticipated 3.3% annual employment growth and a workforce that is approaching retirement, the need for skilled optics technicians is outpacing the number of graduates who are prepared to fill positions.  Beyond the specific workforce needs of these existing companies, demand for skilled photonics worker will grow further with the establishment in 2015 of the Rochester, NY headquartered federal American Institute for Manufacturing Integrated Photonics (AIM Photonics). To grow the optics and photonics workforce, the proposed OPT IN! program will impact 850 high school and college students including underrepresented, non-traditional students like our growing veteran student population to help them advance their careers.  MCC would expand dual enrollment opportunities for high school students, 2+2 and transfer linkages to four-year universities, student internships, and faculty professional development.  Furthermore the program would develop new and revised curriculum, including online curriculum, at MCC’s Optical Systems Technology program to meet current industry standards.  And by broadening industry and community partnerships it will foster recruitment, retention, and outreach activities to promote the awareness of optics and photonics as career option. Again, I am pleased to write in support of this win-win proposal that aims to meet both the needs of a student population seeking the skills needed to gain a career in a high tech industry and for the needs of existing photonics businesses seeking new employees to fill current and future job openings.  I appreciate your consideration of this proposal. Sincerely, Charles E. Schumer United States Senator A copy of Congresswoman Slaughter’s October 2016 letter to the National Science Foundation Director appears below: Dear Director Cordova, I am writing to express my support for Monroe Community College’s (MCC) proposal entitled “Optics and Photonics Technology Innovation – OPT IN” to the National Science Foundation’s (NSF) Advanced Technological Education (ATE) program. Starting in 1963, MCC became the first educational institution in the country to offer a two – year Associates degree in optics and continues to set a national example in optics education.  Under the leadership of Professor Alexis Voigt, MCC is pursuing two objectives through this proposal: First, MCC will strengthen the existing optics program by updating the curriculum to meet industry needs, including adding an online format to accommodate students balancing employment.  The program will also prepare regional high school teachers to teach an “Introduction to Optics” course which will expose younger students to optics and provide them an opportunity to launch an early career.  Secondly, I’m pleased this proposal is increasing the program’s outreach efforts to populations underrepresented in the optics industry, such as Women and minorities. Located within the largest optics and photonics manufacturing region in the world, MCC Optics is playing a central role in providing a qualified workforce to strengthen our nation’s competitiveness in high tech manufacturing.  The Rochester region recently secured the federally supported $600 million American Institute for Manufacturing Integrated Photonics (AIM Photonics) that will bring together experts from government, industry, and academia to work together on solving common problems in photonics manufacturing.  This collaboration will result in improved technology for our military and spur job creation through the commercialization of new discoveries.  These important efforts are sustained by workforce development programs, like MCC Optics, that are producing the qualified workforce needed to keep up with industry demands. Throughout its history, MCC Optics has demonstrated success in providing students the foundation they need for a productive career in optics while also making significant contributions to the region’s economy.  I am proud of the work MCC Optics has done and encourage your full consideration of this proposal. Sincerely, Louise M. SlaughterMember of Congress
https://newyorkphotonics.org/2017/04/21/schumer-gillibrand-announce-monroe-community-college-secures-550000-to-make-college-a-top-photonics-training-center/?ajaxCalendar=1&id=1749678336&yr=2021
Ardigen Supports JUMP-CP Consortium Scaling up Image-based Drug Discovery with the World’s Largest Public Cell Painting Dataset | American Laboratory Ardigen Supports JUMP-CP Consortium Scaling up Image-based Drug Discovery with the World’s Largest Public Cell Painting Dataset Ardigen Supports JUMP-CP Consortium Scaling up Image-based Drug Discovery with the World’s Largest Public Cell Painting Dataset October 27, 2022– Life Science Newswire– Ardigen, one of the world’s leading artificial intelligence (AI) companies advancing precision medicine, has announced that it is supporting the Joint Undertaking in Morphological Profiling-Cell Painting (JUMP-CP) Consortium with its technology and expertise. The consortium of 10 leading pharmaceutical companies and two non-profit research organizations including the Broad Institute of MIT and Harvard, is focused on creating data, validation, and technical know-how to transform drug discovery with Cell Painting technology.The JUMP-CP Consortium’s aim is to validate and scale up image-based drug discovery strategies by creating the world’s largest public cell imaging data set corresponding to both genetic and chemical perturbations. This valuable public resource brings with it hope of reducing the major bottleneck in drug discovery: determining the mechanism of action for drug candidates. Other significant applications include predicting compounds’ activity and toxicity, as well as matching drugs to disease states.Ardigen’s primary scope of research within the JUMP-CP Consortium is aimed at improving the predictive power of the JUMP-CP data by expanding the applicability domain of machine learning models that predict assay activity based on Cell Painting images. Another important contribution of Ardigen is to facilitate the JUMP-CP data exploration by providing a web application that allows scientists to easily search for similarities between various phenotypes and the corresponding genetic and chemical perturbations."We are pleased to welcome Ardigen as a Supporting Partner of the JUMP Cell Painting Consortium, and I look forward to the insights gained from focusing their deep learning expertise on the Consortium’s one-of-a-kind Cell Painting dataset," said Anne Carpenter, Ph.D., Senior Director of the Imaging Platform at the Broad Institute. "We are very excited about supporting the JUMP Cell Painting Consortium with Ardigen’s technology and expertise. I do believe that our joint efforts with the leading pharmaceutical companies and non-profit research organizations will result in a significant improvement of the image-based drug discovery strategy," said Michał Warchoł, Ph.D., Executive Vice President at Ardigen. About Ardigen Ardigen is harnessing advanced AI methods for novel precision medicine. The company accelerates therapy development by designing immunity, decoding microbiomes, analyzing biomedical images, and providing digital drug discovery services. Ardigen’s team is rooted in biology and has extensive expertise in bioinformatics, machine learning, and software engineering. The company’s in-house datasets, together with advanced AI platforms, empower the development of effective precision therapies.About the JUMP-CP Consortium Funded in part by the Bits to Bytes Capital Call of the Massachusetts Life Sciences Center (MLSC), the JUMP-Cell Painting Consortium is creating a new data-driven approach to drug discovery based on cellular imaging, image analysis, and high-dimensional data analytics. We believe it will transform drug discovery by relieving a major bottleneck in the pharma pipeline: determining the mechanism of action of potential therapeutics prior to introduction into patients. We will soon release our unprecedented public data set to validate and scale up this image-based drug discovery strategy. This valuable public resource will then be available for other applications, including predicting compounds’ activity and toxicity, matching drugs to disease states, and more.
https://www.americanlaboratory.com/591610-Ardigen-Supports-JUMP-CP-Consortium-Scaling-up-Image-based-Drug-Discovery-with-the-World-s-Largest-Public-Cell-Painting-Dataset/
Navajo Nation struggles with water access. The Supreme Court just dealt it a blow on water rights. | The Hill Energy & Environment Navajo Nation struggles with water access. The Supreme Court just dealt it a blow on water rights. This week’s Supreme Court decision stating that the U.S. does not have to secure water for the Navajo Nation denies help to a community that struggles with water access, experts and advocates say. The high courtruled Thursday thatthe U.S. does not have to take “affirmative steps” to secure water for the tribe under an 1868 peace treaty. “It makes it harder for us to secure our water rights,” Navajo Nation President Buu Nygren told The Hill. “It doesn’t say that we’re not going to get any. … [It just] puts upbarriers for us.” Many of the Navajo Nation reservation’sapproximately 170,000 residentsdo not have access to a water system. The Navajo Nation’s Department of Water Resourcessays that about 30 percentof the population of Navajo Nation does not have access to clean, reliable drinking water, and the U.S. Environmental Protection Agency’s website says thatabout 15 percentdon’t have access to piped water at their homes. While many of the issues stem from a lack of infrastructure rather than a lack of water itself, some say that a more favorable decision from the court could have helped the tribe as it seeks to address the issue. Heather Tanana, an assistant professor at the University of Utah’s College of Law, noted that the federal government has “a lot of expertise,” including engineers and watershed planners. “That expertise that the federal government has — they could have come in and helped the nation identify, what are their water sources that are available, what are the quality issues,” Tanana said. Without that assistance, Tanana said, it will be more difficult for the tribe to take advantage of federal infrastructure funding. Sarah Porter, director of the Kyl Center for Water Policy at Arizona State University, similarly said that having more clarity on water rights would be a “big step forward.” “Once a tribe knows how much water they have a right to, then they are able to take other actions like seek funding for the infrastructure,” Porter said. Asked to comment, an Interior Department spokesperson said the department is “committed to upholding its trust and treaty obligations to Tribes, as well as to ensuring that water rights for Colorado River users are fulfilled according to the law.“ The federal government does have some projectsaimed at bolsteringNavajo water access. Nygren said that in addition to the infrastructure issues, he also believes that the tribe itself currently does not have enough water. “I don’t think we have enough water at this moment, because people still haul water. They’ll haul water from border towns. They’re drinking out of windmills which [are] supposed to be for livestock,” Nygren said. “As our population continues to grow and develop, we’re not going to have that water that’s needed to sustain our nation,” he added. Similarly, a court brief from advocacy group DigDeep and the Utah Tribal Relief Foundation says that many families are forced to “purchase bottled water, haul water long distances, or use contaminated water to meet their basic needs.” The brief, on which Tanana was one of the lawyers representing the groups, also stated that some individuals were getting by with just two or three gallons of water per day, while the average American uses 88 gallons. “For some families, that’s deciding between whether or not they can use water in a health emergency or use water to make their dinner or … their kid not being able to go to soccer practice because they don’t have enough water to take a shower afterwards,” said Kabir Thatte, DigDeep’s director of policy and coalitions. Porter said the court’s decision now leaves the Navajo to pursue their water rights claims through an adjudication process. “It’s these big judicial proceedings, where all of the tribal claims are in with all of the other water rights claims … that are asserted in watershed,” she said.
https://thehill.com/policy/energy-environment/4065389-navajo-nation-struggles-with-water-access-the-supreme-court-just-dealt-it-a-blow-on-water-rights/amp/
Geographical distribution and extinction risk: lessons from Triassic?Jurassic marine benthic organisms - [scite report] Supporting: 9, Contrasting: 4, Mentioning: 120 - Aim  To evaluate the influence of geographical distribution on the extinction risk of benthic marine invertebrates using data from the fossil record, both during times of background extinction and across a mass‐extinction episode. Total geographical range is contrasted with proxies of global abundance to assess the relationships between the two essential components of geographical distribution and extinction risk. Location  A global occurrence data base of fossil benthic macro‐organisms from the Triassic and Jurassic periods was used for this study. Methods  Geographical distributions and biodiversity dynamics were assessed for each genus (all taxa) or species (bivalves) based on a sample‐standardized data set and palaeogeographical reconstructions. Geographical ranges were measured by the maximum great circle distance of a taxon within a stratigraphic interval. Global abundance was assessed by the number of localities at which a taxon was recorded. Widespread and rare taxa were separated using median and percentile values of the frequency distributions of occurrences. Results  The frequency distribution of geographical ranges is very similar to that for modern taxa. Although no significant correlation could be established between local abundance and geographical range, proxies of global abundance are strongly correlated with geographical range. Taxon longevities are correlated with both mean geographical range and mean global abundance, but range size appears to be more critical than abundance in determining extinction risk. These results are valid when geographical distribution is treated as a trait of taxa and when assessed for individual geological stages. Main conclusions  Geographical distribution is a key predictor of extinction risk of Triassic and Jurassic benthic marine invertebrates. An important exception is in the end‐Triassic mass extinction, which equally affected geographically restricted and widespread genera, as well as common and rare genera. This suggests that global diversity crises may curtail the role of geographical distribution in determining extinction risk. Geographical distribution and extinction risk: lessons from Triassic?Jurassic marine benthic organisms Abstract: Aim  To evaluate the influence of geographical distribution on the extinction risk of benthic marine invertebrates using data from the fossil record, both during times of background extinction and across a mass‐extinction episode. Total geographical range is contrasted with proxies of global abundance to assess the relationships between the two essential components of geographical distribution and extinction risk. Location  A global occurrence data base of fossil benthic macro‐organisms from the Triassic and J… Show more “…Geographic range is increasingly recognized as a primary determinant of extinction risk (10, 11, 14, (48) (49) (50) (51) . In most studies, however, correlates of extinction risk are assessed by pooling taxa from different clades with markedly different evolutionary histories and biological characteristics.…” Section : Model mentioning confidence: 99% 2011 Proc. Natl. Acad. Sci. U.S.A. Biological factors, such as abundance and body size, may contribute directly to extinction risk and indirectly through their influence on other biological characteristics, such as geographic range size. Paleontological data can be used to explicitly test many of these hypothesized relationships, and general patterns revealed through analysis of the fossil record can help refine predictive models of extinction risk developed for extant species. Here, I use structural equation modeling to tease apart the contributions of three canonical predictors of extinction-abundance, body size, and geographic range size-to the duration of bivalve species in the early Cenozoic marine fossil record of the eastern United States. I find that geographic range size has a strong direct effect on extinction risk and that an apparent direct effect of abundance can be explained entirely by its covariation with geographic range. The influence of geographic range on extinction risk is manifest across three ecologically disparate bivalve clades. Body size also has strong direct effects on extinction risk but operates in opposing directions in different clades, and thus, it seems to be decoupled from extinction risk in bivalves as a whole. Although abundance does not directly predict extinction risk, I reveal weak indirect effects of both abundance and body size through their positive influence on geographic range size. Multivariate models that account for the pervasive covariation between biological factors and extinction are necessary for assessing causality in evolutionary processes and making informed predictions in applied conservation efforts.A ll species eventually go extinct, and biological correlates of extinction risk have been the focus of many studies of extant and extinct taxa (1-4). Most studies have analyzed biological factors separately, tacitly assuming independence among them. However, few biological characteristics are independent, and unaccounted for covariation confounds causal interpretation, weakens the power of predictive models, and inhibits successful synthesis. In addition, most studies have considered only the direct effects of biological factors on extinction. However, factors can contribute both directly and indirectly through their influence on other more proximal biological characteristics, and thus, accounting for indirect effects can be important when assessing the relative influence of multiple factors (5-7).Here, I investigate the direct and indirect effects of multiple biological factors on extinction risk using the early Cenozoic marine fossil record of the eastern United States. I focus on the contributions of abundance, body size, and geographic range size to the observed stratigraphic range (termed duration hereafter) of species. Measures of geographic range and abundance are commonly used to set conservation priorities (8), and empirical support exists for the influence of both on extinction risk over geologic time scales (9-14). Body size is also widely believed to influence extinction risk, altho... “…Geographic range is increasingly recognized as a primary determinant of extinction risk (10, 11, 14, (48) (49) (50) (51) . In most studies, however, correlates of extinction risk are assessed by pooling taxa from different clades with markedly different evolutionary histories and biological characteristics.…” Section : Model mentioning confidence: 99% Direct and indirect effects of biological factors on extinction risk in fossil bivalves 2011 Proc. Natl. Acad. Sci. U.S.A. Biological factors, such as abundance and body size, may contribute directly to extinction risk and indirectly through their influence on other biological characteristics, such as geographic range size. Paleontological data can be used to explicitly test many of these hypothesized relationships, and general patterns revealed through analysis of the fossil record can help refine predictive models of extinction risk developed for extant species. Here, I use structural equation modeling to tease apart the contributions of three canonical predictors of extinction-abundance, body size, and geographic range size-to the duration of bivalve species in the early Cenozoic marine fossil record of the eastern United States. I find that geographic range size has a strong direct effect on extinction risk and that an apparent direct effect of abundance can be explained entirely by its covariation with geographic range. The influence of geographic range on extinction risk is manifest across three ecologically disparate bivalve clades. Body size also has strong direct effects on extinction risk but operates in opposing directions in different clades, and thus, it seems to be decoupled from extinction risk in bivalves as a whole. Although abundance does not directly predict extinction risk, I reveal weak indirect effects of both abundance and body size through their positive influence on geographic range size. Multivariate models that account for the pervasive covariation between biological factors and extinction are necessary for assessing causality in evolutionary processes and making informed predictions in applied conservation efforts.A ll species eventually go extinct, and biological correlates of extinction risk have been the focus of many studies of extant and extinct taxa (1-4). Most studies have analyzed biological factors separately, tacitly assuming independence among them. However, few biological characteristics are independent, and unaccounted for covariation confounds causal interpretation, weakens the power of predictive models, and inhibits successful synthesis. In addition, most studies have considered only the direct effects of biological factors on extinction. However, factors can contribute both directly and indirectly through their influence on other more proximal biological characteristics, and thus, accounting for indirect effects can be important when assessing the relative influence of multiple factors (5-7).Here, I investigate the direct and indirect effects of multiple biological factors on extinction risk using the early Cenozoic marine fossil record of the eastern United States. I focus on the contributions of abundance, body size, and geographic range size to the observed stratigraphic range (termed duration hereafter) of species. Measures of geographic range and abundance are commonly used to set conservation priorities (8), and empirical support exists for the influence of both on extinction risk over geologic time scales (9-14). Body size is also widely believed to influence extinction risk, altho... “…Geographic range is often claimed to be a determinant of extinction vulnerability [1] [2] [3] [4] [5] [6] . Groups with restricted ranges are widely believed to suffer extinction more frequently than those with broader ranges 1 because the latter are thought to be afforded some resilience to regional environmental perturbations 7, 8 .…” mentioning confidence: 99% “…Groups with restricted ranges are widely believed to suffer extinction more frequently than those with broader ranges 1 because the latter are thought to be afforded some resilience to regional environmental perturbations 7, 8 . During global biotic crises, by contrast, there is reasoned to be no such selectivity 2, 6 since widespread environmental disturbances simultaneously affect both wide-and narrow-ranging taxa on global scales 1, 3, 6 . Surprisingly, the effect of geographic range on extinction risk has not been tested comprehensively for the terrestrial fossil record, with a striking paucity of studies on vertebrates of any kind.…” “…Surprisingly, the effect of geographic range on extinction risk has not been tested comprehensively for the terrestrial fossil record, with a striking paucity of studies on vertebrates of any kind. Most published studies focus on marine invertebrates [3] [4] [5] [6] [8] [9] [10] , and despite geographic range being used as a major criterion for assessing the extinction risk of modern terrestrial species 11 , it is unclear that the findings from these fossil taxa can be extended to all groups in all major habitats. Moreover, little is known about the difference between intervals with background levels of extinction and those characterized as mass extinctions 3 .…” Geographic range did not confer resilience to extinction in terrestrial vertebrates at the end-Triassic crisis 2015 Nat Commun Rates of extinction vary greatly through geological time, with losses particularly concentrated in mass extinctions. Species duration at other times varies greatly, but the reasons for this are unclear. Geographical range correlates with lineage duration amongst marine invertebrates, but it is less clear how far this generality extends to other groups in other habitats. It is also unclear whether a wide geographical distribution makes groups more likely to survive mass extinctions. Here we test for extinction selectivity amongst terrestrial vertebrates across the end-Triassic event. We demonstrate that terrestrial vertebrate clades with larger geographical ranges were more resilient to extinction than those with smaller ranges throughout the Triassic and Jurassic. However, this relationship weakened with increasing proximity to the end-Triassic mass extinction, breaking down altogether across the event itself. We demonstrate that these findings are not a function of sampling biases; a perennial issue in studies of this kind. “…Wide niche breadth or a generalized ecology have been considered a key predictor of longevity and of speciation rates [20][21] [22] 38, 51 , and the same has consistently been shown for geographic range [23] [24] [25] [52] [53] [54] [55] [56] . Because these traits are not independent, their effects should be decoupled to infer the relationship between specialization and biodiversity dynamics.…” Interdependence of specialization and biodiversity in Phanerozoic marine invertebrates 2015 Studies of the dynamics of biodiversity often suggest that diversity has upper limits, but the complex interplay between ecological and evolutionary processes and the relative role of biotic and abiotic factors that set upper limits to diversity are poorly understood. Here we statistically assess the relationship between global biodiversity and the degree of habitat specialization of benthic marine invertebrates over the Phanerozoic eon. We show that variation in habitat specialization correlates positively with changes in global diversity, that is, times of high diversity coincide with more specialized faunas. We identify the diversity dynamics of specialists but not generalists, and origination rates but not extinction rates, as the main drivers of this ecological interdependence. Abiotic factors fail to show any significant relationship with specialization. Our findings suggest that the overall level of specialization and its fluctuations over evolutionary timescales are controlled by diversitydependent processes-driven by interactions between organisms competing for finite resources.
https://scite.ai/reports/geographical-distribution-and-extinction-risk-5rkxrQ
Pharmacy | Free Full-Text | Using Service Blueprints to Visualize Pharmacy Innovations Background: Applying the principles of service design can help pharmacists manage both the quality and patient perceptions of the services they provide. Service blueprints are a widely used service design tool that are rare in the healthcare literature. They can be used to design new services or revisit the design of established services. This paper describes service blueprints and their uses, and illustrates how to build one using an example. Methods: A blueprint is built for appointment-based medication synchronization services to illustrate the tool. Conclusions: Service blueprints permit pharmacists to better see and understand service processes. They clarify the process of service delivery and the roles of customers, service providers, and supporting services. They provide a way of depicting complex services in a concise visual way that communicates details at a glance. Pharmacists who utilize service blueprints can improve the consistency and quality of services provided, and they can increase the chance that every interaction with patients sends a positive message about the value of pharmacist services. Using Service Blueprints to Visualize Pharmacy Innovations by David A. Holdford Center for Pharmacy Practice Innovation, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA Pharmacy 2019 , 7 (2), 43; https://doi.org/10.3390/pharmacy7020043 Received: 10 April 2019 / Revised: 29 April 2019 / Accepted: 1 May 2019 / Published: 8 May 2019 (This article belongs to the Special Issue Pharmacist Services ) Abstract : Background : Applying the principles of service design can help pharmacists manage both the quality and patient perceptions of the services they provide. Service blueprints are a widely used service design tool that are rare in the healthcare literature. They can be used to design new services or revisit the design of established services. This paper describes service blueprints and their uses, and illustrates how to build one using an example. Methods : Service blueprints permit pharmacists to better see and understand service processes. They clarify the process of service delivery and the roles of customers, service providers, and supporting services. They provide a way of depicting complex services in a concise visual way that communicates details at a glance. Pharmacists who utilize service blueprints can improve the consistency and quality of services provided, and they can increase the chance that every interaction with patients sends a positive message about the value of pharmacist services. Keywords: serviced marketing ; design thinking ; medication synchronization ; community pharmacists ; innovation science ; adherence ; competitive advantage 1. Introduction Pharmacy is a service profession. Although pharmacy practice revolves around the provision of a tangible product, the value of pharmacists lies in the intangible acts delivered along multiple touchpoints of the service experience. Yet, the public stills sees pharmacists as a dispenser of drugs due to the distinct nature of services [ 1 , 2 , 3 , 4 ]. When compared to tangible products, services are much harder to promote due to four distinct attributes they have known as the 4I’s [ 5 ]. The first “I” is intangibility, which characterizes services as intangible actions or events. Services are intangible because they cannot be seen, held, or touched. Thus, their quality cannot be measured, tested, or verified in advance of the sale to ensure excellence. The second “I” is inconsistency in that no two service performances are identical—meaning that they vary from person to person, transaction to transaction, and even time to time. Service quality cannot be easily standardized because of the variations among interactions between buyer and seller. The third characteristic is inseparability—referring to the fact that the service provider, customers, and service itself are inseparable because the service is co-created by both the provider and the customer. Each participates in and determines the quality of the service experience. In pharmacy practice, the more engaged the patient, the more likely that better outcomes will occur. The fourth and final characteristic is inventory, which describes how face-to-face services cannot be put into inventory or on a shelf for later use. With online and mobile services, this characteristic is less applicable because technology now allows us to store many services electronically. The fourth “I” only applies to person-to-person services that are provided in a real-time, synchronous manner. When added up, the “4I’s” of services present special challenges in marketing the value of pharmacists [ 5 ]. It is a challenge for pharmacists to get customers to appreciate and desire an intangible product they cannot see or touch. The intangible nature of pharmacist services makes it hard for consumers to mentally appreciate what pharmacists do. It is much easier for people to grasp the purpose of a drug than to comprehend the pharmacist services associated with that drug. Intangible services are hard for consumers to assess. Although some aspects of pharmacy services are easy to evaluate (e.g., fast, friendly, inexpensive), the clinical and technical aspects of the service experience are difficult to evaluate even with extensive experience. For instance, consumers cannot typically tell if a pharmacist omits critical drug-related information during patient counseling, fails to screen for drug interactions, or misses a chance to intervene in avoiding a drug-related problem. Instead, patients tend to rely on variables that they can assess, such as how a pharmacist looks and acts [ 6 ]. The variability of pharmacist services also makes them a challenge to provide and assess. Pharmacists and pharmacy technicians are imperfect human beings whose service performances can vary from minute-to-minute with changing service conditions. Each service experience can be affected by a host of factors including the atmospherics of the work environment, the engagement of patients, the characteristics of individual pharmacists and technicians, and the workload. Demand for service varies throughout the day and week; there are times when business is relatively slow and other times when it gets quite hectic. It is a problem to synchronize customers’ demand for services with the availability of pharmacy personnel to serve them. When combined with the fact that most pharmacist services are performed behind the scenes out of view of the customer, patients have an uneven and unclear understanding of the value of what a pharmacist does. Applying the principles of service design can help pharmacists manage both the quality and patient perceptions of the service provided [ 7 , 8 ]. Service design is the process of planning and organizing the customer service experience using a number of methods and tools derived from disciplines as diverse as ethnography, systems engineering, management science, and informatics. Service design tools and methods typically attempt to portray services visually, using flow diagrams of the customers, front-facing service providers, and supporting individuals and processes. An established service design tool that would benefit pharmacists is the service blueprint [ 9 ]. 3. Service Blueprints Service blueprints are pictures or maps of service processes intended to help providers and service marketers to design, deliver, and manage new and established service offerings [ 10 ]. They depict the service process and the roles of consumers, service providers, and supporting services involved. These visual depictions help improve the delivery of pharmacy services by identifying gaps and potential points of failure in processes. They are able to improve communications between consumers, pharmacists, support staff, and backstage services by mapping out the various points of contact throughout the service process. Service blueprints can visually communicate complex service processes to stakeholders more clearly and efficiently than verbal descriptions of the services. Although widely used and accepted by service designers in many industries, evidence of the use of service blueprints is lacking in pharmacy. Holdford and Kennedy [ 9 ] used service blueprints in describing the dispensing process for a new prescription and for a smoking cessation program. Other than that single instance, no other mention of service blueprints can be found in the pharmacy literature. This paper will describe how to build service blueprints and discuss how they can be used by pharmacists and when. 4. Uses of Service Blueprints Service blueprints can be used whenever there is interest in improving a service experience. It can be used to design new services or revisit the design of established services. A major benefit of developing a service blueprint is that it forces pharmacists to conduct a detailed analysis of each step in the service process. It challenges pharmacists to question the value of each step and clarify the roles of everyone involved. Pharmacists who utilize service blueprints can improve the consistency and quality of services provided, and they can increase the chance that every interaction with patients sends a positive message about the value of pharmacist services. Blueprints can be used in research to provide explicit details of interventions. A clearly written blueprint can be used in implementation science to allow comparisons at a glance of the exact nature of service innovations in comparison to the status quo. They are also helpful in describing the competitive advantage of one innovation over another, allowing pharmacists to develop service offerings that are sustainable over time [ 11 ]. Service blueprints are especially useful in designing complex services that might include multiple people, processes, and channels of communication. The greater the complexity, the increased likelihood of miscommunication, fumbled handoffs between individuals, and lack of accountability between people. A blueprint can clarify problems and coordinate complicated processes. Finally, blueprints can be used to promote a positive image of pharmacists [ 7 , 9 ]. Because customers often have difficulty evaluating pharmacist services due to the intangible nature of services, they look for tangible clues to quality. Tangible clues are things such as signs, parking, landscaping, cleanliness, advertising, pharmacy layout, and how service personnel are dressed. Service blueprints can be used to identify these visual and physical aspects of services that customers often use as tangible cues of quality. By seeing services from the customer’s perspective, pharmacists can ensure that these tangible cues send the same positive message of professionalism delivered by other touchpoints of the service experience. 5. Components of a Service Blueprint There are no concrete rules for designing service blueprints allowing for a lot of flexibility in their purpose and use. However, most service blueprints have the following key components [ 12 ]: customer actions, “frontstage” contact employee actions, “backstage” contact employee actions, and support processes—as explained below and illustrated in Figure 1 . Customer actions. These are actions performed by the customer when interacting with a service provider. “Customers” can be any recipient of the service including patients, family caregivers, physicians, and nurses, depending on the process. Customer actions associated with a pharmacy visit can be contacting the pharmacy website prior to the visit, driving to the pharmacy, dropping off a prescription, providing information to the pharmacist, waiting, receiving the prescription along with counseling, and leaving the pharmacy. Each customer action is a touchpoint or moment-of-truth where customers judge the quality of pharmacy services and make decisions about whether to continue visiting the pharmacy in the future. The number of customer actions and the level of detail about each depends on the depth of the analysis desired. Frontstage actions. These are the service actions that are directly visible to the customer. They can be actions between the customer and service personnel or with technology, such as a website or mobile app. Frontstage actions associated with a pharmacy visit could include interfacing with the pharmacy website prior to the visit, talking to pharmacy personnel throughout the steps of the dispensing process, and a follow-up phone call to help resolve any concerns the patient has about their medications. Frontstage actions do not always match every customer action. Some customer actions, like waiting for a prescription to be filled, are things that the customer does alone. Backstage actions. These are any actions done for the customer that are not visible. Backstage actions in a pharmacy might include professional decisions made by pharmacists (e.g., checking the patient profile for drug allergies, interactions, and duplicate medications), consultations with physicians about therapy, resolving insurance claims, and remote filling of prescriptions. Support processes. Support processes are any actions that support frontstage and backstage actions in service delivery. For pharmacists, these might include computer support services, billing, prescription claims adjudication, web design, and inventory control. In service blueprints, key components of the blueprint are separated by three horizontal lines: the line of interaction, the line of visibility, and the line of internal interaction ( Figure 1 ). The line of interaction is where customers and providers interact. Service encounters occur wherever a vertical line crosses the line of interaction. The line of visibility separates frontstage contact employee actions and backstage employee actions. Actions below this line are invisible to the customer. This line is critical because patients’ image of a pharmacist is determined to a great extent by what they see the pharmacist do. If the patient’s primary view is of the pharmacist counting and pouring, then the image of pharmacists will be consistent with that view. The line of internal interaction separates frontline employees from supporting individuals. Any action that crosses this line indicates a process that supports the frontline employee. Optional Components of Service Blueprints Additional components can be added to service blueprints depending on the purpose and goals of completing one. These components include physical evidence, arrows, and time. Physical evidence. This describes the tangible features of each step in the service process that might influence a customer’s perception of the service experience and service firm. Physical evidence includes the dress of service employees, the signage in the pharmacy, location, advertising, website design, delivery vehicles, and pharmacy layout. These and other forms of tangible evidence set expectations of service and influence evaluation of service quality. Clarifying the physical evidence of services can help ensure a consistent message across all elements of the service experience. Arrows. Arrows are used to visualize relationships between key components of the blueprints. Arrows are used to indicate dependent relationships between customer and service provider actions. Single arrows indicate linear one-way relationships and double arrows signify collaborative two-way relationships. Time. Time can be added to service blueprints to map out the amount of time needed for the total service experience or elements of it. This can be useful in estimating personnel costs in providing services and estimating the cost effectiveness of each step in the process. 6. Building a Blueprint Building a service blueprint starts by developing an intimate understanding of the customers’ service experience as well as a clear delineation of all of the people, processes, and systems involved. Whether the pharmacy service experience is face-to-face, online, via an app, over the phone, or via multiple service channels, a service blueprint can be used to map out the process. Service blueprints can be developed using a provider-centered or a customer-centered perspective. Provider-centered perspectives start by mapping out the details of the service delivery process and then seeing where customers interact with this process. Provider-centered perspectives might be taken when analyzing an established service for gaps, redundancies, and other inefficiencies in delivery. A customer-centered approach starts by mapping out the service experience from the customer’s perspective. It begins by outlining the points of contact between customers and the service—customer experiences with the pharmacy parking lot, the pharmacy building itself, signage, website, phone calls, printed bag, self-service machines, and contact with frontline employees like clerks, technicians, and pharmacists. Each time a customer interacts with a touchpoint, they have a service encounter that is mapped on the blueprint. The following description of building a service blueprint will use a customer-centered perspective. The process of building a customer-centered service blueprint commences by asking what the customer hopes to achieve by interacting with a pharmacy service. The blueprint will vary depending on whether the visit is to fill a prescription, ask advice, enroll in a smoking cessation program, seek a nonprescription medication, or some other reason. Another question to be asked is the breadth and level of detail desired in mapping the service. An entire service process (e.g., dispensing) can be mapped, or the focus can be on a specific component of the process (e.g., patient counseling). Once these decisions are made, the blueprint is built through the following steps [ 12 ], which will be illustrated using the service blueprint illustrating an appointment-based medication synchronization program shown in Figure 2 [ 13 ]. Draw a template similar to the one in Figure 1 delineating the components of the service blueprint including lines of interaction and any optional components like physical evidence and time. Note that arrows can only be added as the actions are added. Map the customer’s journey through the service experience. From the customer’s perspective, chart each action and choice made by the customer and place them sequentially in the customer actions of the blueprint template. For the appointment-based medication synchronization program in Figure 2 , customer actions are patient learns details of the program, signs a contract, brings in prescriptions to the pharmacy to choose synch date, participates in establishing an appointment and adherence plan, receives a monthly call prior to picking up the medications, and receives the medications and discusses any issues with adherence or therapy. Map frontstage actions. List all of the visible points of contact between the customer and specific service personnel, technologies (e.g., website), or processes. They should generally match the temporal sequence of the customer’s journey throughout the service process although there may not always be a matching frontstage action with each customer action. For the program in Figure 2 , frontstage actions are a discussion of the program with patients, having the patient sign the contract, the pharmacist conducting a comprehensive medication review, the cocreation of a treatment plan, a reminder call, and the interaction with the patient when they visit the pharmacy. Map backstage actions. List all of the service actions which are invisible to customers. In many cases, these are actions in support of frontstage actions but sometimes they involve interactions with other healthcare professionals, healthcare insurers, and other stakeholders. Map internal support activities. Support activities may serve either frontstage or backstage actions. In Figure 2 , internal support activities serve both frontstage and backstage actions and consist of support from information technology, marketing, website design, and the business office. Add additional details as needed including physical evidence, arrows, and time. The blueprint in Figure 2 has single arrows to illustrate one-way relationships (e.g., patient signs the ABMS contract and gives it to a technician or pharmacist). Double arrows illustrate two-way relationships where both customer and provider collaborate in the task (e.g., establishing a patient appointment and adherence plan). Note that some arrows may cross more than one line of interaction. 7. Managerial Uses of Service Blueprints The process of completing service blueprints requires pharmacists to clarify each step of the service experience. This process often leads to obvious opportunities for improving service delivery. Blueprints might suggest a need for minor improvements or a complete overhaul of the service system. The following is a list of actions that might be taken in response to an analysis of a service blueprint: Standardize service delivery by ensuring every frontstage, backstage, and support action is consistently provided. Time-and-motion studies and quality improvement cycles can assist in this standardization. Identify added service steps that might appeal to other customer segments. For instance, some segments might benefit from comprehensive medication reviews in appointment-based medication synchronization while others may not need or want it. Incorporate physical evidence into marketing communications plans. Although some pharmacists only see marketing communications in terms of paid advertising, every touchpoint in the service delivery process is a way of communicating a message of quality to patients. Therefore, cues to quality should be identified within the service experience and changed if needed to provide the messaging desired. Simplify service delivery. Look at every step of the process and remove any that do not add value. Identify those moments of truth that drive customer perceptions of the service process. There may only be a few touchpoints that drive loyalty to a pharmacy. Make certain that delivery at those touchpoints exceeds customer expectations. 8. Conclusions Service blueprints permit pharmacists to better see and understand service processes. It clarifies the process of service delivery and the roles of customers, service providers, and supporting services. It breaks down the service into components and arranges them according to their purpose. Service blueprints are rare in healthcare although they can be used in implementation research, interprofessional service delivery, business modeling, quality improvement interventions, and outcomes studies. They provide a way of depicting complex services in a concise visual way that communicates details at a glance. Services blueprints also use a customer-centered approach to design in which each customer action is matched to service providers and processes. When combined with physical cues to quality, pharmacists can send a consistent positive message to customers. Service blueprints force a careful analysis of each step in the service process and help communicate that information to people such as the frontline employees who help determine its success. When everyone in the service process engages in the development of blueprints, they can understand each step in the process, probe for difficulties, and identify problem areas. Finally, blueprints can facilitate the analysis of cost–benefit tradeoffs in providing services. They provide a template for quantifying the value of each patient contact, customer touchpoint, and support process. In some cases, some frontstage and backstage actions may be added if they add value to the service experience. In other cases, low value activities may be deleted without any impact on perceived value. Service blueprints allow pharmacists to be more strategic in the design and delivery of their services. Funding This research received no external funding. 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Front Matter | Exploration of the Seas: Voyage into the Unknown | The National Academies Press Read chapter Front Matter: In the summer of 1803, Thomas Jefferson sent Meriwether Lewis and William Clark on a journey to establish an American presence ... Exploration of the Seas: Voyage into the Unknown (2003) Chapter: Front Matter Suggested Citation: "Front Matter." National Research Council. 2003. Exploration of the Seas: Voyage into the Unknown . Washington, DC: The National Academies Press. doi: 10.17226/10844. Suggested Citation: "Front Matter." National Research Council. 2003. Exploration of the Seas: Voyage into the Unknown . Washington, DC: The National Academies Press. doi: 10.17226/10844. Suggested Citation: "Front Matter." National Research Council. 2003. Exploration of the Seas: Voyage into the Unknown . Washington, DC: The National Academies Press. doi: 10.17226/10844. Suggested Citation: "Front Matter." National Research Council. 2003. Exploration of the Seas: Voyage into the Unknown . Washington, DC: The National Academies Press. doi: 10.17226/10844. Suggested Citation: "Front Matter." National Research Council. 2003. Exploration of the Seas: Voyage into the Unknown . Washington, DC: The National Academies Press. doi: 10.17226/10844. Suggested Citation: "Front Matter." National Research Council. 2003. Exploration of the Seas: Voyage into the Unknown . Washington, DC: The National Academies Press. doi: 10.17226/10844. Suggested Citation: "Front Matter." National Research Council. 2003. Exploration of the Seas: Voyage into the Unknown . Washington, DC: The National Academies Press. doi: 10.17226/10844. Suggested Citation: "Front Matter." National Research Council. 2003. Exploration of the Seas: Voyage into the Unknown . Washington, DC: The National Academies Press. doi: 10.17226/10844. Suggested Citation: "Front Matter." National Research Council. 2003. Exploration of the Seas: Voyage into the Unknown . Washington, DC: The National Academies Press. doi: 10.17226/10844. Suggested Citation: "Front Matter." National Research Council. 2003. Exploration of the Seas: Voyage into the Unknown . Washington, DC: The National Academies Press. doi: 10.17226/10844. Suggested Citation: "Front Matter." National Research Council. 2003. Exploration of the Seas: Voyage into the Unknown Suggested Citation: "Front Matter." National Research Council. 2003. Exploration of the Seas: Voyage into the Unknown . Washington, DC: The National Academies Press. doi: 10.17226/10844. Suggested Citation: "Front Matter." National Research Council. 2003. Exploration of the Seas: Voyage into the Unknown . Washington, DC: The National Academies Press. doi: 10.17226/10844. Suggested Citation: "Front Matter." National Research Council. 2003. Exploration of the Seas: Voyage into the Unknown . Washington, DC: The National Academies Press. doi: 10.17226/10844. Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages. EXPLORATION O F T H E S E A S VOYAGE INTO THE UNKNOWN Committee on Exploration of the Seas Ocean Stuclies Boa rcl Division on Earth and Life Stuclies NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES THE NATIONAL ACADEMIES PRESS Washington, D C www.nap.eclu THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineer- ing, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropri- ate balance. This study was supported by Contract/Grant No. 56-DKNA-1-95107 and 56-DGNA- 1-00001 between the National Academy of Sciences and the National Oceanic and Atmospheric Administration. This report is funded in part by a contract from the National Oceanic and Atmospheric Administration. The views expressed herein are those of the authorks) and do not necessarily reflect the views of NOAA or any of its subagencies. International Standard Book Number 0-309-08927-1 (Book) International Standard Book Number 0-309-50938-6 (PDF) Library of Congress Catalog Card Number 2003113727 Additional copies of this report are available from the National Academies Press, 500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu Copyright 2003 by the National Academy of Sciences. All rights reserved. Printed in the United States of America THE NATIONAL ACADEMIES Advisers to the Nation on Stienre, Engineering, and Medicine The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Bruce M. Alberts is president of the National Academy of ~ . sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engi- neers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineer- ing programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Wm. A. Wulf is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy's purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M. Alberts and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council. www. nationa l-academies.org COMMITTEE ON EXPLORATION OF THE SEAS JOHN ORCUTT (Chair), Scripps I nstitution of Oceanography, La Jol la, California SHIRLEY A. POMPONI (Vice-Chair), Harbor Branch Oceanographic Institution, Fort Pierce, Florida TUNDI AGARDY, Sound Seas, Bethesda, Maryland GEORGE F. BASS, Texas A&M University, College Station EARL H. DOYLE, Shell Oil (ret.), Sugar Land, Texas TERRY GARCIA, National Geograph ic Society, Wash i ngton, DC BRUCE OILMAN, Sonsub Inc. (ret.), Houston, Texas SUSAN HUMPHRIS, Woods Hole Oceanographic Institution, Massachusetts PAULA KEENER-CHAVIS, College of Charleston, South Carolina (resigned March 2002) ISAO KOIKE, University of Tokyo, Japan RICHARD LUTZ, Rutgers University, New Brunswick, New Jersey MARCIA MCNUTT, Monterey Bay Aquarium Research Institute, Moss Landing, California JOHN NORTON MOORE, University of Virginia School of Law, Charlottesvi I le WALTER PITMAN 111, Lamont-Doherty Earth Observatory, Palisades, New York JORN THIEDE, Alfred Wegener Institute, Bremerhaven, Germany VICTOR M. VICENTE-VIDAL LORANDI, Instituto Politecnico Nacional, Morelos, Mexico Staff JENNIFER MERRILL, Senior Program Officer JODI BACHIM, Sen for Project Assistant SARAH CAPOTE, Project Assistant v OCEAN STUDIES BOARD NANCY RABALAIS (Chair), Louisiana Universities Marine Consortium, Chauvin ARTHUR BAGGEROER, Massachusetts Institute of Technology, Cambridge JAMES COLEMAN, Louisiana State University, Baton Rouge LARRY B. CROWDER, Duke University, Beaufort, North Carolina RICHARD B. DERISO, Inter-American Tropical Tuna Commission, La Jolla, California ROBERT B. DITTON, Texas A&M University, College Station EARL DOYLE, Shell Oil (ret.), Sugar Land, Texas ROBERT DUCK, Texas A&M University, College Station PAUL G. GAFFNEY, 11, National Defense University, Washington, DC WAYNE R. GEYER, Woods Hole Oceanographic Institution, Massachusetts STANLEY HART, Woods Hole Oceanographic Institution, Massachusetts Ml RIAM KASTNER, Scripps I nstitution of Oceanography, La Jol la, California RALPH S. LEWIS, Connecticut Geological Survey, Hartford WILLIAM F. MARCUSON, 111, U.S. Army Corp of Engineers (ret.), Vicksburg, Mississippi JULIAN MCCREARY, JR., University of Hawaii, Honolulu JACQUELINE MICHEL, Research Planning, Inc., Columbus, South Carolina SCOTT NIXON, University of Rhode Island, Narragansett SHIRLEY A. POMPONI, Harbor Branch Oceanographic Institution, Fort Pierce, Florida FRED N. SPIESS, Scripps Institution of Oceanography, La Jolla, California JON G. SUTINEN, University of Rhode Island, Kingston NANCY TARGETT, University of Delaware, Lewes Staff MORGAN GOPNIK, Director ROBERT HAMILTON, Acting Director JENNIFER MERRILL, Senior Program Officer SUSAN ROBERTS, Senior Program Officer DAN WALKER, Senior Program Officer JOANNE BINTZ, Program Officer TERRY SCHAEFER, Program Officer JOHN DANDELSKI, Research Associate Vl ROBIN MORRIS, Financial Officer SHIREL SMITH, Administrative Associate NANCY CAPUTO, Sen for Project Assistant SARAH CAPOTE, Project Assistant BYRON MASON, Project Assistant TERESIA Wl LMORE, Project Assistant v'' Preface The ocean is Earth's least explored frontier. A well-planned, inter- national program of ocean exploration that exploits new technology, takes advantage of recent international agreements, and establishes new partner- ships could lead to untold discoveries about the ocean, its living and non- living resources, and the many species that inhabit it. Our oceans influence global climate, and they contain unknown quantities of biological, chemi- cal, and mineral resources. There is a growing recognition that we have much more to learn about the secrets our oceans hold. In December 2000, the U.S. Congress instructed the U.S. National Academies to assess the feasibility and value of implementing a major, coordinated, international program of ocean exploration and discovery. A Committee on Exploration of the Seas was constituted, with members from the academic, legal, commercial, and nonprofit sectors who were experts in Earth science, biology, engineering, underwater archaeology, and national and international law and policy. The committee convened an international workshop and a series of working meetings to develop the report's findings. Funding for a U.S. program in ocean exploration began in fiscal year 2000, but most of its work has been done in U.S. territorial waters. This report seeks to identify strategies for and benefits of an international effort. It is clear to the members of the committee that the success of any such program will require full international participation from coordinating pro- gram administration and setting priorities for exploration, to planning and implementing expeditions, to informing the public of discoveries. But, as the committee's charge states, it is necessary first to detail the strengths, weaknesses, and gaps in current efforts, including those in the United States. We propose in this report an alternative framework for improving and expanding national and international ocean exploration programs. A workshop in May 2002 was convened to make a first approximation of interest in the idea of establishing a global ocean exploration program. IX x PREFACE ized for leadership, participation, and develop Countries recognized for leadership, participation, and developing programs were invited to send participants to discuss program ideas. The meetings focused on existing exploration programs, areas of exploration for which international participation would be especially beneficial, existing and anticipated technology, and policy or legal arrangements that a new explora- tion program might require. The committee has consolidated the presenta- tions and included a summary in Appendix D to this report. The committee is grateful to the Intergovernmental Oceanographic Commission of the United Nations Educational, Scientific and Cultural Organization for hosting the workshop. The Scientific Committee on Oceanographic Research was a great help in coordinating the meeting and sponsoring the participation of members from developing nations. John Orcutt, Committee Chair Sh i rley A. Pompon i, Committee Vice-Chair Acknowledgments This report was greatly enhanced by the participants of the meetings held as part of this study. The committee would first like to acknowledge the efforts of those who gave presentations at the meetings: Joe Baker, Patricio Bernal, Steven Bohlen, Bryndis Brandsdottir, Harry Breidahl, Melbourne Briscoe, Mario Caceres, Tommy Dickey, Rene Drucker-Colin, Sylvia Earle, Paul Egerton, John Field, Christopher Fox, Montserrat Gorina- Ysern, J. Frederick Grassle, Jeremy Green, James Greenwood, John Haines, Stephen Hammond, Su Jilan, Robert Knox, Suzanne Lacasse, Margaret Leinen, Eric Lindstrom, Larry Mayer, Craig McLean, Michael Meredith, Jean- Francois Minster, Barbara Moore, Alain Morash, Rob Murdoch, Nil Odunton, Annelies Pierrot-Bults, Fangli Qiao, Muthukamatchi Ravindran, Shubha Sathyendranath, Sergey Shapovalov, Sunil Murlidhar Shastri, Victor Smetacek, Kiyoshi Suyehiro, Tamaki Ura, Edward Urban, Jr., and James Yoder. These talks helped set the stage for fruitful discussions in the closed sessions that followed. Edward Urban, Jr., Elizabeth Gross, and Maria Hood were a great assis- tance to the committee and staff in planning the International Global Ocean Exploration Workshop. The committee is also grateful to Margot Bohan and Douglas White, who provided important material for this report, Alfred Duba, who helped make our New York meeting a successful one, and Kate Kelly, who improved the report with her thorough edit. This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with pro- cedures approved by the National Research Council's Report Review Com- mittee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. Xl . . xll ACKNOWLEDGMENTS The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following people for their participation in the review of this report: VERA ALEXANDER, University of Alaska, Fairbanks D. JAMES BAKER, Academy of Natural Sciences, Philadelphia, Pennsylvania KENNETH BRINK, Woods Hole Oceanographic Institution, Massachusetts ROBERT A. DUCK, Texas A&M University, College Station DANIEL FORNARI, Woods Hole Oceanographic Institution, Massachusetts ROBERT FROSCH, Cambridge, Massachusetts ROBERT B. GAGOSIAN, Woods Hole Oceanographic Institution, Massach usetts SCOTT OLSON, Phoenix International, Landover, Maryland KARL TUREKIAN, Yale University, New Haven, Connecticut JAMES G. WENZEL, Marine Development Associates, Inc., Saratoga, California CARL WUNSCH, Massachusetts Institute of Technology, Cambridge MARSH YOUNGBLUTH, Harbor Branch Oceanographic Institution, Fort Pierce, Florida Although the reviewers listed above provided many constructive com- ments and suggestions, they were not asked to endorse the conclusions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by Donald Walsh, Inter- national Maritime, Inc., and Louis J. Lanzerotti, Lucent Technologies. Appointed by the National Research Council, they were responsible for making certain that an independent examination of this report was carried out i n accordance with i Institutional procedures and that al I review com- ments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution. Contents Executive Summary 1 Introduction History of Ocean Exploration, 1 8 Lessons from Earlier Oceanographic Programs, 24 Expectations for a Global Ocean Exploration Program, 24 Organization of the Report, 25 Justification for a New Ocean Exploration Program Interdisciplinary Exploration Is Needed, 31 Access to New Regions Is Needed, 32 Unique Applications of New Capabilities, 37 A New Program of Ocean Exploration Is Necessary, 39 Promising Areas for Ocean Exploration Marine Biodiversity, 43 Arctic Ocean, 52 Southern Ocean and Antarctic Ice Shelves, 59 Exploring the Ocean Through Time, 60 Marine Archaeology, 60 Summary, 62 International Organization and Management of an Ocean Exploration Program International Organizational Structures, 64 Invitation to Ocean Exploration Within the Annual United Nations General Assembly Ocean Resolution, 74 Voluntary Information Sharing, 75 Considerations for I International Programs, 76 . . . x''' 1 6 26 ~2 63 In the summer of 1803, Thomas Jefferson sent Meriwether Lewis and William Clark on a journey to establish an American presence in a land of unqualified natural resources and riches. Is it fitting that, on the 200th anniversary of that expedition, the United States, together with international partners, should embark on another journey of exploration in a vastly more extensive region of remarkable potential for discovery. Although the oceans cover more than 70 percent of our planet's surface, much of the ocean has been investigated in only a cursory sense, and many areas have not been investigated at all. Exploration of the Seasassesses the feasibility and potential value of implementing a major, coordinated, international program of ocean exploration and discovery. The study committee surveys national and international ocean programs and strategies for cooperation between governments, institutions, and ocean scientists and explorers, identifying strengths, weaknesses, and gaps in these activities. Based primarily on existing documents, the committee summarizes priority areas for ocean research and exploration and examines existing plans for advancing ocean exploration and knowledge.
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Behaviour of bioactive glass (S53P4) in human frontal sinus obliteration | Request PDF Request PDF | On Jan 1, 1997, Kalle Aitasalo and others published Behaviour of bioactive glass (S53P4) in human frontal sinus obliteration | Find, read and cite all the research you need on ResearchGate Behaviour of bioactive glass (S53P4) in human frontal sinus obliteration January 1997 DOI: 10.1016/B978-008042692-1/50102-3 In book: Bioceramics (pp.429-432) Authors: Antti Yli-Urpo ... [32,33] BAG is biocompatible, bone-bonding, and osteoconductive in humans. [34] Good results have been achieved with this material in frontal sinus surgery. [35,36] Bioglass is not only bioactive, but it is also bacteriostatic, [37] which may be one reason why there were no acute or late infections after frontal sinus obliteration or orbital floor reconstruction. ... Bioactive glass: A potential next generation biomaterial Historically the function of biomaterials has been to replace diseased or damaged tissues. The first generation biomaterials were selected to be as bio-inert as possible and thereby minimize formation of scar tissue at the interface with host tissues. Bioactive glasses (BAGs) were discovered in 1969 and provided for the first time an alternative; the second generation, interfacial bonding of an implant with host tissues. Tissue regeneration and repair using the gene activation properties of Bioglass® provide a third generation of biomaterials. This article reviews the history of the development of BAGs, with emphasis on the first composition, 45S5 Bioglass®, that has been in clinical use since 1985. A bioactive ceramic is a ceramic that generate a positive reaction in the biological environment of the implants and/or chemical reaction that modify the material in a certain thickness under the surface. Effect of immersion in SBF on porous bioactive bodies made by sintering bioactive glass microspheres Heimo O. Ylänen Kaj Karlsson Experimental Follow-up Model for Clinical Frontal Sinus Obliteration with Bioactive Glass (S53P4) Bioactive glass S53P4 (BG) is an osteoconductive allograft material. Since 1990, BG has been used in the obliteration of frontal sinuses in more than 30 consecutive patients. The patients have been monitored regularly with clinical examinations, computer tomography (CT) scans, laboratory tests and, in a few cases, biopsies have also been obtained. The material has been well tolerated and no loss of volume of obliteration material has been seen in the obliterated sinuses. However, in repeated CT monitoring and with Region of Interest (ROI) analysis, a decrease in the density of the obliteration material inside the frontal sinuses has been seen. In the present study, the clinical conditions after an obliteration operation were simulated and the behaviour of the BG in the obliterated area was observed. The aim was to study whether it is possible indirectly to estimate the resorption of a massive amount of BG with ROI analysis for monitoring the clinical success of the treatment. Thus two sizes of granules (0.63-0.8 mm and 0.8-1.0 mm) in eight separate BG amounts, weight 25 g, were tested in simulated body fluid (SBF) in standard conditions. The dissolution of silicon (Si) and phosphate (P) was detected with direct plasma atom emission spectroscopy (DCP-AES) monthly up to 6 months. The BG amounts were scanned with CT and the slices analysed using the ROI technique at 1, 3 and 6 months. The cumulative loss of Si and P in SBF was significant during the study ( p <0.0001) it and was stronger with smaller than with larger granules ( p <0.0001). This was shown correspondingly by the decrease of Hounsfield units ( p <0.0001) in ROI analysis. The method seems reliably to reveal the resorption of BG for clinical purposes. Bioactive glass granules: A suitable bone substitute material in the operative treatment of depressed lateral tibial plateau fractures: A prospective, randomized 1 year follow-up study Kimmo Mattila Purpose of this study was to compare bioactive glass and autogenous bone as a bone substitute material in tibial plateau fractures. We designed a prospective, randomized study consisting of 25 consecutive operatively treated patients with depressed unilateral tibial comminuted plateau fracture (AO classification 41 B2 and B3).14 patients (7 females, 7 males, mean age 57 years, range 25-82) were randomized in the bioglass group (BG) and 11 patients (6 females, 5 males, mean age 50 years, range 31-82) served as autogenous bone control group (AB). Clinical examination of the patients was performed at 3 and 12 months, patients' subjective and functional results were evaluated at 12 months. Radiological analysis was performed preoperatively, immediately postoperatively and at 3 and 12 months. The postoperative redepression for both studied groups was 1 mm until 3 months and remained unchanged at 12 months. No differences were identified in the subjective evaluation, functional tests and clinical examination between the two groups during 1 year follow-up. We conclude that bioactive glass granules can be clinically used as filler material instead of autogenous bone in the lateral tibial plateau compression fractures. Antibacterial Effects of a Bioactive Glass Paste on Oral Microorganisms Eva Söderling Bioactive glasses contain oxides of calcium, sodium, phosphorus, and silicon in a proportion that provides the material with surface activity and concomitantly with the property of forming a strong bond with bone. Bioactive glasses have been tested as bone substitutes in different clinical situations. In an aqueous environment, Ca2+, Na+, PO4(3-) , and Si4+ are released from the glass, resulting in a rise in pH and in osmotic pressure in its vicinity. Since these are factors that potentially influence the viability of oral microorganisms at the dentogingival margin, we studied the effects of bioactive glass S53P4 on the oral microorganisms Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Actinomyces naeslundii, Streptococcus mutans, and Streptococcus sanguis. This was done by incubating each microbe in a suspension, in the presence of bioactive glass S53P4 in powder form. A. naeslundii was found to lose its viability within 10 min under the experimental conditions. A. actinomycetemcomitans, P. gingivalis, and S. mutans lost their viability within 60 min. Also for S. sanguis a significant loss of viability was seen within 60 min, but it was the only microbe that had any viable cells left after 60 min. Thus, in aqueous solutions the powdered bioactive glass S53P4 appears to have a broad antimicrobial effect on microorganisms of both supra- and subgingival plaque. Consequently, it could be useful as an ingredient in tooth-care products that may have beneficial effects on oral health both from a cariologic and a periodontal point of view. Patricia Stoor Eva Söderling R Grénman Interpositional grafts between mucoperiosteal flaps are commonly used in the repair of septal perforations. We studied the use of bioactive glass (BAG) S53P4 as an interpositional graft in 11 patients suffering from septal perforations. In aqueous environments, ions are released from the BAG and the pH rises in its vicinity, both of which may influence the growth and adhesion of microorganisms. Thus, we also studied the effects of the BAG S53P4 as granules or discs on the respiratory infection-associated microorganisms Haemophilus influenzae and Streptococcus pneumoniae. Growth inhibition was studied using an agar plate test and adhesion was analyzed both with and without serum precoating of the BAG S53P4. The perforations were successfully closed in 10 of 11 patients. One patient had a near total septum perforation, which could not be closed. No BAG-associated infections were seen during the follow-up. The BAG S53P4 did not show any clear growth inhibition of the microorganisms, which showed low adhesion to the material. Serum precoating increased the adsorption. Thus, uncoated BAG S53P4 seems to be a good graft in the repair of septal perforations. J ORAL MAXIL SURG Kalle M J Aitasalo Ilpo Kinnunen Jarkko Palmgren Matti Varpula Teemu Tirri Pekka K Vallittu Unlabelled: The aim of this study was to evaluate glass-fiber-reinforced composite as a bone reconstruction material in the critical size defects in rabbit calvarial bones. The bone defect healing process and inflammatory reactions were evaluated histologically at 4 and 12 weeks postoperatively. Possible neuropathological effects on brain tissue were evaluated. The release of residual monomers from the fiber-reinforced composite (FRC) was analyzed by high performance liquid chromatograph (HPLC). Results: At 4 weeks postoperatively, fibrous connective tissue ingrowth to implant structures was seen. Healing had started as new bone formation from defect margins, as well as woven bone islets in the middle of the defect. Woven bone was also seen inside the implant. Inflammation reaction was slight. At 12 weeks, part of the new bone had matured to lamellar-type, and inflammation reaction was slight to moderate. Control defects had healed by fibrous connective tissue. Histological examinations of the brain revealed no obvious damage to brain morphology. In HPLC analysis, the release of residual 1,4-butanedioldimethacrylate and methylmethacrylate from polymerized FRC was low. Conclusions: This FRC-implant was shown to promote the healing process of critical size calvarial bone defect in rabbits. After some modifications to the material properties, this type of implant has the potential to become an alternative for the reconstruction of bone defects in the head and neck area in the future. Toxicology and biocompatibility of bioglasses Nov 1981 June Wilson G H Pigott Frederick Schoen Larry L. Hench Evidence for the lack of toxicity of various bioglass formulations has been deduced from studies carried out, both in vivo and in vitro, in several different centers. Recent studies of the authors, described here, include testing of solid bioglass implants in the soft tissues of rats and rabbits for time periods of up to eight weeks. Two new techniques are described for the toxicological testing of particulate biomaterials. These tests, which involve rat peritoneal macrophages in culture and a mouse pulmonary biomaterial embolus model, indicate the biocompatibility of bioglass powders. Thus, the surface activity so critical in bone adhesion is without toxic effect in non-osseous tissues in contact with solid bioglass implants. Should wear occur and produce particulate bioglass, the material should be eliminated without consequence. Matti Peltola
https://www.researchgate.net/publication/283702592_Behaviour_of_bioactive_glass_S53P4_in_human_frontal_sinus_obliteration
Viruses | Free Full-Text | Monkeypox Virus in Nigeria: Infection Biology, Epidemiology, and Evolution Monkeypox is a zoonotic disease caused by monkeypox virus (MPXV), which is a member of orthopoxvirus genus. The reemergence of MPXV in 2017 (at Bayelsa state) after 39 years of no reported case in Nigeria, and the export of travelers’ monkeypox (MPX) from Nigeria to other parts of the world, in 2018 and 2019, respectively, have raised concern that MPXV may have emerged to occupy the ecological and immunological niche vacated by smallpox virus. This review X-rays the current state of knowledge pertaining the infection biology, epidemiology, and evolution of MPXV in Nigeria and worldwide, especially with regard to the human, cellular, and viral factors that modulate the virus transmission dynamics, infection, and its maintenance in nature. This paper also elucidates the role of recombination, gene loss and gene gain in MPXV evolution, chronicles the role of signaling in MPXV infection, and reviews the current therapeutic options available for the treatment and prevention of MPX. Additionally, genome-wide phylogenetic analysis was undertaken, and we show that MPXV isolates from recent 2017 outbreak in Nigeria were monophyletic with the isolate exported to Israel from Nigeria but do not share the most recent common ancestor with isolates obtained from earlier outbreaks, in 1971 and 1978, respectively. Finally, the review highlighted gaps in knowledge particularly the non-identification of a definitive reservoir host animal for MPXV and proposed future research endeavors to address the unresolved questions. Monkeypox Virus in Nigeria: Infection Biology, Epidemiology, and Evolution by Emmanuel Alakunle 1 , Ugo Moens 2 , Godwin Nchinda 3,4 and Malachy Ifeanyi Okeke 1,* Department of Natural and Environmental Sciences, Biomedical Science Concentration, School of Arts and Sciences, American University of Nigeria, 98 Lamido Zubairu Way, PMB 2250 Yola, Nigeria Laboratory of Vaccinology and Immunology, The Chantal Biya International Reference Center for Research on the Prevention and Management HIV/AIDS (CIRCB), P.O Box 3077 Yaoundé-Messa, Cameroon 4 Department of Pharmaceutical Microbiology & Biotechnology, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, P.O Box 420110 Awka, Nigeria * Author to whom correspondence should be addressed. Viruses 2020 , 12 (11), 1257; https://doi.org/10.3390/v12111257 Received: 30 September 2020 / Revised: 22 October 2020 / Accepted: 30 October 2020 / Published: 5 November 2020 (This article belongs to the Special Issue Smallpox and Emerging Zoonotic Orthopoxviruses 2.0: What Is Coming Next? ) Abstract : Monkeypox is a zoonotic disease caused by monkeypox virus (MPXV), which is a member of orthopoxvirus genus. The reemergence of MPXV in 2017 (at Bayelsa state) after 39 years of no reported case in Nigeria, and the export of travelers’ monkeypox (MPX) from Nigeria to other parts of the world, in 2018 and 2019, respectively, have raised concern that MPXV may have emerged to occupy the ecological and immunological niche vacated by smallpox virus. This review X-rays the current state of knowledge pertaining the infection biology, epidemiology, and evolution of MPXV in Nigeria and worldwide, especially with regard to the human, cellular, and viral factors that modulate the virus transmission dynamics, infection, and its maintenance in nature. This paper also elucidates the role of recombination, gene loss and gene gain in MPXV evolution, chronicles the role of signaling in MPXV infection, and reviews the current therapeutic options available for the treatment and prevention of MPX. Additionally, genome-wide phylogenetic analysis was undertaken, and we show that MPXV isolates from recent 2017 outbreak in Nigeria were monophyletic with the isolate exported to Israel from Nigeria but do not share the most recent common ancestor with isolates obtained from earlier outbreaks, in 1971 and 1978, respectively. Finally, the review highlighted gaps in knowledge particularly the non-identification of a definitive reservoir host animal for MPXV and proposed future research endeavors to address the unresolved questions. Keywords: Poxviridae ; orthopoxviruses ; monkeypox viruses ; ; ; ; ; ; 1. Introduction 1.1. Introduction to Family Poxviridae Poxviruses belong to family Poxviridae , a large and diverse family of double-stranded DNA viruses that multiplies in the cytoplasm of infected cells [ 1 , 2 ]. The poxviruses are known to have brick-shaped or oval structures measuring 200–400 nm when viewed with electron microscopy [ 3 ]. The wide host range of poxvirus, as well as their successful evolution, is partly due to their manipulation and modulation of host immune responses. The poxviruses are also called ancient viruses because they have been found in insects, reptiles, birds, and mammals. It is believed that these viruses, before the divergence of invertebrates and vertebrates, form visible “pox” [ 1 , 4 , 5 , 6 ]. The family Poxviridae is subdivided (based on their animal hosts) into two subfamilies, namely Chordopoxvirinae and Entomopoxvirinae . The former subfamily is known to infect vertebrates, and it is differentiated into 18 genera, including Avipoxvirus , Capripoxvirus , Cervidpoxvirus , Leporipoxvirus , Molluscipoxvirus , Orthopoxvirus , Parapoxvirus , Suipoxvirus , and Yatapoxvirus , while the latter subfamily is known to infect invertebrates, and it is grouped into four genera ( Alphaentomopoxvirus , Betaentomopoxvirus , Deltaentomopoxvirus, and Gammaentomopoxvirus ) [ 7 ]. The subfamilies of Poxviridae were each divided into its genera based on the shared antigenic similarity, induction of immunological cross protection, and phylogenetic grouping [ 1 , 4 ]. Although the infection biology and epidemiology of MPXV have been widely studied and published, there is still paucity of data and published results on the occurrence, distribution and virus transmission dynamics in Nigeria. Thus, the objective of this paper is to review the current state of knowledge concerning the infection biology, epidemiology, and evolution of MPXV in Nigeria. In addition, this review also chronicles and explores the knowledge gaps as they pertain to MPXV reservoir hosts and the ecological dynamics that modulate the maintenance of the virus in nature, as well as their spillover into human populations and subsequent human-to-human transmission. 1.2. History of Monkeypox Monkeypox virus was first reported in 1959 as an outbreak of a pox-like disease in monkeys kept at a research institute in Copenhagen, Denmark [ 8 ]. The first human MPXV case in medical history was recognized when, on 1 September 1970, a nine-month-old child was admitted to the Basankusu Hospital in the Democratic republic of Congo (at that time, known as the Republic of the Congo). The boy had a smallpox-like disease from which MPXV-like virus was isolated [ 8 , 9 , 10 , 11 ]. Six cases of human MPXV were described in Liberia, Nigeria, and Sierra Leone between October 1970 and May 1971. The first index MPXV case in Nigeria was recorded in 1971, and 10 MPXV cases were reported between 1971 and 1978 [ 12 ]. Since then, several thousand human cases of monkeypox have been confirmed in 15 different countries, with 11 of them in African countries. Monkeypox was imported to the United Kingdom, the USA, Israel, and Singapore [ 13 ]. 1.3. Monkeypox Virus: Morphology, Genome Organization, and Morphogenesis Having the same morphological characteristics as other orthopoxviruses the morphology of MPXV reveals that virions are ovoid or brick-shaped particles which are enclosed by geometrically corrugated lipoprotein outer membrane. MPXV size ranges are known to be 200 by 250 nm [ 14 , 15 ]. Membrane bond as well as densely packed core containing enzymes, a double-stranded DNA genome, and transcription factors are protected by the outer membrane. Due to an electron microscopy fixation artifact, the core is being described as biconcave, and it has lateral body on each side [ 4 , 16 , 17 ]. The MPXV genome consists of a linear double-stranded DNA (≈197 kb) [ 18 ] covalently joined at its ends by palindromic hairpins, and the inverted terminal repeats (ITRs) are made up of hairpin loop, tandem repeats, and some open reading frames (ORF). Although MPXV is a DNA virus, its entire life cycle occurs in the cytoplasm of infected cells. All the proteins required for viral DNA replication, transcription, virion assembly, and egress are encoded by the MPXV genome. The genes encoding for housekeeping functions are highly conserved among OPVs and are present in the central region of the genome while those that encode for the virus–host interactions are less conserved and are located in the termini region [ 1 , 15 , 16 , 17 , 19 , 20 , 21 , 22 , 23 ]. In VACV (and most in likely MPXV) intracellular mature virus (IMV) and extracellular-enveloped virus (EEV) are two forms of infectious virions produced in poxvirus-infected cells. IMV is released on cell lysis, while EEV is released from cells via interaction with actin tails, and this is said to be the cause of rapid long distance spread of the virus within the infected host. Although the aforementioned features are for VACV, it is likely that these features are common to all OPVs [ 22 ]. However, cell-associated virions (CEVs) are formed following the microtubule-mediated transport of intracellular enveloped virus (IEV) to the cell periphery, in which the outer membrane of IEV fuses with the plasma membrane and remains attached to the cell surface. CEVs are mostly responsible for cell-to-cell spread [ 24 ]. IEV is formed when IMV is wrapped by a double membrane derived from early endosomal component [ 17 ] or the trans-Golgi network (TGN) [ 25 ]. However apart from IEV exocytosis, an alternative route for the formation of EEV is by the budding of IMV through the plasma membrane [ 26 ]. In the prototype VACV, virion morphogenesis can be defective resulting in non-infectious dense particles (DPs) [ 26 , 27 ], but this has not yet been reported for MPXV. In addition, unlike some strains of CPXV in which IMVs are occluded within A-type inclusions (ATI) [ 28 , 29 ], MPXV do not form ATIs or sequester IMVs into ATIs because of truncation in the ATIP gene [ 30 ]. 2. Monkeypox Virus Infection Biology, Diagnosis and Treatment 2.1. Animal Models In choosing an ideal animal model for a study of human disease, there are characteristics that the animals must possess in order to get a desirable result. The animal models must have similar mode(s) of transmission as in human cases, similar disease course, morbidity, and mortality as that of human cases, utilization of infection route identical to the natural transmission of the pathogen, and potentiality of obtaining disease with the same infectious rate as that of causing disease in humans [ 31 ]. Experimental infection of Guinea pigs and Golden Hamsters (being challenged with MPXV via intracardial, intranasal, oral, and route inoculation) showed that these animals were resistant to MPXV with the former (Guinea pigs) having no observable symptoms of the disease except edema at the inoculation site (foot pad), and the later (Golden Hamsters), in spite of large dosages of virus, showed no apparent signs of disease. Adult rabbits have no observable signs of the disease following oral inoculation with the same strain of MPXV, but acute illness, as well as, generalized rash was observed when the route of infection was intravenous [ 31 , 32 ]. When adult ground squirrels ( Spermophilus tridecemlineatus ) were challenged with 10 5.1 pfu (plaque-forming unit) of the West African MPXV via intranasal or intraperitoneal inoculation, anorexia and lethargy (as symptoms) were shown within four to five days of infection, and no other noticeable symptoms. However, when challenged with the Congo Basin MPXV, the animals were found to have more rapid and uniform severe respiratory distress from the onset, and the animals died earlier than the West African MPXV challenged animals. A hundred percent and sixty percent mortality were recorded when Prairie dogs were exposed to 10 5.1 pfu of West African MPXV via intranasal or intraperitoneal route of infection, respectively. According to Huston et al., generalized rash was observed in asymptomatic black-tailed prairie dogs ( Cynomys ludovicianus ) after 9–12 days of exposition to 10 4.5 pfu of both Congo Basin or West African MPXV via an intranasal and scarification routes. The notable symptoms observed in the animals included lethargy, inappetence, nasal discharge, respiratory distress, morbidity, and mortality. Lesser morbidity and mortality rate were observed for the West African MPXV, and LD 50 (median lethal dose) was found to be hundred-times higher for the West African clade compared to Congo Basin clade (1.29 × 10 5 and 5.9 × 10 3 , respectively) in the prairie dog MPXV model via intranasal route [ 31 , 33 , 34 ]. Hatch et al. tested the efficacy of the smallpox vaccines Imvamune (a.k.a JYNNEOS TM ) and ACAM2000 TM against 10 5 pfu aerosolized monkeypox virus in Cynomolgus macaques ( Macaca fascularis ) via intranasal route. Besides the red patches on all MPXV challenged animals at the vaccination site, declination of body weight was also observed in most animals especially in those mock vaccinated with TBS (Tris-buffered saline) with 10–18% loss in weight, and there was a consistent increment in body weight of all surviving animals in the vaccination groups from day 14 post-challenged [ 35 ]. African dormice ( Graphiurus kelleni ), previously treated with Dryvax vaccine, were protected from mortality following challenge with 2 × 10 4 PFU of MPXV-ZAI-79, and the unvaccinated group of dormice experienced uniform mortality [ 36 ]. The efficacy of the nucleotide analogue Cidofovir, via intranasal route, was tested in some African dormice, which were challenged with Congo Basin clade virus MPXV-ZAI-79. Nineteen percent mortality rate was observed in animals treated with Cidofovir while vehicle or placebo treated animals were susceptible to the disease. The antiviral drug Tecovirimat (ST246) was administered to prairie dogs, via the oral route of infection, after they had been exposed to 65 × LD 50 of Congo Basin clade virus ROC-2003-358, and generalized rash coupled with 10–24% decrease of animals’ body weight was observed. There was deterioration of the symptoms of the disease, as well as an increase in viral titers, in untreated groups of animals. However, all animals (at rash onset) in the treatment group survived. Thus, ST246 was established to provide potent antiviral activity against MPXV infection [ 31 ]. Out of the 38 inbreed strains of mice (32 classical inbreed strains and six wild-derived strains) screened for susceptibility to MPXV, only three (CAST/EiJ, PERA/EiJ, and MOLF/EiJ) of the wild derived strains were highly susceptible to MPXV, and all the classical inbreed strains were highly resistant to intranasal MPXV infection. CAST/EiJ (abbreviated as CAST) is the most sensitive (of the three susceptible mouse strains) to MPXV with LD 50 of 680 and 14 infectious units via intranasal and intraperitoneal infections [ 37 , 38 , 39 , 40 ]. CAST was also used as a model for testing efficacy of smallpox vaccines and antivirals (Dryvax and Cidofovir) against MPXV. Although both therapeutics gave protection to MPXV-infected CAST mice, Dryvax was more effective than Cidofovir [ 39 ]. 2.2. Transmission The two possible means of MPXV transmission are animals–human transmission and human–human transmission. Respiratory droplets and contact with body fluids, contaminated patient’s environment or items, skin lesion of an infected person have been found to be associated with inter-human transmission. Congo Basin clade (Central Africa clade) is reported to be more virulent than West Africa clade and thereby contributes more to inter-human transmission [ 41 , 42 , 43 , 44 , 45 , 46 ]. Animal-to-human transmission, which is also known as zoonotic transmission, occurs via direct contact with any of the aforementioned natural viral hosts or consumption of these hosts. In addition, zoonotic transmission could occur by direct contact with the blood, body fluids, and inoculation from mucocutaneous lesions of an infected animal [ 41 , 47 , 48 , 49 , 50 ]. Nosocomial transmission has been reported for CB and WA clades of MPXV [ 51 , 52 , 53 ] while sexual transmission has been speculated for infected individuals with groin and genital lesions [ 54 ]. At present human-to-animal transmission has not been reported. Human-to-human transmission, secondary attack rates (SARS), and serial transmission events is much higher with the CB clade compared to the WA clade [ 55 ]. The reproduction number R0 for the CB clade is estimated to be in the range of 0.6–1.0 [ 56 , 57 ]. The R0 has not be estimated for the WA clade of MPXVs, but it is presumed to be lower than that of the CB clade. The upper limit R0 of 1.0 in the CB clade indicates that the viruses will not only sustain human-to-human transmission but may persist in human population. Presumably, if as expected the R0 of the WA clade is much lower than what was estimated for the CB clade, then sustained human–human transmission and persistence in human population are highly unlikely and outbreaks will be largely due to spillover events from zoonotic hosts. 2.3. Diagnosis 2.3.1. Genetic Methods This involves using PCR or real-time PCR (RT-PCR), and it is advisable that this test is carried out in a Biosafety level-three facility [ 58 ]. Routine detection of MPXV DNA from clinical and veterinary specimens, as well as from MPXV-infected cell cultures, is accomplished by RT-PCR targeting conserved regions of extracellular-envelope protein gene ( B6R ) [ 59 ], DNA polymerase gene, E9L [ 60 ]. DNA dependent RNA polymerase subunit 18, rpo18 [ 61 ], and F3L gene [ 62 ]. Restriction length fragment polymorphism (RFLP) of PCR-amplified genes or gene fragments are also used in detection of MPXV DNA [ 63 , 64 , 65 ] but RFLP is time consuming and does require virus culture. RFLP of PCR products which also require enzyme digestion followed by gel electrophoresis and thus may not be the appropriate method in clinical setting where rapidity, sensitivity, and the specificity of the method is paramount. Whole-genome sequencing, using next-generation sequencing (NGS) technologies, remains the gold standard for characterization of MPXV and other OPVs [ 66 , 67 , 68 , 69 ], but the technology is expensive, and downstream processing of sequencing data requires enormous computation power. Thus, NGS may not be the appropriate method for characterization especially in the resource poor countries of sub-Sahara Africa. Although RT-PCR remain the method of choice for routine diagnosis of MPXV, it has to be complemented by field genome sequencing technology, like Oxford Nanopore MinION, in order to provide real-time virus genome data, which are indispensable for evidence-based epidemiological interventions. MinION field sequencing was successfully used for genome surveillance of Ebola outbreak in resource limited settings of West Africa [ 70 ]. 2.3.2. Phenotypic Methods Based on the clinical diagnoses, the incubation period of MPXV is within 4–21 days, and it is usually followed by a prodromal illness with several signs including lymph node enlargement, headache, fever, back pain, myalgia, intense asthenia, severe headache, pharyngitis, drenching sweats, and malaise. The exanthema phase, following the prodromal phase, comes with vesiculopustular rashes that appear within 1–10 days of development spreading all over the body starting with the face. The lesions in MPXV patients appear monomorphic, pea-sized and hard which is similar with that of smallpox. Crop-like appearance of MPXV lesion and its non-strong centrifugal spread make it different from smallpox. Presence of lymphadenopathy in MPXV is the notable clinical feature that differentiates it from smallpox [ 6 , 42 , 43 , 58 , 71 , 72 ]. Presumptive identification of MPX based on clinical symptoms is important for identification of suspected cases during surveillance but clinical case definition for MPX in the absence of laboratory confirmation have been shown in a cohort of 645 individuals to have high sensitivity (93–98%) and low specificity (9% to 26%) [ 55 , 73 ]. 2.3.3. Immunological Methods This includes using enzyme-linked immunosorbent assay (ELISA) for IgG and IgM antibodies detection and immunohistochemistry for viral antigen detection. Immunochemistry analysis can be used to differentiate between poxvirus infection and herpes virus, using polyclonal or monoclonal antibodies against all OPVs. It has been established that antiviral antibody, as well as T-cell responses, increases around the time of disease onset. However, IgM and IgG are detected in serum about five days and more than eight days after the onset of rash, respectively. Indirect MPXV diagnosis may arise if IgM and IgG antibodies are present in an unvaccinated individual with a history of rash and severe illness. However, none of these methods is specific for MPX [ 43 , 44 , 46 , 58 , 71 , 74 ] and can indicate the presence of other OPV species. IgM can be used to assess MPX infection in an individual with prior history of smallpox vaccination [ 75 ]. Positive IgM capture ELISA is indicative of recent exposure to OPV (likely MPXV in endemic areas) in both naïve and vaccinated individuals whereas a positive IgG capture ELISA suggests that the individual has been previously exposed to OPV either through vaccination or natural infection [ 76 , 77 ]. Consequently, the presence of both IgM and IgG in a sample is a strong evidence for recent exposure to OPV in individuals that has been previously vaccinated or exposed to natural infection. Thus, the presence of IgM in individuals previously vaccinated against smallpox in regions of MPX endemicity is indicative of a recent exposure to MPXV. 2.3.4. Electron Microscopy MPXV under electron microscope appears intracytoplasmic brick-shaped with lateral bodies and a central core measuring about 200–300 nm. Although this method is not definitive diagnosis because OPV species cannot be differentiated morphologically, but it gives a clue that the virus belongs to Poxviridae family [ 6 , 43 , 71 , 78 ]. 2.4. Virus–Host Interaction 2.4.1. Host and Tissue Tropism Horizontal gene transfer (HGT) has been an obvious explanation for accumulation of immune evasion genes (tumor necrosis factor (TNF) receptor, interferon (IFN)-γ receptor, MHC class 1, interleukins among many others) among poxviruses, and the ability of poxviruses to become host-restricted could be ascribed to the coevolution of the viruses and their hosts over many years [ 1 ]. McFadden highlighted three levels of viral tropism (cellular tropism, host or organism tropism, and tissue tropism) [ 79 ]. Tissue and host tropism affect, to a large extent, the distribution and propagation of the virus in an infected hosts and between hosts, respectively [ 79 ]. Members of the genus OPV are believed to have different spectrum of host tropisms, and such variability may enhance host–virus interface, reduction in pathogenesis, and different immune evasion molecules [ 1 , 80 , 81 , 82 , 83 ]. Although the reservoir host of MPXV has not been definitively identified, many mammalian species have been naturally infected with MPXV ( Table 1 ). Thus, MPXV is presumed to have a wide host range. Huston et al. detected high levels of viral DNA and viable virions in a wide range of tissues in animals that died following challenge with Congo Basin MPXV [ 80 ], and this may suggest a wide tissue tropism. Immunohistochemistry and histopathology tests (using mice with severe combined immunodeficiency) conducted by Osorio et al. have revealed that MPXV antigen was detected in the ovarian tissue, brain tissue, heart tissue, kidney tissue, liver tissue, pancreatic tissue, and lung tissue; however, the viral titers were higher in ovarian tissues than other tissues, and therefore ovarian tissues proved to be highly susceptible to MPXV [ 110 ]. The histopathological studies conducted on cynomolgus monkeys ( Macca fasicularis ) by Zaucha et al. showed that lymphoid tissues are good tropism for MPXV, and the viral antigen was also detected in the salivary epithelium, follicular, sebaceous tissue of the lip among many other tissues [ 111 ]. The presence of MPXV DNA in multiple tissues and virus isolation in different animals (like dormice, praire dogs, giant pouched rats, rope squirrels and others) highlight the difficulty in targeting a particular tissue as a site of infection [ 99 , 112 ]. 2.4.2. Signaling in Orthopoxvirus Infection Viruses are obligate intracellular parasite [ 113 ]. Replication of viruses inside their host cells serves as means of viral propagation, and this possible because viruses are host-dependent for their survival. The adaptability of viruses to their hosts involves manipulation of host cell signaling. Signaling in any viral infection is very crucial as it serves as portal of entry to viral genomes or proteins as the case maybe, and it usually determines the outcome of an infection [ 114 ]. The two signaling networks most targeted by viruses are cell growth and immunoregulation [ 115 ]. Inhibition or retardation of apoptosis, suppression of antiviral host defense, and exploitation of host cell machinery are well-known features of OPVs [ 116 ]. Of the three classical mitogen-activated protein kinase (MAPK) pathways (MEK-ERK, Jun amino-terminal kinases or JNK and p38/SAPK or stress-activated protein kinase) [ 117 ], the MEK (MAPK/ERK kinase)-ERK (extracellular signal regulated kinase) cascade is induced by many DNA and RNA viruses to create an optimal intracellular environment for their replication cycle. Extracellular signals which induce cellular proliferation, differentiation, and survival are transmitted primarily by the MAPK-ERK pathway (the central regulator of cellular response to environmental stimuli). Alteration of MAPK-ERK signaling by DNA viruses dysregulates the cell cycle, promotes viral internalization, regulates viral replication, and prevents host-cell death. The MAPK-ERK pathway is activated upon initial VACV infection so as to promote the expression of viral proteins like O1 which is needed for viral replication. The MAPK-ERK activation is sustained by the expression of O1 [ 113 ]. Deacetylating histones is a way implored by histone deacetylases (HDACs) to repress gene expression which in return strengthens histone DNA interactions and chromatin condensation. The 18 HDACs found in human are characterized into four groups, namely class I (HDACs 1,2,3, and 8), class III (sirtuins 1–7), class IV (HDAC 11), and class II, which is subdivided into class IIa (HDACs 4,5,7, and 9) and class IIb (HDACs 6 and 10). Lu et al. used the osteosarcoma U2OS cell line to determine the effect of HDAC4 on the replication and spread of VACV and HSV-1, and found that HDAC4 is not only required for type I IFN signaling, but it also restricts the replication and spread of the viruses due to the overexpression. Similarly, the enhancement of VACV replication and spread was observed due to the loss of HDAC4. Protein C6 and the proteasome are responsible for HDAC4 degradation during VACV infection [ 118 ]. There are large number of members in the heat shock proteins (HSPs) family including DNAJ (HSP40), HSPD, HSPA (HSP70), HSPC (HSP90), HSPH, and HSPB (small HSPs). These HSPs have multiple isoforms and act as chaperons that help in protein folding [ 119 ]. Heat shock factor 1 (HSF1), the regulator of cytoprotective heat shock response, is necessary for OPV infection. Filone et al. discovered that the VACV early, intermediate, and late gene expressions were reduced following the depletion of HSF1, and this suggests that HSF1 is essential for VACV lifecycle. An increase in the phosphorylated form of HSF1 following the VACV infection suggests the activation of HSF1, and translocation of phosphorylated HSF1 to the nucleus indicates that VACV activates HSF1 in a similar manner to heat shock. Furthermore, the VACV infection reported to reduce following the activation or reduction of heat shock protein activity by HSF1 inhibitors (triptolide, KNK437, quercetin, KRIBB11, KRIBB3, myricetin, and gentespib (STA-9090)) [ 120 , 121 ]. Shchelkunov noted that the cell antiviral signaling and inflammatory responses are activated by the viral infections, and the nuclear factor kappa B (NF-κB) is crucial for many responses like cell proliferation, apoptosis, inflammation, and immune responses. He further stated that cellular protein kinase phosphorylates IκBα kinase (IKK) in order to phosphorylates IκBα at the serine residue at positions 32 and 36, respectively, and the ability of OPVs to block the function of STAT (signal transducer and activator of transcription) proteins (which serves as antiviral responses) has become the common mechanism or strategy for viral immune evasion. MPXV has eight ankyrin (ANK) genes, and ANK controls the activation of NF-κB. VACV A46R, CPXV A49R, MPXV A47R, and VARV A52R are Bcl-2-like proteins that inhibit activation of NF-κB and IRF3 by interacting with MyD88, TIRAP and TRIF, and TRAM. MPXV B13R interacts with IKK so as to inhibit the activation of NF-κB [ 122 , 123 ]. Wiskott-Aldrich syndrome protein (WASP) and elevated ATP level are essential for VACV infection. Nicotinamide adenine dinucleotide dehydrogenase 4 (ND4) and cyclooxygenase-2 (COX2) are mitochondrial proteins which generate ATP in the electron transport chain and are said to be increased by VACV. Liem and Liu stated that the components of the eukaryotic translation initiation complex eIF4F are recruited to viral factories during VACV infection, and these components are m7G-cap-binding subunit (eIF4E), a small RNA helicase (eIF4A), and a large scaffold protein (eIF4G). The eIF4G with its associated proteins, during VACV infection, are brought into close propinquity with viral factories by the single-stranded DNA (ssDNA) binding phosphoprotein I3. The MAP kinase-activated protein kinase Mnk1, which has a direct association with eIF4G, regulates eIF4E activity and promotes eIF4E phosphorylation. ERK1/2MAP kinases and p38/SAPK regulate Mnk1 activity. The activation of ERK and p38, which occurs during VACV infection, is associated with eIF4E activation. Deletion or inhibition of Mnk1 hinders VACV infection severely. Therefore, VACV boost the viral protein synthesis by manipulating Mnk1 activity in addition to sequestering of translation initiation complex [ 120 ]. Members of integrins family are cell surface receptors with 18 different α and eight different β subunits. Multiple α subunits which include α1-11 and αV are associated with integrins β1. Integrins β1, via interaction with the extracellular matrices, regulates multiple intracellular kinase activation pathways [ 124 ]. During the experiment carried out by Izmailyan et al., using HeLa cells and mouse cells, respectively, VACV entry was reduced upon knockdown and knockout of integrins β1. The activation of phosphophatidylinositol-3-kinase (PI3K)/Akt, which leads to virus endocytosis in HeLa cells, was observed to occur as a result of binding of Vaccinia MV to integrins β1. ERK, protein kinase C, and p21-activated kinase 1 are said to be activated by VACV [ 124 ], but the biological relevance for VACV replication is not known. 2.4.3. Host Immune Responses to MPXV There are many mechanisms or strategies developed by PXVs to evade or worsen host immune response to infection [ 125 ]. More studies on the pathology and pathogenesis of MPXV have been done, but knowledge of innate and adaptive immune response of MPXV infection is not well understood due to insufficient data. Natural killer (NK) cells, a major component of innate immunity, directly kill virus-infected cells by secretion of cytokines in order to modulate functions of other cell types like T-cells and dendritic cells. The interaction between activating or inhibitory receptors on NK cells and their ligands like major histocompatibility complex 1 (MHC-1) molecules initiates activation or inhibition of NK cells. Secretion of granules (containing perforin and granzymes) and cell–cell interactions mediate the killing effect of NK cells. Inflammatory responses in inflamed tissues are mediated by IFN-γ and TNF-α that were secreted at early stages of infection by NK cells, and these cytokines are also involved in coordinating the dendritic cells to induce T-helper type 1 (Th1) cell polarization [ 126 ]. Earl et al. observed that CAST was highly susceptible to MPXV, and inadequate or insufficient interferon-γ response in the lung is correlated with the vulnerability of CAST mice following intranasal infection [ 37 , 38 , 40 ]. Similarly, susceptibility of CAST mice to MPXV is due to low numbers of NK cells. CAST mouse NK cells, which were purified and expanded in vitro with IL-15, were protected against MPXV [ 40 ]. According to Song et al., MPXV infection is responsible for changes in the number of lymphocytes including NK cells in NHPs, and lymphadenopathy, as well as lymphoid depletion, in MPXV-challenged NHPs, is a result of MPXV infection [ 127 ]. At the end of an experiment conducted by Townsend et al., using Prairie dogs as models, there was a significant increase in the following: the number of all NK subsets at day seven postinoculation, CD16− CD56−, CD16+, CD56+, and CD16+CD56+ NK cells. The number, as well as composition, of NK cells in the lymph nodes during MPXV infection was observed to increase by 4.6%, and the observations made on the expression of chemokine receptors (CXCR3, CCR5, CCR6, and CCR7) on each NK cell subset suggest that, following the MPXV challenge, the receptors expression was delayed or reduced [ 126 ]. Studies have shown that MPXV disseminate poorly by inter-human contact [ 128 ]. and VARV and MPXV, as opposed to VACV, make use of cell-associated viremia to spread through their infected hosts [ 110 , 128 , 129 , 130 , 131 ]. Although the mechanisms involved in immune evasion of poxviruses against antiviral cytokines, chemokines, and antigen presentation are not well understood, interference with intracellular transport of MHC class I by CPXV also correlate the mechanisms used by CPXV in evading antiviral CD8+ T-cell responses [ 128 ]. Hammarlund et al. expected MPXV to have similar mechanisms of immune evasion as CPXV because MPXV encodes a close homologue of CPXV203 which retains MHC class I in the endoplasmic reticulum. However, the mode of evasion mechanism used by MPXV inhibited the activation of CD4+ and CD8+ T cell after cognate interactions with MPXV-infected cells, and this protects the viral reservoir from immune surveillance. Poor recognition of MPXV-infected monocytes by antiviral CD4+ and CD8+ indicated that MPXV did not trigger inflammatory cytokine production (IFNγ or TNFα) via virus-specific T cells, but the virus is efficient in infecting primary human monocytes [ 128 ]. Antiviral T cell responses increased greatly after only VARV infection, but following co-infection of MPXV and VARV, T-cell-mediated cytokine responses reduced by 95% and dropped by 80% when a low dose of MPXV was added (VARV:MPXV ratio of 10:1). This result indicated that T cell activated by VARV was inhibited by MPXV, and the immunomodulatory protein that is absent from VARV is encoded by MPXV. After peripheral blood mononuclear cells had been infected or uninfected, in the presence or absence of cytosine arabinoside (AraC) to block late gene expression, with VARV or MPXV, an early gene product was observed because inhibition of anti-CD3 responses in the presence of AraC was detected. This indicates that an early gene was responsible for immunosuppression of T cells (CD4+ and CD8+) by MPXV [ 128 ]. The identify of this gene remains unknown. In Nigeria, there is no report on T cell and antibody responses to human MPXV infections. There are also no data or reports on immune responses following experimental infections in animal models. Yinka-Ogunleye et al. reported that IgM ELISA was carried out on the cases during the 2017–2018 MPX outbreak but the results were not published. However, smallpox vaccination ceased in Nigeria since 1970. Thus, those 50 years or below were not vaccinated against smallpox and presumably are not protected against OPV infections including MPXV. As at 2019, about 90.2% of the 200 million Nigerians are under 50 years, of which 62.9% are 24 years or younger [ 132 , 133 , 134 ]. The absence of cross-protection elicited by smallpox vaccine, the probable waning of herd immunity and immunosuppression as a result of HIV/AIDS have in tandem resulted in an immunologically naive population that is very susceptible to MPXV infection. This may in part explain the recent re-emergence of MPXV in Nigeria. 2.5. Treatment 2.5.1. Vaccination Studies have shown that vaccination against smallpox provides cross-protection against other OPV species including MPXV. According to the available data, about 90% of the identified cases are naive to OPV infection of which many of them were born after the cessation of smallpox eradication program [ 46 ]. Individuals who had previously been vaccinated against smallpox were identified to have 85% protection against MPXV [ 43 , 46 , 74 , 78 ]. The smallpox vaccine (ACAM2000 TM ) recommended by the Center of Disease Control and Prevention (CDC), during the 2003 USA MPXV endemic, proved to reduce the symptoms and did not prevent disease [ 46 ]. Therefore, this vaccination is neither available to the public nor used in MPXV endemic areas due to some hiccups like unknown effects of the vaccine in immunosuppressed individuals and safety of the vaccine containing live vaccinia virus. IMVAMUNE, a replication deficient, attenuated third generation modified vaccinia Ankara (MVA) vaccine, has also been licensed by Food and Drug Administration (FDA) and the European Medicine Agency (EMA) for the prevention of smallpox and monkeypox for adults (18 years or older) determined to be at high risk of infection to VARV and MPXV [ 135 , 136 ]. Unlike ACAM2000, IMVAMUNE is not contradicted for use in individuals with immunodeficiencies such as AIDS and atopic dermatitis [ 135 , 136 ]. Currently, neither ACAM2000 nor IMVAMUNE have been approved for use in the general population. Consequently, whether or not these licensed smallpox vaccines will provide effective protection against MPX in MPXV endemic areas remain to be determined [ 43 , 46 , 50 , 71 , 74 ]. 2.5.2. Antivirals A 4-trifluoromethylphenol derivative or Tecovirimat (ST-246 or TPOXX ®® ), having been approved by the FDA, has undergone clinical trial, using an animal model. The drug has proven to be effective in the infected animals by blocking the release of the intracellular virus from the cell. According to CDC report, the human clinical trial with Tecovirimat suggested that the drug was tolerable and safe, but there are not enough data on its effectiveness in treating human cases of MPX. Similarly, animal and in vitro studies, using cidofovir and Brincidofovir (CMX001 or hexadecyloxypropyl-cidofovir), proved to be effective. These two drugs inhibit the viral DNA polymerase [ 42 , 46 , 58 , 71 , 78 , 137 , 138 , 139 ], and the former is an acyclic nucleoside phosphate while the latter is a liquid conjugate of cidofovir [ 140 ]. The cellular cytotoxicity of TPOXX ®® in several cell lines, including human, was >50 µM, and interaction of TPOXX ®® with F13L gene product inhibits the production of extracellular viruses. Meanwhile the formation of protein complex, which catalyzes the envelopment of intracellular mature virus particles, requires phospholipase that is encoded by F13L gene product [ 140 , 141 ]. Although the Brincidofovir has higher cellular toxicity and better antiviral activity than cidofovir against VARV, MPXV, VACV, and CPXV in vitro, Brincidofovir has greater selective index due to its better efficacy which was at least 25-fold higher than cidofovir’s. Increased cellular uptake alongside with better conversion to the active form by intracellular enzymes are responsible for better efficacy seen in Brincidofovir. Cidofovir is a monophosphate nucleotide analog and incorporation of a second phosphate group by cellular kinases converts it into an inhibitor of the viral DNA polymerase, which is also tantamount to inhibition of viral DNA synthesis by Brincidofovir activity. The phosphorylated cidofovir is formed via the conversion by intracellular kinases of cidofovir which is released by cleavage after Brincidofovir has entered the cells through the endogenous liquid uptake pathways [ 140 ]. Aside from the aforementioned drugs, Delaune and Iseni had done justice in exploring or evaluating the possibility of other potential drugs with antiviral activity against poxviruses. Nucleoside analogue inhibitors (N-Methanocarbathymidine, 4′-thio derivative of idoxuridine, and KAY-2-41) were among the potential drugs that were tested due to their antiviral activity. The efficacy of N -methanocarbathymidine (N-MCT) was observed in a mouse model infected with VACV, Balb/c mice infected with CPXV Brighton, and against herpesviruses. The N-MCT triphosphate metabolite, whose formation is viral thymidine kinase-dependent, mediates the antiviral activity of the drug. In vitro studies revealed that 4′-thio derivative of idoxuridine (4′-thioIDU) showed efficacy against CPXV, as well as VACV and against viral strains which are resistant to cidofovir or Tecovirimat. The efficacy of KAY-2-41 OR 1′-Carbon-substituted 4′ thiothymidine derivative had been said to be greater than cidofovir but lower than Brincidofovir or Tecovirimat. It had been shown that KAY-2-41 provided protection against VACV, CPXV, and CMLV in vitro. Another potential drug tested against poxviruses was NIOCH-14 which is a derivative of tricyclodicarboxylic acid and a precursor of Tecovirimat. Even though the efficacy of NIOCH-14 was similar to Tecovirimat in in vitro studies against VARV, MPXV, and ECTV, but NIOCH-14 remains a relevant antiviral candidate for the future due to its potent antiviral activity against many OPVs, and its production is easier than Tecovirimat [ 140 ]. Baker et al., were able to test potential drugs against OPVs and grouped these drugs into five categories ( S -adenosylmethione, Inosine monophosphate (IMP) dehydrogenase, DNA polymerase inhibitors, reverse transcriptase (RT) and protease inhibitors, and other compounds) based on their antiviral activities. Ribavirn and tiazofurin, which are IMP dehydrogenase inhibitors, proved to inhibit the replication of all the tested OPVs with VARV and MPXV being more sensitive than the other viruses. The protease inhibitors (saquinavir, ritonavir, and nelfinavir) and reverse transcriptase inhibitors (efavirenz, stavudine, and zidovudine) were inactive against OPVs while the two adenosine analogs (C-ca3-Ado and C3-Npc A) were shown to have protective effect against the tested OPVs by the viral replication, and these drugs are also S -adenosylhomocysteine (SAH) hydrolase inhibitors. Even though with a wide-range of antiviral activity of these SAH hydrolase inhibitors, they showed no detectable activity against CPXV in vitro. The DNA polymerase used by Baker et al. are the following: acyclovir, brovavir, lobucavir, cidofovir, adefovir (PMEA), adefovir dipivoxil (bis-POM-PMEA), and [(S)-9-(3-hydroxy-2-phosphonomethoxypropyl) adenime] or (HPMA), and they are all nucleoside analogs. The first three nucleoside analogs failed to be effective in inhibiting the OPVs replication, and this could be as a result of inability of the OPV thymidine kinase to recognize the drugs as a substrate for phosphorylation. Cidofovir and HPMA showed activity against PXVs by inhibiting the viral replication, using the same mechanisms, but adefovir and dipivoxil showed no significant activity against poxviruses. In addition, adenosine N1-oxide (ANO) showed significant activity against the OPVs by blocking the translation of viral mRNAs and thereby inhibiting viral replication [ 142 ]. There has not been any specific curative treatment for MPXV, it is only managed through supportive care and symptomatic treatment [ 143 , 144 ], but the problem with this type is that it could only cater for symptomatic individuals. Therefore, effective vaccination or antiviral drugs against MPXV are needed to prevent spread from asymptomatic individuals to other people. 3. Ecology and Epidemiology of Monkeypox Virus in Nigeria 3.1. Geographic Distribution of Human Monkeypox in Nigeria Nigeria is a sovereign country located in West Africa with a population of over two hundred million [ 133 , 145 ]. The country is made up of 36 states and federal capital territory as illustrated in Figure 1 . MPX has been reported in some regions or states in Nigeria. As at 27th October 2017, the Nigeria Center for Disease Control (NCDC) reported some cases to WHO, and these cases were confirmed in Abuja, Enugu, Bayelsa, and Akwa Ibom. The suspected cases were from Delta, Nassarawa, Niger, Rivers, Abuja, Lagos, Imo, Enugu, Ekiti, Akwa Ibom, Bayelsa, and Cross River. In January 2019, many suspected cases were reported across 26 states while confirmed cases were recorded in 17 states [ 41 , 42 , 52 , 58 , 144 , 146 , 147 ]. NCDC reported, as at September 2019, MPXV cases across nine states which include Oyo, Bayelsa, Lagos, Delta, Rivers, Enugu, Akwa Ibom, Anambra, and Cross River [ 43 , 47 , 149 , 150 ]. Meanwhile MPXV cases were reported in six additional states (Imo, F.C.T Abuja, Bauchi, Zamfara, Borno, and Plateau) as at December 2019, and this makes the total reported cases to 113 and confirmed cases to 45 between January and December 2019 [ 151 ]. Although there are not enough data to suggest that this disease is endemic in any region of Nigeria, some states in the Southern Nigeria (Southwest, South-South, and Southeast) happened to record outbreaks of the disease over the years. 3.2. Reservoir Host Species of Monkeypox Virus in Nigeria Even though the natural reservoir of MPXV in Nigeria is yet to be known, isolation of MPXV from the Gambian pouched rat, tree squirrel, rope squirrel, and sooty mangabey monkey, among other primates, suggests that the reservoir species are African rodents [ 46 , 48 , 55 , 60 , 149 , 152 ]. However, there is a lack of data on potential reservoir species of MPXV in Nigeria. Currently, there are no published reports on the presence of MPXV in small mammals and rodents in Nigeria. The mangrove and tropical rainforest of Southern Nigeria where most of the recent monkeypox outbreaks have occurred is rich in different species of small mammals, rodents, and primates [ 153 , 154 , 155 ]. Serological, genetic, and virus isolation epidemiological surveys of rodents, small mammals, primates, and wildlife for MPXV should be conducted to identify the animal reservoir, and natural and incidental hosts of MPXVs in Nigeria. Future studies should also look at the possibility of MPXV not having natural reservoir(s) but circulates in a wide variety of natural and incidental animal host species. 3.3. Epidemiology of Monkeypox Virus in Nigeria In Nigeria, the first human case of MPXV was recorded in a four-year old girl in 1971, and the second case was the mother of the four-year old girl. The affected individuals were residents of Ihie Umduru located in the present Abia state, and the mother was presumed to have gotten infected by her child. Similarly, the third case of MPXV in Nigeria occurred in 1978 in a thirty-five-year old man living in Omifunfun (Oyo state) [ 12 , 54 , 60 , 147 ]. Out of 10 reported cases between 1971 and 1978, only three cases were confirmed, and zero death was recorded [ 156 , 157 ]. After almost 40 years of no reported MPXV cases in Nigeria, there was reemergence of MPXV in September 2017. The Niger Delta University Teaching Hospital (NDUTH) notified NCDC of a suspected MPXV case in an eleven-year old with an eleven-day history of fever, generalized rash, headache, malaise, and sore throat [ 52 , 54 , 55 , 74 , 147 ]. One hundred and ninety-seven suspected cases across 23 states in Nigeria had been reported since the onset of MPXV outbreak in September to December 2017 [ 157 ]. The highest numbers of suspected cases were recorded in Bayelsa, Rivers, Lagos, Cross River, and Akwa Ibom with 40, 29, 21, 22, and 15 cases, respectively ( Figure 2 A). A total of 68 confirmed cases was recorded in 2017, and two deaths reported were from two states. Only nine states out of 23 states with suspected cases had no confirmed cases while 14 states had between 1 and 20 confirmed cases [ 158 ]. As at 13 November 2018, 104 suspected cases had been recorded (by NCDC) in 19 states, 38 confirmed cases in twelve states, and one death in Imo state. Rivers, Cross River, Bayelsa, and Akwa Ibom states constitute 68% of suspected cases while Rivers, Bayelsa, Delta and Oyo states constitute 66% of confirmed cases [ 159 ]. Lagos, Rivers, and Delta states were at the vanguard of 2019 MPXV cases with 35, 20, and 15 suspected cases and 14, 10, and 8 confirmed cases, respectively ( Figure 2 B) [ 151 ]. By and large, Nigeria has a record of 424 MPXV suspected cases and 155 confirmed cases with the highest number of confirmed cases in 2017 outbreak ( Figure 3 ). A declination in the number of confirmed and suspected cases in 2018 could suggest that Nigeria’s efforts in combating MPXV proved to be effective, but the 2019 data suggested otherwise ( Figure 3 ). MPXV cases between 2017 and 2019 were reported in the 21-to-40-year age group (median age = 30) [ 52 , 159 , 160 , 161 ], with the male-to-female ratio of confirmed cases being 3:1 [ 151 , 158 , 159 , 160 ]. Although no MPXV cases have yet been recorded or reported in 2020, this could be due to many factors particularly the migration of resources and personnel from MPXV surveillance and response to more deadly viral diseases especially covid-19 and Lassa fever [ 162 , 163 ]. Virtually the whole resources of NCDC have been channeled to battling covid-19 pandemic and Lassa fever epidemics in 2020. The reemergence of MPX in Nigeria after more than three decades of no reported cases maybe due to the fact that a large section of the Nigerian population is immunologically naïve to OPV infection as they did not receive smallpox vaccination which cross protects against monkey pox or the smallpox vaccine induced immunity have waned in vaccinated individuals [ 126 , 164 , 165 , 166 ]. Other factors for the re-emergence will include (i) increased encroachment of the wildlife habits of human and non-human primates by humans due to urbanization and hunting, (ii) increased trade in rodents and other species of wildlife fueled by the increased demand for and consumption of barbequed rodents/wildlife mammals (referred to as “bush meat”) in Nigeria, (iii) heavy rainfall and flooding that brought humans and MPXV-infected animal host close together, (iv) immunosuppression due to co-infection with HIV, and (v) a young population [ 166 ]. The reemergence is not just a public health concern for Nigeria only but has global health implication as trade in rodents have exported MPX to USA in 2003 [ 167 , 168 ] while human travelers from Nigeria have also exported the disease to Israel, Singapore, and the United Kingdom in 2018 and 2019, respectively [ 51 , 169 , 170 , 171 ]. More worrisome is that there is now evidence of human-to-human transmission of the West African clade of MPXV not just in Nigeria [ 60 ] but also in the United Kingdom [ 170 ]. Overall, MPX should no longer be considered a rare disease that is geographically limited to countries in the West and Central Africa. It is a global health threat, as well as a biodefence/biosecurity threat, and huge efforts must be directed in deciphering the zoonotic hosts, the epidemiological factors that maintain and sustain the virus in ecosystems, as well as the viral and host factors that modulate animal-to-human transmission and human-to-human transmission. 4. Phylogeny and Evolution of Monkeypox Virus in Nigeria 4.1. Phylogeny The genomic sequences of 29 MPXVs (eight Nigerian isolates including one export to Israel) and 23 other OPXVs, were retrieved from The Virus Pathogen Database and Analysis Resource (ViPR) website ( https://www.viprbrc.org ) [ 172 ]. Genomes of five Nigerian isolates (MPXV-3019, MPXV-3020, MPXV-3025, MPXV-3029, MPXV-3030) were from 2017 outbreak in Rivers State [ 60 ] and the two other genomes from Nigeria isolates (MPXV-SE-Nigeria, MPXV-W-Nigeria) were from earlier outbreaks in 1971 (Abia State) and 1978 (Oyo State), respectively [ 173 ]. The genome of the isolate exported to Israel (MPXV-Israel) in September 2018 was from an individual resident in PortHarcourt, Rivers state who returned to Israel a week after disposal of two rodent carcasses in his PortHarcourt residence [ 68 ]. All sequences were aligned by using MAFFT version 7 [ 174 ]. A phylogenetic tree was constructed from the aligned sequences, using a Maximum Likelihood (ML) algorithm as implemented in MEGA X software [ 175 ]. The tree shows that MPXVs were resolved into two major clades: the West Africa (WA) and the Congo Basin (CB) clades. The WA clade includes all the eight Nigerian isolates and other isolates from Liberia, the Ivory Coast, and the USA (exported from Ghana) ( Figure 4 ). In addition, the WA clade has two major subgroups, the Nigerian isolates formed a subgroup that is distinct from a second sub-cluster consisting of isolates from Liberia, Ivory Coast and USA. MPXV-Nigeria W (isolated in 1978) and MPXV-Nigeria-SE-1971 are genetically distant from the other recent Nigerian MPXV-isolates ( Figure 4 ). The monophyly of recent Nigerian isolates with the exported isolate to Israel suggest that the viruses may have emerged from the same infection pool. This is consistent with a recent Bayesian phylogenetic analysis of MPXVs exported from Nigeria to other parts of the world [ 176 ]. The CB clade consists of isolates from Democratic Republic of Congo, Sudan, Gabon, and Cameroon. Although Gabon and Cameroon are countries in West Africa, MPXVs isolated from these two countries resolved into the CB clade and these isolates may have originated from DRC since these Central African countries share the Congo Basin habitat. The MPXV tree topology in this paper is in agreement with previously published results [ 157 , 173 , 177 ]. Although genome-wide phylogenetic analyses of Nigerian MPXVs have been reported before [ 157 ], the results presented here represented the most comprehensive analysis, as it includes more genome sequences than previously documented. Moreover, the phylogenetic tree described here ( Figure 4 ) is in conformity with what is generally known about OPV tree topology: (i) ECTV is the most distant species in the group [ 178 ], (ii) CPXV is polyphyletic, and CPXV-like 2 clade is more related to VACV clade than to other CPXVs [ 178 , 179 ]; (iii) VACVs are sister to MPXVs, and the resolution of VACV clade is clouded by low bootstrapping support [ 178 , 180 ]; and (iv) CMLV and TATV share a common ancestor, and are sisters to VARV [ 178 , 179 ]. Future studies should also look at the possibility of MPXV not having natural reservoir(s) but circulates in a wide variety of natural and incidental animal host species. Research studies on evolutionary divergence of the two clades should be done because it is possible that the two clades have two different reservoir species. 4.2. Recombination Poxviruses undergo high-frequency recombination during infection of cells [ 182 , 183 ]. Among OPVs, naturally occurring inter-specie recombination events have been detected between CPXV and ECTV [ 182 , 184 ] and intra-species recombination between strains of VARV [ 185 ] and VACV [ 186 ]. However, natural recombination events have not been reported for MPXVs. Recombination is believed to be one of the drivers of poxvirus evolution [ 182 ], but Babkin did not find evidence in support of the role of recombination in OPV evolution [ 187 ]. Nevertheless, there is substantial evidence that tandem gene duplications are a result of recombination [ 188 , 189 ]. Estep et al. used homologous recombination to replace the D14L gene with an EGFP-GPT cassette in MPXV-Z genome in order to determine the role of MOPICE in MPXV pathogenesis [ 190 ], and a recombinant MPXV encoding green fluorescent protein was engineered in order to study MPXV infection in a monkey model [ 191 ]. The ease of construction of recombinant MPXVs in the lab raises the possibility that such recombination may occur or have occurred in nature between co-infecting MPXVs, MPXVs, and naturally occurring OPVs, including VARV, as well as smallpox vaccine strains. Genome-wide recombination analysis of Nigerian MPXVs isolated from humans and animals will shed light on the role of recombination, if any, on the evolution of MPXVs in Nigeria. 4.3. Gene Loss, Gene Gain, and SNPs OPV evolution is also driven by variation in genome content. OPVs adapt to their host by gene loss and gain [ 192 ]. Genome-sequence length and gene content positively correlates with wide host range but has an inverse relationship with pathogenicity [ 193 ]. The WA clade of MPXV (in particular, the Nigerian isolates) have larger genomes (197,566–197,792 bp) and content compared to the CB clade (especially the Zaire isolates) (196,850–196,959 bp), and that may contribute to the less virulence of the WA clade [ 194 ]. This is underscored by studies in ground squirrels that demonstrated that animals infected with Congo Basin MPXV had more severe symptoms and died compared to West African MPXV challenged animals [ 35 , 94 ]. However, in some instances gene loss may result in attenuation instead of increased virulence as has been demonstrated with the evolution of Chorioallantois vaccinia virus Ankara (CVA) to Modified vaccinia virus Ankara (MVA) [ 194 ] or by the deletion of virulence genes in MPXV [ 91 ]. It follows that OPVs adopt reductive evolution by gene loss in order to optimize their response to the host antiviral mechanisms. There is a strong evidence that the main mechanism for gene loss is the introduction of early stop mutation (ESMs) that progressively lead to fragmentations, truncations, and complete deletion of the ORF [ 195 ]. Indeed, there is an inverse relationship between genome size and the combined total number of gene fragmentations, truncations, and missing ORF. Recently, it was demonstrated that under selection pressure triggered by antiviral host response, OPVs deploy transient gene expansion to overcome the host antiviral assaults. Mutant VACV in which E3L was deleted was shown to counteract the antiviral activity of human protein kinase R (PKR) by increasing the copy number of K3L, expanding its genome size by 7–10% [ 196 ]. Tandem K3L duplication stopped once adaptive H47R mutation was acquired, and this was followed by genome contraction evidenced by the rapid loss of K3L copies without the H47R mutation [ 196 ]. It is likely that this novel but transient mechanism of gene expansion and homogenization of adaptive SNPs may also be drivers of evolutionary adaptation in other OPV species including MPXV. Two recent studies have used haploid network mapping based on SNP matrix of the whole genome to infer epidemiologically linked clusters for 2017 MPX outbreak in Nigeria [ 60 ] and exported MPX from Nigeria to the UK, Israel, and Singapore [ 176 ]. Both studies inferred that the PortHarcourt prison cluster (MPXV-3018, MPXV-3019, MPXV-3020, MPXV 2029) has an average SNPs (point mutation) of 1.5, whereas the average SNP for export related MPXV genomes were found to be 5.9 [ 176 ]. However, the problem with haplotype network mapping for MPXVs is that there is no demonstrated threshold above which epidemiological related cluster hypothesis can be rejected. For instance, there is variation in the average SNPs for known MPX epidemiological clusters; the 2003 USA MPXV and 2017 PortHarcourt outbreaks had average SNPs of 0.4 and 1.5, respectively. In addition, genomes from virus isolates from different outbreaks and geographical regions may have as few as three SNPs separating them (M5312 from Rivers vs. M2972 from Lagos), whereas samples from the same geographic region and outbreak has as much as 10 SNPs (MPXVs-3018/3019_Rivers vs. MPXV-3030_Rivers) between them [ 176 ]. Overall, haploid network mapping based on SNP matrices need to be corroborated by epidemiological, phylogenetic and phylogeographic evidences in order to identify epidemiological linked or unlinked clusters during MPX outbreaks in Nigeria and elsewhere. 5. Gaps in Knowledge, Omitted Research, and Conclusion 5.1. Reservoir Host Species and Tissue Tropism There is no definitive reservoir or natural host for MPXV [ 60 , 136 , 197 ], but rodents and non-human primates have been determined to be potential natural reservoir and incidental hosts of the virus [ 198 , 199 ]. The difficulty in understanding the pathogen–host associations, the epidemiology, the natural history, and the ecological and climatic effects of MPXV could be ascribed to the detection of MPXV in a wide range of rodent species and non-human primates [ 74 ], as well as the paucity of data on natural reservoirs and maintenance hosts of the virus. Knowledge of tissue tropism will give a good grasp about the spread and the immune responses of the virus between the hosts [ 79 ]. There is no specific or definite tissue tropism of MPXV because it has been detected in a number of tissues, and this is no surprise as MPXV has been detected in a wide variety of animals. Ultimately, identifying the definite natural host of MPXV could lead to its specific tissue tropism. Future research should also focus in identifying the virus and host factors that modulate zoonotic spillover events, human-to-animal transmission, human-to-human transmission, and animal-to-animal transmission. 5.2. Co-Infection and Recombination Recombination is one of the drivers of evolution among the Poxviridae family [ 195 ], and it is in part also responsible for most genetic and phenotypic diversity among OPVs [ 200 ]. However, little is known about recombination between MPXVs and other OPVs during co-infection or superinfection in a host, and the role of recombination in MPXV infection biology and pathophysiology. In Nigeria and other monkeypox endemic regions of West and Central Africa, it is not known whether or not MPXV co-infected or superinfected the same human host with VARV during the smallpox pandemic. Did potential natural superinfection of VARV in human hosts already infected with MPXV contribute to the eradication of smallpox in West Africa and was there attenuation of smallpox in West Africa due to cross-protection elicited by pre-existing MPXV antibodies? However, the low incidence of MPXV infection, low human-to-human transmission, and the observation that MPX is an acute rather than persistent infection makes superinfection or co-infection with VARV unlikely. While these speculations cannot be examined experimentally due to ethical consideration and dual use risk [ 201 ], analysis of historical/retrospective samples by using next generation sequencing and proteomic technologies [ 202 , 203 ] will shed light on the role of co-infection/superinfection, recombination and preexisting MPXV antibodies to VARV and MPXV infection biology. These studies are essential to our understanding of the host and viral factors that modulate MPXV pathogenesis and its possible emergence as a VARV-like pathogen. There are reports of co-infection of MPXV and VZV (Varicella-Zoster virus) [ 72 , 93 , 136 , 204 , 205 , 206 ] and co-infection of MPXV and HIV [ 206 , 207 , 208 ]. Ogoina et al. hypothesized that the alteration (in co-infected patients) in MPXV natural history and course of infection could be related to HIV immunosuppression. Thus, more studies are warranted to test this claim especially in Nigeria where MPXV and HIV co-infection has been reported [ 207 ]. 5.3. Monkeypox Virus Infectome Global analysis of virus and host gene expression patterns in MPXV infected cells has been done both in cell cultures and animal models [ 96 , 116 , 198 , 209 , 210 ]. Transcriptomic [ 209 ], proteomic [ 211 ], and system kinomics [ 96 ] all show the down regulation of host anti-viral responses especially in the CB clade compared to the WA clade [ 96 , 198 , 209 ]. Studies also demonstrated functional redundancy of some genes in MPXV since immune evasion strategies against the host antiviral arsenal were elicited although MPXV has truncated version of those genes [ 212 , 213 ]. While there are data on virus and host genes expression patterns, information is still scanty on the functional implication of these gene expression profiles to virus infection biology and the molecular basis of MPXV pathogenicity. Most published work on MPXV infectome was done with MPXV Zaire and MPXV WRAIR7-61 strains. While this may have provided insight into the inter-clade specific variability with regard to the virus infection biology, it supplied no answers with respect to intra-clade specific variability. Thus, there is no basis to assume that MPXV WRAIR7-61 infection biology will be similar to that of Nigerian isolates just because they belong to the same WA clade. In this connection further infectome studies should deploy more isolates from the two major clades. This will provide a more holistic picture of the infection biology of MPXV and possibly define specie-specific antiviral strategies. 5.4. Antibody-Dependent Enhancement (ADE) of Infection Viral infection is reduced and neutralized by antiviral antibodies which are major component of the host immune response against viral infections, and ADE of infection occurs when these antibodies facilitate the replication and uptake of the virus into target cells and tissues. Kulkarni [ 214 ] hypothesized that antibodies elicited through vaccination may trigger ADE and increase the severity of the disease [ 214 , 215 , 216 , 217 ]. Although IgM and IgA antibodies alongside with their complement have penchant of ADE which has been observed in some viruses like Zika virus, Dengue virus and Ebola virus [ 214 , 217 ], none has been reported in MPXV cases. However, scenarios where humans, domesticated animals, and wildlife populations have pre-existing antibodies to MPXV or other naturally occurring OPVs and are then exposed to smallpox vaccine or natural superinfection with OPVs might conceivably enhance infectivity and change MPXV host range, tissue, and cell tropism Thus, examination of ADE in MPXV during natural and experimental infections will enhance our knowledge about the associated risk in using new generation smallpox vaccines, vaccine-induced antibodies, and antiviral immunoglobulins as therapy against MPX. 5.5. Conclusions The wane in herd immunity as a result of cessation of smallpox vaccination, increased contact between humans and potential MPXV animal reservoir hosts as a result of climate change and deforestation, bush meat consumption, and inadequate health and research infrastructure among others may have created an immunological and ecological niche for MPXV to re-emerge in Nigeria and other countries within the tropical rain forest belt. MPX is no longer confined to the endemic regions as travelers have exported MPX from Nigeria and Ghana to the USA, the UK, Israel, and Singapore in recent years. Therefore, MPXV is a very serious re-emerging pathogen with global outreach. To prevent MPXV from occupying the ecological niche vacated by VARV and possibly evolve to a much deadlier pathogen than it is at present, national and global research efforts should be intensified in order to identify virulence markers of disease, host and viral factors that modulate MPXV evolution, human behaviors that support zoonotic spillover events, surrogates for asymptomatic infection, as well as virus and host determinants of immunity. In Nigeria in particular MPXV epidemiological surveillance in humans and potential host species should be pre-emptive, that is, it should be conducted on a routine basis and not just in response to an outbreak. Fennoscandia [ 218 , 219 , 220 , 221 , 222 , 223 ] and Germany’s [ 6 , 224 , 225 , 226 ] extensive surveillance for CPXVs, a cousin of MPXV, can serve as a model for MPXV surveillance in Nigeria. A recent deployment and implementation of the Surveillance Outbreak Response Management and Analysis System (SORMAS) for MPX outbreak in Nigeria by NCDC [ 147 ] is a step in the right direction, and we advocate that routine, periodic epidemiological surveillance for MPXV in humans and animals should be integrated into SORMAS. Author Contributions E.A. reviewed literature, acquired and analyzed data, and drafted the manuscript; U.M. and G.N. helped in drafting the final version of the manuscript and revised it for improved intellectual content; M.I.O. conceived and designed the study, acquired and analyzed data, and drafted the manuscript. All authors have read and agreed to the published version of the manuscript. Funding This research received no external funding. The APC was funded by UIT—The Arctic University of Norway. Acknowledgments We thank Nigerian Center for Disease Control (NCDC) for making publicly available the epidemiological data reported in this paper. 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Map of Nigeria [ 148 ], reproduced with permission from the authors and Oxford University Press (Oxford, England). Figure 2. ( A ) Total MPXV cases across affected states in Nigeria, in 2017. ( B ) Human MPXV cases across Nigeria states, in 2019. Figure 2. ( A ) Total MPXV cases across affected states in Nigeria, in 2017. ( B ) Human MPXV cases across Nigeria states, in 2019. Figure 3. All human MPXV cases in Nigeria over the years. Figure 3. All human MPXV cases in Nigeria over the years. Figure 4. Maximum Likelihood (ML) phylogeny of orthopoxvirus genomes. Full-length genome sequences of 53 OPVs, including 23 MPXVs, were retrieved from The Virus Pathogen Database and Analysis Resource (ViPR) website [ 172 ]. The genomes were aligned with MAFFT version 7 [ 174 ]. The full-length genome alignment was stripped of gaps, and phylogenetic analysis was conducted, using Maximum Likelihood algorithm, as implemented in MEGA X [ 175 ]. Bootstrapping was set to 1000 replicates, and a General Time Reversal (GTR) model was used, as suggested by JModel test [ 181 ]. Figure 4. Maximum Likelihood (ML) phylogeny of orthopoxvirus genomes. Full-length genome sequences of 53 OPVs, including 23 MPXVs, were retrieved from The Virus Pathogen Database and Analysis Resource (ViPR) website [ 172 ]. The genomes were aligned with MAFFT version 7 [ 174 ]. The full-length genome alignment was stripped of gaps, and phylogenetic analysis was conducted, using Maximum Likelihood algorithm, as implemented in MEGA X [ 175 ]. Bootstrapping was set to 1000 replicates, and a General Time Reversal (GTR) model was used, as suggested by JModel test [ 181 ]. Table 1. Natural monkeypox virus (MPXV)-infected animals. Table 1. Natural monkeypox virus (MPXV)-infected animals. Geographic Location/Countries Method of Detection References Sooty mangabey monkey ( Cercocebus atys ) Côte d’Ivoire PCR [ 66 , 84 ] Gambian-pouched rat ( Cricetomys gambianus ) Africa PCR and viral isolation [ 85 , 86 , 87 , 88 , 89 ] Rhesus macaques ( Macaca mulatta ) Copenhagen Serological test [ 15 , 90 , 91 , 92 , 93 , 94 ] Cynomolgus Macaque ( Macaca fascicularis ) Singapore/Copenhagen Viral isolation [ 49 , 92 , 95 , 96 ] Asian Monkeys ( M. fascicularis ) Copenhagen Viral isolation [ 97 , 98 , 99 , 100 ] Southern opossum ( Didelphis marsupialis ) South America PCR and viral isolation [ 88 , 89 , 98 , 99 ] Sun squirrel ( Heliosciurus sp.) Zaire Antibody detection test [ 62 , 88 , 89 , 98 , 101 , 102 ] African hedgehogs ( Atelerix sp.) Africa PCR, antibody detection test, and viral isolation [ 81 ] Jerboas ( Jaculus sp.) Illinois, USA PCR, antibody detection test, and viral isolation [ 49 , 81 ] Woodchucks ( Marmota monax ) USA PCR and viral isolation [ 98 , 100 ] Shot-tailed opossum ( Monodelphis domestica ) USA PCR and viral isolation [ 98 , 100 ] Porcupines ( Atherurus africanus ) Zaire PCR and viral isolation [ 58 , 61 , 78 , 89 ] Giant anteaters ( Myrmecophaga tridactyla ) Rotterdam Viral isolation [ 103 ] Prairie dogs ( Cynomys spp.) USA PCR and viral isolation [ 33 , 81 , 99 , 104 , 105 , 106 ] Elephant shrew ( Petrodromus tetradactylus ) DR Congo Serological test [ 99 , 107 ] Domestic pig ( Sus scrofa ) DR Congo Serological test [ 99 , 108 ] Rope squirrel ( Funisciurus sp.) Zaire PCR and viral isolation [ 55 , 87 , 88 , 104 , 107 , 108 , 109 ] African dormice ( Graphiurus spp.) USA PCR and viral isolation [ 55 , 104 , 109 ]
https://www.mdpi.com/1999-4915/12/11/1257
Energies | Free Full-Text | Analytical Approach to Understanding the Effects of Implementing Fast-Frequency Response by Wind Turbines on the Short-Term Operation of Power Systems The significant presence of variable-speed wind turbines in worldwide power systems has led to planners and grid operators requiring them to participate in frequency control tasks. To address this demand, a large number of wind frequency control proposals have been reported in the literature in recent years. Many of these solutions have been tested by specific experiments carried out in computer simulation environments. This paper proposes a methodology to evaluate the effects of enabling frequency support by wind turbines on the magnitudes that characterize the inertial response of a power system by using an analytical approach. The derived formulation and the illustrations are designed to provide a better understanding of both the mechanisms that determine the frequency stability indices and the improvement achieved by enabling the inertial response of wind turbines by implementing a virtual inertia-based method on the active power controllers of these machines. To facilitate the comprehension of the results obtained, the analytical approach is complemented with time-domain simulations in a predefined test system implemented in MATLAB/Simulink®. The proposed methodology achieves a generalization of the results and can be used for the assessment of any power system configuration. Analytical Approach to Understanding the Effects of Implementing Fast-Frequency Response by Wind Turbines on the Short-Term Operation of Power Systems by Danny Ochoa 1,* and Sergio Martinez 2 1 Department of Electrical, Electronic and Telecommunication−DEET, Universidad de Cuenca, Cuenca 010203, Ecuador 2 Area of Electrical Engineering, Escuela Técnica Superior de Ingenieros Industriales, Universidad Politécnica de Madrid, 28006 Madrid, Spain * Author to whom correspondence should be addressed. Energies 2021 , 14 (12), 3660; https://doi.org/10.3390/en14123660 Received: 17 May 2021 / Revised: 11 June 2021 / Accepted: 16 June 2021 / Published: 19 June 2021 (This article belongs to the Topic Power System Modeling and Control ) Abstract . The proposed methodology achieves a generalization of the results and can be used for the assessment of any power system configuration. Keywords: load frequency control ; low-inertia power systems ; power system modeling ; virtual inertia ; wind power integration 1. Introduction The imminent depletion of fossil fuel reserves, the growing concern for the preservation of the environment and the constant increase in energy needs are some of the factors that have motivated the use of renewable energy sources for production of electrical energy in recent decades. From the various alternatives available for the use of non-conventional renewable energy resources, wind generation has been making its way in the electricity generation market, so that, nowadays, it presents a significant share of participation in the energy mix of many power systems in the world and a high level of technological maturity [ 1 , 2 ]. Among the factors that have motivated this trend in the use of this generation technology are: the cost of the energy produced, the annual availability of the resource, the efficiency in energy conversion, the geographical areas required for its exploitation and the flexibility to respond to the technical requirements of the grid operator. However, the variable nature of wind and the uncertainty associated with its prediction make wind generation management complex, compared to conventional electricity generation, making its integration into the grid somewhat difficult, even more so when the level of its participation becomes significant [ 3 , 4 ]. One of the main challenges the grid operator must deal with in its effort to guarantee the quality, stability and reliability standards of the system, is related to frequency control, a task that has traditionally been performed by spinning synchronous generation. When the power system begins to experience an important penetration level of wind generators, displacing synchronous ones, the inertial response that the remaining generators can provide could be seriously weakened [ 5 , 6 ]. This is because wind generators do not contribute to the equivalent inertia of the system, since their mode of operation differs from that of conventional synchronous generators. A variable speed-wind turbine varies its rotor speed, depending on the availability of the primary energy resource, with the aim of optimizing the efficiency in the conversion of wind energy into mechanical energy in its rotor [ 7 ]. Consequently, the rotor speed of this machine is decoupled from the grid frequency and, therefore, its inertial resources cannot be directly exploited by the power system in order to ensure an acceptable frequency stability level [ 8 ]. To address this concern, many researchers have investigated the Load Frequency Control (LFC) in high penetrated power systems in recent years. A decentralized model of LFC of interconnected power systems with a massive integration of wind generation with stochastic fluctuations is presented in [ 9 ]. In addition, research reported in [ 10 ] describes the application of genetic and fuzzy logic controller on LFC in a power system dominated by variable-speed wind turbines devised to enhance the system frequency response. In [ 11 ], an exhaustive literature review on the topic of LFC addressing its challenges and opportunities in conventional, modern and future power systems is presented. The apparition of unintentional electrical islands is another problem of interest in literature due to the massification of distributed generators, particularly in weak or isolated systems and microgrids. In networks with these characteristics, wind turbines controllers must be able to detect an off-grid operation and disconnect to avoid safety hazards and damage to the electrical infrastructure [ 12 , 13 ]. Nowadays, there are many methods of islanding detection that can be classified into three groups: passive, active, and communication-based [ 14 ]. An effective passive islanding detection algorithm for all types of distributed generators is designed in [ 15 ]. There, the measured frequency, voltage, and current are used by the proposal to successfully discriminate the islanding and non-islanding operating mode, as it is evidenced by simulation results on the IEEE 13-bus distribution system. Examples of active islanding detection methods are presented in [ 16 , 17 ], where an advanced method based on synchronized injection of small AC-signals and a control algorithm based on the observation and disturbance technique are proposed, respectively. Finally, ref [ 18 ] reports a communication-based islanding detection algorithm, where an intelligent micro-phasor measurement unit is leveraged for islanding detection. The design also includes a cyber-attack shield feature. In case of extreme frequency collapse caused by a severe instantaneous imbalance between generated and consumed power, under-frequency load shedding (UFLS) procedure is a commonly accepted solution to avoid a power outage. Examples of recently published scientific contributions on this topic are found in [ 19 , 20 ]. In [ 19 ], a novel UFLS-method for inverter-based microgrids by using droop-characteristics is proposed. This method is aimed at estimating the power deficit, in several shedding stages, without using a broad communication platform. In [ 20 ], the use of higher order polynomial curve fitting to predict the minimum frequency and the power deficit is proposed. This technique leads to obtaining an improved UFLS scheme, whose effectiveness is proved by simulation in a real power system. Now, getting into the research scope of this work, currently, there is considerable interest in addressing the technical challenges posed by the massive integration of wind turbines on the grid in terms of frequency support, evidenced in the publication of a significant number of works that present highly innovative proposals. For example, the following literature proposes different control techniques that implement an inertial response capability in a wind turbine similar to that offered by a conventional synchronous generator: a temporary frequency-support scheme designed to improve the frequency nadir while ensuring rapid frequency stabilization, particularly for high wind power penetration levels, is presented in [ 7 ]. The effectiveness of that proposal is evaluated in the IEEE-14 bus test system implemented in EMTP-RV simulator. A methodology for the analysis of frequency dynamics in large-scale power systems with a high level of wind energy penetration by means of a simplified model for wind generators and load frequency control-scheme is presented by the authors in [ 21 ]. In this work, an aggregated representation of the Spanish bulk system is used as a test bench in MATLAB/Simulink ® simulation tool. In addition, by using a similar approach to a previous work, a novel frequency sensitive-based virtual inertia control to extract the kinetic energy of the wind turbine and stored energy from the DC-link capacitor for short-term grid frequency regulation is proposed in [ 22 ]. There, the MATLAB/Simulink ® simulation results are complemented with hardware-in-the-loop simulations implemented in OPAL-RT software. An exhaustive assessment of the impact on the grid by wind power short-term frequency support by taking advantage of pitch angle de-loading [ 23 ], kinetic energy extraction [ 24 ], and wind turbine over-speeding is investigated [ 25 ]. A common aspect that characterizes all these research papers is the use of MATLAB/Simulink ® as a simulation tool, except for [ 25 ] which assessed the effectiveness of its proposal in the IEEE-39 bus system implemented in DIgSILENT/PowerFactory software. In all the works described here, very promising results are obtained that justify the participation of wind turbines in grid frequency control tasks. Conclusions from these works are based on both simulation and experimental tests under certain operating scenarios and controlled environments, designed to accurately evaluate the benefits of the proposed control strategies. To address the study of frequency stability issues in power systems, two main different approaches can be found in the literature: one based on the concept of load frequency control (LFC) [ 26 , 27 ], and the other based on detailed computational simulations, sometimes including hardware-in-the-loop [ 28 ], or real-time simulations [ 29 ]. Each approach has its capabilities and advantages, although one can complement the other [ 30 ]. The literature review presented here shows that there are innovative proposals that successfully address the problem of high-level penetration of wind generators when these participate in the frequency control tasks. Various computer simulation programs are used to evaluate the proposals on a test-bench designed for the purpose of applying different approaches regarding the detailed representation of the system under analysis. From this review, it has been found that: (1) none of these studies offers a detail of how the corrective actions of the frequency control support by wind generators might impact on the parameters that define the inertial characteristics of the system as a whole, and (2) the proposals for participation of wind generators in frequency control are evaluated on specific operating scenarios under controlled environments. In the first case, the cited papers conclusions are based on the final response of the system when the frequency control actions of the wind turbines are implemented. Although, in these results the reduction of frequency nadir and rate of change of frequency (RoCoF) when enabling frequency support by wind turbines is evident, it is not possible to identify which specific characteristic of the implemented frequency control strategy in wind turbines is responsible for improving both the equivalent inertia constant as the damping constant of the system. Finding this relationship would lead to a better understanding of the effect of the implementation of fast-frequency response by wind turbines on the short-term operation of the system. In the second case, the design, modeling, and simulation of a specific test-bench to evaluate the performance of the wind-frequency control strategies, provide a restricted vision of the problem, since it would be necessary to carry out as many simulations as so many scenarios need to be represented with different operating conditions (for example, various wind generation penetration levels and incoming wind speeds) in order to obtain more general results. These research gaps have motivated the development of our proposal, which consists of: The proposal of a methodology for deriving the LFC-transfer function of a weak and isolated power system that incorporates the participation of wind turbines in frequency control, which is based on the theory of small-signal analysis. With the derived LFC-transfer function, the authors design an analysis tool devised for studying the frequency response of the power system under contingency by considering all the possible scenarios characterized by different wind penetration levels and wind speed conditions. The numerical evaluation of the LFC-transfer function to get the main parameters that characterize the inertial response of the whole system, instead of implementing a specific test system in simulation, make it possible to represent a vast number of contingency scenarios without these having to run one at a time in the simulation environment. With the numerical results generated, an inertial chart is designed to show the locus of the values of the main frequency response parameters: frequency nadir and time-derivative of frequency as a function of the equivalent constant of inertia of the system. The resulting chart provides an outlook of the status of the frequency resilience of the system when wind generation is incorporated in substitution of the synchronous one. Based on the symbolic representation of the derived transfer function, this work proposes a method to identify which specific inertial parameters of the system (equivalent inertia constant or damping constant) the frequency response by wind turbines really impacts. This is done with the purpose of providing a comprehensive understanding of the corrective action provided by wind generation during its contribution to smoothing grid frequency fluctuations. This work is organized as follows: Section 2 presents the conceptual framework and the analytical approach to the problem of primary frequency control in a power system and introduces a case study. As an example of a frequency control strategy for wind turbines, Section 3 explains the theoretical foundation and mechanics of the extended optimized power point tracking (OPPT) method [ 21 ] to allow for a better understanding of Section 4 , which constitutes the main part of the work. Section 4 proposes a methodology for the assessment of the effects on the magnitudes that characterize the inertial response of the whole power system when wind turbines contribute to frequency support tasks. The application of the methodology is illustrated with the implementation of the OPPT method. In addition, the most relevant results are presented here and preliminary conclusions are established. Finally, Section 5 presents the lessons learned in this study. 2. Representation of a Power System for Primary Frequency Control Studies Figure 1 illustrates the typical time scale of different physical processes involved in the operation and control of a power system [ 31 , 32 , 33 , 34 ]. Since the most relevant magnitudes in a frequency control study, i.e., maximum frequency deviation, maximum rate of change of frequency, and frequency deviation in quasi-steady state, take place a few seconds after a disturbance appears, the modeling and analysis efforts used in this work are focused on the time range that characterizes the primary frequency control (see the highlighted time frame in the figure). Figure 1. Typical time ranges in which the phenomena involved in the operation and control of a power system take place. 2.1. Load Frequency Control Scheme Within the time frame of interest shown in Figure 1 , it is common practice to represent the dynamics of the power system using the LFC approach, in which the dynamics of the mechanical variables of the prime movers of conventional synchronous generation predominates over the dynamics of electromagnetic variables, whose time constants are significantly lower [ 35 , 36 ]. In addition, it can be verified in the same figure that the typical dynamics of the power converter interfacing the wind turbine to the grid is much faster than the mechanical dynamics of the wind turbine. From the perspective of the time frame of interest in this study, the practically instantaneous response of power converters usually leads to their dynamics being ignored in the analytical approach to modeling [ 33 , 37 ]. For that reason, this work focuses its efforts on modeling the power systems components within the time window shaded in Figure 1 . Figure 2 shows the typical representation of the LFC scheme for the case of n operating synchronous generators. The equivalent inertia constant of the synchronous machines is represented by H eq , and is calculated by means of Equation (1), where H i is the individual inertia constant of each generator and w i is the participation factor, defined as the ratio of the nominal capacity of each generation unit to a certain base power. The introduction of this factor in the scheme is very useful when there is a need to represent different levels of participation of different generation agents, both in demand coverage and frequency support. In Figure 2 , Δ P mi is the mechanical power deviation experienced by the speed control system of each generator in response to a deviation of its angular speed, which, for the time frame of interest, is common to all synchronous machines, Δ ω eq . It is worth noting that this simplification of a unique common frequency for the whole system drastically reduces the integration step in simulations and obtains analytical expressions for describing the dynamic behavior of the power system. The deviation of power demand in the system is denoted by Δ P L . Additionally, the damping constant of the supplied load is represented by D eq . R i is the droop of each speed controller, whose dynamics is modeled by a transfer function TC i ( s ). H e q = ∑ i = 1 n w i H i (1) Figure 2. Representation of power system dynamics using the LFC-scheme. To evaluate the frequency response of the system, Δ ω eq , in the event of a disturbance, Δ P L , the following transfer function is derived from Figure 2 : Δ ω e q ( s ) Δ P L ( s ) = − 1 2 H e q s + D e q + ∑ i = 1 n 1 R i T C i ( s ) ⏟ Δ P m w i (2) This equation represents the LFC-transfer function of the power system. 2.2. Case Study A case study for evaluating the effects of the frequency support provided by variable speed-wind turbines on the inertial response of a given power system for facing mismatches between generation and demand is presented in Figure 3 . It represents a power system (with a rated frequency of 50 Hz) dominated by thermal and wind generation within a frequency control area. This is a typical case of many island electric systems, in which the excursions of the frequency (either under normal conditions, due to intermittent injection of power from non-conventional renewable energy sources, or in contingency situations, due to the sudden loss of generation units or consumption centers) are very pronounced compared to a continental system [ 38 , 39 ]. In the example illustrated in Figure 3 , the thermal generation is represented by the linearized model of the prime mover of a steam turbine and its speed governor [ 35 ]. The input, Δ ω eq , is applied to a droop characteristic, R 1 , in order to generate signals to be applied to the first-order turbine model with time constant τ G (stage of admission of steam to the turbine). Then, the resulting signal is input to a block that represents the dynamics of each turbine stage: from high to lower pressure stages with contribution gain F HP and the time constants T HP , T RH , and T CH . More details of this tandem-compound configuration of the steam turbine can be consulted in [ 35 ]. Finally, the complete thermal generation model generates a control signal, Δ P m 1 , intended to compensate the power mismatch in the LFC-scheme. Figure 3. LFC scheme for the power system under study. In the same figure, a block can be seen implementing the mathematical model used to represent the dynamics of the wind generation (variable speed-wind turbine, VSWT) within the LFC scheme. This model, which can be consulted in detail in [ 40 ], outputs an active power deviation signal, Δ P g , according to the incoming wind speed v . By default, the wind turbine model dispatches its active power according to an optimal power conversion criterion, and it is not expected that it provides frequency support to the system in any case, unless a wind-frequency control feature is enabled. The latter is discussed extensively in Section 3 . The values of all the parameters of these two models are indicated in the Appendix A and Appendix B . In this example, the thermal unit has an inertia constant H 1 = 3.6 s and a participation factor w 1 = 0.8 (where the base power is the total generation capacity of the system). Accordingly, the participation of wind generation is 20% ( w WT = 0.2). It is also assumed that the wind speed is constant, v = 9.6 m/s, and that the active power of wind turbines is dispatched using the Maximum Power Point Tracking (MPPT) criterion. For the frequency control study, a contingency event characterized by a sudden load increase (for example, due to the loss of part of the operating generation) Δ P L = 1% is analyzed. This situation provokes a grid sub-frequency, through which it is possible to evaluate the inertial response of the system and the effectiveness of the frequency recovery tasks carried out by the synchronous generation. Figure 4 shows some results from simulations (with MATLAB/Simulink ® ) of the LFC scheme of Figure 3 under the operational situation previously described. It illustrates the time domain behavior of the following variables of interest: deviation of the mechanical power experienced by the primary mover of the synchronous generator, ∆ P m 1 , active power dispatched by the wind turbine, P g , frequency of the system, f s , and the absolute value of its time derivative, |ROCOF|. Figure 4. Response of the system to a sub-frequency event (base case). ( a ) Thermal power deviation, ( b ) wind power generation, ( c ) grid frequency, ( d ) absolute value of RoCoF. The simulation results show a typical behavior of these variables in response to a sudden power mismatch: the grid frequency (defined by the synchronous generator speed, Figure 4 c) suffers a decay that triggers the frequency recovery task, carried out by the speed controllers of thermal groups ( Figure 4 a), leading to a maximum deviation, Δ f max = 0.083 Hz, and eventually a new equilibrium point with a quasi-steady deviation Δ f qs = 0.03 Hz. Figure 4 d shows the evolution of the absolute value of the rate of change of frequency (RoCoF), where its maximum value is |ROCOF| max = 0.0837 Hz/s. Since the power injected into the grid by the wind turbine ( Figure 4 b) depends solely on the incident wind speed ( v = 9.6 m/s), which is assumed constant in this study, no response is expected, in terms of power, to contribute to the frequency recovery process. This situation highlights one of the challenges posed by the incorporation of wind power displacing conventional synchronous generation, as the latter is responsible for guaranteeing the frequency stability of the grid. To maintain the inertial characteristics of the system, wind turbines need to contribute to mitigating these negative effects by providing an effective inertial response. 2.3. Analytical Approach to the Problem The simple experiment carried out in the previous subsection has been designed to warn the reader about the need to involve non-synchronous generators (e.g., variable speed-wind turbines), whose integration in an electrical system implies a displacement of conventional synchronous generation that is detrimental to the equivalent inertial response of the system. In order to broaden the results obtained up to this point and to draw more general conclusions, this problem is now approached analytically, taking the transfer function of the previous power system as a starting point. This function is presented in Equation (3), obtained from the definition expressed in Equation (2) and particularized for the system outlined in Figure 3 . As it can be seen in the resulting expression, the response of the system frequency, Δ ω s , to a disturbance, Δ P L , is by no means conditioned by any parameter or variable related to the incorporated wind generation. This is because, as demonstrated in the previous example, the criterion with which variable speed-wind turbines deliver their active power makes a natural inertial response from this machine impossible. Therefore, it is to be expected that the higher the level of participation of these generators, the poorer the inertial response that the resulting conventional synchronous generation can provide to face power imbalances. Δ ω s ( s ) Δ P L ( s ) = − 1 2 w 1 H 1 ⏟ H e q s + D e q + 1 R 1 ( 1 1 + τ G s ) [ 1 + F H P T R H s ( 1 + T C H s ) ( 1 + T R H s ) ] w 1 (3) From the expression in Equation (3), it is possible to systematically analyze the frequency response of the system to a certain disturbance with different levels of participation of synchronous generation in frequency control tasks. For example, the response to a Δ P L = 0.01 pu step (as defined in Section 2.2 ) is evaluated below for all possible values of w 1 . The numerical calculation of the step response is focused on the evaluation of the following quantities: Peak value of the step response, max{Δ ω s ( t )}: for calculation of the maximum frequency deviation, Δ f max . Steady state value of the step response, lim t →∞ {Δ ω s ( t )}: for calculation of the quasi-steady state frequency deviation, Δ f qs . Maximum absolute value of d Δ ω s /dt : for calculation of |RoCoF| max . From this numerical procedure, the set of curves illustrated in Figure 5 is obtained, where the different participation factors, w 1 , are expressed in terms of the equivalent inertia constant, H eq , normalized for the base case ( w 1 = 0.8). In this example, 100 possible values of w 1 have been used to evaluate Equation (3), which means that the generated chart represents an equal number of simulated scenarios. In this chart, each simulation result is represented by one round marker placed over the corresponding curve. For this example, the chart contains a total of 300 numerical results (∆ f max , ∆ f qs , and |ROCOF| max ) for 100 simulated scenarios. If the user requires a chart with a higher resolution, a finer variation of the values of participation factors, w 1 , must be done. The inertial chart of Figure 5 allows for visualizing the effect of conventional synchronous generation displacement on the parameters that characterize the inertial response of the system within the time frame of interest. As a fact, the inertial characteristics of the system under study tend to degrade as operating synchronous generation is displaced. Therefore, non-synchronous generators should participate in the frequency recovery tasks in a similar way as the displaced conventional synchronous units did. In Figure 5 it can be seen that, for the base case (in which thermal generation is 80% of the total installed capacity), the numerical results obtained from evaluation of Equation (3) are very close to those achieved by simulation in Figure 4 . Figure 5. Effect of conventional synchronous generation displacement on the inertial response of the system. 3. Frequency Support Provided by Wind Generation 3.1. Method Based on the Concept of Virtual Inertia Making use of the significant amount of inertial resources available in a wind turbine, several works (e.g., [ 7 , 21 , 22 , 23 ]) address the issue of providing an effective inertial response from this machine, so that it participates in the grid frequency control. This is achieved through additional control loops that complement the main MPPT controllers of the wind turbine. These auxiliary control loops introduce additional active power set points, depending on the system requirements, as a function of the frequency deviation that may exist, thereby enabling an inertial response from the wind turbine. At this point, it must be taken into account that this inertial response would be forced, controlled, virtual, or synthetic, but energetically supported by a real physical property of the wind turbine: its natural inertia. To fulfill the central objective of this work, the virtual inertia control strategy proposed by the authors in [ 21 ], called the extended optimized power point tracking (OPPT) method, whose mechanics are explained below, has been considered. Generally, the active power dispatched by variable speed wind turbines follows a set point signal, P MPPT , which is applied to the corresponding control system implemented in the machine. Equation (4) shows the definition of this signal for the optimization zone, where: f Kopt is a multiplication factor (equal to unity, by default), K opt is the optimization constant of the turbine (which depends on aerodynamic and constructive characteristics of the rotor), and ω g is the shaft speed. If this expression is plotted on the P- ω plane of the wind turbine, taking into account the technical limits of the machine, the locus shown in Figure 6 (blue line) is obtained, known as the MPPT curve. P MPPT [ pu ] = f K o p t K o p t ω g [ pu ] 3 (4) Figure 6. Mechanics of the method based on virtual inertia control. The control function of the extended OPPT method is shown in Equation (5), where: ω g 0 is the rotor speed prior to the requirement of frequency support, k vir is a design constant of the method, W vir is a weighting factor, and H WT is the inertia constant of the wind turbine. This expression, derived in detail in [ 21 ], has two components that determine the magnitude of the wind inertial response sought: one dependent on the grid frequency deviation, Δ f s , and another dependent on the time derivative of frequency, df s /dt . f K o p t = ( ω g 0 [ pu ] ω g 0 [ pu ] + k v i r Δ f s [ pu ] ) 3 ⏟ ( a ) f 1 − W v i r K 0 K o p t ω g [ pu ] 3 f s [ pu ] d f s [ pu ] d t ⏟ ( b ) f 2 (5) where K 0 = 2 ω g 0 [ pu ] ω s 0 [ pu ] k v i r H WT [ s ] . To explain the inertia emulation process of the wind turbine achieved by implementing the extended OPPT method (whose implementation scheme in the active power control system of the wind turbine is illustrated in Figure 7 ), let us return to Figure 6 . Starting from the hypothesis that the wind turbine is driven by a constant wind speed ( v = 9.6 m/s), under normal operating conditions, the generator will deliver an active power P A , associated with a speed ω g 0 , according to the MPPT control. If, for example, the power system experiences an underfrequency event caused by a sudden decompensation between generated and consumed power, the presence of non-zero values of Δ f s and df s /dt in Equation (5) will cause the corresponding implementation scheme to start the inertial response emulation process by moving the MPPT curve upwards, in order to drive the operation of the wind turbine towards point B of its P- ω characteristics. Figure 7. Scheme of the virtual inertia control implemented in the wind turbine (the values assigned to the main parameters are given in the Appendix C ). At this point, the value adopted by P B will depend on the severity of the frequency event, measured in terms of the magnitude of Δ f s and df s /dt . Under this operational situation, the value of the active power extracted from the electric generator will exceed the value of the mechanical power delivered by the turbine, causing an internal power imbalance, which will lead to the deceleration of the rotating masses of the wind turbine. This use of kinetic energy, seen as a decrease in the speed of the turbine-generator set, moves the operating point from B to C, following the path imposed by the MPPT curve shifted to the left. At point C, the active power produced by the generator, P C , equals again the mechanical power given by the turbine, at a new equilibrium condition. The excursion of the active power of the wind turbine along the path A→B→C makes its contribution to the frequency support of the system feasible. Once this support is finished, the method forces the turbine to recover an optimal operating condition (point A), thus preparing it to meet future requirements. Similarly, in case of an over-frequency event in the system, the inertial support provided by the turbine will follow the path A→D→E→A by shifting the MPPT curve downwards. 3.2. Evaluation of the Inertial Response Provided by the Wind Turbines in the Study System Figure 8 shows the simulation results of implementing the scheme of Figure 7 in the wind turbines that integrate the power system under study. The benefits of using the kinetic energy available in a wind turbine to contribute to the grid frequency support can be appreciated. First, the inertial response of wind generation to the frequency drop ( Figure 8 b) makes the mechanical power control action from thermal generation somewhat smoother and of a lower magnitude ( Figure 8 a). The combined control action of wind and thermal generation in frequency support gives, in this case, a 24% reduction of the maximum frequency deviation, compared to the base case ( Figure 8 c). Additionally, a 19% reduction in the maximum magnitude of RoCoF is obtained ( Figure 8 d). Here, it is important to note that the results presented are due to a particular wind generation situation. The effectiveness of the virtual inertia algorithm (extended OPPT-method) in reducing Δ f max and |RoCoF| max will depend, on the one hand, on the magnitude of the disturbance (measured in terms of the state of Δ f s and df s /dt ), and on the other hand, on the level of kinetic energy stored in the machine before the request for the frequency support service (see the influence of the term ω g 0 in Equation (5)). Since the shaft speed, ω g 0 , is determined by pre-existing wind conditions, a more general analysis is required. This is discussed in detail in the next section. Figure 8. System response to a sub-frequency event considering the inertial support provided by wind generation. ( a ) Thermal power deviation, ( b ) wind power generation, ( c ) grid frequency, ( d ) absolute value of RoCoF. 4. Effect of the Frequency Support from Wind Turbines on the Inertial Characteristics of the System 4.1. Linearization of the Extended OPPT Method In order to study the effects that frequency support from wind generation has on the inertial characteristics of the system, similar to the analysis presented in Section 2.3 , it is necessary to include the particular control function of the frequency control method used, in this case the extended OPPT one in Equation (5), in the transfer function of Equation (3) that defines the dynamics of the system within the time frame of interest to this work. To get a rational transfer function, in the first place, it is necessary to carry out a linearization process. Considering the term dependent on Δ f s in Equation (5): f 1 = ( ω g 0 [ pu ] ω g 0 [ pu ] + k v i r Δ f s [ pu ] ) 3 (6) Since, in frequency stability studies, small disturbances are considered (that is, Δ f s ≈ 0), it is possible to linearize the previous expression as follows: f 1 ( x ) ≈ f 1 ( 0 ) + d f 1 ( 0 ) d x x f 1 ( Δ f s ) ≈ 1 − 3 k v i r ω g 0 [ pu ] Δ f s [ pu ] (7) Then, as explained in Section 3.1 , an increase in the active power dispatched by the wind turbine, by shifting the MPPT curve upwards (from point A to point B in Figure 6 ), can be formulated as follows: Δ P g [ pu ] = P B − P A = f 1 K o p t ω g 0 [ pu ] 3 − K o p t ω g 0 [ pu ] 3 (8) By substituting Equation (7) in Equation (8), and making Δ f s [pu] = Δ ω s [pu] : Δ P g [ pu ] ( 1 ) = − 3 k v i r K o p t ω g 0 [ pu ] 2 Δ ω s [ pu ] (9) Now, the term dependent on df s /dt in Equation (5) is obtained from the definition in [ 21 ]: Δ P g [ pu ] = − d d t E WT = − K 0 ω s [ pu ] d ω s [ pu ] d t (10) With some algebra in Equation (10) and expressing ω s in terms of its deviation from the nominal value ω s 0 : Δ P g [ pu ] = − 1 2 K 0 d ω s [ pu ] 2 d t = − 1 2 K 0 d ( Δ ω s [ pu ] + ω s 0 [ pu ] ) 2 d t (11) Considering small disturbances (Δ ω s ≈ 0): Δ ω s 2 < < 2 Δ ω s ω s 0 , and the previous equation can be reduced to: Δ P g [ pu ] ( 2 ) = − K 0 ω s 0 [ pu ] d Δ ω s [ pu ] d t (12) Then, adding Equations (9) and (12) to obtain the control function of the linearized extended OPPT method and taking into account the weighting factor of the frequency derivative dependent term, W vir , in the Laplace domain: Δ P g [ pu ] = − 3 k v i r K o p t ω g 0 2 ⏟ α Δ ω s − W v i r K 0 ω s 0 ⏟ β s Δ ω s (13) Or, in compact form: Δ P g [ pu ] = − ( α + β s ) Δ ω s [ pu ] (14) Next, in order to evaluate the numerical accuracy of the linearization process with respect to the control method outlined in Figure 7 and implemented on the diagram in Figure 3 , the control function in Equation (14) is included in the transfer function of the power system in Equation (3), finally being: Δ ω s ( s ) Δ P L ( s ) = − 1 2 w 1 H 1 ⏟ H e q s + D e q + 1 R 1 ( 1 1 + τ G s ) [ 1 + F H P T R H s ( 1 + T C H s ) ( 1 + T R H s ) ] w 1 ⏟ Synchronous generation speed governor + ( α ′ + β ′ s ) w WT ⏟ Wind turbine frequency control ( extended OPPT - method ) (15) where: α ′ = α ( s 1 / T w o + s ) ⏟ Δ f s dependent loop high - pass filter and β ′ = β ( 1 1 + T l p s ) ⏟ d f s / d t dependent loop low - pass filter . At this point, it is essential to discuss the scalability and the complexity of the developed model in larger power systems with their generation units disaggregated. In order to obtain a general equation for implementing the proposal on a multimachine power system, let us take the complete transfer function in Equation (15) and pay particular attention to the denominator terms. The contribution to the grid-frequency support from synchronous generator and wind turbine, SG 1 ( s ) and WT 1 ( s ) terms, respectively, can be extracted from Equation (15) and defined as follows: S G 1 ( s ) = 2 w 1 H 1 s + D e q + 1 R 1 ( 1 1 + τ G s ) [ 1 + F H P T R H s ( 1 + T C H s ) ( 1 + T R H s ) ] w 1 (16) W T 1 ( s ) = ( α ′ + β ′ s ) w WT (17) According to the representation of the LFC-scheme for a multimachine power system illustrated in Figure 2 , and expressed in Equations (1) and (2), the denominator term corresponding to the synchronous generation speed governor model and its inertia in Equation (16) can be extended to the case of n -synchronous generation units, as below: S G ( s ) = 2 ∑ i = 1 n w i H i s ⏟ H e q + D e q + ∑ i = 1 n 1 R i T C i ( s ) ⏟ Δ P m w i (18) where, H i , R i , w i and TC i are the parameters and functions of the i th synchronous generator unit (similar to those introduced in Section 2.1 ). Now, if we consider the denominator term corresponding to the wind turbine equipped with a frequency control characteristic (extended OPPT-method, in this study), as in Equation (17), it can be extended to the case of N -wind turbines as: W T ( s ) = ∑ i = 1 N ( α ′ i + β ′ i s ) w WT i (19) where, α’ i , β’ i , and w WT i are functions and parameters of the i th wind turbine that incorporates a frequency response characteristic. Note that, according to the definition of α and β in Equation (13), α i and β i will depend on the pre-disturbance rotor speed ω g 0 i , which is a function of the incoming wind speed to the i th wind turbine, v i (see Appendix D ). If the user is interested in disabling the participation of a specific wind turbine in frequency support, it is enough to make the corresponding functions α’ i and β’ i equal to zero. Finally, the general form of the transfer function for the implementation of the proposed method in case of multimachine power systems is: Δ ω s ( s ) Δ P L ( s ) = − 1 S G ( s ) + W T ( s ) = − 1 2 ∑ i = 1 n w i H i s ⏟ n − synchronous generators + D e q + ∑ i = 1 n 1 R i T C i ( s ) w i ⏟ n − synchronous generators + ∑ i = 1 N ( α ′ i + β ′ i s ) w WT i ⏟ N − wind turbines (20) Now, returning to our case of study, note that, in Equation (15), the transfer functions of the high pass and low pass filters (from the Δ f s and df s /dt dependent loops of Figure 7 ) have been included. The final form of this transfer function is the one that was sought to fulfill the main objective of this research. Finally, the control action of the extended OPPT method can be expressed as follows: Δ P g [ pu ] = − ( α ′ + β ′ s ) Δ ω s [ pu ] = Δ P f 1 [ pu ] + Δ P f 2 [ pu ] (21) It is important to note that, since the linearized model, which represents the inertial response by the wind generation, that has been incorporated into the transfer function of the power system Equation (15) does not take into account the dynamics of the wind turbine’s mechanical system, its accuracy will be limited to a time window of the order of the wind turbine’s natural inertia constant, H WT (which for the model considered, corresponds to a value of 5.29 s). This can be verified in Figure 9 , where the inertial response offered by the wind turbine for the studied contingency scenario (∆ P L = 1%) has been plotted using two approaches: the exact one, by implementing Equation (5) in the electromechanical model of the wind turbine ( Figure 3 ), and the linearized one, by means of the direct application of Equation (21) in the LFC-transfer function of the power system (Equation (15)). The values for the numerical evaluation of Equation (21) can be found in the Appendix B , Appendix C and Appendix D . Figure 9. Inertial response provided by wind generation: exact formulation vs. linearized formulation. ( a ) Wind power generation, ( b ) numerical error. Note that the error when using the linearized approach does not exceed 0.4% in any case. This is reflected in the high numerical accuracy of the results in terms of frequency and its derivative ( Figure 10 ) within the time frame of interest. Figure 10. Comparison of results: exact formulation vs. linearized formulation. ( a ) Grid frequency, ( b ) absolute value of RoCoF. 4.2. Evaluation of the Effect of Wind Generation Contribution to Frequency Support on the Inertial Characteristics of the System After evaluating the numerical accuracy of the approximate approach, this section follows a procedure similar to that described in Section 2.3 (which led to the results of Figure 5 ) to evaluate the transfer function in Equation (15), considering the same contingency event for different incident wind conditions and different values of the participation factor, w 1 . As a result, the inertial charts in Figure 11 are obtained, which show the effect of the displacement of the spinning synchronous generation on the Δ f max and |RoCoF| max indicators when the contribution of wind generators to frequency support is enabled. Since 100 different values of w 1 were assigned, each of the curves represents 100 simulated scenarios. This figure shows the corrective action of wind turbines if the extended OPPT method is implemented. The participation of these generation units in the frequency recovery contributes to reducing the level of degradation of the inertial characteristics of the system as a whole, the benefit being much more pronounced, the higher the wind speed is. The fact that the increase in wind generation penetration has the effect of shifting the curves upwards means that the contribution of wind generators to frequency support makes their integration (displacing synchronous generators) less harmful, in terms of the parameters of interest: Δ f max and |RoCoF| max . Figure 11. Effect of synchronous generation displacement on the inertial response of the system considering the participation of wind generation in frequency control. ( a ) Maximum frequency deviation, ( b ) maximum absolute value of RoCoF. To better understand the corrective effect that the implementation of the wind turbine frequency control strategy has on the inertial response of the system, one can take a look at the denominator of the transfer function in Equation (15). By regrouping terms, it is possible to write the following expressions: 2 H T s = ( 2 H e q + β ′ w WT ) s (22) D T = D e q + α ′ w WT (23) From Equations (22) and (23) it is inferred that the loop of the extended OPPT method dependent on df s /dt directly influences the equivalent inertia constant of the system, H T (influence of the term β ’), whereas the loop dependent on Δ f s affects the equivalent damping constant of the system, D T (effect of the term α ’). Therefore, when the extended OPPT control scheme starts operating during the frequency event, it forces the wind turbine to produce variations in the active power injected into the grid, in such a way that the system perceives a variation in its H T and D T parameters, although temporarily and while the control action implemented in the wind turbine lasts. To provide a notion of this phenomenon in the time domain, the case study presented in Section 3.2 will be considered again. According to Equation (21), the dynamics of coefficients α ’ and β ’ can be calculated by using Equations (24) and (25), respectively, using the numerical results obtained when evaluating Equation (15). α ′ = − Δ P f 1 Δ ω s (24) β ′ = − Δ P f 2 s Δ ω s (25) Finally, by replacing the results of this calculation in expressions Equations (22) and (23), it is possible to obtain the dynamics of H T and D T ( Figure 12 ), whose precision, once again, is limited to the time interval covered by H WT (the unshaded time window). Note in this figure that the participation of wind generation in the frequency support of the system has an amplifying effect of the synchronous equivalent constant of inertia of the system, H T , even as to double the pre-disturbance value at a specific moment. Theoretically, it is expected that, once the wind power participation has ended, H T will stabilize at a new value, defined only by the spinning synchronous generation. Figure 12. Influence of the inertia emulation of wind generation on the parameters that define the equivalent inertial response of the system. ( a ) Equivalent inertia constant, ( b ) load damping constant. The main effect of the transient increase of H T on the inertial characteristics of the system is the reduction of |RoCoF| max with respect to the base case, as already shown in Figure 8 d and Figure 11 b. Something similar happens with the dynamics of D T . The implemented virtual inertia method introduces a sudden and significant increase in the equivalent damping constant of the load, a fact that contributes to the reduction of the Δ f max ( Figure 8 c and Figure 11 a). In this case, the tendency of D T to recover its original D eq value, as the wind turbine contribution to frequency control ends, is evident. 5. Conclusions This paper proposes a methodology for the analysis of the effects of the contribution of wind generation to frequency control tasks on the inertial characteristics of power systems. This problem is approached from an analytical perspective through the study of the transfer function that represents the dynamics of the system frequency in response to power disturbances in the primary frequency control stage. This analytical approach allows the researcher to go from implementing a specific test system in a time-domain simulation to directly studying the results generated by the numerical evaluation of the wind-penetrated power system transfer function, in order to get the main parameters that characterize the inertial response of the whole system. In this way, it is possible to represent a vast number of contingency scenarios without these having to be run one at a time in the simulation environment, as has been a common practice in the literature. With these results, an inertial chart that represents the locus of the frequency nadir and its maximum time derivative, as a function of the wind-penetration level and the incoming wind speed, is constructed to show the improvement of the frequency recovery capability of the whole system offered by the participation of the wind generation in the frequency control task. As seen by the example plotted in Figure 11 , 100 possible scenarios of wind generation penetration in the system were represented, each one evaluated for five different wind conditions and one base case (600 scenarios to quantify the frequency nadir and 600 to evaluate RoCoF; 1200 numerical results in total). These results were generated by the proposed analysis tool in a single run. Furthermore, with the symbolic form of the derived transfer function it is possible to identify the influence of implementing virtual inertia in wind turbines on the equivalent system inertia constant and load damping constant (Equations (22) and (23)). Both parameters are decisive in characterizing the equivalent inertial response of the power system as a whole, measured in terms of the maximum frequency deviation and its maximum rate of change. In the particular case used as an example illustrating the proposed methodology, the results of this analysis ( Figure 12 ) show the benefits achieved by promoting the participation of wind generators in this task for the operation and control of a power system, reducing the negative impact of their massive integration in terms of an adequate frequency response to power imbalances: on the one hand, the equivalent constant of inertia of the system is transiently boosted ( Figure 12 a), passing from the pre-disturbance value 2.88 s to 5.22 s in the fast-frequency response stage. This improvement of the inertial characteristics caused by wind generation leads to a decrease in the frequency nadir by about 24% to the base case ( Figure 8 c). On the other hand, with the participation of wind turbine in the frequency control tasks, the instantaneous load damping constant is rapidly increased after the disturbance appears, passing from a steady-state value of 0.5 pu to 2.368 pu ( Figure 12 b). This effect explains the mitigation of the frequency change rate ( Figure 8 d), where the maximum absolute value of RoCoF reduces by about 19% if it is compared with the base case. Without Equations (22) and (23), derived through the proposed methodology, it would have been complicated to identify the influence of the fast-frequency response from wind turbines on the system parameters H eq and D eq . This application justifies the benefits of the analytical approach used for the design of the proposal. It also constitutes an analytical tool that allows for obtaining general conclusions and having a first vision about the behavior of the system under contingency and how different control parameters affect this behavior. For example, it can be used as a tuning tool for the virtual inertia controllers of wind turbines. It can also be used to understand the interactions with other elements connected to the network through power electronics. Of course, it is a high-level analysis that needs to be complemented with detailed studies for each specific case. Finally, it is important to note that the spirit of this paper is to present to the scientific community the formulation and benefits of the proposed methodology. Thus, in order to achieve a final model that can be run with a low computational burden without punishing the numerical accuracy of the tool, some simplifications have been introduced: use of linearized models of the speed-governor of the synchronous generation, linearization of the frequency control characteristic of wind turbines, disregard of the dynamics of wind turbine power converters and non-linearities, among others. All these practices are well justified in the literature, and they have been indicated in the corresponding part of the article’s body. Author Contributions D.O.: conceptualization, methodology, software, validation, investigation, resources, data curation, writing—original draft, writing—review and editing, visualization, funding acquisition. S.M.: conceptualization, methodology, validation, resources, writing—review and editing, supervision, project administration, funding acquisition. All authors have read and agreed to the published version of the manuscript. Funding This work was supported by the Secretaría de Educación Superior, Ciencia, Tecnología e Innovación (SENESCYT), Government of the Republic of Ecuador [grant number 2015-AR6C5141] and by the Spanish National Research Agency Agencia Estatal de Investigación [grant number PID2019-108966RB-I00/AEI/10.13039/501100011033]. Conflicts of Interest The authors declare no conflict of interest. Nomenclature LFC Load frequency control f Kopt Virtual inertia multiplication factor Appendix A Parameters of the steam turbine model [ 35 ]: R 1 = 5%, τ G = 0.2 s, F HP = 0.3, T RH = 5 s, T CH = 0.3 s. Appendix B Parameters of the wind turbine model [ 21 ]: Rated power (base power): P base = 1.5 MW. Wind speed base ( P vbase = 0.73 pu): v base = 12 m/s. Optimization constant: K opt = 0.4225. Turbine-generator inertia constant: H WT = 5.29 s. Pitch controller gains: K Ppc = 500, K Ipc = 0. Speed controller gains: K Psc = 3, K Isc = 80. Appendix C Parameters of the frequency control scheme of the wind turbine: K opt = 0.4225, k vir = 8, W vir = 0.2, T wo = 10 s, T lp = 100 ms. 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Effect of conventional synchronous generation displacement on the inertial response of the system. Figure 6. Mechanics of the method based on virtual inertia control. Figure 7. Scheme of the virtual inertia control implemented in the wind turbine (the values assigned to the main parameters are given in the Appendix C ). Figure 8. System response to a sub-frequency event considering the inertial support provided by wind generation. ( a ) Thermal power deviation, ( b ) wind power generation, ( c ) grid frequency, ( d ) absolute value of RoCoF. Figure 9. Inertial response provided by wind generation: exact formulation vs. linearized formulation. ( a ) Wind power generation, ( b ) numerical error. Figure 10. Comparison of results: exact formulation vs. linearized formulation. ( a ) Grid frequency, ( b ) absolute value of RoCoF. Figure 11. Effect of synchronous generation displacement on the inertial response of the system considering the participation of wind generation in frequency control. ( a ) Maximum frequency deviation, ( b ) maximum absolute value of RoCoF. Figure 12. Influence of the inertia emulation of wind generation on the parameters that define the equivalent inertial response of the system. ( a ) Equivalent inertia constant, ( b ) load damping constant. MDPI and ACS Style Ochoa, D.; Martinez, S. Analytical Approach to Understanding the Effects of Implementing Fast-Frequency Response by Wind Turbines on the Short-Term Operation of Power Systems. Energies 2021, 14, 3660. https://doi.org/10.3390/en14123660 AMA Style Ochoa D, Martinez S. Analytical Approach to Understanding the Effects of Implementing Fast-Frequency Response by Wind Turbines on the Short-Term Operation of Power Systems. Energies. 2021; 14(12):3660. https://doi.org/10.3390/en14123660 Chicago/Turabian Style Ochoa, Danny, and Sergio Martinez. 2021. "Analytical Approach to Understanding the Effects of Implementing Fast-Frequency Response by Wind Turbines on the Short-Term Operation of Power Systems" Energies14, no. 12: 3660. https://doi.org/10.3390/en14123660
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IJERPH | Free Full-Text | Prevalence of Self-Reported Food Allergies and Their Association with Other Health Conditions among Adults in Saudi Arabia Food allergies are a potentially life-threatening health issue, and few studies have determined their prevalence throughout Saudi Arabia. The main objective of our study was to estimate the prevalence and distribution of self-reported food allergies, and explore their association with other health conditions among adults in Saudi Arabia. This study was a nationwide cross-sectional survey conducted via phone interviews in June 2020. A proportional quota-sampling technique was used to obtain equal distributions of participants by age and gender across the 13 regions of Saudi Arabia. Self-reported food allergy, height, weight, health conditions, mental health status, and demographic variables were collected. Of the 6239 participants contacted, 4709 (75.48%) participants responded and completed the interview. Furthermore, 50.1% of the participants were female, with a mean age of 36.4 & plusmn; 13.5 years (18& ndash;90 years). The prevalence of food allergies was 19.7%. The most self-reported food allergies were egg, shellfish and shrimp, and peanuts, with a prevalence of 3.7%, 3.1%, and 3.0%, respectively. There was an association between the presence of food allergies and reported bariatric surgery, asthma, colon disease, and being at risk of depression. Bariatric surgery was significantly associated with lower likelihood of self-reported allergy (OR 1.69, 95% CI 1.22& ndash;2.34, p = 0.002). This study revealed, for the first time, a high prevalence of self-reported food allergies among adults in Saudi Arabia in a large nationwide sample, and food allergy association with bariatric surgery, asthma, colon disease, and being at risk of depression. This information is valuable for clinicians and policymakers, particularly in terms of food allergen labeling. Prevalence of Self-Reported Food Allergies and Their Association with Other Health Conditions among Adults in Saudi Arabia Mada H. Basyouni 1,2 , Norah AlMousa 3 , Nasser F. BinDhim 1,5,6 and Saleh A. Alqahtani 7,8 1 Sharik Association for Health Research, Riyadh 13326, Saudi Arabia 2 Ministry of Health, Riyadh 11176, Saudi Arabia 3 Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia 4 King Faisal University, AlAhsa 31982, Saudi Arabia 5 College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia 6 Saudi Food and Drug Authority, Riyadh 13513, Saudi Arabia 7 Liver Transplant Centre, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia 8 Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD 21218, USA Author to whom correspondence should be addressed. Int. J. Environ. Res. Public Health 2021 , 18 (1), 347; https://doi.org/10.3390/ijerph18010347 Abstract : Food allergies are a potentially life-threatening health issue, and few studies have determined their prevalence throughout Saudi Arabia. The main objective of our study was to estimate the prevalence and distribution of self-reported food allergies, and explore their association with other health conditions among adults in Saudi Arabia. This study was a nationwide cross-sectional survey conducted via phone interviews in June 2020. A proportional quota-sampling technique was used to obtain equal distributions of participants by age and gender across the 13 regions of Saudi Arabia. Self-reported food allergy, height, weight, health conditions, mental health status, and demographic variables were collected. Of the 6239 participants contacted, 4709 (75.48%) participants responded and completed the interview. Furthermore, 50.1% of the participants were female, with a mean age of 36.4 ± 13.5 years (18–90 years). The prevalence of food allergies was 19.7%. The most self-reported food allergies were egg, shellfish and shrimp, and peanuts, with a prevalence of 3.7%, 3.1%, and 3.0%, respectively. There was an association between the presence of food allergies and reported bariatric surgery, asthma, colon disease, and being at risk of depression. Bariatric surgery was significantly associated with lower likelihood of self-reported allergy (OR 1.69, 95% CI 1.22–2.34, p = 0.002). This study revealed, for the first time, a high prevalence of self-reported food allergies among adults in Saudi Arabia in a large nationwide sample, and food allergy association with bariatric surgery, asthma, colon disease, and being at risk of depression. This information is valuable for clinicians and policymakers, particularly in terms of food allergen labeling. Keywords: Saudi Arabia ; food allergy ; allergens ; prevalence ; risk factors 1. Introduction Food allergies are an “adverse health event arising from a specific immune response that occurs reproducibly on exposure to a given food” [ 1 , 2 ]. Depending on the severity of the food allergy, reactions to foods can range from tingling or itching in the mouth, to severe and possibly life-threatening allergic reactions called anaphylaxis [ 3 ]. The severity of food reactions depends on the amount of ingested food, its stability against digestion, and epithelial permeability [ 4 ]. Family history, age, asthma, and having other food allergies are risk factors for having allergic reactions to certain types of food [ 3 ]. The most common foods which can be eaten separately or included as an ingredient, even in trace amounts, that elicit hypersensitivity reactions are milk, eggs, wheat, fish, and nuts [ 5 ]. In general, 90% of food allergies are to milk, peanuts, wheat, fish, tree nuts, shellfish and shrimp, soy, and eggs [ 6 ]. However, food allergens and prevalence of food allergies are known to vary regionally [ 7 ]. There is convincing evidence that food allergy prevalence is increasing across the world [ 8 ]. In fact, research suggests that rates of emergency department visits related to food allergies is increasing among children and young adults [ 9 , 10 , 11 ]. However, in a survey of 83 World Allergy Organization member countries and six non-member countries, more than half (52 out of 89) had no data on food allergy prevalence [ 8 ]. Many of these studies examined the prevalence of food allergies among children or patients, with far fewer focused on the prevalence of food allergies among adults or in community settings [ 8 ]. In Saudi Arabia, most studies have been conducted among children, patients, students, or in specific regions [ 12 , 13 , 14 , 15 , 16 , 17 ]. For instance, a study that was carried out at allergy clinics on 103 patients (79% children) found that prevalence of food allergies was 1.5%, among those 14 years and older and 6% among pediatric patients [ 12 ]. Another study of university students found diagnosed food allergies in 9.6% of the 5497 participants [ 17 ]. However, they found that there was a lack of public understanding of food allergy diagnoses and management in Saudi Arabia [ 16 ]. Thus, poor food labeling and lack of awareness are among the major challenges related to food allergy management [ 2 ]. To our knowledge, there have been no nationwide studies investigating the prevalence of food allergies among adults in Saudi Arabia in a community setting. Thus, this study aims to examine the prevalence of self-reported food allergies and specific food allergens among adults in Saudi Arabia, and to explore the association between the presence of food allergies and comorbidities, mental health status, and demographic characteristics. 2. Method 2.1. Study Design For this study, we conducted a nationwide cross-sectional survey in Saudi Arabia by phone interviews in June 2020. 2.2. Sampling and Sample Size A proportional quota sampling technique was employed to acquire an equal distribution of participants in terms of age and gender across the 13 regions of Saudi Arabia (Riyadh, Macca, Eastern Province, Asir, Baha, Jazan, Najran, Madinah, Qassim, Hail, Tabuk, Northern Border, and Al-Jouf). Two age groups based on the median age of Saudi Arabian adults (36 years) were used, leading to a quota of 52. The required sample size was calculated based on a medium effect size of approximately 0.25, with 80% power and 95% CI, to compare the age and gender across regions [ 18 ]. Thus, each quota required 90 participants, and the total targeted sample size for this study was 4680 participants. The QPlatform ® data collection system, which has integrated eligibility and sampling modules, was used to control the sample distribution [ 19 ]. The eligibility module included three questions to determine the adherence to the sampling quota, on age, gender, and region. 2.3. Participant Recruitment Participant recruitment was limited to Arabic-speaking adult (≥18 years old) Saudi residents. A random phone number list was generated from the Sharik Association for Health Research to identify potential participants [ 20 ]. The Sharik database comprises individuals who are interested in participating in research projects. The database contains more than 70,000 individuals distributed across the 13 regions of Saudi Arabia and continues to grow [ 20 ]. Potential participants were contacted by phone on up to three occasions. If there was no response, a new number with similar demographics was generated from the database. After obtaining consent to participate, the interviewer assessed the eligibility, based on the above-mentioned quota completion criteria. Once the quota was complete, it was closed automatically. 2.4. Survey and Outcome Measures Demographic information (age, gender, education level, and region) was captured in the survey. Health conditions were assessed by asking the participants, “Have you ever been diagnosed by a doctor with any of the following chronic conditions?” The conditions included were hypertension, diabetes, hypercholesterolemia, asthma, colon disease, arthritis, sleep apnea, heart disease, cancer, kidney disease, liver disease, thyroid disease, celiac disease, and gastric ulcer. The answer was validated by asking whether the participants were currently taking any medication, or under treatment for the same condition. Food allergies were assessed by asking participants if they were allergic to any of the eight most common food allergens; participants were also able to report allergies to other foods, if applicable. BMI was calculated from self-reported height and weight. BMI was categorized into four groups: underweight (<18.5 kg/m 2 ), normal weight (18.5 to 24.9 kg/m 2 ), overweight (25 to 29.9 kg/m 2 ), and obese (≥30 kg/m 2 ). The Patient Health Questionnaire (PHQ-9), a mental health screening tool, was used. The PHQ-9 is well validated and has been used for mental health screening in various national surveys in Saudi Arabia [ 21 , 22 ]. After the first draft of the survey was finalized, a linguistic validation to ensure clarity and understanding of questions was conducted via a focus group, where members were asked to discuss and answer the survey. According to the results of the focus group and feedback from the researchers and interviewers, the questionnaire was further edited, and a final version was produced. 2.5. Primary Outcomes of Interest 1. Prevalence of food allergies in the sample of Saudi Arabian adults. 2. Associations between self-reported food allergy, demographics, and health-related conditions. 2.6. Ethical Considerations The ethics committee of Sharik Association for Health Research approved this research project (Approval no. 2020-3), in accordance with national research ethics regulations. Participant consent was obtained verbally during the phone interview with the participants and recorded in the data collection system; no call recording took place in this study. 2.7. Data Analysis Descriptive analysis was used to describe the variables. Prevalence results were weighted to equal the adult population in Saudi Arabia, according to the General Authority of Statistics 2017 Census Report [ 23 ]. Bivariate analysis (chi-square) was used to compare categorical data. Significant associations were then included in a logistic regression model controlling for age and gender. 3. Results 3.1. Demographics and Response Rate Of the 6239 participants contacted, only 4709 (75.48%) participants responded and agreed to complete the interview. There was an equal distribution between the 13 administrative regions of Saudi Arabia. Of the total sample, 50.1% were female, the mean age was 36.4 ± 13.5 years (18–90 years), the median age was 36 years, and 59.6% had a bachelor’s degree or higher. Table 1 shows the demographic characteristics of the participants. 3.2. Prevalence of Food Allergy Overall, the weighted national prevalence of Saudi adults who reported having at least one current food allergy was 19.7%, of whom 16.5% have an allergy to one food and 3.9% have an allergy to more than one food. The proportion of participants in the Najran ( p < 0.001) and Qassim ( p < 0.001) regions with food allergies was significantly higher than in other regions based on chi-square ad-hoc analysis. In addition, 17.8% of those who reported having a diagnosed health condition reported at least one food allergy. Table 2 shows distribution and estimation of food allergies among participants. 3.3. Association between Food Allergies and Diagnosed Health Conditions and Mental Health This study shows that there was a significant association between participants reporting food allergies and being diagnosed with asthma (X 2 (df = 1, N = 4709) = 39.89, p < 0.001), colon disease (X 2 (df = 1, N = 4709) = 23.83, p < 0.001), and bariatric surgery (X 2 (df = 1, N = 4709) = 27.21, p < 0.001), in which participants with these health outcomes were more likely to report having food allergies. This study also investigated the association between food allergies and mental health, and found that participants reporting food allergies were more likely to be at risk of depression (X 2 (df = 1, N = 4709) = 111.01, p < 0.001). There was no association between food allergies and the other health conditions assessed. A logistic regression model including asthma, colon disease, and bariatric surgery controlling for age and gender showed that only bariatric surgery was significantly associated with a lower likelihood of self-reported allergy (OR 1.69, 95% CI 1.22–2.34) p = 0.002. 3.4. Common Food Allergens The most common self-reported food allergens were egg (3.7%), shellfish and shrimp (3.1%), and peanut (3.0%), and 8.8% of participants reported allergies to other foods ( Table 3 ). 4. Discussion This was a cross-sectional study that explored the prevalence of self-reported food allergies and specific food allergens among adults in Saudi Arabia, and the association between the presence of food allergies and comorbidities, mental health status, and demographic characteristics through a nationwide phone survey. The present population-weighted data revealed that an estimated 19.7% of adults in Saudi Arabia have at least one type of food allergy. Egg, shellfish and shrimp, and peanuts were the most frequently reported food allergens. Although there were no significant differences between prevalence of self-reported food allergies for gender and age group, there was a significant difference between regions. In addition, there were significant associations between reports of food allergies and presence of asthma, colon disease, bariatric surgery, and risk of depression. Logistic regression analysis revealed a significant association between bariatric surgery and a lower likelihood of self-reported food allergy. To our knowledge, this is the first study investigating the prevalence of self-reported food allergies among adults in Saudi Arabia at the community level. Findings suggest that the prevalence of self-reported food allergies in this sample was relatively high (21.4%). These results are similar to, or higher than, other studies conducted in the Middle East on the prevalence of self-reported food allergies. The prevalence of self-reported food allergies was 8% among university students in the United Arab Emirates [ 24 ] and 12% among university students in Kuwait [ 25 ]. Results from the present study are much higher than the findings from other work conducted in Saudi Arabia. Research on a smaller sample size in a clinical setting in Saudi Arabia found that only 1.5% of participants over 14 years of age had been diagnosed with food allergies [ 12 ]. Another study conducted among 5497 university students in Saudi Arabia found that 9.6% of participants had been diagnosed with food allergies [ 17 ]. However, self-reporting food allergies tend to overestimate actual prevalence [ 8 , 26 ], which may explain some of the discrepancies between previous findings of diagnosed allergies and the present study. For instance, the last published data from the 2015 National Health and Nutrition Examination Survey (NHANES) report an overall prevalence of self-reported food allergies in adults as 13%, while physician-diagnosed food allergy prevalence was only 6.5% [ 27 ]. Similarly, another study conducted in the US found that 19% of adult participants ( n = 40,443) self-reported food allergies; however, this prevalence was reduced to 10.8% when including only convincing reports [ 9 ]. Thus, comparisons between the present study and others should be made with caution. This study demonstrated a significant difference between the prevalence of participants who reported food allergies among the 13 regions in Saudi Arabia, mainly Qassim and Najran. The reasons for the variation between regions are not clear. However, it might be related to social factors such as marriage from the same tribe or cousin marriage; thus, the genetics factor may play a role in the high prevalence of food allergies recorded in these two cities. The most common food allergens reported in the present study were egg, shellfish and shrimp, and peanuts. This finding conflicts with the results of a small clinical study conducted at the allergy clinics at King Khalid University Hospital in Saudi Arabia, which found that the most common allergens among 280 participants were milk (61.96%), egg whites (59.78%), wheat (45.65%), and peanuts (38.04%), with some participants reporting more than one allergen [ 28 ]. Limited data on the most common food allergens in Saudi Arabia prevent us from conducting further comparative analysis. However, the patterns of food allergy across countries are quite different, reflecting the varied diets consumed in different countries [ 8 ]. For example, unique food allergens include bird’s nest from swiftlets causing allergic reactions in Singapore and Malaysia, and royal jelly causing allergic reactions in Hong Kong [ 8 ]. Our results indicate a significant association between food allergies and asthma. This is an expected finding, given that people who have food allergies are more likely to develop asthma symptoms such as wheezing, coughing, and difficulty breathing [ 29 ]. One study has found that the prevalence of asthma in the Arabian Gulf Region (AGR), Kuwait, Saudi Arabia, and Qatar, in particular, is higher than in other Eastern Mediterranean countries [ 30 ]. Children who have both asthma and food allergies are more likely to have fatal allergic reactions to food and severe asthma, particularly if the asthma is not well controlled [ 31 ]. This may provide an interpretation of our finding of the association between food allergy and asthma. Food allergies can make persistent asthma more likely in young children. According to a study from 2017, between 4% and 8% of children with asthma have a food allergy. However, nearly 50% of children with a food allergy have experienced respiratory symptoms during an allergic reaction, including wheezing and shortness of breath [ 32 ]. However, there are few studies that have investigated these relationships in adults. Our study found a significant association between food allergies and colon disease. However, limited data are available on the relationship between food allergy and colon diseases [ 33 ]. It appears that an adverse reaction to food items may be associated with symptom onset or exacerbation [ 33 ]. A study conducted on patients with colon diseases in England used food-specific immunoglobulin (Ig) G testing with borderline positive tests [ 33 ]. Although protein reactions are rare in colon disease, intolerance to poorly absorbed carbohydrates, such as fructose, lactose, sorbitol, and other fermentable sugars and starches, is related to worsening symptoms in patients with colon diseases [ 33 ]. Our results also show a positive association between food allergies and risk of depression, a relationship supported in the literature. The presence of food allergies has been shown to negatively impact quality of life. Psychological distress, which includes anxiety, depression, social isolation, and stress, has been demonstrated in children and adolescents with a food allergy [ 34 ]. For instance, one study showed that adults and children who are suffering from food allergies have impaired quality of life and higher levels of stress and anxiety [ 35 ]. In addition, a recent Canadian study found that teenagers with food allergies are more likely to have depression, attention-deficit hyperactivity disorder (ADHD), and anxiety [ 36 ]. Another study on 1300 Australian adolescents, showed that at 14 years old, nearly one-third of teens with food allergies were self-reporting depression and other behavioral problems. However, when researchers examined the reports from mothers of the same teens, the number of those with depression or other mental health problems increased to 46% [ 34 ]. This study found that bariatric surgery is significantly associated with lower likelihood of self-reported food allergy. We searched the literature to establish whether similar results were published about this association via PubMed using the general keywords “bariatric surgery” and “food allergy”: out of only 10 results, one case report in 2017 highlighted the increase in food allergy (birch pollen) severity after bariatric surgery [ 37 ]. Another report, in 2020, showed a similar increase in severity of the same type (birch pollen) of allergy in 13 patients [ 38 ]. Although there is a lack of knowledge about the validity of such association, digestion and digestibility of carbohydrates and proteins critically affect the risk of food allergy development [ 39 ]. The major limitation to this study is that food allergy was self-reported. Self-reporting may lead to overestimating food allergy prevalence by three or four times the actual prevalence [ 8 , 26 ]. This may be due to participants’ confusing a food allergy with other adverse reactions to food [ 8 , 26 ]. Data on the public awareness of the difference between food allergies and intolerances are scarce. Accurate reports on the prevalence of food allergies require tests to confirm food allergies, such as skin allergen testing, food item specific allergen serum Immunoglobulin E (IgE), or oral food challenges. Future research efforts could focus on diagnosing food allergies using oral food challenges. On the other hand, underestimation of the number of diagnosed food allergies can also occur, because some people might not seek medical help if they experience mild food allergies or are not aware of their condition due to inadequate exposure to the type of food in question. Furthermore, this study was cross-sectional, precluding conclusions about causation. However, this study design was strengthened by the use of quota sampling, potentially limiting the risk of selection bias and allowing for the recruitment of a balanced study sample in terms of gender and age. A large study sample with high coverage of adults in Saudi Arabia is a strength of this work, especially considering the limited information available on food allergy prevalence in this population. Furthermore, the use of a research participant database might introduce bias, given that participation in the database was voluntary. Nevertheless, such a database is useful for conducting research with large sample sizes without encountering prohibitive barriers, especially considering that the survey took place during the COVID-19 pandemic, which could have otherwise inhibited recruitment strategies. Data integrity checks, inherent to the QPlatform data collection system, minimized invalid or erroneous data entry. Linguistic validation and questionnaire piloting were employed to strengthen the questionnaire’s reliability. 5. Conclusions Prior to this study, most food allergy research in the Saudi Arabian population was collected from specific and non-generalizable settings or regions, or among children. There had not been a nationwide study on Saudi Arabian adults. This study provides insights into the prevalence of self-reported food allergies and sources of allergens among adults. This information is valuable for clinicians and policymakers, particularly in terms of food allergen labeling. This study showed that there was a significant association between participants reporting food allergies and participants with asthma, colon disease, and bariatric surgery. This association may need to be investigated further and may be used as an indicator for the risk of having a food allergy. This study’s results will also open the door for future research in food allergy prevalence and characteristics in Saudi Arabia, and further elaboration is needed to properly distinguish, diagnose, and manage food allergies. Author Contributions N.A.A., M.H.B., N.F.B., S.A.A. participated in the conceptual design and formulation of the research questions. All authors participated in the development and review of the manuscript. N.A.A., N.A. and M.F.A. supervised and managed the data collection process. N.A.A. and N.F.B. analyzed the data. All authors have read and agreed to the published version of the manuscript. Funding This research received no external funding. Institutional Review Board Statement The ethics committee of Sharik Association for Health Research approved this re-search project (Approval no. 2020-3), in accordance with national research ethics regu-lations. Informed Consent Statement Informed consent was obtained verbally during the phone interview with the participants and recorded in the data collection system. Data Availability Statement Available from Sharik Association for Health Research upon request. Acknowledgments The authors want to extend their attitude to the data collection team members: Nadin Amin Althabet, Eyad Tariq AlShaheen, Alhanoof Rashid Alsuwaidani, Yousef Bin Meshari Bin Tuwaym, Sarah Abdullah Alothman, Maryam Abdullah Alfahad, Wafa al homaide Rushedan alruwaily, Abdulaziz Alrajeh, Mubarak Nishaa Alqaaboubi, Muhannad Mohammed Basheer, Abdulrahman Abdulaziz Nasser Alfayez, Malik Hellaiel Alhumaid, Abeer Ali Alenazi, Sarah Yahya Saeed Ogran, and Abdullah Hassan Majrashi. 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Variable n (%) Chi-Square p -Value Overall 1009 (21.4) - Gender Male 490 (20.8) 0.329 Female 519 (22.0) Age Group 18–19 59 (23.1) 0.416 20–29 335 (21.5) 30–39 228 (22.6) 40–49 202 (19.3) 50–59 127 (22.9) 60+ 58 (20.0) Region Al-Jouf 54 (15.0) <0.001 Northern Border 68 (18.8) Tabuk 84 (23.2) Hail 81 (22.6) Madinah 68 (23.5) Qassim 102 (28.3) Macca 70 (19.3) Riyadh 60 (16.5) Eastern Province 70 (19.4) Baha 75 (20.6) Asir 73 (19.9) Jazan 72 (19.9) Najran 114 (31.5) Presence of comorbidities No diagnosed health condition 551 (25.8) <0.001 ≥1 diagnosed health condition 458 (17.8) Table 3. Prevalence of self-reported specific food allergies in general adult population weighted sample ( n = 4709). Table 3. Prevalence of self-reported specific food allergies in general adult population weighted sample ( n = 4709). Type of Food Allergy n (%) a Egg 172 (3.7) Shellfish and Shrimp 145 (3.1) Peanut 141 (3.0) Milk 123 (2.6) Fish 118 (2.5) Tree Nuts 82 (1.7) Soy 44 (0.9) Wheat 39 (0.8) Other 410 (8.8)
https://www.mdpi.com/1660-4601/18/1/347/xml
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https://lasp.colorado.edu/maven/sdc/public/data/sites/site-20180918T173254/anc/eng/sff/mvn_rec_170531_170603_updated_v03.sff
Shrimp type/colour/grade? And feeding question | Cherry Shrimp Forum | FishLore Aquarium Forum 2 questions in 1 post to stop me Spamming! First question.. my frozen food shows that it's suitable for tropical fish but not invertebrates: Ingredients... Shrimp type/colour/grade? And feeding question 2 questions in 1 post to stop me Spamming! First question.. my frozen food shows that it's suitable for tropical fish but not invertebrates: Ingredients: bloodworm , daphnia , cyclops, brine shrimp , algae and some nutrients. Does that mean I shouldn't really be feeding it in my tank (it's meant for the fighter fish in there but I caught my cherry shrimp eating it too). Are those ingredients harmful to the shrimp or are they actually okay to eat it? I wonder if it's because as shrimp they shouldn't be eating brine shrimp? My other question is those shrimp... what grade would you say they are? I saw the grade guide and they are a very solid deep red with black marks to me. I thought maybe a high fire red but they don't mention the black marks so wasn't sure? Unless that relates to the gender? I have 3 very deep red, plump ones so I assumed they were all girls (never had fry so figured they were all the same gender). I was thinking of trying to breed them as I love the deep colour so wanted to figure which colour they were first. Where does it say it is not suited for shrimp? The ingredients seem fine to me That shrimp is probably fire red or close to painted fire red, it also seems to have slight molting issues. Painted fire reds usually have a racing stripe as well. Where does it say it is not suited for shrimp? The ingredients seem fine to me That shrimp is probably fire red or close to painted fire red, it also seems to have slight molting issues. Painted fire reds usually have a racing stripe as well. At the front on the bottom of the pack it has dots over the first few 'types' but but there are no dots for marine or inverts (First picture in my original post) Moulting issues?! Good job I posted that picture as I never would have noticed! Thank you! Is that more likely water parameter related or diet? At the front on the bottom of the pack it has dots over the first few 'types' but but there are no dots for marine or inverts (First picture in my original post) Moulting issues?! Good job I posted that picture as I never would have noticed! Thank you! Is that more likely water parameter related or diet? One of them usually has a stripe down their back which goes a peachy colour. My photos of the shrimp are awful as the bottom of the tank is usually covered in hard algae and the tank is curved! Ah I see, I don't think you have to worry too much about feeding it to cherry shrimp. Seems like it is just bloodworms and some copepods which they will gladly eat With one shrimp it's hard to say. It could just be having trouble adjusting to a new tank and nothing else. Google the "white line of death" (When cherries have that they are guaranteed to die). Yours is a less severe version which means that it may not die and may continue to live happily It could be low GH in the water, or a bunch of other issues or it could be nothing. But if you are seeing consistent molting issues then there could be something wrong Ah I see, I don't think you have to worry too much about feeding it to cherry shrimp. Seems like it is just bloodworms and some copepods which they will gladly eat With one shrimp it's hard to say. It could just be having trouble adjusting to a new tank and nothing else. Google the "white line of death" (When cherries have that they are guaranteed to die). Yours is a less severe version which means that it may not die and may continue to live happily It could be low GH in the water, or a bunch of other issues or it could be nothing. But if you are seeing consistent molting issues then there could be something wrong Oh dear, that sounds awful and having read about it seems just as awful! My poor shrimp! They've been in there for about 10-12 months now so it won't be adjusting. Maybe low calcium , I'll try get hold of an egg shell or pop to the shops tomorrow at my fish store. Thanks for spotting that! I'll stop adding carbon to the tank. Hardness has been decreasing a bit recently: Oh dear, that sounds awful and having read about it seems just as awful! My poor shrimp! They've been in there for about 10-12 months now so it won't be adjusting. Maybe low calcium , I'll try get hold of an egg shell or pop to the shops tomorrow at my fish store. Thanks for spotting that! I'll stop adding carbon to the tank. Hardness has been decreasing a bit recently: View attachment 759963 Ah yes dropping hardness is definitely a concern...shrimps don't like fluctuating GH or KH levels. Is there a reason you are adding carbon? Removing organics is not necessary for cherry shrimp as they feed on a lot of biofilm and bacteria growth... Feeding some boiled spinach or kale is a good way to give them calcium Where does it say it is not suited for shrimp? The ingredients seem fine to me That shrimp is probably fire red or close to painted fire red, it also seems to have slight molting issues. Painted fire reds usually have a racing stripe as well. How is it molting issues? I'm not trying to sound mean just want to know how you identified it. How is it molting issues? I'm not trying to sound mean just want to know how you identified it. There is a small white line in the middle of the shrimp, a small gap. It's basically exposed flesh from improper molting. Google "white line of death cherry shrimp" to see more severe examples. This one is very small and may not harm the shrimp at all. The actual white line of death is fatal though, and I've never seen mine recover from it. Ah yes dropping hardness is definitely a concern...shrimps don't like fluctuating GH or KH levels. Is there a reason you are adding carbon? Removing organics is not necessary for cherry shrimp as they feed on a lot of biofilm and bacteria growth... Feeding some boiled spinach or kale is a good way to give them calcium The addition of carbon is because I don't have a CO2 system so I add an 'carbon dioxide alternative'. Weirdly, I just watched a blue rili shrimp die in my other tank. It had that white death line too. I added Fluval Plant Gro + fertiliser earlier today for the first time. I just saw that one die and one of the super dark blue ones has suddenly come out into the open and whilst it is just eating/grazing, it is very unusual for me to see out and about being so bold! Weird coincidence or the new fertiliser playing a part? I don't know! The addition of carbon is because I don't have a CO2 system so I add an 'carbon dioxide alternative'. Weirdly, I just watched a blue rili shrimp die in my other tank. It had that white death line too. I added Fluval Plant Gro + fertiliser earlier today for the first time. I just saw that one die and one of the super dark blue ones has suddenly come out into the open and whilst it is just eating/grazing, it is very unusual for me to see out and about being so bold! Weird coincidence or the new fertiliser playing a part? I don't know! Ohh I thought you meant activated carbon . That's completely different then. Okay, if you add CO2 then yes your shrimps will be affected because the pH will drop. Generally, you will see some impact on shrimp when first introducing CO2, but cherry shrimps are hardy and will eventually adjust. You may not get as much of a population explosion in CO2 tanks though. HOWEVER, since you said 'carbon dioxide alternative' does that mean liquid CO2 like Excel? Those do not affect carbon levels and they are actually a very strong disinfectant. They will kill algae and microorganisms in the tank and should not be used with shrimp in my opinion. As for the other ferts , I would not any fertilizers to a shrimp tank Ohh I thought you meant activated carbon. That's completely different then. Okay, if you add CO2 then yes your shrimps will be affected because the pH will drop. Generally, you will see some impact on shrimp when first introducing CO2, but cherry shrimps are hardy and will eventually adjust. You may not get as much of a population explosion in CO2 tanks though. HOWEVER, since you said 'carbon dioxide alternative' does that mean liquid CO2 like Excel? Those do not affect carbon levels and they are actually a very strong disinfectant. They will kill algae and microorganisms in the tank and should not be used with shrimp in my opinion. As for the other ferts, I would not any fertilizers to a shrimp tank. They are sensitive creatures and the less I mess with the tank the better. I'm surprised to hear that. I've since cut back, but for a good while I used Excel in my shrimp tanks several times each week, and I still dose them with Easy Green fertilizer twice each week. I haven't had any issues. I'm surprised to hear that. I've since cut back, but for a good while I used Excel in my shrimp tanks several times each week, and I still dose them with Aquarium Co-op's Easy Green fertilizer twice each week. I haven't had any issues. Yeah look up Glutaraldehyde it is quite toxic, a strong irritant, and can cause lung damage. The wiki page has some links to studies. There's also this widely cited study: https://www.jstage.jst.go.jp/article/joh/48/2/48_2_75/_pdf Yeah look up Glutaraldehyde it is quite toxic, a strong irritant, and can cause lung damage. The wiki page has some links to studies. There's also this widely cited study: https://www.jstage.jst.go.jp/article/joh/48/2/48_2_75/_pdf I agree about the glutaraldehyde part, but actual aquarium fertilizers are fine (as long as you don't overdose and it's shrimp safe). Grade my red cherry shrimp? Meet my cherry shrimp!! And a question
https://www.fishlore.com/aquariumfishforum/threads/shrimp-type-colour-grade-and-feeding-question.485381/
Tiger Muskie Stocking in Lake Carl Etling Cimarron County, Oklahoma Environmental Assessment - Draft - DocsLib Tiger Muskie Stocking in Lake Carl Etling Cimarron County, Oklahoma Environmental Assessment - Draft U. S. Department of the Interior U.S. Fish and Tiger Muskie Stocking in Lake Carl Etling Cimarron County, Oklahoma Environmental Assessment - Draft U. S. Department of the Interior U.S. Fish and Wildlife Service Wildlife and Sport Fish Restoration Program Albuquerque, New Mexico January 2016 Environmental Assessment Stocking of Tiger Muskie Lake Carl Etling, Cimarron County, Oklahoma January 2016 U.S. Fish and Wildlife Service Wildlife and Sport Fish Restoration Program Mission Statements The mission of the Department of the Interior is to protect and provide access to our Nation's natural and cultural heritage and honor our trust responsibilities to Indian Tribes and our commitments to island communities. The mission of the U.S. Fish and Wildlife Service is working with others to conserve, protect, and enhance fish, wildlife, plants, and their habitats for the continuing benefit of the American people. PURPOSE AND NEED FOR ACTION Introduction The Oklahoma Department of Wildlife Conservation (ODWC) is seeking the U.S. Fish and Wildlife Service’s (Service) approval (through Federal Assistance grant) for a project intending to improve angling opportunities at Lake Carl Etling, located in northwest Oklahoma. This Environmental Assessment (EA) is being prepared to evaluate the potential effects of the Proposed Action of stocking tiger muskie ( Esox masquinongy X E. lucius) into Lake Carl Etling, located in Cimarron County, Oklahoma (Figure 1). This project would be funded by the U.S. Fish and Wildlife Service’s Wildlife and Sport Fish Restoration (WSFR) Program. Purpose and Need for the Action Lake Carl Etling has historically provided angling for northern pike (Esox lucius). Northern pike were introduced in the 1960s and sustained a fishery until the 1990s when they were extirpated due to limited reproduction and reduced water levels. Recent prolonged drought conditions have caused exceedingly low water levels, which in turn have negatively impacted all sport fish populations. Rain events during summer of 2013 have caused lake levels to return to normal pool. However, this also resulted in increased densities of undesirable nongame species such as common carp (Cyprinus carpio), gizzard shad (Dorosoma cepedianum), and green sunfish (Lepomis cyanellus). Tiger muskies are highly piscivorous and have been stocked throughout the United States to control populations of undesirable fish species. Tiger muskies grow rapidly and quickly obtain desirable size when stocked in reservoirs with abundant forage. In addition, tiger muskies are sterile hybrids which allow managers to control recruitment and population size, and to modify stocking if it is deemed detrimental to other fisheries management objectives. The purpose of the Proposed Action is to provide a unique trophy sport fishing opportunity in the State of Oklahoma with tiger muskie and to reduce undesirable fish abundance in Lake Carl Etling. This action is needed at this time due to the increase in undesirable fish community in the lake and the current lack of angling opportunities at the site. Proposed Action The Proposed Action is to enhance Oklahoma angling opportunities by stocking tiger muskie (Esox masquinongy X E. lucius) into Lake Carl Etling in Cimarron County, Oklahoma. Lake Carl Etling is a 159-acre reservoir located near the town of Kenton in Cimarron County, Oklahoma (GPS Coordinates 36.848888, -102.867037), which is owned and managed by the ODWC. The reservoir is situated on 349 acres operated as Black Mesa State Park by the Oklahoma Department of Tourism and Recreation (Figure 1). Recreational opportunities in the area include fishing, camping, hiking, and wildlife viewing. Due to past drought conditions, the lake has lost the original sport fish community and is currently dominated by undesirable nongame fish species. Figure 1. Map of Lake Carl Etling within Black Mesa State Park. Cimarron County, Oklahoma. This Proposed Action will: 1) create a unique angling opportunity in the State of Oklahoma, 2) reduce undesirable fish populations, and 3) improve recreational angling of other sportfish species. ALTERNATIVES Discussion of the Proposed Action and No Action Alternatives Proposed Action The Service, under the WSFR Program, proposes to approve ODWC’s project to improve Oklahoma angling opportunities by stocking tiger muskie (Esox masquinongy X E. lucius) into Lake Carl Etling. The Proposed Action will also help control the increase in undesirable fish species that are currently dominating the fish community. Initially, tiger muskie stocking with be three to five fish/acre annually for three years to establish the population. Once established, annual maintenance stockings of 1 fish/acre may be needed annually to meet management objectives of controlling unwanted species and providing angling opportunities. Tiger muskie will be obtained in October each year as advanced fingerling (10 inches) from the Wyoming Fish and Game Department’s Speas Fish Hatchery located in Casper, Wyoming. Access to the lake by ODWC staff will be public access. The location for stocking will be at the boat ramp located on the southwest side of the lake. All routes used for access are paved roads. No ground disturbance will occur with stocking activities. No Action Alternative The No Action Alternative is defined as maintaining the current conditions of Lake Carl Etling fish community and not stocking additional sport fish in the lake. Adoption of this alternative would ultimately result in a lack of recreational sport fish experiences at the lake. The probable outcome of the No Action Alternative would be continued dominance of the lake by undesirable nongame fish species, and declining use by anglers. The No Action Alternative includes no direct costs; however, loss of recreational fishing opportunities will impact local economies. Monitoring of existing conditions, with particular emphasis on Lake Carl Etling’s fish community, would be conducted as part of the No Action Alternative. AFFECTED ENVIRONMENT Introduction This section describes the environment in which the Proposed Action would be implemented. The various associated environmental resources, including physical resources such as land use, water resources, water quality, air quality, and soil; and biological resources such as vegetation, wetlands, noxious weeds, fish and wildlife resources, and threatened and endangered species (critical habitat); and socio-economic resources such as cultural resources are discussed. Physical Resources Land Use The project site is located at Lake Carl Etling within Black Mesa State Park in Cimarron County, Oklahoma. The lake is managed by ODWC, and the surrounding Black Mesa State Park is managed by Oklahoma Department of Tourism and Recreation. Lake Carl Etling is 159 surface acres with 5 miles of shoreline. The lake and state park are designated for recreational use and as a nature preserve which provides opportunities for fishing camping, hiking, and wildlife viewing. Amenities on site include: campsites, grills, picnic area, playground, restrooms, and WiFi. Water Resources and Water Quality South Carrizo Creek, which connects Lake Carl Etling to the Cimarron River, is an ephemeral, intermittent stream (Figure 2). Likewise, the Cimarron River through Cimarron County is also intermittent. Current streamflow information is available nearby on the Cimarron River near Kenton, Oklahoma (Figure 3), located upstream of the South Carrizo Creek confluence with the Cimarron River. Streamflow at this gage is characterized by a high degree of variability and responds to storm events, which is typical of South Carrizo Creek as well. Intermittent Stream Drainage System Lake Carl Etling Figure 2: Location of Lake Carl Etling and intermittent stream drainage system, southeast of the City of Kenton, Oklahoma approximately 6 linear miles, Cimarron County, Oklahoma. Figure 3. Recent steamflow data (gage height and discharge) (January 2013 to July 2015) at USGS gage 07154500 Cimarron River near Kenton, OK. Current information on the water quality of Lake Carl Etling and the Cimarron River is available from Oklahoma Water Resources Board (OWRB). Oklahoma’s Beneficial Use Monitoring Program (BUMP), established in 1998, was the state's first truly comprehensive water quality monitoring effort. Data provided by the program is essential in the state's water quality management decision-making process by helping to identify waters experiencing impairments as well as the cause of declining water quality. The northwestern tip of Oklahoma’s panhandle is encompassed by the diverse Mesa de Maya/ Black Mesa ecoregion. Many streams are spring-fed and ephemeral, and the Cimarron River is of much higher quality in this area than downstream. Although many nearby streams have good water clarity, Lake Carl Etling is fair with an average Secchi depth of 0.75 feet. Nutrient values are relatively high in the lake with total phosphorus ranging from 0.12 to 0.29 ppm and total nitrogen from 2.31 to 4.51 ppm. It is also considered hyper-eutrophic (defined as: excessive primary productivity and excessive nutrients). Conductivity is relatively high at an average of 2,000 μS, and closely resembles the upper portion of the North Canadian River . (Oklahoma Water Resources Board 2012) Biological Resources Vegetation The Black Mesa and Carl Etling area supports 23 speices of plants ranging from short grass prairie plants such as bluestem-grama grasses to tree fauna such as mixed juniper/shrub oak communities. Majority of the shoreline at Lake Carl Etling is encompassed with rocky outcropping slopes that supports mainly yucca (Yucca linnaeus), sand sage (Salvia eremostachya), and cholla cactus (Cylindropuntia imbricata). The tree community that surrounds the lake consist of cottonwoods (Populus deltoides), American elm (Ulmus americana), and black willow (Salix nigra) trees. The shoreline is sparsely scattered with plants while the majority of ground cover is comprised mostly large boulders mixed with intermediate sized rock/gravel with high levels of silt on the lake bed itself. Fish and Wildlife Resources The current fish community in Lake Carl Etling consists of largemouth bass, flathead catfish, walleye, and smallmouth bass, which are stocked. As stated previously, the lake has become dominated by undesirable species such as common carp, gizzard shad, and green sunfish. Wildlife in the project area is typical for the Mesa de Maya/ Black Mesa region, including: golden eagles, scaled quail , black-billed magpies, pinyon jays, black bear , bobcat , mountain lion , mule deer , bighorn sheep , and antelope. The habitat surrounding Lake Carl Etling , as previously stated, is that of mixed shortgrass vegetation with intermittent shrubs and some larger trees. Threatened and Endangered Species (Critical Habitat) In accordance with Section 7(a)(2) of the Endangered Species Act of 1973, as amended, federally funded, constructed, permitted, or licensed projects must take into consideration impacts to federally listed and proposed threatened or endangered species. There are currently four federally listed avian species found in Cimarron County and the Black Mesa State Park area (Table 1). There are no federally listed fish or aquatic insect species found in Cimarron County or Lake Carl Etling. There are no designated critical habitats in the project area Table 1. Federally Listed Species Potentially in the Project Vicinity. Lake Carl Etling, Cimmaron County, Oklahoma Species Listing Status Critical Habitat Interior least tern1 Endangered Not designated (Sterna antillarum) Piping Plover Threatened Designated; includes project area (Charadrius melodus) Lesser prairie- chicken Threatened Not designated (Tympanuchus pallidicinctus) Rufa Red Knot Threatened Not designated (Calidris canutus rufa) 1The least tern only needs to be considered in Cimarron County if any of the following conditions apply: •Wind Turbines and Wind Farms •Towers (i.e. radio, television, cellular, microwave, meterological) The Lake Carl Etling area is not considered to be an area of high concern for migrating birds such as terns, plovers, or knots due to lack of appropriate habitat at this site that these birds need while in migration routes. The shoreline, being very steep and rocky in most areas, is not conducive for these species for forage or resting. The areas surrounding the lake are not suitable for prairie chickens or their leks. The ODWC does not conduct any bird surveys on or near the project area, conversely there is no presence/absence data that is available at this time in relation to bird surveys or species account at Lake Carl Etling. Though a site inspection to the project site was conducted by ODWC to review the habitat and spatial characteristics of the study area, no formal surveys were conducted for threatened or endangered avian species. Information was compiled by reviewing previous reports and communicating with local experts, ODWC employees, and by obtaining a list of threatened and endangered species that occur in Cimarron County and the Oklahoma Heritage Inventory List. Topics covered for these species include relevant life history information and current knowledge on the presence and utilization of the action area. Piping Plover The piping plover (Charadrius melodus) (plover) is a small (approximately 6.7 to 7.1 inches long) and 1.5 to 2.2 ounces in weight (Haig 1992), migratory member of the shorebird family. It is one of six species of belted plovers in North America. During the breeding season, adults have single black bands across the forehead and breast, orange legs and bill, and pale tan upper parts and are white below. The adults lose the black bands, and their bill becomes grayish-black during the winter. Plovers use wide, flat, open, sandy beaches with very little grass or other vegetation. Nesting territories often include small creeks or wetlands. They are migratory birds, and in the spring and summer, they breed in northern United States and Canada . There are three locations where piping plovers nest in North America: the shorelines of the Great Lakes, the shores of rivers and lakes in the Northern Great Plains , and along the Atlantic Coast. Their nesting range has become smaller over the years, especially in the Great Lakes area. In the fall, plovers migrate south and winter along the coast of the Gulf of Mexico or other southern locations. Many of the coastal beaches traditionally used by piping plovers for nesting have been lost to commercial, residential, and recreational developments. Through the use of dams or other water control structures, water levels of many lakes and rivers are raised and lowered at plover inland nest sites. Too much water in the spring floods the plovers' nests. Too little water over a long period of time allows grasses and other vegetation to grow on the prime nesting beaches, making these sites unsuitable for successful nesting. The project area is not suitable for stopover or foraging areas for plovers due to the habitat parameters that are found at Lake Etling. As previously stated, the shoreline and surrounding habitats are that of course rocky substrate surrounded by shortgrass prairie . Lesser prairie-chicken The lesser prairie chicken (Tympanuchus pallidicinctus) (chicken) is a species of prairie grouse that occupies a five-state range including portions of Texas, New Mexico, Oklahoma, Kansas, and Colorado . The species was listed as threatened in 2014 in response to sharp declines in their population. Once abundant across much of the five range states, historical range of native grasslands and prairies has been reduced by an estimated 84 percent. The chicken is commonly recognized for its feathered feet and stout build. Plumage of the chicken is characterized by a cryptic pattern of alternating brown and buff -colored barring. Males display brilliant yellow-orange eyecombs and reddish-purple air sacs during courtship displays. Lesser prairie-chicken populations need large tracts of relatively intact native grasslands and prairies to thrive. Threats to the chicken include habitat loss, modification, degradation, and fragmentation within its range. (USFWS 2015) There are no chicken leks within a 20 mile radius of Lake Carl Etling or in Cimarron County; the closest known lek is located approximately 30 miles northwest of Carl Etling in Colorado . The species accounts for prairie chickens around the project area are very rare, and the area is not known to be conducive for prairie chicken habitat. Rufa Red Knot The rufa red knot (Calidris canutus rufa) is a medium-sized shorebird about 9 to 11 inches in length. The species was listed as threatened in January 2015, after it has experienced a population drop of more than 75 percent since the 1980s. (Audubon 2015) Each year red knots make one of the longest distance migrations known in the animal kingdom, traveling up to 19,000 miles annually. Red knots undertake long flights that may span thousands of miles without stopping. No site specific data is available for red knots in the project area. Socio-Economic Environmental Justice Executive Order 12898 (Federal Actions to Address Environmental Justice in Minority and Low- Income Population; February 11, 1994) was designed to focus the attention of federal agencies on the human health and environmental conditions of minority and low-income communities. It requires federal agencies to adopt strategies to address environmental justice concerns within the context of agency operations and proposed actions. In an accompanying memorandum, President Clinton emphasized that existing laws, such as NEPA, should provide an opportunity for federal agencies to assess the environmental hazards and socioeconomic impacts associated with any given agency action upon minority and low income communities. In April of 1995, the U.S. Environmental Protection Agency (USEPA) released a guidance document titled Environmental Justice Strategy: Executive Order 12898. This document defines the approaches by which the USEPA would ensure that disproportionately high environmental and/or socioeconomic effects on minority and low income communities are identified and addressed. Further, it establishes agency-wide goals for all Native Americans with regard to environmental justice issues and concerns. The Proposed Action is located on State land, which is not a low-income or minority community. Cultural Resources Cultural resources include archaeological sites and localities identified as having traditional religious or cultural importance also known as Traditional Cultural Properties (TCPs). The Proposed Action will not involve any ground disturbance and will not impact any cultural sites. ENVIRONMENTAL CONSEQUENCES Introduction This section is an evaluation of the potential environmental effects of the Proposed Action and the No Action Alternative. This analysis includes likely beneficial and adverse effects on the human environment, including those that are short term or long term, direct or indirect, and cumulative. More detailed consideration is given to those resources that have a potential for environmental effects. Description of Relevant Affected Issues and Resources The following is a description of the relevant affected issues and resources that potentially could be impacted through this project. Any impacts for each identified issue or resource, both positive and negative, are discussed below. Physical Resources Land Use Under the Proposed Action, land use would not change and there would be no permanent impacts. Lake Carl Etling is a recreational site within Black Mesa State Park. This project would add recreational fishing opportunities at this site and could potentially increase visitation at the lake. Access by ODWC fisheries personnel would be at existing public areas. Fish will be stocked at the boat ramp located on the southwest side of the lake. All routes used for access are paved roads. No ground disturbance will occur with stocking activities. Farmland is not present where the project would occur and therefore, none would be impacted by the Proposed Action. Under the No Action Alternative, land use would also not change. However, the No Action Alternative would allow the current trends associated with the fish community to continue, ultimately resulting in potentially decreased angling opportunities and undesirable fish species in Lake Carl Etling. Water Resources and Water Quality The Proposed Action would not cause impacts to water quality or water resources. Any short- term disturbance related to stocking activities would be considered minor and temporary in nature. Under the No Action Alternative, the current water quality would be unchanged and monitoring of existing conditions would be conducted as part of the No Action Alternative. Biological Resources Vegetation No vegetation would be disturbed or removed to accomplish the Proposed Action. All access to the lake for stocking will be at existing public roads and boat ramps. The No Action Alternative would result no change to the vegetation in the project area. Fish and Wildlife Resources Fish The Proposed Action would have an effect on the fish community in Lake Carl Etling. By stocking tiger muskie in the lake, it is expected that the addition of this species will control undesirable fish species (common carp, gizzard shad, and green sunfish) that currently dominate the lake. Tiger muskies are highly piscivorous and have been stocked throughout the United States to control populations of undesirable fish species. Tiger muskies grow rapidly and quickly obtain desirable size when stocked in reservoirs with abundant forage. In addition, tiger muskies are sterile hybrids which allow managers to control recruitment and population size and to modify stocking, if it is deemed detrimental to other fisheries management objectives. The Proposed Action is also expected to provide a unique trophy sport fishing opportunity in the State of Oklahoma. To evaluate the Proposed Action, ODWC will continue the current monitoring program of the fish community in Lake Carl Etling. Tiger muskie may escape the lake and enter South Carrizo Creek. However, as stated previously, South Carrizo Creek, which connects Lake Carl Etling to the Cimarron River, is an ephemeral, intermittent stream. Likewise, the Cimarron River through Cimarron County is also intermittent. Due to intermittent stream conditions and the environmental constraints (thermal, salinity, and ecological tolerance) on tiger muskie, the ability for these fish to survive in South Carrizo or the Cimarron River, if water were present, would be very limited in scope. There are no threatened or endangered aquatic species present in South Carrizo Creek or in Cimarron County. The No Action Alternative would allow the fish community in the lake to continue to be dominated by undesirable fish species. This would decrease fishing opportunities at the lake and not attract additional anglers to the area. Wildlife Minor disturbance to terrestrial wildlife would result from the Proposed Action’s stocking activities and from general presence of humans during stocking. Animals disturbed during stocking would only be displaced from the area on a temporary basis, with most likely moving short distances into areas adjacent to the stocking location. The No Action Alternative would result in no change to conditions for terrestrial wildlife. Threatened and Endangered Species and Critical Habitat In accordance with Section 7(a)(2) of the Endangered Species Act of 1973, as amended, federally funded, constructed, permitted, or licensed projects must take into consideration impacts to federally listed and proposed threatened or endangered species. Of the species listed in Table 1, the piping plover and the rufa red knot have a potential to occur in the project vicinity. Potential relationships from the Proposed Action and No Action alternatives to these species are discussed below. A summary of the effect determinations for these species is presented below in Table 2. Table 2. Effect Determinations on Listed Species in the Project Vicinity Species Effect Determination Critical Habitat Determination Piping plover No Effect Designated; includes project area (Charadrius melodus) Lesser prairie-chicken No Effect Not designated (Tympanuchus pallidicinctus) Rufa red knot No Effect Not designated (Calidris canutus rufa) Overall, these three species tend to use terrestrial habitats and are not expected be affected by stocking of tiger muskie in Lake Carl Etling. Stocking will occur in October and will not be scheduled during peak migration periods or nesting seasons of these species. A visual survey of the Lake Carl Etling watershed will be conducted for the presence of any avian species of concern before each stocking event. If a species is noted, an alternative stocking date will be selected. There will be no effect to the surrounding habitats found within the area of Carl Etling Lake. Piping Plover The general lack of habitat and poor habitat quality make it unlikely for plovers to be present in the project area. The shoreline, being very steep and rocky in most areas, is not conducive for forage or resting. Plovers prefer wide, flat, open, sandy beaches with very little grass or other vegetation. In the unlikely event that plovers would be present, stocking dates will not be scheduled during peak migration periods or nesting seasons. As stated above, a visual survey of the Lake Carl Etling watershed will be conducted for the presence of any avian species of concern before each stocking event. If a species is noted, an alternative date will be selected for stocking. Because of the lack of suitable habitat, conducting visual surveys, and scheduling stocking dates outside of peak migration periods or nesting seasons, a determination of “no effect” on the plover and its habitat was made. No effects to plover critical habitat will happen with the Proposed Action. The No Action Alternative would result in continuation of the current fish species found in the lake and have no effect on plovers. Lesser Prairie Chicken No suitable chicken habitat is present in the proposed action area. The areas surrounding the lake are not suitable for prairie chickens or their leks. There are no known chicken leks within a 20 mile radius of Lake Carl Etling or in Cimarron County; the closest known lek is located approximately 30 miles northwest of Carl Etling in Colorado. The species accounts for prairie chickens around the project area are very rare. Due to the rarity of chickens in the area and lack of habitat, the Service has determined that there would be “no effect” on the lesser prairie chicken. The No Action Alternative would result in no change to chicken habitat and fish community in the lake would remain the same. Rufa Red Knot This long distance migratory species prefers sandy, shoreline habitats. No site specific data is available for red knots in the project area; however, suitable habitat is not present at the site. Red knots may migrate through the area. In the unlikely event that red knots would be present, stocking dates will not be scheduled during peak migration periods or nesting seasons. As stated above, a visual survey of the Lake Carl Etling watershed will be conducted for the presence of any avian species of concern before each stocking event. If a species is noted, an alternative date will be selected for stocking. The Service has determined that there will be “no effect” on red knots. The No Action Alternative would result in no change to red knot habitat and fish community in the lake would remain the same. Socio-Economic With the Proposed Action, the possible increase in angling opportunities could result in increased use of Lake Carl Etling, and associated benefits to the State, Cimarron County, and local community. Benefits would be in the form of increased recreation related spending and tax revenue. The No Action Alternative would result in no change to current socioeconomic conditions. Environmental Justice No minority or low-income populations have been identified that would be adversely impacted by the Proposed Action. Therefore, in accordance with the provisions of E.O. 12898 and FHWA Order 6640.23, no further analysis is required. Cultural Resources There would be no impacts to cultural resources under the Proposed Action; no ground disturbance would occur. ODWC personnel would use existing roads and public access for stocking activities. The Service has determined that this undertaking is not of the type of activity that has the potential to cause effects on historic properties, and has determined that the project would have no potential to affect cultural resources. Under the No Action Alternative, there would be no change to cultural resources. Irreversible and Irretrievable Commitment of Resources of the Proposed Action The implementation of this project would result in the commitment of resources such as fossil fuels and labor. In addition, federal funds would be expended for the implementation of the proposed project. Cumulative Impacts Cumulative effects under NEPA are the direct and indirect effects of a proposed project’s incremental effects, when they are added to other past, present, and reasonably foreseeable actions regardless of who carries out the action (40 CFR, Part 1508.7). The Proposed Action would expand upon ongoing sport fish stocking activities at Lake Carl Etling and provide additional angling opportunities at this location. The beneficial and minor negative impacts associated with stocking activities would likely be similar to those of the Proposed Action. Tiger muskies have been previously stocked in October of 2014 and 2015 with state funds. Other species stocked in this lake include: largemouth bass, bluegill, walleye, and hybrid striped bass. Because the lake is located within an intermittent drainage, cumulative effects to other aquatic species within South Carrizo Creek and downstream would be less likely to occur. Recreation at the lake, stocking of sport fish, and maintenance at the site could also affect resources including listed avian species. When combined with the effects of other cumulative actions, the effects of the Proposed Action would be largely beneficial and not contribute to any negative cumulative impacts on any resource or threatened or endangered species or critical habitat. ENVIRONMENTAL COMMITMENTS The following environmental commitments would be carried out as part of this project: • ODWC will continue fish community monitoring at Lake Carl Etling. • ODCW will conduct visual surveys of the project area for listed avian species. If found, an alternate stocking date will be selected. Conservation Measures The Service and ODWC will implement the following conservation measures to further minimize any risk of adverse effects of implementing the proposed action: • All equipment will undergo heated high-pressure power wash and inspection prior to initial operation in the project area to reduce contamination by invasive plants or aquatic species according to ODWC HACCP procedures. SUMMARY The purpose and goals of this project are to provide unique angling opportunities to Oklahoma at Lake Carl Etling and to control undesirable fish species that are currently dominating the lake. Measures to minimize effects have been incorporated into the Proposed Action. Environmental commitments described in Section 5 would be implemented. This EA has addressed Land Use, Water Resources, Water Quality, Vegetation,, Fish and Wildlife, Threatened and Endangered Species, Socioeconomics, Environmental Justice, and Cultural Resources. No other resources are expected to be affected. With the implementation of environmental commitments, effects are largely beneficial and only minor and/or temporary impacts have been identified. Based on the analysis in this EA, implementing the entire Proposed Action would have no potentially significant direct, indirect, or cumulative effects on the quality of the natural or human environment. In accordance with the NEPA of 1969, as amended, and based on the analysis in this EA, The Service has determined that implementing the proposed action would not result in a significant impact on the human environment and does not require preparation of an Environmental Impact Statement. LIST OF PREPARERS • Kelly Oliver-Amy, U.S. Fish and Wildlife Service, Region 2,WSFR Program • Chas Patterson, Oklahoma Department of Wildlife Conservation
https://docslib.org/doc/8176642/tiger-muskie-stocking-in-lake-carl-etling-cimarron-county-oklahoma-environmental-assessment-draft
Relationships | Scarleteen Relationships Finding Our Light in The Dark: An Interview with Author Kimberly Dark "Folks, the main thing I hope to realize is that you are a very powerful social creator, no part of human culture exists without humans creating it and you literally have the power to do that. Of course, you don’t have all the power, but listen: power is not just out there in some kind of blob form, power is inside of everyone of us. We don’t have all the power but we have our power and we can decide how to use it." How to Care for Friends Who've Experienced Trauma It’s likely that you will or already do know someone who will experience or has experienced trauma of some form. As friends, it’s important that we understand the responsibilities and limitations of our role, so we can best support our friends who are survivors and maintain our boundaries. Has someone disclosed to you a traumatic experience they’ve had? How can you best support that person and yourself? Here’s some information about trauma, the role of friends, and what it means to really support survivors. Learning My Way Through My Poly Fears Dynamics like mine require a lot of honesty, and often speaking honestly can make you feel vulnerable, but showing vulnerability to a partner is a good way to build trust and intimacy. At the same time, you learn a lot about yourself as you're forced to ask yourself tough questions and to think carefully about what you want from a relationship and why - in turn, this makes you appreciate the reasons you want to be with your partner(s), and what it is about being with them that makes you happy. Support from the Start: How to Talk About Disability With A Disabled Partner When You're a Nondisabled Person Disability may feel scary if you’re new to it - there is a lot of language involved to learn, maybe more medical information than you feel capable of handling, or you might have a fear about possibly being cast in a caregiver role more so than a partner. All of these fears can be dispelled or addressed through ongoing, healthy communication. In my experience, disclosure is an ongoing conversation and there is no single “correct” way to do it, but there are ways that our partners can be stronger allies. The Benefits of Being Vulnerable With Other Queer Guys It’s extremely disingenuous to pretend that everyone but men struggle with emotions, and doesn’t help liberate us from the toxic ideal that “real men don’t cry,” or exhibit sadness.  Men who date other men have additional obstacles to navigate if both they and their partners have difficultly accessing vulnerability.  That’s why I’d like to take the time with you to discuss how social norms have shaped the emotional health of queer men and how crucial vulnerability is as an empowering vehicle towards deeper connection and compatibility in your relationships.  I’ll also share some tips with you on how to uncover your own latent feelings and offer some suggestions on how to share these thoughts with someone you’re interested in or dating. An Autistic's Guide to Being Ghosted Suddenly, a person you’ve been regularly communicating with is M.I.A. Without warning, a fixture of recent life can become a memory. Somebody you’d bonded with has abruptly stopped contacting you. The text messages have ceased, all traces of their presence in your life have been yanked away by them, and without warning or explanation. But just because the experience is stressful doesn’t mean it’s impossible to endure. There are ways for autistic people to come out the other side of getting ghosted. Weights and Measures: How to have healthy and affirming conversations about weight with a partner When you gain weight and want to talk about it -- whatever your feelings about it are -- with partners or others you're in intimate relationships with, how can you do that, especially in a world where so few people are equipped with the skills to talk about weight in healthy, sensitive, supportive ways? It's Never Too Late To Start To Date Being autistic, some things just haven’t come as naturally for me as they seem to for other people. Unfortunately, these have included hallmarks of American life often used to symbolize being “an adult” like driving on my own or getting my first paid job. But human beings are not on a strict timetable to do all the same things at the same time. This is just as true of dating like anything else. Just because you (or I) haven’t been actively dating when a lot of other people in your life have doesn’t make you (or me) a failure. You’re just on your own timetable. So am I. Hi, Bi Guy: Dating Guys For The First Time If you’re a bisexual guy and you haven’t been with other guys yet, the idea might seem a little daunting, for a number of reasons. The reality doesn’t have to be so tricky, however, despite the worries you might have. Friends or Lovers? The Complexities of Queer Love Relationships, like gender and sexuality, don’t fit into a binary. The phrase queer platonic, which comes from the asexual community, means a deep and meaningful intimate relationship which isn’t based on sex. You can have this with anyone – no matter their gender or sexuality. Perhaps if the term were more normalised (I hadn’t heard of it before researching this article), more people would be comfortable with such a relationship.
https://www.scarleteen.com/article/relationships?page=0%2525252C0%2525252C11%25252C0%25252C12%252C0%252C4%2C0%2C0%2C1%2C0%2C1
(PDF) Knowledge to Wisdom: We Need a Revolution PDF | The following document is a very brief summary of a thesis and argument that I have devoted the last 30years of my life to trying to get across to... | Find, read and cite all the research you need on ResearchGate Article PDF Available Knowledge to Wisdom: We Need a Revolution September 2006 Philosophia34(3):377-378 DOI: 10.1007/s11406-006-9037-5 Authors: <here is a image 211b1d20ba7f8fc4-d89d2723e9d19859> Nicholas Maxwell University College London Abstract The following document is a very brief summary of a thesis and argument that I have devoted the last 30years of my life to trying to get across to my fellow human beings. It was first spelled out in What’s Wrong With Science? (Bran’s Head Books, 1976) and subsequently in From Knowledge to Wisdom (Blackwell, 1984), Is Science Neurotic? (Imperial College Press, 2004) and numerous articles, references to which can be found on http://www.nick-maxwell.demon.co.uk. Three years ago an international group was formed, called Friends of Wisdom, which seeks to get across to academics and the public the compelling arguments and urgent need to transform academic inquiry so that its basic aim becomes to seek and promote wisdom. The document below is taken from the website of Friends of Wisdom, the URL of which is http://www.knowledgetowisdom.org. It is the mission statement of Friends of Wisdom. You are invited to join. <here is a image 175d1bd4b7439d95-754927124da715c1> Discover the world's research Content uploaded by Nicholas Maxwell Introduction ( Philosophia vol. 34, No. 3, September 2006, pp. 377-8) The following document is a very brief summary of a thesis and argument that I have devoted the last 30 years of my life to trying to get across to my fellow human beings. It was first spelled out in What’s Wrong With Science? (Bran’s Head Books, 1976) and subsequently inFrom Knowledge to Wisdom (Blackwell, 1984), Is Science Neurotic?(Imperial College Press, 2004) and numerous articles, references to which can be found on www.nick-maxwell.demon.co.uk Three years ago an international group was formed, called Friends of Wisdom, which seeks to get across to academics and the public the compelling arguments and urgent need to transform academic inquiry so that its basic aim becomes to seek and promote wisdom. The document below is taken from the website of Friends of Wisdom, the URL of which is www.knowledgetowisdom.org It is the mission statement of Friends of Wisdom. You are invited to join. Nicholas Maxwell (Emeritus Reader and Honorary Senior Research Fellow at University College London) Knowledge to Wisdom: We Need a Revolution We need a revolution in the aims and methods of academic inquiry. Instead of giving priority to the search for knowledge, academia needs to devote itself to seeking and promoting wisdom by rational means, wisdom being the capacity to realize what is of value in life, for oneself and others, wisdom thus including knowledge but much else besides. A basic task ought to be to help humanity learn how to create a better world. Acquiring scientific knowledge dissociated from a more basic concern for wisdom, as we do at present, is dangerously and damagingly irrational. Natural science has been extraordinarily successful in increasing knowledge. This has been of great benefit to humanity. But new knowledge and technological know-how increase our power to act which, without wisdom, may cause human suffering and death as well as human benefit. All our modern global problems have arisen in this way: global warming, the lethal character of modern war and terrorism, vast inequalities of wealth and power round the globe, rapid increase in population, rapid extinction of other species, even the aids epidemic (aids being spread by modern travel). All these have been made possible by modern science dissociated from the rational pursuit of wisdom. If we are to avoid in this century the horrors of the last one - wars, death camps, dictatorships, poverty, environmental damage - we urgently need to learn how to acquire more wisdom, which in turn means that our institutions of learning become devoted to that end. The revolution we need would change every branch and aspect of academic inquiry. A basic intellectual task of academic inquiry would be to articulate our problems of living (personal, social and global) and propose and critically assess possible solutions, possible actions. This would be the task of social inquiry and the humanities. Tackling problems of knowledge would be secondary. Social inquiry would be at the heart of the academic enterprise, intellectually more fundamental than natural science. On a rather more long-term basis, social inquiry would be concerned to help humanity build cooperatively rational methods of problem-solving into the fabric of social and political life, so that we may gradually acquire the capacity to resolve our conflicts and problems of living in more cooperatively rational ways than at present. Natural science would change to include three domains of discussion: evidence, theory, and aims - the latter including discussion of metaphysics, values and politics. Academic inquiry as a whole would become a kind of people's civil service, doing openly for the public what actual civil services are supposed to do in secret for governments. Academia would actively seek to educate the public by means of discussion and debate, and would not just study the public. These changes are not arbitrary. They all come from demanding that academia cure its current structural irrationality, so that reason - the authentic article - may be devoted to promoting human welfare. ... Ackoffian messes are not solvable because of their interactivity and dynamism but can only be ameliorated. Maxwell (1984) discussed the 'problems of living' (which is what messes are) and their relation to science and reductionism when used to create definable problems with implicit or artificial borders (Simon, 1957). Messes and problems of living are unstructured and not definable: indeed, they are complex (adaptive) systems (cas) that need different ways of thinking. ... The digital and natural worlds: Crisis or challenge? Article Jan 2016 <here is a image 8468fb10dfa3d2a2-b0d77ec1f3f7d1eb> Denis Loveridge The digital world appeared 80 years ago. Little attention was paid to it until WW II when code breaking became of paramount importance. The subsequent evolution of the electronics industry was challenge driven typical of a digital world of technical specialists, a situation that existed until the arrival of consumer electronics. The digital world quickly became ubiquitous acquiring an unstoppable momentum, especially once parallel developments in software created the so-called 'killer' applications. The digital worlds' ubiquitous penetration of human societies raised the spectre of a crisis between existence and extinction, an ever-present phenomenon throughout human existence. The crisis takes many interconnected forms perceived as a cascade of situations containing many turning points involving multiple and interconnected themes. For this reason the paper suggests that all research be underlain by the notion of a crisis in preference to that of a challenge based on well-defined problem-solving. The digital world will shape all lives well into the future, providing mutual existence in opposition to extinction. View Show abstract
https://www.researchgate.net/publication/226129240_Knowledge_to_Wisdom_We_Need_a_Revolution
Animals | Free Full-Text | Relationship between Vegetation Habitats and Bird Communities in Urban Mountain Parks The coastal areas of southeast China have typical high-density urbanization characteristics, and urban mountain parks are important green spaces in these urban green space systems. Our study was conducted in five typical urban mountain parks in Fuzhou, China. The bird survey was carried out in 25 transects of different vegetation habitats for 10 months, and the vegetation survey was conducted in 25 habitats to investigate the characteristics of bird communities in different vegetation habitats and the causes of their differences. The results showed: (1) From 1 October 2021 to 15 July 2022, we recorded a total of 90 bird species in 8 orders, 37 families, and 64 genera, with 1879 individuals in five vegetation habitats in the urban mountain parks. (2) Abundance and diversity of trees are vegetation variables affecting bird diversity (bird species richness, abundance, and Shannon diversity) in urban mountain parks, and the average branch height under trees has a significant effect on bird evenness. (3) We found more bird species and higher bird diversity in both sparse and dense forest habitats, but fewer bird species in waterfront, shrub, and grassland habitats; (4) Average tree height (AVE_HEIt) was only present in the best model of bird abundance and evenness. However, none of the best models found a significant effect of the number of tourists and predators on bird diversity. Our results could provide a theoretical basis and guidance for the future improvement of ecological service functions of bird habitats in urban mountain parks in subtropical coastal areas. Relationship between Vegetation Habitats and Bird Communities in Urban Mountain Parks by Weizhen Xu 1 , Jiao Yu 1 , Peilin Huang 1 , Dulai Zheng 1 , Yuxin Lin 1 , Ziluo Huang 1 , Yujie Zhao 1 , Jiaying Dong 2 , Zhipeng Zhu 3 and Weicong Fu 1,4,* 1 College of Landscape Architecture, Fujian Agriculture and Forestry University, 15 Shangxiadian Rd, Fuzhou 350002, China 2 School of Architecture, Clemson University, 105 Sikes Hall, Clemson, SC 29634, USA 3 College of Architecture and Urban Planning, Fujian University of Technology, 33 Xuefunan Rd, Fuzhou 350118, China 4 Engineering Research Center for Forest Park of National Forestry and Grassland Administration, 63 Xiyuangong Rd, Fuzhou 350002, China * Author to whom correspondence should be addressed. Animals 2022 , 12 (18), 2470; https://doi.org/10.3390/ani12182470 Received: 21 August 2022 / Revised: 9 September 2022 / Accepted: 14 September 2022 / Published: 19 September 2022 (This article belongs to the Special Issue Recent Advances in Bird Diversity from Mountains and Lakes ) Simple Summary The complexity of urban green space vegetation is an extremely vital influential factor and predictor of biodiversity, and vegetation habitat factors have been shown to explain more variation in bird diversity than other environmental factors. In this study, we explored the characteristics and differences in bird diversity among vegetation habitats in five typical urban mountain parks in coastal areas of southeast China. Our study showed that: (1) Sparse forest supports more bird species and higher bird diversity. (2) Tree diversity significantly affects bird diversity in urban mountain parks. (3) The average subbranch height of trees has a significant effect on the evenness of birds. (4) The number of tourists and predators has little impact on bird diversity. This study could provide suggestions for the rational allocation of vegetation in urban mountain parks in southeast coastal areas to improve local ecological service functions as habitats for urban wildlife, especially wild birds. Abstract The coastal areas of southeast China have typical high-density urbanization characteristics, and urban mountain parks are important green spaces in these urban green space systems. Our study was conducted in five typical urban mountain parks in Fuzhou, China. The bird survey was carried out in 25 transects of different vegetation habitats for 10 months, and the vegetation survey was conducted in 25 habitats to investigate the characteristics of bird communities in different vegetation habitats and the causes of their differences. The results showed: (1) From 1 October 2021 to 15 July 2022, we recorded a total of 90 bird species in 8 orders, 37 families, and 64 genera, with 1879 individuals in five vegetation habitats in the urban mountain parks. (2) Abundance and diversity of trees are vegetation variables affecting bird diversity (bird species richness, abundance, and Shannon diversity) in urban mountain parks, and the average branch height under trees has a significant effect on bird evenness. (3) We found more bird species and higher bird diversity in both sparse and dense forest habitats, but fewer bird species in waterfront, shrub, and grassland habitats; (4) Average tree height (AVE_HEIt) was only present in the best model of bird abundance and evenness. However, none of the best models found a significant effect of the number of tourists and predators on bird diversity. Our results could provide a theoretical basis and guidance for the future improvement of ecological service functions of bird habitats in urban mountain parks in subtropical coastal areas. Keywords: bird diversity ; spatial and temporal variation ; urban mountain parks ; vegetation habitats 1. Introduction With the continuous acceleration of urbanization, urban ecosystems are seriously damaged [ 1 , 2 , 3 ]. In the process of creating a harmonious landscape between humans and nature, the level of regional biodiversity continues to decline, and how to effectively maintain biodiversity is one of the greatest challenges for environmental protection in the 21st century [ 4 ]. Bird species, as one of the critical components of biodiversity and important elements in different trophic levels of the food chain, are vital indicators of the urban ecosystem’s health [ 5 ]. Urban green space [ 6 , 7 ] plays a crucial role in providing suitable habitats for urban wildlife, and plants, as the physical environment on which most wildlife depends, are an essential element in maintaining the balance of urban ecosystems themselves and protecting biodiversity. Bird species are not only an important indicator to evaluate the quality of the ecological environment in a certain area but are also considered one of the best objects to study urban biodiversity [ 8 , 9 ]. In recent years, studies on the relationship between bird diversity and vegetation have mostly been conducted in natural environments [ 10 , 11 , 12 ]. However, with the rapid development and spread of urbanization, it is particularly important to conduct such research in urban areas [ 13 , 14 , 15 ]. The complexity of urban green space vegetation is an extremely vital influence and predictor of biodiversity, and vegetation habitat factors have been shown to explain more variation in bird diversity than other environmental factors [ 16 , 17 ]. Previous studies have also shown that changes in vegetation habitat composition can indirectly or directly alter bird composition and that increasing vegetation structural complexity and species diversity can effectively increase bird diversity [ 18 , 19 , 20 ]. In urban vegetation communities, the canopy cover of tree forests is reduced compared to the natural environment, and the reduction in tree cover has a negative effect on bird communities [ 21 ]. Therefore, the study of urban bird habitats can focus on a certain type of urban green space to provide more effective planning guidelines for decision-makers, and then provide references for future urban green space biodiversity enhancement. Fuzhou has a richness of bird resources, with 455 species recorded in the China Birding Record Center ( http://www.birdreport.cn/ , accessed on 13 August 2022) as of August 2022. Therefore, the conservation of wild bird resources in Fuzhou is significant not only for the improvement of local biodiversity but also for the protection of all wild bird species along their migratory routes through Fuzhou [ 22 ]. Unlike ordinary urban parks, urban mountain parks are usually built on the unique environment of special topography and natural ecology and are a major part of the urban green space system [ 23 ]. Moreover, urban mountain parks exist in a large number of subtropical coastal areas in China, so they are typical and have certain research significance [ 24 ]. However, the vegetation configuration of urban mountain parks has been mainly considered for landscape and recreation needs, and its ecological service function as a wildlife habitat has not received sufficient attention [ 25 ]. Therefore, studying the relationship between bird communities and vegetation habitats in urban mountain parks is a crucial basic study that can effectively improve the level of bird diversity in urbanized areas. In this study, we explored the characteristics and differences in bird diversity among vegetation habitats in five typical urban mountain parks in coastal areas of southeast China, intending to address the following four questions: (1) Does bird diversity differ among vegetation habitats in subtropical coastal urban mountain parks? What are the causes of such differences? (2) Does bird diversity vary seasonally in different vegetation habitats? (3) Which vegetation habitat factors affect bird diversity in urban mountain parks? What is the importance of these habitat factors for bird diversity? (4) How can the vegetation habitat of urban mountain parks be reasonably created to enhance bird diversity? In this context, we intend to provide a theoretical basis and suggestions for the rational allocation of vegetation in urban mountain parks in southeast coastal areas to improve their ecological service functions as habitats for urban wildlife, especially wild birds, by answering these questions. 2. Study Area and Methods 2.1. Study Area Fuzhou, a typical coastal city in southeast China, was selected as the study area, with latitude and longitude ranging from 25°15′ N~26°39′ N and 118°08′ E~120°31′ E. It is a mountainous city surrounded by many mountains, and there are 58 mountain ranges of different scales in its area [ 26 ]. In addition, the Fuzhou Municipal Government has built a number of mountain parks for tourists and citizens to enjoy, all of which are based on the original natural mountain terrain [ 27 ]. Therefore, Fuzhou is a representative city for studying bird diversity in mountain parks. According to the urban planning and vegetation situation in Fuzhou and regarding the previous selection methods, the urban mountain parks were systematically sampled according to the following requirements: (1) different and representative locations, and within the main urban area of Fuzhou, i.e., within the Third Ring Expressway; (2) high green area and vegetation coverage, diverse plant composition, and typical habitats; and (3) rich bird resources, which are the main places for surrounding residents or visitors to watch birds. The following five urban mountain parks were selected for the study: Fushan Country Park (235.59 ha, 4~143 m a.s.l.), Meifeng Mountain Park (18.44 ha, 24~103 m a.s.l.), Niugang Mountain Park (29.89 ha, 11~60 m a.s.l.), Feifeng Mountain Park (39.41 ha, 5~62 m a.s.l.), and Pingshan Park (11.86 ha, 12~39 m a.s.l.) ( Figure 1 ). Moreover, all the five urban mountain parks have similar vegetation structures. Figure 1. The location map of five urban mountain parks in the subtropical coastal areas of China was selected in this study. 2.2. Vegetation Habitats and Sampling Criteria We conducted a pre-survey of vegetation habitats in the selected five urban mountain parks between 10 and 20 October 2021. Based on the pre-survey, and referring to Ossola (2016) et al. [ 28 ] and Yang (2015) et al. [ 29 ], a total of five categories of urban mountain park vegetation habitats were classified as follows ( Figure 2 ): Figure 2. Schematic diagram of five typical vegetation habitats in urban mountain parks. From left to right are dense forest habitat, grassland habitat, waterfront habitat, shrub habitat, and sparse forest habitat. (1) Sparse forest: 30% ≤ tree canopy cover ≤ 70%, mainly tree-turf or trees; (2) dense forest: tree canopy cover > 70%, mainly tree-shrub-ground cover or tree-ground cover; (3) waterfront: lakes, ponds, streams, ditches, etc., vegetation mostly reeds, irises, and other aquatic plants; (4) grassland: tree canopy cover < 30%, mainly herbaceous plants or grassland space; and (5) shrub: tree canopy cover < 30%, mainly shrub-ground cover or shrub. The above five habitats were all present in the five selected urban mountain parks. Transects [ 30 ] of 100 m × 50 m are randomly laid along the internal road of the mountain park as the basic unit of bird survey, with 100 m being the length of the transects and 25 m being the radius within which individuals of each species were counted [ 31 ]. The shortest distance between transects should be longer than 100 m to provide spatial independence, and the locations should be scattered as evenly as possible. To ensure scientific and fair results, we used “systematic sampling [ 32 ]” to select a sample section containing the above five vegetation habitats in each urban mountain park, and finally, a total of 5 × 5 vegetation habitats were selected for subsequent analysis. 2.3. Vegetation Habitat Variables A standard 20 m × 20 m sample square [ 33 , 34 ] was set in the middle of each transect as the basic unit of the plant survey (randomly sampled along the side of the road toward the interior of the plant community). From May to July 2022, the vegetation survey was carried out in all sample squares using “five-point sampling [ 35 ]”. A large sample square of 20 m × 20 m was set up with the survey sample point as the center, and the species and number of tree layers were counted. Within the 20 m × 20 m sample square, five 4 m × 4 m medium sample squares and five 1 m × 1 m small sample squares were randomly selected. The species and number of shrub layers were investigated in the middle sample square, and the species of the ground cover layer were investigated in the small one. The stratification structure of vegetation [ 36 ] was divided according to the height of above-ground parts of plants (tree layer, h > 2.5 m; shrub layer, 0.5 m ≤ h ≤ 2.5 m; ground cover layer, h < 0.5 m), and information on 14 vegetation variables ( Table S1 ) was collected as follows. (1) Diversity of tree layer (DIVt), the diversity index of tree layer within the large sampling square, diversity index was calculated using the Shannon–Wiener index with the formula: H′ = −Σ P i lnP i (1) P i is the ratio of the number of individuals of plant species i to the total number of individuals in the community, i = 1, 2, …, S . S is the total number of plant species. (2) Diversity of shrub layer (DIVs), the diversity index of shrub layer plants within the medium sampling square, calculated by the same formula as the tree layer diversity index. (3) Richness of tree layer (RICt), the number of species in a tree layer within the large sampling square. (4) Richness of shrub layer (RICs), the number of species of shrub layer plants in the middle sampling square. (5) Richness of ground cover (RICg), the number of species of ground cover plants in the small sampling square. (6) Coverage of tree layer (COVt), the percentage of canopy area of a tree layer to the total area of a large sampling square. (7) Coverage of shrub layer (COVs), the percentage of shrub layer cover area to medium sampling square. (8) Coverage of ground cover (COVg), the percentage of ground cover area to a small sampling square. (9) Abundance of trees (ABUt), the number of individuals in the tree layer in the large sampling square. (10) Maximum tree height (MAX_HEIt), the maximum tree height of the tree layer in the large sampling square. (11) Average branch height under trees (AVE_HBt), the average branch height under trees in the tree layer within the large sampling square. (12) Average shrub heights (AVE_HEIs), the average height of shrub layer plants within the medium sampling square. (13) Average tree diameter at breast height (AVE_DBH), the average diameter at breast height of plants in the tree layer within the large sampling square. (14) Average tree height (AVE_HEIt), the average height of plants in the tree layer within the large sampling square. In addition, we also investigated two environmental variables [ 37 , 38 ] that may significantly affect bird communities: (15) Number of predators (NoP), the average number of predators (cats, dogs, and other animals that may prey on birds) within the transects during the survey period. (16) Number of tourists (NoT), the average number of tourists within the transects during the survey. 2.4. Bird Survey A total of four observers participated in this study, all of whom have a specialized ecological background and have been members of the Fujian Bird Watching Society for more than one year. “ A field guide to the birds of China [ 39 ]” was used to identify bird species. Further identification is carried out by photographing or recording the case when bird species cannot be identified at the time. A fixed number of two observers was used for each observation to minimize the influence of personnel changes during the bird survey. Line transect methods [ 40 ] were used, and transects were selected at random at the beginning of each survey to control the randomness of observation time. Each survey lasted 10–20 min per transect and ended until no new species were present. The official bird survey period was from 1 October 2021 to 15 July 2022, and the survey frequency was once every three months. Bird surveys were performed once every three months for one day. According to the classification of the four seasons in Fuzhou by the Fujian Meteorological Bureau ( http://fj.cma.gov.cn/fzsqxj/ , accessed on 10 October 2021), the bird survey in each season is as follows: spring (April 2022), summer (July 2022), autumn (October 2021), and winter (January 2022) to enter the subsequent analysis. In addition, we classified the behavior of birds [ 41 ] among different vegetation habitats into the following three categories: (1) Perching: birds were observed in resting, calling, preening, singing, etc. (2) Moving: birds were observed moving among different places, chasing, searching, fighting, etc. (3) Feeding: birds were observed pecking for food or eating worms, plants, or other food resources. 2.5. Analysis 2.5.1. Bird Diversity Species richness represents the number of all species surveyed in each habitat, measured using the Chao1 estimator [ 42 ], which is the lower limit of undetected species richness, calculated as the number of singletons and doubletons. Abundance is calculated as the total number of individuals of all species surveyed in each habitat. The Pielou index [ 43 ] is measured using the interspecific encounter probability, which controls for sampling effort and bird species density and uses repeated resampling of data to calculate the probability that two randomly sampled individuals in a combination represent two different species. Bird diversity is measured by the Shannon diversity [ 44 ], which is based on the frequency of species and does not favor rare or common species. All four indexes (species richness, abundance, Pielou, and Shannon diversity) were performed in the “vegan” package [ 45 ] of R 4.0.2. We then used integrity curves estimated from sample coverage to assess the completeness of sampling. The total species richness of the overall bird community was estimated and compared with individual-based interpolation and extrapolation of abundance data to a multi-indicator model in the “iNEXT” package [ 46 ] which takes into account the undetectability of rare species. Further, we checked the Gaussian distribution of the four indexes, and a log10 transformation was performed when indexes did not conform to the normal distribution [ 47 ]. Because the shortest distances between transects were all longer than 100 m, there may not be any serious spatial autocorrelation. Finally, we used the Mann–Whitney–Wilcoxon test [ 48 ] to compare whether bird diversity differed among vegetation habitats. 2.5.2. Bird Behavior When birds were observed to occur directly in vegetation within 25 m of the transect, we counted the frequency of each behavior. The frequencies of each bird’s behavior in the five vegetation types were compared using a chi-squared test [ 49 ]. Bird species that fly by or are identified by sounds were excluded from behavior analysis because no direct vegetation layer information was collected in these cases. 2.5.3. Non-Metric Multidimensional Scaling Variation in species composition was measured by species variability. It is determined from the log(X + 1) transformed Bray–Curtis similarity matrix of the abundance data. Its equation is as follows. BC ij = 1 − 2 C ij S i + S j (2) where C ij is the sum of the minimum values for bird species common to both i and j only. S i and S i are the total numbers of bird species in both i and j . To investigate species variability among different vegetation habitats, nonmetric multidimensional scaling (NMDS) [ 50 ] was used to analyze the composition of bird communities in different vegetation habitats. Then, we derived the species composition of bird communities between habitats and we compared them using analysis of similarity (ANOSIM), a nonparametric multidimensional ranking method for detecting differences between sample groups of communities, using the function “anosim” from the vegan package of R 4.0.2. ANOSIM generates R statistics [ 45 ] that range from 0 to 1 and give an absolute measure of the degree of separation of the groups (R > 0.75, well separated; 0.25 < R < 0.75, overlapping to some extent but different; R < 0.25, almost impossible to separate). 2.5.4. Response of Bird Communities to Different Vegetation Habitats Fourteen vegetation variables from each vegetation habitat sample were subjected to principal component analysis (PCA) [ 51 ] and varimax normalized rotation procedures to facilitate interpretation. PCA reduced the dimensionality of the 14 variables by transforming them into three principal components (the first four principal components explained more than 60% of the total variance). We identified vegetation variables with absolute loading values greater than 0.4 in the four principal components and processed them using Pearson correlation [ 52 ] to assess their independence. PCA was calculated using the “prcomp” function of R software. The four PC values and NoP and NoT were then defined as six predictor variables. These six factors were examined using multiple linear regression models to identify factors that had significant effects on the bird community. The selection of the best model by stepwise regression was based on an information-theoretic approach using the Akaike information criterion [ 53 ]. Models that differed from the best model by less than 2 AICc units (ΔAICc ≤ 2) were selected as the most parsimonious models. Stepwise regression was performed in the R software “MuMIn” package. In addition, we used regression trees to assess how vegetation variables changed bird diversity. Regression trees [ 54 ] allow hierarchically analyzing the effects of variables using a tree diagram, thus avoiding the problem of multicollinearity between variables. The variables and their tendency to influence the dependent variables were observed by tracking the presence of variables at each branch node. Regression tree analysis was performed using the “rpart” package [ 55 ]. All statistical analyses were performed in R 4.0.2. 3. Results 3.1. Overview From 1 October 2021 to 15 July 2022, we recorded a total of 90 bird species in eight orders, 37 families, and 64 genera, with 1879 individuals in five vegetation habitats in the urban mountain parks ( Table S2 ). Among them, the five most common bird species were Japanese White-eyes ( Zosterops japonicus) (243 individuals), Chinese Bulbuls ( Pycnonotus sinensis) (187 individuals), Tree Sparrows ( Passer montanus) (187 individuals), Black-throated Tits ( Aegithalos concinnus ) (102 individuals), and Red-whiskered Bulbuls ( Pycnonotus jocosus) (95 individuals). In terms of residence type, resident bird species occupied the largest proportion (66.67%, 0), followed by winter visitors (16.67%, n = 15), summer visitors (11.11%, n = 10) and passing migrants (5.56%, n = 5). For the IUCN Red List of Threatened Species, LC (least concern) species occupied a larger proportion (97.78%, n = 88). One VU (vulnerable) species, Collared Crow ( Corvus torquatus) , was recorded in Fushan Country Park, and one NT (near threatened) species, Japanese Paradise Flycatcher ( Terpsiphone atrocaudata) , was recorded in Pingshan Park. We found that 41.43% (261/630) of the perching behavior was observed in the sparse forest ( Figure 3 ). The chi-square test showed that the number of perching behaviors of birds in the sparse forest was significantly different from other habitats (X 2 = 418.29, df = 4, p < 0.001). In terms of moving behaviors, 42.30% of the behaviors occurred in dense forest (291/688). Birds in sparse forest (8.87%, 61/688) and waterfront habitats (9.59%, 66/688) had a similar frequency of moving behaviors. Moreover, the dense forest was highly significantly different from the other habitats (X 2 = 277.89, df = 4, p < 0.001). Similarly, the chi-square test showed that in terms of feeding behavior, the shrub habitat (27.84%, 164/589) had the most feeding behavior and was significantly different from other habitats (X 2 = 63.963, df = 4, p < 0.001), while the water habitat had the least feeding behavior (9.68%, 57/589). The sparsity curve ( Figure 4 ) showed a gradual flattening curve with an increasing number of individuals. Additional bird individuals made a small marginal contribution to the discovery of new species, indicating a gradual saturation of bird species. The sampling completeness of bird surveys in urban mountain parks was greater than 85% ( Figure 5 ), indicating that the entire data set is reasonable and meets the need for further analysis. Figure 3. Distribution of different behavioral types of birds in different vegetation habitats in urban mountain parks. Figure 4. Comparison of individual-based interpolation (sparsity) and extrapolation of bird communities in different vegetation habitats in urban mountain parks under a multi-indicator model. Figure 5. Sample completeness curves of bird communities in different vegetation habitats in urban mountain parks. The filled graphs (triangles, circles, etc.) represent the sample coverage. 3.2. Spatial and Temporal Variation of Bird Communities in Different Habitats 3.2.1. Spatial Variation of Bird Communities in Different Habitats Among the five different vegetation habitats in the urban mountain park, the sparse forest habitat had the highest Shannon diversity (3.556, mean ± SD = 3.05 ± 0.22), while the water habitat had the lowest Shannon diversity (2.818, mean ± SD = 2.22 ± 0.38) ( Figure 6 A). The results of the Wilcoxon paired test showed that there were significant differences in Shannon diversity between sparse forest and dense forest (W = 8, p = 0.016). The ranking of species richness was sparse forest ( n = 76, mean ± SD = 30.67 ± 8.07) > dense habitat ( n = 58, mean ± SD = 21.59 ± 2.12) > shrub ( n = 50, mean ± SD = 17.53 ± 3.97) > grassland ( n = 44, mean ± SD = 15.65 ± 3.45) > waterfront ( n = 37, mean ± SD = 14.15 ± 4.09) ( Figure 6 B). We also found significant differences between sparse forest and grassland (W = 1, p = 0.016), shrub (W = 1.5, p = 0.028) and waterfront (W = 25, p = 0.008) habitats in species richness. In terms of the number of bird individuals ( Figure 6 C), sparse forest had the highest number of individuals ( n = 564, mean ± SD = 112.80 ± 25.60), followed by dense forest ( n = 410, mean ± SD = 82 ± 18.81), while grasslands had the lowest number of individuals ( n = 256, mean ± SD = 51.20 ± 7.14). Regarding the Pielou index ( Figure 6 D), shrub habitat (Pielou index = 0.614, mean ± SD = 0.64 ± 0.03), sparse forest (Pielou index = 0.595, mean ± SD = 0.64 ± 0.16), and grassland (Pielou index = 0.598, mean ± SD = 0.62 ± 0.03) all had high evenness, but waterfront (Pielou index = 0.554, mean ± SD = 0.60 ± 0.06) maintained a lower evenness. Figure 6. Comparison of bird diversity ( A ), richness ( B ), abundance ( C ), and Pielou index ( D ) in five vegetation habitats in urban mountain parks in Fuzhou, China. DF, dense forest; SF, sparse forest; S, shrub; G, grassland; W, Waterfront. The Bray–Curtis function calculated the distances between overall bird communities of five vegetation habitats and ranked the results. Among them, ANOSIM similarity analysis was applied to non-parametric tests. Surprisingly, the results of 999 permutations showed that there was little difference between the groups of overall birds in different vegetation habitats ( Figure 7 ) (Stress = 0.163, ANOSIM statistic R = 0.085, Significance = 0.121). Figure 7. Differences in bird community composition for 25 sampled transects (five dense forest habitats = red circles, five sparse forest habitats = blue circles, five grassland habitats = brown circles, five shrub habitats = green circles, and five waterfront habitats = purple circles) in five different vegetation habitats in urban mountain parks. 3.2.2. Temporal Variation of Bird Communities in Different Habitats The sparse forest habitat supported higher bird diversity in all seasons ( Figure 8 A). Moreover, in all habitats, bird diversity was maintained at a lower level in summer. In winter, the shrub habitat (Shannon diversity = 3.056) had about the same level of bird diversity as the sparse forest (Shannon diversity = 3.075). In terms of richness, the number of bird species in sparse forest (richness = 19) decreased significantly in summer and was almost equal to that of shrub habitats (richness = 18). In contrast, bird richness in waterfront and grassland habitats varied similarly throughout the year ( Figure 8 B). In terms of annual variation in abundance ( Figure 8 C), the sparse forest maintained a high level of bird abundance throughout the year, and the trend was more consistent with that of dense forest habitat. The number of bird individuals in both habitats decreased to some extent in summer and gradually increased in autumn and winter, reaching a higher value during winter. In terms of annual changes in the Pielou index ( Figure 8 D), the waterfront, shrub, dense forest, and grassland habitats showed an “N” trend with seasonal migration. In contrast, the Pielou index of sparse forest habitat showed a small increase in summer and a significant decrease in autumn and winter. Figure 8. Comparison of bird diversity ( A ), richness ( B ), abundance ( C ), and Pielou index ( D ) with seasonal variation in five habitats in urban mountain parks in Fuzhou, China. 3.3. Relationship between Bird Diversity and Vegetation Habitats We used PCA to assess vegetation composition variables for five vegetation habitats in urban mountain parks. The first four components accounted for 62.5% of the total variance ( Table 1 ), so they were selected for further analysis. The variables DIVt, DIVs, and RICt had absolute loading values greater than 0.4 in the first component (PC1, Table 1 ), and the Pearson correlation test showed a highly significant correlation between DIVt and RICt (correlation = 0.855, p -value < 0.001). Thus, PC1 mainly represents the diversity of trees in vegetation habitats. The variables DIVs and AVE_HEIs had absolute loading values greater than 0.4 in PC2, and they symbolize the vegetation diversity in the shrub layer. In the third principal component (PC3), the absolute loading values of COVt, COVg, and AVE_DBH were greater than 0.4, and they mainly represented the shrub cover and the average diameter at breast height of trees in the sample square. In the fourth principal component, only one variable, AVE_HBt, had absolute loading values greater than 0.4, which represented the average height of the branch height of trees in the sample square. Table 1. Principal component analysis was performed on the variables (predictor variables) of different vegetation habitats in urban mountain parks. Multiple linear regression models showed that PC1 was a significant factor affecting richness (F-statistic = 4.929, R 2 = 0.141, p = 0.037), abundance (F-statistic = 4.426, R 2 = 0.222, p = 0.024) and Shannon diversity (F statistic = 8.27, R 2 = 0.265, p = 0.009) were essential factors because in these best models of bird diversity (models 1, 4, and 9), they all had ΔAICc < 2 ( Table 2 ). PC4 was only present in the models of abundance (model 4) and Pielou index (model 14), where it had a lower fit (F-statistic = 2.498, R 2 = 0.059, p = 0.013), but also indicated that the average height under tree branches was vital in both bird abundance and evenness. However, neither NoP nor NoT appeared in any of the best models. Table 2. A multiple linear regression model based on the relationship between simulated bird diversity (predictor variables) and vegetation habitat variables (response variables) under the Akaike information criterion. PC1 all appeared as relevant vegetation factors in the best regression models for richness, abundance, and Shannon diversity ( Table 2 ), so the important variables in PC1 (DIVt and RICt) were used to construct regression trees. Since PC4 (AVE_HBt) also appeared in the best regression models for abundance and Pielou, we used PC1 and PC4 to construct regression trees for abundance, but only PC4 was used to construct regression trees in Pielou. For the regression tree of Shannon diversity with PC1 ( Figure 9 A), DIVt was the main vegetation variable with the most positive effect on Shannon diversity in PC1. And, at DIVt > 1.6, it had a positive effect on bird diversity. Similarly, in the regression tree between richness and PC1 ( Figure 9 B), DIVt had a positive effect. In addition, at DIVt < 1.6, bird richness decreased. In the regression tree of abundance with PC1 and PC4 ( Figure 9 C), DIVt was the most dominant vegetation variable with a positive effect, and abundance had a more significant increase when DIVt > 2. In Figure 9 D, only AVE_HBt occurred, indicating the average branch height under trees had a more positive effect on the evenness of birds. Figure 9. Relationships between bird diversity ( A ), richness ( B ), abundance ( C ), and Pielou index ( D ) of urban mountain parks based on regression tree and vegetation variables from the results of principal component analysis (PC1 to PC4). DIVt, diversity of trees; AVE_HBt, average branch height under trees. 4. Discussion 4.1. Distribution of Bird Communities in Different Vegetation Habitats Previous studies emphasized that habitat structure type and its compositional complexity were also two critical determinants of bird diversity [ 16 , 20 , 56 , 57 ]. Erdelen (1984) [ 58 ] found that bird species richness and diversity were often related to vegetation structure rather than just woody species richness. The planning and design of urban mountain parks needs to provide for not only the recreational needs of tourists but also issues such as providing habitats for wildlife [ 22 ]. Therefore, various types of vegetation structures have emerged in urban mountain parks, such as dense forests, sparse forests, shrubs, grasslands, and waterfronts as five typical vegetation habitat types, which represent an increase in structural complexity. We recorded more bird species in the sparse forest, dense forest, and shrub habitats, which have a diverse vegetation structure and a more natural land cover than heavily managed vegetation (e.g., artificial grasslands or regular woodlands), giving wild species a better living quality. 4.2. Response of Bird Communities to Vegetation Habitat Factors Tree layers are often considered to be one of the most essential vegetation factors for enhancing bird diversity in urban green spaces because they provide nesting and foraging sites for birds [ 59 ]. The regression model of bird diversity and vegetation habitat factors showed that the tree diversity (i.e., PC 1 in Table 1 ) had a positive effect on bird diversity ( Table 2 ), which indicated that both the structural complexity and diversity of vegetation have a significant positive effect on bird communities in urban mountain parks. Based on regression tree analysis, we highlighted that tree diversity was a critical vegetation variable affecting bird diversity ( Figure 8 A), richness ( Figure 8 B), and abundance ( Figure 8 C). However, in contrast to Fontana et al. (2011) [ 60 ] and Yang et al. (2015) [ 29 ], we did not find a positive effect of COVt on bird communities, as it was not significant in any of the best regression models. The diversity of the shrub layer was also a vital indicator for the bird community compared to the tree layer [ 61 ]. Moreover, the shrub layer had the highest foraging behavior in the results of bird behavior (27.84%, 164/589). Dense shrubs in mountain parks usually reduce the visibility of human visitors, thus reducing human disturbance so that high bird diversity can be maintained in shrub habitats. Waterfront habitats are thought to promote bird activity, and they provide a good food resource in addition to being a daily source for bird species. Therefore, we similarly suggest that the value of water resources for bird communities could be studied in more urban parks based on various types of water system designs. 4.3. Temporal and Spatial Changes in Bird Diversity Birds usually migrate spatially along with the change of seasons [ 62 , 63 ]. As a critical stop station on the East Asian–Australian migratory route of birds, Fuzhou usually undergoes large changes in bird communities during seasonal changes, especially in urban mountain parks. Because mountain parks are covered with natural/semi-natural vegetation and usually have more superior habitats than ordinary urban parks, they become important stopover sites for lots of bird species during migration. Our results showed that bird diversity (Shannon diversity, richness, and abundance) maintained high values in both spring and winter. This may be due to the fact that spring is generally the breeding season for birds and winter is the arrival period for migratory birds, so high bird diversity is maintained during these two periods. Although Fuzhou is a coastal city [ 64 ], it has very high temperatures in summer, which seriously affects the survival and occurrence of bird species, especially on the waterfront in summer, and all four indexes maintained low values in summer. In autumn, a crucial period for vegetation flowering and fruiting as well as feeding behavior of bird species, there was a significant increase in bird diversity in all habitats, especially in sparse forests and dense forests. Interestingly, the Pielou index for shrub, grassland, and waterfront habitats showed similar changes throughout the year. The regression tree results showed that the Pielou index was positively correlated with the average branch height of trees, and in general, a higher average branch height of trees indicated the ability to provide different ecological niches for birds, which, in turn, reduced competition among birds and maintained a higher Pielou index. 4.4. Implications for Urban Mountain Parks Management In urban mountain parks, we found sparse forest supported higher bird diversity. In addition, studies from other regions have identified variables such as the number of tourists and predators as important negative drivers of bird abundance, richness, and diversity [ 12 , 17 ]. However, no significant effects of these two variables on bird diversity were found in our study, which may be attributed to the good ecosystem services of the mountain parks themselves that provide diverse refuge spaces for bird species. Meanwhile, our study found that the compositional diversity of trees had a positive effect on maintaining bird diversity, richness, and abundance, which was also confirmed in previous studies. We found fewer bird species in waterfronts ( n = 37, mean ± SD = 14.15 ± 4.09) and grasslands ( n = 44, mean ± SD = 15.65 ± 3.45) than in other habitats, further supporting the role of tree diversity in supporting bird community structure, and urban managers and planners should incorporate these measures into urban green space design and management. The regression tree results showed that the average subbranch height of trees had a positive effect on the aspect of Pielou index enhancement, and it is also one of the key points that should be focused on during the construction of urban mountain parks or other kinds of parks in the future. Moreover, in the construction of mountain parks, in addition to meeting the daily service needs of visitors, diversified and multifunctional vegetation habitats are not only a critical way to enhance biodiversity but also an indispensable part in the process of promoting the synergistic development of humans and nature [ 65 ]. 5. Conclusions Urban mountain parks are an essential ecological space in the urban green space system of China’s subtropical coastal areas. The construction of these urban mountain parks relies on the original topography, emphasizes the opportunities for natural plant growth, and contains a combination of various types of vegetation. Our study led to the following conclusions: (1) We found more bird diversity and species in both sparse forest and dense forest habitats. However, fewer species were found in waterfront, shrub, and grassland habitats in different seasons. Moreover, Heyman (2010) [ 66 ] confirmed that the removal of 50% of shrubs did not affect local bird diversity, which is useful information for designing management plans for urban green spaces. Previous studies have confirmed that improving bird diversity throughout the city requires enhancing the quality of various types of habitats in urban green spaces, which, in turn, has a contributory effect on bird diversity enhancement. (2) Both the complexity and structure of vegetation have a significant effect on the bird community in urban mountain parks. Among them, the abundance and diversity of trees are critical vegetation variables affecting bird diversity, while the average branch height under trees has a significant effect on the Pielou index. The diversity and abundance of trees are integral parts of influencing the bird community in urban mountain parks, which facilitates the survival of birds in areas with high levels of human disturbance. (3) In all regression models, the number of tourists and predators found no significant effect on bird diversity in urban mountain parks. The reason may be that urban mountain parks have good natural vegetation resources, which are the main places for bird species to roost and shelter, and this also emphasizes the maintenance and protection of the existing green space resources in mountain parks. In addition, we hypothesize that bird communities may be greatly influenced by the degree of urbanization or disturbance of other environmental factors. Therefore, we suggest that further research could be conducted in the future to include more green spaces to examine the integrated relationships between bird communities and other environmental variables. In addition, our study only focused on the direct effects of habitat factors on bird species, while ignoring the indirect effects of interactions within the ecosystem, which is one of the priorities for future research. Our results may provide a theoretical basis and guidance for the future enhancement of the ecological service functions of bird habitats in urban mountain parks in subtropical coastal areas. Supplementary Materials The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/ani12182470/s1 , Table S1: Five vegetation habitats and 11 vegetation variables in urban mountain parks in Fuzhou, China. Table S2: Bird list of urban mountain parks and the locations where the birds were observed in Fuzhou, China. Author Contributions Conceptualization, W.X., W.F., J.Y., Y.L. and Z.H.; data curation, W.X., J.Y., P.H., D.Z. and Z.Z.; formal analysis, W.X. and J.Y.; funding acquisition, W.F.; investigation, W.X., J.Y., P.H. and D.Z.; methodology, W.X., J.D., Y.Z. and J.Y.; project administration, W.F.; software, W.X.; supervision, W.F.; writing—original draft, W.X.; writing—review and editing, W.F. All authors have read and agreed to the published version of the manuscript. Funding This study was funded by (1) Green Urbanization across China and Europe: Collaborative Research on Key technological Advances in Urban Forests, grant number 2021YFE0193200; (2) Horizon 2020 strategic plan: CLEARING HOUSE—Collaborative Learning in Research, Information-sharing, and Governance on How Urban tree-based solutions support Sino-European urban futures, grant number 821242; (3) Research on sustainable development of human settlements in Fujian of the plateau discipline construction project of Fujian Agriculture and Forestry University, grant number ysyl-kjtd-2; (4) Forest Park Engineering Technology Research Center of State Forestry Administration, grant number PTJH15002; (5) Special Project of Wuyishan National Park Research Institute, grant number KJg20009A. Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. 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Comparison of individual-based interpolation (sparsity) and extrapolation of bird communities in different vegetation habitats in urban mountain parks under a multi-indicator model. Figure 5. Sample completeness curves of bird communities in different vegetation habitats in urban mountain parks. The filled graphs (triangles, circles, etc.) represent the sample coverage. Figure 6. Comparison of bird diversity ( A ), richness ( B ), abundance ( C ), and Pielou index ( D ) in five vegetation habitats in urban mountain parks in Fuzhou, China. DF, dense forest; SF, sparse forest; S, shrub; G, grassland; W, Waterfront. Figure 7. Differences in bird community composition for 25 sampled transects (five dense forest habitats = red circles, five sparse forest habitats = blue circles, five grassland habitats = brown circles, five shrub habitats = green circles, and five waterfront habitats = purple circles) in five different vegetation habitats in urban mountain parks. Figure 8. Comparison of bird diversity ( A ), richness ( B ), abundance ( C ), and Pielou index ( D ) with seasonal variation in five habitats in urban mountain parks in Fuzhou, China. Figure 9. Relationships between bird diversity ( A ), richness ( B ), abundance ( C ), and Pielou index ( D ) of urban mountain parks based on regression tree and vegetation variables from the results of principal component analysis (PC1 to PC4). DIVt, diversity of trees; AVE_HBt, average branch height under trees. Table 1. Principal component analysis was performed on the variables (predictor variables) of different vegetation habitats in urban mountain parks. Variables PC1 PC2 PC3 PC4 DIVt 0.490 0.108 0.085 0.123 DIVs 0.243 −0.454 0.168 −0.305 RICt 0.465 0.054 0.171 0.246 RICs 0.185 −0.382 −0.295 −0.344 RICg −0.220 −0.265 0.002 0.180 COVt 0.131 0.115 −0.430 0.209 COVs 0.326 −0.066 −0.287 −0.109 COVg 0.046 0.383 0.420 −0.117 ABUt 0.398 0.008 0.179 0.371 MAX_HEIt 0.294 0.223 −0.351 −0.325 AVE_HBt 0.021 0.349 −0.001 −0.451 AVE_HEIs 0.099 −0.420 0.059 0.154 AVE_DBH −0.047 0.216 −0.450 0.323 AVE_HEIt −0.138 −0.068 −0.208 0.192 Standard deviation 1.834 1.453 1.321 1.239 Proportion of Variance 0.240 0.151 0.125 0.110 Cumulative Proportion 0.240 0.391 0.516 0.625 Table 2. A multiple linear regression model based on the relationship between simulated bird diversity (predictor variables) and vegetation habitat variables (response variables) under the Akaike information criterion. NO. Model Intercept df Loglik AICc ΔAICc w i Richness (Chao1) 1 PC1 19.917 3 −83.785 174.712 0.000 0.181 2 PC1 + PC2 19.917 4 −83.154 176.309 1.596 0.081 3 NoT + PC1 21.353 4 −83.579 177.157 2.445 0.053 4 PC1 + PC4 19.917 4 −83.743 177.487 2.774 0.045 5 NoP + PC1 20.176 4 −83.764 177.529 2.817 0.044 Abundance 4 PC1 + PC4 75.160 4 −115.353 240.706 0.000 0.144 5 PC1 75.160 3 −116.828 240.800 0.093 0.137 6 PC1 + PC2 75.160 4 −116.606 243.213 2.507 0.041 7 NoT + PC1 + PC4 80.976 5 −115.083 243.325 2.619 0.039 8 NoT + PC1 79.901 4 −116.669 243.338 2.632 0.039 Shannon diversity 9 PC1 2.549 3 −6.692 20.528 0.000 0.208 10 NoT + PC1 2.649 4 −6.208 22.416 1.888 0.081 11 NoP + PC1 2.594 4 −6.401 22.802 2.274 0.067 12 PC1 + PC4 2.549 4 −6.488 22.975 2.447 0.061 13 PC1 + PC3 2.549 4 −6.506 23.011 2.484 0.060 Pielou index 14 PC4 0.619 3 46.284 −85.425 0.020 0.065 15 PC3 0.619 3 45.957 −84.772 0.673 0.047 16 PC3 + PC4 0.619 4 47.355 −84.710 0.735 0.045 17 PC1 0.619 3 45.839 −84.535 0.910 0.041 18 PC1 + PC4 0.619 4 47.223 −84.446 0.999 0.040 Chicago/Turabian Style Xu, Weizhen, Jiao Yu, Peilin Huang, Dulai Zheng, Yuxin Lin, Ziluo Huang, Yujie Zhao, Jiaying Dong, Zhipeng Zhu, and Weicong Fu. 2022. "Relationship between Vegetation Habitats and Bird Communities in Urban Mountain Parks" Animals12, no. 18: 2470. https://doi.org/10.3390/ani12182470 Article Metrics Xu W, Yu J, Huang P, Zheng D, Lin Y, Huang Z, Zhao Y, Dong J, Zhu Z, Fu W. Relationship between Vegetation Habitats and Bird Communities in Urban Mountain Parks. Animals. 2022; 12(18):2470. https://doi.org/10.3390/ani12182470
https://www.mdpi.com/2076-2615/12/18/2470/htm
Chapter 12 Aristocrats, Mercenaries, Clergymen and Refugees: Deliberate and Forced Mobility of Armenians in the Early Medieval Mediterranean (6th to 11th Century a.d.) in: Migration Histories of the Medieval Afroeurasian Transition Zone Abstract Since Late Antiquity, individuals and groups of Armenian origin were highly mobile across the Middle East and the Mediterranean, providing the basis for what later became the “Armenian diaspora”. The paper systematically explores motives, infrastructures and effects of these migrations, both in the society of departure and in the receiving societies, especially the Byzantine Empire, between the 6th and the 11th century a.d. It focuses on networks of noble elites, of learning, ecclesiastical exchange and pilgrimage as well as professional and mercantile mobility, but also on cases of forced mobility and mass exodus. 1 Introduction Armenian mobility in the early Middle Ages has found some attention in the scholarly community. This is especially true for the migration of individuals and groups towards the Byzantine Empire. A considerable amount of this research has focused on the carriers and histories of individual aristocrats or noble families of Armenian origin. The obviously significant share of these in the Byzantine elite has even led to formulations such as Byzantium being a “Greco-Armenian Empire”.1While, as expected, evidence for the elite stratum is relatively dense, larger scale migration of members of the lower aristocracy (“azat”, within the ranking system of Armenian nobility, see below) or non-aristocrats (“anazat”) can also be traced with regard to the overall movement of groups within the entire Byzantine sphere. In contrast to the nobility, however, the life stories and strategies of individuals of these backgrounds very rarely can be reconstructed based on our evidence. In all cases, the actual significance of an “Armenian” identity for individuals and groups identified as “Armenian” by contemporary sources or modern day scholarship (on the basis ofonomastic material, for instance2) respectively the changeability of elements of identity (language, religious affiliation, naming practices) has found less attention in comparison with efforts to trace the “Armenian element” in Byzantium. Similar observations can be made with regard to scholarship on Armenian mobility into the spheres of the “Eastern” empire of Sasanian Persia and later the Arab Caliphate respectively the Islamic states; especially the change of the religious affiliation and the emergence of “Muslim Armenians” has caused some debate with regard to their qualification as “real” Armenians. For the Byzantine case, the magisterial article by Nina Garsoïan on “The Problem of Armenian integration into the Byzantine Empire” (1998) has not only summed up earlier research, but has also highlighted the complexities and dynamics of identity and of spatial as well as “cultural” mobility.3Regarding the Islamic World the three volumes by Seta B. Dadoyan, who already had written an important study on Armenians in the Fatimid Empire, equally have produced new insights into similar phenomena.4 On this basis, also an attempt to adapt recent approaches from migration history on the early medieval mobility of Armenians is possible. Within the field, the “Armenian diaspora” of course has found attention, but this is especially true for its development since the early modern period;5one has to mention here also the monograph by Sebouh Aslanian on the global trading diaspora of the Armenians of New Julfa in Persia in the 17th century.6Yet, as we will demonstrate in this paper, concepts developed by historians of migration in the last decades can be also be implemented effectively for earlier periods. Useful are of course also categories of a more traditional typology of migration such as duration, distance or scale (in terms of numbers of individuals) of mobility. However, in order to illustrate the actual complexity of mobilities and identity constructions as outlined by Garsoïan or Dadoyan, a “systems approach” towards migration phenomena seems promising.7Therefore, wesurvey material on the interplay between socio-economic, political and spatial structures both in the “society of departure”8and in the “receiving societies”,9which very much defined the scope of action, and the actual agency of individuals and groups. Equally, we will try to identify networks established and/or used by individuals to effect mobility as well as integration within the social framework in the places of destination; yet, these networks could also work as constraining factors.10The character of evidence from our period of course does not allow for a systematic quantitative survey on a large sample, but enables us to accumulate “micro-histories” of individuals and smaller groups across the centuries, which may provide inferences on general trends and mechanisms.11In the following, we will (mostly based on Armenian, Greek and Latin sources) focus on Armenian migration towards the Byzantine Empire, while we have dealt with Armenian mobility towards the imperial spheres in the east (Sasanian Persia, the Caliphate) as well as with migration movements into early medieval Armenia in another study.12 2 The Society of Departure: Early Medieval Armenia between Empires 2.1 Geopolitical and Socio-Political Parameters For migration as spatial phenomenon, geographical parameters of course very much matter. Since the 1st centuryb.c., the Armenian highlands constituted the peripheries of competing empires and a centre of confrontations between them; this position also influenced attitudes of observers from imperial elites towards them. Already Tacitus called the Armenians “ambigua gens”,13situated between the Roman and Iranian great powers and sustaining political and cultural connections to both sides (seeMap 12.1). This “ambiguity” became even stronger when the Armenians started to adopt Christianity since the beginning of the 4th centurya.d. and (also in the eyes of the Iranian imperial centre) strengthened their ties to the new ChristianImperium Romanumof Constantine the Great and his successors.14At the same time, the traditionalsocial structure with its powerful aristocratic houses, which was very similar to that of ancient Iran,15remained strong.16The struggle over Armenia at last lead to the partition of the country between Rome and the Sasanians in 387a.d. (seeMap 12.1) and the abolishment of the Armenian kingship over the next decades. In contrast to the Europeanbarbaricum,17the invention of the Armenian alphabet at the beginning of the 5th century initiated the emergence of a rich indigenous literature, which includes several important historiographical works. These texts provide us with a valuable view on three empires (Rome-Byzantium, Persia and, since the 7th century, the Arab Caliphate) from the perspective of individuals which lived on the edge of these powers. As I was able to show in earlier studies, especially the image of the Byzantine empire in the Armenian historiography of the period moved between admiration of an Christian Empire, its power and civilisation, and – after the divergence of theological interpretations in the mainstreams of Byzantine and Armenian Christianity had become obvious since the late 6th century – contempt for an heretic power of oppression, often in coalition with other enemies of Armenia.18In an often-quoted passage of the history attributed to Sebēos (7th century) we encounter a very grim interpretation of the policy of the neighbouring empires (and the mobility they forced upon the military of the country) vis-à-vis Armenia: At that time [around the year 591] the king of the Greeks (t‛agawor Yunac‛), Maurice, ordered a letter of accusation (gir ambastanut‛iwn) to be written to the Persian king [Xusrōii] concerning all the Armenian princes and their troops: “They are a perverse and disobedient race,” he said: “they are between us and cause trouble. Now come, I shall gather mine and send them to Thrace; you gather yours and order them to be taken to the east. If they die, our enemies die; if they kill, they kill our enemies; but we shall live in peace. For if they remain in their own land, we shall have no rest.” They both agreed.19 At the same time, Armenian historians were very well aware that especially the internal framework of political power allowed Byzantium, Persia or the Caliphate to exert their influence within the country or even to divide it into spheres of interest. Neither during the time of monarchic rule before 390/428 and after 884/885 (when the noble houses of Bagratuni and of Arcruni succeeded in the restoration of – again competing – monarchies20) nor during the period of direct imperial suzerainty over Armenia’s nobility, the fragmentation of the country’s political structures (again also promoted by the geographical fragmentation of the Armenian highlands) allowed for the formation of a regional power centre which could compete with the empires on its borders.21 Armenian society, as far as we are able to reconstruct especially based on the indigenous texts, was divided along the line “noble” (azat) – “not noble” (anazat; including artisans, peasants and merchants). The nobility was dominated by several dozens of houses (tun) of magnates (thenaχarark‛), who based their power on their hereditary landed property worked byanazat, the number of their armed retainers from the lower aristocracy and their hereditary offices and positions of honours, which followed an elaborate ranking system, at the royal court.22Within this framework, sources describe a constant struggle among the great houses for power and prestige, already in the period of Arsacid monarchy and even more afterwards. And already before the end of the kingdom (in 428a.d.), the material and symbolic distinctions bestowed by superior external imperial powers (such as the emperor or the Great King) could become essential for the manifestation of rank and power within the Armenian aristocracy, even more so afterwards. Therefore, exterior powers usually would find a faction within the nobility prepared, at least for some time, to support their efforts for control over the Armenian highlands.23A description of the ideal state ofmiabanut‛iwn(unity, concord) among the aristocracy is given in the history of T‛ovma Arcruni (10th century), together with the insinuation of the decline of this unity and its consequences: For the Armenian princes with their hosts of knights and troops were still living in unison and harmony and concord, though in secret they had suspicions of treachery. However, when discord began to insinuate itself within that unity, they grace of the divine power departed and withdrew.Concerted plans were disregarded in combat and in other matters affecting the administration of the country. (…) They sent letters and messengers to the Caliph secretly from each other.24 Discord (oranmiabanut‛iwn) is a far more prominent motif in Armenian historiography;25it is the main reason of the failure of common actions against imperial powers.26It also describes the state that prevailed in Armenia on the eve of the first Arab invasion.27Yetanmiabanut‛iwndid not only restrict the chances of collective action of the Armenian aristocracy, but also the stability of foreign domination; just as the Armenian kings, also the representatives installed by the imperial overlords were not able to enforce universal allegiance to the suzerain. Therefore, the structure of the Armenian society also allowed for a certain degree of flexibility in relations with the great powers. As Nina Garsoïan has stated: “…the strength and permanence of thetunforged a social structure capable of surviving even in moments of political eclipse and the decentralized character of the society diminished its chances of total annexation.”28This “decentralized character” permitted the adaptation to the separation between various rulers and spheres of interest of the neighbouring empires and the existence of multiple layers of authority and loyalty.29Thus, one member of the Mamikonean clan (the most prominenttunin this period) could lead a rebellion in Persian Armenia in 450/451, whereas a relative served as imperial general in Roman Armenia; forming “trans-local families” therefore could be one strategy for noble houses to maintain power.30Individual noblemen and clans could gain a variety of options, and even the aristocracy at large could achieve a certain degree of autonomy for the country’s affairs if equilibrium between the neighbouring great powers or a momentary power vacuum would allow it. However, the number of options declined as soon as oneimperial power achieved predominance in the region; then, individually or at large, the aristocracy sometimes had to choose between collaboration, resistance, or emigration. 2.2 Deliberate and Forced Noble Mobility31 Within this framework, noble mobility towards the neighbouring imperial spheres became an essential element of the strategies of individuals and of aristocratic houses. As Tim Greenwood has stated, recurring motives in the depiction of the deeds of Armenian aristocrats in our period are “the service to an external authority, the titles and material rewards available to the individual princes and instances of direct contact between Emperor and client.”32As I demonstrated in an earlier study, for the “greatest nobles,” their rank within the Armenian aristocracy became manifest due to its recognition by the Emperor, the Great King or the Caliph, performed in personal encounters either during imperial campaigns in Armenia or in most cases during receptions in the imperial capital. Especially Armenian sources emphasise that noblemen were permitted to stay near the monarch and dine with him and received material rewards from his hands. As within the court societies in Constantinople, Ctesiphon or Baghdad, “the public display of proximity to an Emperor mattered.”33 Noble mobility towards one of the imperial spheres could become long lasting or permanent if service for and integration into the elite of an empire seemed very attractive and/or if the alternative of remaining in Armenia respectively a part of Armenia under suzerainty of another imperial power was less inviting. This was especially the case when aristocrats or entire noble houses had compromised themselves in the eyes of local imperial authorities by participating in attempts to remove foreign suzerainty, often provoked by efforts of the imperial centre to enforce stronger political and economic control (Roman Armenia in the period of Justinian, Arab Armenia in the 8th and 9th century) or religious conformity (Persian Armenian in the 5th century, Byzantine Armenia in the 6th and 7th century). Under changing circumstances, aristocrats were also willing to cross borders several times.34 Also measures of the imperial suzerain to enforce mobility by ordering the relocation of noblemen and their armed retinues to other theatres of war could motivate individuals to evade them by crossing borders. After therestoration of Xusroiion the Sasanian throne with the help of Emperor Maurice, Byzantium in 591 gained suzerainty over most of former Persarmenia up to a line near the capital of Dvin (seeMap 12.1).35The emperor, eager to recover control over the Balkans in the face of the advance of the Avars and Slavs,36transferred many troops from the East to Thrace and equally tried to recruit soldiers among the Armenians. Various aristocrats, convinced by means of promises and presents or of force, marched with their troops to Constantinople, presented themselves to the emperor, and then fought against his enemies. However, some nobles reacted with rebellion and, after its failure, with flight into the Persian Empire.37In the history attributed to Sebēos we find, as we have seen, an Armenian interpretation of the empire’s policy in the form of the letter allegedly written by Maurice to Xusroii(see above). Sebēos also informs us that in the year 602 the Emperor ordered the resettlement of 30,000 households from Armenia in Thrace, but this plan was not executed because of Maurice´s overthrow.38 Thus, while honourable and lucrative service to the Emperor abroad earned praise in the Armenian historiography, measures to enforce stronger imperial control and mobility were interpreted as plans to destroy the socio-political framework of the country. Limitations both to the presence of imperial authority (especially armed forces) as well as to the spatial range of mobility in imperial service were also core conditions under which the Armenian nobility at large under the leadership of Tʻēodoros, lord of the house of Ṙštunik‛, exchanged Byzantine suzerainty for the Caliph´s one in 653: Now the prince of Ismael spoke with them and said: “Let this be the pact of treaty between me and you for as many years as you may wish. I shall not take tribute from you for a three-year period. Then you will pay (tribute) with an oath, as much as you may wish. You will keep in your country 15,000 cavalry, and provide sustenance from your country; and I shall reckon it in the royal tax. I shall not request cavalry for Syria; but wherever else I command they shall be ready for duty. I shall not send amirs to (your) fortresses, nor an Arab army – neither many, nor even down to a single cavalryman. An enemy shall not enter Armenia; and if the Romans attack you I shall send you troops in support, as many as you may wish. I swear by the great God that I shall not be false.”39 Yet, as we learn later, also the Arab authorities enforced mobility on a considerable number of aristocrats and their families in order to guarantee their allegiance in the form of hostages. When the Armenian nobility in 656 decided to return to Byzantine suzerainty, this proved fatal for most of these individuals, while it had the desired effect on some of the aristocrats who abstained from changing the sides: Then when the king of Ismael [= the Caliph] saw that the Armenians had withdrawn from submission to them, they put to the sword all the hostages whom they had brought from that land, about 1,775 people. A few were left, in number about 22, who had not happened to be at that spot; they alone survived. But Mušeł, lord of the Mamikoneank‛ (…), because he had four sons among the hostages with the Ismaelites, was therefore unable to withdraw from their service.40 Until the beginning of the 8th century, the Armenian nobility, reacting to changes in the balance of power between the Caliphate and Byzantium, switched sides several times before the Arabs achieved more permanent dominion in the Armenian highlands. The relatively beneficial conditions of thetreaty of 653 were replaced by a more strict regime with garrisons especially in the strategically important frontier regions to Byzantium and an Arab governor (ostikan) residing in the country and enforcing regular tax payments. As in most cases, different factions of the Armenia nobility reacted differently: while a group around the until then leading house of Mamikonean tried several times to remove Arab rule with violence, especially the increasingly important family of the Bagratuni followed a policy of collaboration with the Arab authorities.41These put down all rebellions by force and executed or deported unruly individuals, often into far away regions of the Caliphate (such as Yemen).42 Under such circumstances, migration into the Byzantine Empire was again an option. The historian Łewond reports for the year 788 such a larger scale movement: Left without property and food, naked and barefoot, (the inhabitants of Armenia) were exposed to the horrors of famine. They left their country and fled to the Greek territory to seek refuge. The mass of the population, over twelve thousand men, women, and children, as we were told, migrated from their land under the leadership of Šapuh from the house of Amatunik‛, Hamam his son, and other Armenian nobles with their cavalry. (…) As they crossed the river [Akampsis], the Greek Emperor Constantine [vi] was immediately notified. He called them unto him and gave the nobles and their cavalry high honours. (The Emperor) accommodated the bulk of the lower class people on good fertile lands.43 In the period under consideration, refugees were welcome, even in high numbers, if they could provide valuable manpower for military and economic purposes. 2.3 Byzantium as (not so) Desirable Destination Besides the prospect to find more beneficial conditions for living or of simply avoiding acts of revenge by irritated imperial authorities, Byzantium as Christian polity was regarded an empire of different quality in comparison with Persia or the Caliphate. The 8th century historian Movsēs Xorenac‛i interprets the decision of King Aršak as well as his retainers to opt for Roman suzerainty in 387 along these lines (but highlighting also the significance of kinship ties): So Aršak left the native kingdom of his fathers, Ayrarat, and all the part of the Persian sector, and went to rule over the western regions of our country, in the Greek sector (i bažnin Yunac‛), not only because of his mother who was in the imperial capital (i kayserakan k‛ałak‛ēn), but because he thought that it was better to rule over a smaller region and serve a Christian king than to control most (of the country) and submit to the yoke of heathens. The princes of Šapuh’s sector followed him with their wives and sons, abandoning each one’s possessions and villages and estates.44 A similar interpretation Łewond provides when describing the deliberate emigration of Armenians from the environs of Theodosioupolis (Erzurum) on the occasion of an imperial campaign in the region in the 750s (accompanied also by the deportation of Muslim population into the Empire): (…) the king of the Greeks [Constantinev] moved from his imperial portals with a massive multitude of followers and arrived at the city called Theodosioupolis in the region of Karin. (…) Furthermore, he took the city troops and the local Saracens, along with their families, to the land of the Greeks. Many of the inhabitants of the same districts asked the king to allow them to follow him, in order to be relieved of the heavy yoke of servitude to the Arabs. Having secured permission from (Emperor Constantinev), the inhabitants of the Armenian districts prepared themselves, packed their belongings and moved, placing their trust in the power of the dominical cross and in the glory of the King. They separated themselves (from the rest), left their homeland, and went to the country of the pious king.45 Yet, as already mentioned, doctrinal differences between Byzantine and Armenian Orthodoxy since the later 6th century led to an alienation between the two churches, accompanied by attempts of imperial authorities to enforce conformity with Constantinople during periods of Byzantine pre-dominance in the Armenian highlands in the 6th and 7th century.46Afterwards, Byzantium could also be regarded as shelter of heresy and staying there could threaten the true faith of Armenian Christians.47Katholikos Yovhannēs Drasχanakertc‛i at the beginning of the 10th century for instance explained why he decided not to follow an invitation of the emperor to Constantinople (in contrast to the Armenian king): I decided not to go, thinking that there might be people who might look askance at my going there, and assume that I sought communion with the Chalcedonians. It was for this reason that I did not wish to go, lest I might scandalize the minds of the weak.48 Therefore, we also find in the same work of Łewond, who describes the decision of the Armenians near Theodosioupolis to move to Byzantium by placing their trust into the Christian faith of its emperor, a different interpretation of the option to emigrate to the Empire in a later episode shortly before a revolt of the nobility against the Arabs in 774/775: Ašot son of Prince Sahak from the house of the Bagratids, did not take part in this dangerous enterprise, because he was full of wisdom and prudence. On the contrary, he kept counselling the rest to abandon the perilous enterprise (…) and think of their own security as well as that of their families. He told them: “(…) Even the Roman Empire was unable to raise its hand against this dragon (= the Arabs), and it still continues to tremble before it and has not dared to act against the dominical command. (…) you will be forced to flee from your land with your entire households (…) and live under the foreign yoke of the king of the Greeks.49 2.4 Ecclesiastical and Learned Mobility Besides doctrinal issues, the Christianisation of the Roman Empire and of Armenia brought about also a new framework for mobility via the emergence of channels of ecclesiastical authority, pilgrimage and education. From the beginning of the establishment of an Armenian ecclesiastical hierarchy in the 4th century onwards, its representatives were closely connected with neighbouring churches and church provinces. Until the end of the 4th century, the Senior Bishop (later “Katholikos”) of Armenia was ordained by the metropolitan of Caesarea in Cappadocia. Armenian hierarchs took part in the ecclesiastical councils of the 4th and 5th centuries in Nicaea, Constantinople, Ephesus and Chalcedon. The Armenian clergy communicated also with ecclesiastics in Syria and Mesopotamia, in Georgia and Caucasian Albania and in Persia. These exchanges on doctrine and praxis of faith intensified in the period of Christological disputes between the 5th and the 7th century, when the Armenian church ultimately repudiated both the teaching of Nestorius (whose theological position became most prominent in Persia) and of the Council of Chalcedon (the dogma of the Byzantine and later also of the Georgian Church) and sided with the mono/miaphysite Churches of Egypt and Syria. Many of these communications have been collected in the so-called “Book of letters” (Girkʽ Tʽłtʽocʽ).50From these letters and other sources we learn however that despite the rift between the churches in the 6th and 7th century and the Arab conquest of Armenia, contacts with the Byzantine church did not break down in the 8th and 9th centuries (letter of Patriarch Germanosito Bishop Daniel of Siwnikʽ [ca. 720, see below], exchange of letters with Patriarch Photios [between 862 and 886, see below]). Equally, the picture of a united anti-Chalcedonian Christianity produced in the Armenian historiography does not withstand closer inspection as does the image of a united Armenian monarchy. The number of Armenian clergymen and laymen, who (and not only under Byzantine pressure) also in the 7th and 8th century and later on had sympathies for the Chalcedonian creed was not insignificant.51 Clerics and monks found also their way to Palestine before and after the Arab conquest, where we encounter a vivid Armenian community in and around Jerusalem; we also possess several Armenian mosaic inscriptions from the 5th to 7th century, which are among the oldest epigraphic testimonies inArmenian language at all.52A text attributed to a Vardapet Anastas and dated to the 7th–10th century lists (for sure exaggerating) 70 churches and monasteries, which had been build or bought by Armenians in Jerusalem between the 4th and 7th century.53At least several churches are mentioned in the exchange of letters between Modestos, the head of the Armenian community in at this time Persian-ruled Jerusalem, and Katholikos Komitas in Armenia from the year 617, included in the history attributed to Sebēos.54In his answer to Modestos, the Katholikos also explains the motivation and spiritual value of the pilgrimage to Jerusalem and beyond: But know this, О beloved brother, no little consolation was conveyed to our people by the coming and going of those journeys. First, because they forgot all the troubles and sadness of this country. Secondly, because they cleansed their sins through repentance, fasts and mercy, through sleepless and unresting travelling by day and night. Thirdly, because they baptized their bodies in the water of holiness, in the fiery currents of the Jordan, whence the divine grace flowed to all the universe.55 As Komitas equally wrote, Armenian pilgrims and monks found their way to the Monastery of St. Catherine on Mt. Sinai. This is also documented by Armenian inscriptions and Armenian manuscripts56as well as hagiographic sources: in theNarrationes de patribus Sinaïtiswe find for the 7th century an Armenianmonachosnamed Elissaios who saw a vision of fire above the altar almost every night.57In addition, later, theNarrationesmention a group of not less than 800 Armenians, who, together with a large number of Arabs, became witnesses of a fire vision on Mt. Sinai.58However, Armenian clergymen travelledeven beyond the Arab and the Byzantine sphere to Italy and even to France and Central Europe, where we find their traces in Latin sources, as Ralph-Johannes Lilie has demonstrated, for instance.59Thus, the geographical range of Armenian ecclesiastical mobility is comparable with the aristocratic one. In addition, learning in Armenian Church was strongly influenced by both Greek and Syriac Christianity, whose centres of education could be found in the Roman Empire. The establishment of such educational links was attributed by the 5th century historian Agatʿangełos already to the first Christian king of Armenia Trdatiiiin the early 4th century, who allegedly had founded schools in order to teach pupils in Syriac (yAsori dprutʿiwn) as well as in Greek (i Hellen).60Soon after Mesrob Maštocʿ at the beginning of the 5th century had developed an alphabet for the Armenian language, a large-scale translation activity from Syriac and from Greek started, which also influenced the linguistic development of Armenian literature. Scholarship speaks of a “Hellenising school” especially in the 6th century.61Still for Movsēs Xorenacʿi in the 8th century, “Greece (was) the mother or nurse of all sciences”.62Armenians had studied at places of education in the Roman Empire already in the 4th century. Ammianus Marcellinus mentions that one of his schoolmates in Antioch in the 330s/340s was the princely heir of the Satrap of Corduene (in Southern Armenia), held as hostage in Syria.63Another one of the Armenian Satraps in this region was Thomas, who in the early 6th century was educated “in the wisdom of the Greeks” in Berytus and Antioch.64 The desire for Christian education intensified scholarly mobility. Koriwn, disciple and biographer of Mesrob Maštocʿ, in the early 5th century and the historian Łazar Pʿarpecʿi in the late 5th century studied in Constantinople, which the latter praises as source of “flows of wisdom (…). Prominent scholars from all parts of the Greek Empire hurry to go there”.65The famous 7th centuryscholar Anania of Širak reports in his so-called “autobiography” about his educational journey to Theodosioupolis and Trebizond in the 630s, where he studied especially mathematics with a teacher named Tychikos, who in turn under the Emperors Tiberius and Maurice had served in the Byzantine Army in Armenia, where he had learned the Armenian language, before his studies had led him to Jerusalem, Alexandria, Rome and Constantinople (seeMap 12.3).66 2.5 Non-Elite Mobility and Borderlands Therefore, we encounter a multitude of voices regarding mobility and migration in the Armenian sources, often within the same text. However, as indicated above, we are (besides pilgrims, who also may have come from a non-elite stratum of society) mostly informed about (military, ecclesiastical or educational) elite mobility and elite considerations. One example for the mobility of an artisan from Armenia to Byzantium is Trdat, architect and mason, who according to the Armenian historian Stephen of Taron travelled to Constantinople and was entrusted with the restoration of the Hagia Sophia, which had been damaged by an earthquake in October 989. However, to our disappointment, his accomplishment found no echo in the Byzantine sources, which mention the damage and reconstruction of the Hagia Sophia, but not Trdat. At the same time, we learn from Stephen of Taron that Trdat was the architect of the church of the Armenian Katholikos in Argina and of the Cathedral of Ani for King SmbatiiBagratuni; we can therefore assume that he was closely connected with the Armenian elite.67 Nevertheless, as we have seen, in many cases aristocrats moving across borders were accompanied by their retainers, both noble and not noble, and sometimes their families. Bringing with him valuable manpower of course strengthened also the position of a nobleman in his negotiations with the authorities of his destination.68Even more, imperial authorities relied on these networks of allegiance when attempting to mobilise larger numbers of soldiers or settlers for their purposes. Again, the period of Byzantine control over most of Armenia under Emperor Maurice between 590 and 602 provides an illustrating example: He (Emperor Maurice) further commanded all the cavalry from Armenia to assemble, and the chief nobles, (and those) who were experienced and capable of standing firm and fighting in battle in the line of spearmen. He also ordered other forces to be brought from the land of Armenia in great numbers, all of them willing and of elite stature, to be formed into battalions and that, equipped with arms, they should all cross to the land of Thrace against the enemy, and Mušeł Mamikonean as their general.69 On another occasion during the reign for Maurice we learn that these ties of allegiance between noble commander and retainers could also work to the detriment of imperial interests, since they enabled them to follow own interests also after having moved into the imperial sphere. In this episode, the Emperor has to use considerable diplomatic and material resources to separate the mass of soldiers from their aristocratic leader: At that time, another command came from the Emperor to seek out again and find from Armenia elite armed cavalry, 2,000 in number, and put them under two reliable men, and to despatch them in great haste. They sought out and chose 2,000 armed men and put these 2,000 under two reliable men: 1,000 to Sahak Mamikonean und 1,000 under the command of Smbat Bagratuni, son of Manuēl. (…) Sahak set out, brought his force to the palace, and presented himself to the king. But when Smbat reached Xałtik‛, he baulked, because his force had become frightened en route, not wishing to go to that place (= Thrace) in compliance with the king’s request. The king was informed of these events. Then through letters (hrovartaks) and trustworthy messengers he promised with an oath to send him back promptly to his own country with great honour. He also promised great rewards and gifts to the troops, and in this way he cajoled them into reconciliation. They proceeded in unity and presented themselves to the king. The king fully equipped the troops and despatched them to the borders of Thrace; Smbat he sent in great honour back to the land of his own people with many gifts.70 Yet, non-noble mobility was possible without or against the wishes of imperial authorities, especially since borders in this period were no “iron curtains”, often not even clearly defined. This was also true for the Roman-Persian border in the 6th century as described by Procopius in his book on buildings: On the way from Kitharizon to Theodosioupolis and the other Armenia lies a region called Chorzane; it extends over a march of three days and it is not separated from Persia by a lake, a river or mountains, which would impede the crossing of a pass but the borders of the two merge. Because of this the inhabitants, whether subjects of the Romans or of the Persians, do not fear one another or suspect mutual attacks but even engage in intermarriage, hold common markets for their daily needs and run their farms together. Whenever the military commanders on each side lead an army against the other because their rulers instructed them to do so they find their neighbours unguarded. The densely populated settlements are very close to each other and from old times there were no mounds anywhere.71 Emperor Justinian later tried to secure and control the frontier in this region by the construction of a fortress, since Persian armies had criss-crossed the area relatively unimpededly in an earlier war. Especially where more densely settled areas met, there was also a higher frequency of cross-border interaction and of possible diffusion of information, against the wishes of official authorities. Deserted or sparsely settled areas on the contrast may have constituted obstacles for the dispersion of information.72The military handbook attributed to Emperor Maurice (“Strategikon”) from the period around 600 advises marching through less settled areas in order to conceal the movement of troops, but only for smaller scale armies.73Supplying larger numbers of troops from less densely settled and less cultivated areas would have caused severe logistic problems. According to this logic, along the Byzantine-Arab frontier in the 7th and 8th century there emerged a zone of deserted and depopulated no-man´s-land, which should impede the advance of larger armies, especially of the Arabs towards Byzantine territory. A Syrian Chronicle from the year 775 describes the formation of this zone on the occasion of an Arab assault in 716/717: When a great and innumerable army of Arabs gathered and surged forwards to invade Roman territory, all the regions of Asia and Cappadocia fled from them, as did the whole area from the sea and by the Black Mountain and Lebanon as far as Melitene and by the river Arsanias [Murat Nehri] as far as Inner Armenia [the region of Theodosioupolis/Erzurum]. All this territory had been graced by the habitations of a numerous population and thickly planted with vineyards and every kind of gorgeous tree; but since that time it has been deserted and these regions have not been resettled.74 In fact, these areas did not remain unpopulated, but served as zone of transfer and refuge for several groups who wished to evade political or religious authorities. One of these was the dualistic sect of the Paulicians, which (according to their own tradition) emerged in 6th century Armenia and appeared in the eastern frontier provinces of Byzantium since the 7th century; in the face of persecutions by the state, they migrated into this “space between”. Finally since the middle of the 9th century they even created their own polity around the fortress of Tephrike (today Divriği in Eastern Turkey) and fought the Byzantines as allies of the Emir of Melitene until their defeat in 871/872. Paulician groups, which included significant elements of Armenian origin, then in the 9th and 10th century were deported to the Balkans.75Byzantium on the contrast tolerated and even encouraged the settlement of Armenian aristocrats with their retinue in these territories. This process intensified since the early 10th century and contributed to the restoration of settlement and administrative structures when Byzantium re-expanded into the East; the newly established, relatively small military districts then were subsumed under the terminus “mikra armenika themata”.76 From there, benefiting from the fragmentation of political power in Caliphate since the 9th century, Byzantine suzerainty expanded again over most ofArmenia in the second half of the 10th and first half of the 11th century. One after the other of the princedoms and kingdoms, which had emerged since the 9th century, was turned into a province and its elites compensated with titles and possessions in the interior of Anatolia. These annexations in many cases were also accompanied by larger scale migrations of population into Byzantine Asia Minor, as the Continuator of Tʿovma Arcruni describes for the case of the Kingdom of Vaspurakan (around Lake Van) in the year 1022: They [the Byzantines] gave them gifts, appointed them at the royal court, gave them great cities in exchange for their cities and in return for their castles, impregnable fortresses and provinces, villages, estates, and holy hermitages. So the Artsrunik’, descendants of Hayk [and] Senek’erim, exchanged their ancestral homes in the year 470 of the Armenian era, and moved into Greek territory with fourteen thousand men, not including women and children, passing under the yoke of servitude to the Romans. Likewise the Bagratid Gagik, son of King Yovhannes, also exchanged his ancestral [lands] in the year 490 of the same era, and went to Roman territory.77 In the case of Vaspurakan at least the demographic impact of these migrations described in the sources can also be checked against other evidence: an actual dramatic demographic decline in the region can be detected both in core drill data from Lake Van (using the sedimentation of charcoal as proxy for human activity) as well as in the rapid decline of building activity from the 10th century, the apex of Arcruni power, to the 11th century.78The political and religious tensions emerging from this large scale migration of Armenians into central Asia Minor in the 11th century and its longer term significance for the emerging of another Armenian polity in Cilicia have been studied in detail elsewhere and would deserve at least a paper of their own;79I therefore close this section and continue with a more detailed inspection of the mobility and networks of several mobile Armenians. 3 Mobilities and Networks Recent works of migration history have highlighted the significance of social networks and of the “multiplexity” of ties of ethnic or regional affiliation, of kinships, of politics or of economy between individuals, groups and organisations, which make up complex “migration systems”.80While our evidence does not allow us to reconstruct such webs with equal detail as for the modern period, we are able to detect and map various categories of ties for individuals, which may hint at the general complexity of connections which made Armenian mobility possible. 3.1 Networks of Nobility and the “military labour market” of Byzantium The work of Procopius is a rich source for Armenian noble mobility across the Roman-Persian frontier and within the empire for the 6th century.81Such an episode from the time around 530 illustrates several possible channels for the initiation and negotiation of mobility: At about the same time Narses and Aratius who at the beginning of this war, as I have stated above, had an encounter with Sittas and Belisarius in the land of the Persarmenians,82came together with their mother as deserters to the Romans; and the Emperor’s steward, Narses, received them (for he too happened to be a Persarmenian by birth), and he presented them with a large sum of money. When this came to the knowledge of Isaac, their youngest brother, he secretly opened negotiations with the Romans, and delivered over to them the fortress of Bolum, which lies very near the limits of Theodosioupolis. For he directed that soldiers should be concealed somewhere in the vicinity, and he received them into the fort by night, opening stealthily one small gate for them. Thus he too came to Byzantium.83 The defection of the three brothers (who may have been members of the otherwise well-known noble house of Kamsarakan) was facilitated through the connection to an Armenian already well-established in the Byzantine elite, the famous eunuch Narses.84It was additionally motivated by material rewards. Inaddition, the movement of some members of the clan across the borders of course established a trans-local kinship network, which could be used by others. Procopius allows us also to trace the further carriers of Narses, Aratius and Isaac in the military service of Justinian, which led them sometimes together, sometimes far apart from each other across the entire empire from Armenia to Palestine and Southern Egypt and to Italy and the Balkans (seeMap 12.2). However, their story also highlights the dangers of imperial service, since all three of them ultimately fell fighting for Byzantium: Narses in 543 after the battle of Anglon in Persarmenia, Isaak in 546 in Italy as prisoner of war of the Goths and Aratios in 552 fighting in Illyricum.85Under these auspices, the decision of a group of noblemen faced with the imperial desire to transfer them to the Balkans in the period of Maurice “to extricate themselves from service to the king of the Greeks (…), so that they too would not be obliged to die in the regions of Thrace, but could live or die for their own country”86becomes comprehensible. The term which Armenian historians used to describe the relationship of allegiance and patronage between the Emperor or the Great King and the individual aristocrats iscaṙayut‛iwn. This is the same term, which describes the allegiance of the Armenian princes to their king in earlier times.87In that way, the Emperor took the place of the Armenian king in this relationship. For the aristocrat,caṙayut‛iwnincluded the obligation for military service to his lord (tēr). However, this relationship also included mutual commitments, which according to the Armenian tradition were sealed through a reciprocal oath (uχt, erdumn). Because of this oath, one side took upon itself the duties of lordship and protection, and the other those of faithful service and obedience.88The new fiduciary relation was also manifested in ritual and material ways; the new retainer was honoured in a ceremonial reception at the court in Constantinople and received valuable presents.89One example of such a very mobile nobleman described in the history attributed to Sebēos is Atat Xoṙχoṙuni, who crossed the border into or out of the empire several times. He started his careeras participant in a conspiracy against Persian rule in Eastern Armenia around the year 590; when this attempted rebellion failed, he crossed the border to Byzantium. There Emperor Maurikios received him with honours in Constantinople and gave him a command in the army fighting the Avars on the Balkans. Nevertheless, on his way to the troops, Atat Xoṙχoṙuni decided against joining this fight and fled across the Black Sea and Asia Minor back to Persian territory, where Great King Xusrōiireceived him friendly. Yet, after some years in Persian services, Atat Xoṙχoṙuni planned to defect to Byzantium once again; this time, his intention was detected and Xusrōiihad him executed.90 The motivations behind such movements could be different – some aristocrats hoped for certain benefits, others would have no other choice. The initiative for a change in thecaṙayut‛iwncould come from the respective nobleman as well as from an imperial authority trying to persuade a retainer of the opposing great power to defect.91Imperial authorities of course were anxious to impede such noble mobility when working against their interest. One instrument to do so was the demand of hostages, as did the Caliphate after its first agreement on suzerainty over Armenia with the nobility at large; nevertheless, a majority of the aristocracy defected to the emperor in 656 (see above). While it was impossible to stop such a mass defection without an equally massive use of force, individuals intending to cross borders could be impeded to do so when detected early enough – as in the case of Gurgēn Arcruni in 856, whose correspondence with the Byzantine emperor became known to Arab authorities, who had him arrested.92In the peace treaty of 562, Byzantium and Persia agreed that “those who in time of peace (between the two empires) defected, or rather fled, from one to the other shall not be received, but every means shall be used to place them, even against their will, in the hands of those from whom they have fled.”93Yet, already soon afterwards, the temptation to weaken the competing empire by depriving it of important clients was too strong for both signatories. The persisting importance of ties of kinship and ethnic affiliation in this regard is also documented for late periods; according to the 11th century ArabMelkite historian Yaḥyā of Antioch, the conquest of the Arab fortress of Rhabaine in Northern Syria in 980 was brought about by a female Armenian slave in the fortress, who got in contact with her relatives in the Byzantine Army and helped them to cross the walls and to occupy the citadel.94 However, as we have indicated above in the case of the rebellion of Smbat Bagratuni and his troops against Emperor Maurice, the same networks of kinship and ethnic affiliation, which had supported noble mobility in the interest of the empire, could also be effective against them. One illustrative example comes again from Procopius in the shape of Artabanes, scion of the Armenian royal house of the Arsacids (seeMap 12.2). He first appears in the year 538/539 in the region of Armenia interior, controlled by the Romans; there the descendants of the last Arsacid king still had considerable possessions and traditional tax privileges.95When these prerogatives were abolished and Armenia interior turned into a province by Emperor Justinian, the Armenian nobility stood up in an armed rebellion, which themagister militumSittas was ordered to quell.96Among these rebels was also Artabanes, who first excelled himself by murdering the imperial governor Akakios and then by killing Sittas in hand-to-hand combat.97Yet, the imperial forces proved insurmountable, so that Artabanes and his clan had to flee to the Persian Empire, where contacts already had been established with Great King Xusrōi. Nevertheless, before 545, he and many noblemen returned to Roman soil, bowed to the Emperor and joined the imperial army; one can assume that the conditions for the imperial pardon had been negotiated in advance, although we receive no information on this. Together with his brother Ioannes, his cousin Gregorios and other troops of Armenian origin, Artabanes in 545/546 was sent to recently conquered North Africa. There they soon found themselves involved in the rebellion of themagister militumGuntharis (a commander of Germanic origin), who seized powerin Carthage and declared himself independent from Constantinople. Artabanes with his troops joined Guntharis after having received some guarantees, but secretly plotted his assassination together with his relatives and the imperial official Athanasius.98The plan succeeded in 546 and Artabanes was appointedmagister militum per Africamby the emperor. Soon he returned to Constantinople according to his own wishes, where he planned to marry Praeiecta, a niece of Justinian, whom he had got to know in Africa after Guntharis had killed her first husband Areobindus. Thereby, he would have joined the imperial clan and could have hoped for even higher honours, after he had already received the consulate. According to Procopius, Artabanes even dreamed about obtaining the imperial crown (basileia). Yet, these hopes were balked when an earlier wife of Artabanes appeared in the capital und effected with the support of Empress Theodora that he received her back into his household. Frustrated, Artabanes let himself roped in into a conspiracy by his relative Arsakes together with another Armenian, Chanaranges, who intended to replace Justinian with his cousin Germanus.99The conspiracy was detected, yet Artabanes was not severely punished by Justinian; instead, already in 550 he was appointedmagister militum per Thraciasand sent first to Sicily and then to Northern Italy, where he served under the command of another prominent Armenian, the eunuch Narses. After 554, we lose his track in the sources. The life story of the noble migrant Artabanes as depicted by Procopius for mere 15 years demonstrates remarkable dynamics of Armenian noble mobility, both spatial and social, within 6th century Byzantium. On the one side, we observe a stunningly rapid integration into the imperial Roman elite and almost into the imperial family itself; on the other hand, Artabanes in the most crucial and dangerous moments of his career – the rebellion against Roman rule in Armenia interior, the plot to murder Guntharis and the conspiracy against Justinian – relies on networks established by kinship and common Armenian origin (see 12.1 and 12.2). Artabanes is not a single case for Byzantium in this regard – and similar observations can be made for other Armenian noblemen who made their career in the Persian Empire after having defected from the Roman side such as Smbat Bagratuni, whom we have already encountered above with his rebellious troops in the time of Emperor Maurice. After leading another rebellion in Roman Armenia, deportation to Constantinople and (similarly to Artabanes) military service for the emperor in Africa, he defected to Persia and within afew years achieved a most honoured position at the court of the Sasanian Great King Xusrōii, who awarded him with the title “Xosrov Šum” (Xusrō´s joy). In addition, Smbat relied on an already existing network of Armenian noblemen and their retinues in the service of the Sasanians.100The ability of the same Armenian noblemen “to fit in” both a the courts in Constantinople and in Ctesiphon was based on these networks, but also on an “aristocratic koine”, a language of ritual exchange mutually understandable across borders in order to establish and maintain ties of patronage and loyalty in the wide area from Byzantium to Central Asia. We also have cues that the Christian nobility in the Caucasus region considered itself part of a more far-reaching noble tradition: in his history of the Armenians, Movsēs Xorenacʿi reports the stories of origin of 50 of the most important noble houses, which I systematically surveyed. More than 50 % related themselves (or were related by Xorenacʿi) to the eponymous ancestor of the Armenians Hayk respectively to other “autochthonous” ancestors. However, a large number of families traced themselves back to royal or significant noble houses of neighbouring countries such as Georgia, Caucasian Albania, Mesopotamia or – most prominently – Persia. Connections to even more remote regions were created with ancient Israel respectively Canaan, Bulgaria or even the royal house of China.101Therefore, mobility and trans-local connections were deeply integrated into the traditions of the Armenian nobility. The military “labour market” of Byzantium provided opportunities for aristocrats and non-aristocrats also in the centuries after the Arab expansion.102Around 750 Kūšān al-Armanī, commander in Arab services in the region of Armeniaiv, defected to Byzantium and was madestrategosby Emperor Constantinev. He conquered and plundered Theodosioupolis (Erzurum); many of the captured Armenians were settled in Cappadocia. Together with some of them, Kūšān returned into the Arab sphere some years later, which again demonstrates the double-edged validity of ties of ethnic affiliation.103 Despite such defections, Byzantium in the 8th century employed Armenian noblemen in leading commanding positions on a significant scale; as Theophanes informs us for the year 778, during a successful campaign of the thematic armies of Anatolia against Germanikeia under the supreme command of Michael Lachanodrakon, the army of thethemaAnatolikon was commanded by Artabasdos (maybe Artawazd Mamikonean, who left Armenia after a rebellion in 771), the Opsikion by Gregoriostou Mousoulakiou(maybe also a Mamikonean, son of Mušeł) and the Boukellarion by Tatzates (Tačat Anjevac‛i, who had defected to Byzantium around 750, but in 782 returned to Armenia, where he became presiding prince in Arab services and died in 785 in battle against the Khazars).104 Desired qualities for military men were of course strength and bravery. Theophylaktos Abastaktos, a soldier of Armenian origin, saved the life of Basiliin a battle against the Paulicians and received a position in the service of the Emperor. Theophylaktos became father of the future Emperor RomanosiLakapenos.105Early in the reign of BasilI´s son Leonvi(886–912) an Armenian nobleman Azatos or Azotos with the telling nickname “Makrocheir” (“with big hands”, “with long arms”) came to Constantinople with his retinue. His impressive stature prompted the emperor to make Makrocheirexarchosof the guard regiment of the Exkoubites. In 896, Azotos fell in the battle of Boulgarophygon against the Bulgarians.106 In the retinue of Azotos was also Melias (Arm. Mleh), who survived the Battle of Bulgarophygon and returned to Armenia. However, around 904 he most probably was again in Byzantine services and fought together with Eustathios Argyros in the East. Shortly afterwards, both of them fell from favour. In 907/908, Melias together with four other Armenian noblemen, Ismael and the three brothers Baasakios, Krikorikes and Pazunes, was in exile at the court of the Emir of Melitene, but returned to the Byzantine Empire via the intermediation of Eustathios Argyros, who had regained imperial favour before. All five Armenians then received commands at the Eastern frontier. Leonvimade Meliastourmarchesof Euphrateia, ta Trypia and “eremia”, the deserted no-mans-land at the frontier. Between 909 and 912 Melias fortified and resettled the town of Lykandos together with his Armenian retinue, and used it as basis for further operations against the Arabs. In 917 Melias together with his retinueagain fought the Bulgarians on the Balkans, where the Battle at the Acheloos ended with another Byzantine defeat. He then executed further campaigns at the Eastern border; his greatest success was the conquest of Melitene in 934 together with Ioannes Kourkouas, equally of Armenian origin.107These campaigns and migrations marked also the beginning of the emergence of the above-mentionedmikra armenika themata. At the same time, they illustrate the impact of network mechanisms similar to those we have inspected for the earlier period. 3.2 Networks of Learning and Commerce Some information on non-military networks across borders in the 7th century we obtain from two texts of the already mentioned Armenian scholar Anania of Širak. In one, he describes how he as young student in the 630s, dissatisfied with the quality of education in his homeland, set out for Byzantium to find an adequate instructor. He first travelled to Theodosioupolis/Karin (Erzurum) and the in the province of Armenia quarta (the region around Martyroupolis/today Silvan), where he studied with a scholar named Kʿristosatur, who could not satisfy his appetite for knowledge. Therefore, Anania intended to move to Constantinople, but on the way near Trebizond, he encountered another group of Armenian students, who (after a maritime voyage to Sinop) were on the
https://brill.com/display/book/edcoll/9789004425613/BP000016.xml
RCSB PDB - 5AM1: ligand complex structure of soluble epoxide hydrolase ligand complex structure of soluble epoxide hydrolase 5AM1 ligand complex structure of soluble epoxide hydrolase PDB DOI: https://doi.org/10.2210/pdb5AM1/pdb Classification: HYDROLASE Organism(s): Homo sapiens Expression System: Spodoptera frugiperda Mutation(s): No Deposited: 2015-03-08 Released: 2015-05-13 Deposition Author(s): Oster, L. , Tapani, S. , Xue, Y. , Kack, H. Experimental Data Snapshot Method: X-RAY DIFFRACTION Resolution: 2.15 Å R-Value Free: 0.233 R-Value Work: 0.196 R-Value Observed: 0.198 1 Better Ligand structure goodness of fit to experimental data Best fitted I5T Literature Successful Generation of Structural Information for Fragment-Based Drug Discovery. Oster, L. , Tapani, S. , Xue, Y. , Kack, H. (2015) Drug Discov Today20: 1104 PubMed : 25931264 Search on PubMed DOI: https://doi.org/10.1016/j.drudis.2015.04.005 Primary Citation of Related Structures: 5AHX , 5AI0 , 5AI4 , 5AI5 , 5AI6 , 5AI8 , 5AI9 , 5AIA , 5AIB , 5AIC , 5AK3 , 5AK4 , 5AK5 , 5AK6 , 5AKE , 5AKG , 5AKH , 5AKI , 5AKJ , 5AKK , 5AKL , 5AKX , 5AKY , 5AKZ , 5ALD , 5ALE , 5ALF , 5ALG , 5ALH , 5ALI , 5ALJ , 5ALK , 5ALL , 5ALM , 5ALN , 5ALO , 5ALP , 5ALQ , 5ALR , 5ALS , 5ALT , 5ALU , 5ALV , 5ALW , 5ALX , 5ALY , 5ALZ , 5AM0 , 5AM1 , 5AM2 PubMed Abstract: Fragment-based drug discovery relies upon structural information for efficient compound progression, yet it is often challenging to generate structures with bound fragments. A summary of recent literature reveals that a wide repertoire of experimental procedures is employed to generate ligand-bound crystal structures successfully ... Fragment-based drug discovery relies upon structural information for efficient compound progression, yet it is often challenging to generate structures with bound fragments. A summary of recent literature reveals that a wide repertoire of experimental procedures is employed to generate ligand-bound crystal structures successfully. We share in-house experience from setting up and executing fragment crystallography in a project that resulted in 55 complex structures. The ligands span five orders of magnitude in affinity and the resulting structures are made available to be of use, for example, for development of computational methods. Analysis of the results revealed that ligand properties such as potency, ligand efficiency (LE) and, to some degree, clogP influence the success of complex structure generation. Organizational Affiliation : Structure and Biophysics, Discovery Sciences, Innovative Medicines, AstraZeneca R&D, Mölndal, Sweden. Electronic address: [email protected]. Macromolecules (by identity cutoff)  | 3D Structure Entity ID: 1 Molecule Chains Sequence Length Organism Details Image BIFUNCTIONAL EPOXIDE HYDROLASE 2 A 549 Homo sapiens Mutation(s) : 0 Gene Names: EPHX2 EC: 3.3.2.10 (PDB Primary Data), 3.1.3.76 (PDB Primary Data) UniProt & NIH Common Fund Data Resources Find proteins for P34913 (Homo sapiens) Explore P34913 Go to UniProtKB: P34913 PHAROS: P34913 Entity Groups Sequence Clusters 30% Identity 50% Identity 70% Identity 90% Identity 95% Identity 100% Identity UniProt Group P34913 Protein Feature View Expand Reference Sequence Small Molecules Ligands 3 Unique ID Chains Name / Formula / InChI Key 2D Diagram 3D Interactions I5T Query on I5T Download Ideal Coordinates CCD File Download Instance Coordinates SDF format, chain F [auth A] MOL2 format, chain F [auth A] F [auth A] 4-oxidanylidene-N-[(1S,2R)-2-phenylcyclopropyl]spiro[3H-chromene-2,4'-piperidine]-1'-carboxamide C 23 H 24 N 2 O 3 SWEAYHBSAXRXDZ-MOPGFXCFSA-N Ligand Interaction SO4 Query on SO4 Download Ideal Coordinates CCD File Download Instance Coordinates SDF format, chain B [auth A] SDF format, chain C [auth A] SDF format, chain D [auth A] MOL2 format, chain B [auth A] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] B [auth A], C [auth A], D [auth A] SULFATE ION O 4 S QAOWNCQODCNURD-UHFFFAOYSA-L Ligand Interaction DMS Query on DMS Download Ideal Coordinates CCD File Download Instance Coordinates SDF format, chain E [auth A] MOL2 format, chain E [auth A] E [auth A] DIMETHYL SULFOXIDE C 2 H 6 O S IAZDPXIOMUYVGZ-UHFFFAOYSA-N Ligand Interaction Binding Affinity Annotations ID Source Binding Affinity I5T BindingDB: 5AM1 IC50: 3 (nM) from 1 assay(s) Binding MOAD: 5AM1 IC50: 3 (nM) from 1 assay(s) Experimental Data & Validation Experimental Data Method: X-RAY DIFFRACTION Resolution: 2.15 Å R-Value Free: 0.233 R-Value Work: 0.196 R-Value Observed: 0.198 Space Group: P 6 5 2 2 Unit Cell : Length ( Å ) Angle ( ˚ ) a = 92.936 α = 90 b = 92.936 β = 90 c = 244.702 γ = 120 Software Package: Software Name Purpose BUSTER refinement XDS data reduction SCALA data scaling Structure Validation Ligand Structure Quality Assessment Created with Raphaël 2.3.0 Worse 0 1 Better Ligand structure goodness of fit to experimental data Best fitted I5T View more in-depth experimental data Entry History Deposition Data Released Date: 2015-05-13 Deposition Author(s): Oster, L. , Tapani, S. , Xue, Y. , Kack, H. Revision History (Full details and data files) Version 1.0: 2015-05-13 Type: Initial release Version 1.1: 2015-09-23 Changes: Database references Version 1.2: 2018-04-04 Changes: Data collection Version 1.3: 2021-02-24 Changes: Derived calculations, Other Usage & Privacy
https://www.rcsb.org/structure/5am1
EWG's Food Scores | Creminelli Uncured Pepperoni, Uncured Check out the food score for Creminelli Uncured Pepperoni, Uncured from EWG's Food Scores! EWG's Food Scores rates more than 80,000 foods in a simple, searchable online format to empower you to shop smarter and eat healthier. Creminelli Uncured Pepperoni, Uncured Lower scores accompany better foods. Image source: Missing Image Lower scores accompany better foods. How it compares to other pepperoni? (Click to Learn) EWG Overall Score Breakdown The product score is based on weighted scores for nutrition, ingredient and processing concerns. Generally, nutrition counts most, ingredient concerns next and degree of processing least. The weighted scores are added together to determine the final score.Read more about scores here. EWG Overall Score Breakdown EWG scored on three factors: nutrition, ingredient concerns, and the degree of processing.Read the full scoring methodology. Lower concern I Ingredient Concern P Processing Concern Nutrition Concern Details Considers calories, saturated fat, trans fat, sugar, sodium, protein, fiber and fruit, vegetable and nut content to differentiate between healthful and less healthful foods. For more information on nutrition concerns,read our full methodology. Contains a high level of saturated fat [read more] Contains 33% of the Institute of Medicine's daily sodium (salt) recommendations based on adequate intake [read more] This product contains added sugar ingredients: Sugars [read more] The nutrition factors used for scoring Creminelli Uncured Pepperoni, Uncured Positive factors Fruit, vegetable, bean or nut content Protein content Fiber content Omega-3 fatty acids Negative factors Calorie density Sugar/low-calorie sweetener content Sodium content Saturated fat content Trans fat content Ingredient Concern Details Considers food additives, pesticides, hormones, antibiotics and contaminants like mercury and BPA, which can affect human health and the environment. For more information on ingredient concerns,read methodology. This product is not certified organic [read more] No ingredient concerns identified for this product [read more] Antibiotics were likely used in the production of this meat [read more] Hormones and/or growth promoters were likely used in production of meat ingredients [read more] This product has 1 ingredient with concerns: Natural Flavor This additive is of lower concern in food. Learn why. Processing Concern Details Estimates how much the food has been processed. Considers many factors, chief among them, modification of individual ingredients from whole foods and number of artificial ingredients. For more information on processing concerns,read our full methodology. Product has been classified as having moderate processing concerns Products with moderate and high processing concerns generally have more artificial ingredients, more ingredients that have been significantly modified from whole foods, and more ingredients overall. EWG's Top Findings This product is not certified organic [read more] This product is not certified organic Products bearing the USDA certified organic seal must contain at least 95 percent organic ingredient, and must be produced without the use of synthetic pesticides and fertilizers and free of genetically engineered ingredients. No ingredient concerns identified for this product [read more] No ingredient concerns identified for this product EWG has not identified any ingredient concerns for this product. Contains food additives of lower concern Antibiotics were likely used in the production of this meat [read more] Antibiotics were likely used in the production ... Many animals are fed low doses of antibiotics throughout their lifespan to speed growth and prevent diseases. These non-essential uses promote antibiotic resistance, posing a serious risk to human health. Hormones and/or growth promoters were likely used in production of meat ingredients [read more] Hormones and/or growth promoters were likely us... Hormone implants and artificial growth promoters are commonly used to speed the growth of meat animals. These practices are not allowed in Europe due to health concerns. Contains the non-specific ingredient "flavor" [read more] Contains the non-specific ingredient "flavor" Added "flavors" are secret and often complex mixtures of chemicals that modify and manipulate the taste and smell of food. The lack of disclosure is a public right to know issue and especially concerning to people with unusual food allergies or on restricted diets. Contains a high level of saturated fat [read more] Contains a high level of saturated fat Saturated fat is not an essential nutrient and with increasing intakes there is a increased risk of coronary heart disease (IOM 2005a; USDA and DHHS 2010). For this reason it has long been known as a "bad" fat that raises the "bad" cholesterol, LDL. Numerous authoritative bodies support the recommendation to limit saturated fat to 10 percent of calories -- equivalent to a reasonable limit of 14 slices of bacon's worth of saturated fat a day (WHO 2002; USDA and DHHS 2010). A 2012 review by the Cochrane Collaboration, an independent non-profit organization, found that reducing or replacing saturated fat with other healthy fats reduced the risk of cardiovascular events by 14 percent (Hooper 2012). Other recent reviews have found that there in no evidence of a benefit from reducing saturated fat (Chowdhury 2014; Schwingshackl & Hoffmann 2014). While it's clear that we still have a lot to learn about how fats behave and contribute to disease, the evidence supporting a moderate level of saturated fat consumption remains strong and consistent. Contains 33% of the Institute of Medicine's daily sodium (salt) recommendations based on adequate intake [read more] Contains 33% of the Institute of Medicine's dai... This product contains a high percentage of the Institute of Medicine's recommended adequate intake for sodium of 1500 mg a day (IOM 2005). This value is much lower than what the FDA requires be listed on food labels -- 2400 mg. Americans average 3,400 mg of sodium a day. Most of this sodium comes from processed foods where sodium is added to mask the lack of freshness by enhancing the flavor, texture or palatability and extending shelf-life (IOM 2010). Many of these uses are for the manufacturers benefit and not the consumer's health as excess sodium intake is linked to high blood pressure, heart disease, stroke and kidney disease (IOM 2010). This product contains added sugar ingredients: Sugars [read more] This product contains added sugar ingredients: ... Eating too much of any type of sugar can lead to tooth decay. Added sugars like high fructose corn syrup, honey, sugar and dextrose are more concerning than natural sugars like raisins because they can lead to obesity by adding calories without being accompanied by important nutrients like potassium, vitamin C or fiber. Americans average 22 teaspoons of added sugar a day (NCI 2010; USDA and DHHS 2010). The World Health Organization recommends no more than 6 to 12 teaspoons of added sugar a day for adults, children should eat even less (WHO 2002; WHO 2014). Product has been classified as having moderate processing concerns EWG Food Reports Natural vs. Artificial Flavors EWG's Good Food On A Tight Budget Getting Arsenic Out of Your (And Your Kids') Diet EWG's 2014 Shopper's Guide to Avoiding GE Food Why GE Foods are not "Natural" Ingredient List From the Package UNCURED+ PEPPERONI INGREDIENTS: PORK, SEA SALT, SPICES, NATURAL FLAVORS, LACTIC ACID STARTER CULTURES, SUGAR * Older Product * Discontinued Product Product Images Please note that EWG obtains the displayed images of products from third parties and that the product's manufacturer or packager may change the product's packaging at any point in time. Therefore, EWG assumes no responsibility for the accuracy of images presented. Other Information This product contains the following ingredient(s) that may be genetically engineered or derived from GE crops: Sugars [read more] This product contains the following ingredient(... Scientists have not determined whether GE food poses risks to human health. Still, consumers have many good reasons to avoid eating genetically engineered ingredients, including limited safety studies, the development of "superweeds" and increased pesticide use. For more information on the topic visit: http://www.ewg.org/research/shoppers-guide-to-avoiding-ge-food Note: The presence or absence of genetically engineered ingredients or ingredients derived from GE crops does not affect a product's overall score. Environmental Impact: Contains pork, which has a higher carbon footprint relative to chicken, eggs and plant proteins. Contains ingredients derived from milk - these are considered major food allergens according to the FDA [read more] Contains ingredients derived from milk - these ... While over 160 food ingredients may cause allergic reactions current Food and Drug Administration (FDA) regulations stipulate that 8 major food allergens must be labeled on products. These allergens include; milk, eggs, fish, crustacean shellfish, tree nuts, peanuts, wheat and soybeans. Note: The presence of potential allergens does not affect the overall product score. Nutrition Facts 0.0 servings per containerServing Size1 oz. 14.0 g 28.0 g (1x) 42.0 g 56.0 g (2x) 84.0 g (3x) 112.0 g (4x) Amount Per 28 g Calories 120 % Daily Value (based on a 2,000 calorie diet and adult bodyweight) Update the values for someone: -age- 1-3 years 4-8 years 9-13 years 14-18 years 19-30 years 31-50 years 51-70 years over 70 years -gender/life stage- male female pregnant female lactating female goQUICK FACTS: 15.0 15.0 % Total Fat 10 g 0.0 0.0 % Total Carbs 1 g Sugars 0 g 12.0 12.0 % Protein 6 gAVOID TOO MUCH: 18.0 18.0 % Saturated Fat 3 g 8.0 8.0 % Cholesterol 25 mg 20.0 20.0 % Sodium 490 mg Added Sugar Ingredients: SugarsNUTRIENTS: 0.0 0.0 % Dietary Fiber 0 g Vitamin D (no value on present label) 2.0 2.0 % Vitamin A 35.0 35.0 % Vitamin C 2.0 2.0 % Calcium 2.0 2.0 % Iron Potassium (no value on present label)† Institute of Medicine. 2010. "Dietary Reference Intakes Tables and Application." Accessed April 8, 2014:link eat well guide find sustainable food! The Eat Well Guide helps consumers find locally grown and sustainably produced food. Listings include farms, restaurants, stores, farmers' markets, and CSAs throughout the United States.
https://www.ewg.org/foodscores/products/810014150390-CreminelliUncuredPepperoniUncured/
Interleukin-34 Enhances the Tumor Promoting Function of Colorectal Cancer-Associated Fibroblasts - DocsLib cancers Article Interleukin-34 Enhances the Tumor Promoting Function of Colorectal Cancer-Associated Fibroblasts Eleonora Franzè 1, Antonio Di cancers ArticleInterleukin-34 Enhances the Tumor Promoting Function of Colorectal Cancer-Associated Fibroblasts Eleonora Franzè 1, Antonio Di Grazia 1, Giuseppe Sigismondo Sica 2, Livia Biancone 1, Federica Laudisi 1 and Giovanni Monteleone 1,* 1 Department of Systems Medicine, University of Rome “TOR VERGATA”, 00133 Rome, Italy;[email protected](E.F.);[email protected](A.D.G.);[email protected](L.B.);[email protected](F.L.) 2 Department of Surgery, University “TOR VERGATA” of Rome, 00133 Rome, Italy;[email protected]* Correspondence:[email protected]; Tel.: +39-06-7259-6158; Fax: +39-06-7259-6391  Received: 15 October 2020; Accepted: 24 November 2020; Published: 27 November 2020  Simple Summary: In colorectal cancer (CRC), cancer-associated fibroblasts (CAFs) promote tumor growth and progression through the synthesis of various molecules targeting the neoplastic cells. Here, we demonstrate that IL-34, acytokinehighly expressed in CRC tissue, regulates the function of CAFs in a paracrine and autocrine manner. Specifically, IL-34 induces normal fibroblasts (NFs) to acquire a cellular phenotype resembling that of CAFs, while IL-34 knockdown in CAFs reduces their tumorigenic properties and proliferation. Moreover, IL-34 stimulates NFs to produce netrin-1 and b-FGF—two factors that enhance CRC cell growth and migration. Altogether, our data support the involvement of IL-34 in CRC. Abstract: The stromal compartment of colorectal cancer (CRC) is marked by the presence of large numbers of fibroblasts, termed cancer-associated fibroblasts (CAFs), which promote CRC growth and progression through the synthesis of various molecules targeting the neoplastic cells. Interleukin (IL)-34, a cytokine over-produced by CRC cells, stimulates CRC cell growth. Since IL-34 also regulates the function of inflammatory fibroblasts, we hypothesized that it could regulate the tumor promoting function of colorectal CAFs. By immunostaining and real-time PCR, we initially showed that IL-34 was highly produced by CAFs and to lesser extent by normal fibroblasts isolated from non-tumoral colonic mucosa of CRC patients. CAFs and normal fibroblasts expressed the functional receptors of IL-34. IL-34 induced normal fibroblasts to express α-SMA, vimentin and fibroblast activationproteinand enhanced fibroblast growth, thus generating a cellular phenotype resembling that of CAFs. Consistently, knockdown of IL-34 in CAFs with an antisense oligonucleotide (AS) decreased expression of such markers and inhibited cell proliferation. Co-culture of CRC cells with IL-34 AS-treated CAFs supernatants resulted in less cancer cell proliferation and migration. Among CAF-derived molecules known to promote CRC cell growth/migration, only netrin-1 and basic-fibroblastgrowth factorwere induced by IL-34. Data suggest a role for IL-34 in the control of colorectal CAF function. Keywords: colon cancer; stromal cells; netrin-1; b-FGF;cytokines 1. Introduction In carcinomas, neoplastic epithelial cells actively interact with various immune cells, stromal cells and endothelial cells, thus generating a microenvironment that fosters carcinogenetic processes. Specifically, the tumor-associated stromal cells play a pivotal role in tumor initiation, progression, Cancers 2020, 12, 3537; doi:10.3390/cancers12123537 www.mdpi.com/journal/cancers Cancers 2020, 12, 3537 2 of 15 drug resistance, and relapse of cancer [1]. This has been shown, for instance, in colorectal cancer (CRC)—one of the most common cancers accounting for nearly 10% of cancer-related deaths worldwide [2]. Large numbers of fibroblasts, which express α-smooth muscle actin (α-SMA), are evident in the stromal compartment of CRC [3]. Functional studies showed that such cells, termed cancer-associated fibroblasts (CAFs), promote malignant cell growth and metastasis through bidirectional signaling with both neoplastic cells and other cells within the tumor microenvironment [4,5]. Moreover, specific stromal gene profiles have been associated with resistance to chemotherapy and poor prognosis [6,7] Within the tumor microenvironment, both immune and non-immune cells synthesize various cytokines, which trigger specific signaling in fibroblasts, thereby instructing them to produce a pro-tumorigenic secretome [8]. Interleukin-34 (IL-34), a cytokine produced by a variety of immune and non-immune cells, is spontaneously produced in the human gut, and its expression is up-regulated in the inflamed gut of patients with inflammatory bowel disease (IBD) and in CRC tissue [9–12]. Specifically, both CRC cells and non-tumoral cells infiltrating CRC tissue express IL-34, and the cytokine stimulates CRC cell growth [9]. Moreover, by using fibroblasts isolated from IBD patients, we have recently shown that IL-34 induces collagen synthesis [13]. Altogether, these observations raise the possibility that IL-34 can mediate the interplay between cancer cells and stromal cells during the colon carcinogenesis process. In the present study, we sought to ascertain whether IL-34 regulates the CAF-mediated tumor-promoting functions. 2. Results 2.1. Intestinal Fibroblasts Express Interleukin-34 and Its Receptors We extracted fibroblasts from surgical specimens of both tumor tissue and normal, adjacent colonic mucosa (at least 2 cm from the outer tumor margin) of patients undergoing resection for CRC. The tumor masses were dissociated, and various cell types were separated to obtain populations of CAFs and normal fibroblasts. The experiments were performed by comparing these pairs of CAFs and the corresponding normal fibroblasts, thereby avoiding bias due to inter-individual differences. Initially, we verified the purity of the various fibroblast populations by immunostaining. These fibroblast populations strongly expressed the fibroblastic marker vimentin and were negative for cytokeratin and CD31 (Figure1A), thus indicating that our fibroblast populations were prepared with minimal contamination by epithelial cell and endothelial cells. Flow cytometry analysis confirmed that both CAFs and NFs expressed α-SMA, while they were negative for CD31 (endothelial marker) and EpCAM (epithelial marker) (Figure S1). By real-time PCR, we next showed that IL-34 RNA transcripts were significantly increased in CAFs compared to the corresponding normal fibroblasts, and this result was confirmed by immunostaining (Figure1B,C). Moreover, IL-34 expression was more pronounced in fibroblasts isolated from ulcerative colitis-associated cancer as compared to normal fibroblasts (Figure1C). Flow cytometry analysis confirmed the major expression of IL-34 in CAFs as compared to NFs (Figure S1). Real-time PCR and immunostaining analysis showed that CAFs and normal fibroblasts expressed both M-CSFR-1 and PTP-ζ, two functional receptors of IL-34 [14,15] (Figure2). Cancers 2020, 12, 3537 3 of 15 Figure 1. Cancer-associated fibroblasts express interleukin-34 (IL-34). (A) Representative images of immunofluorescence staining of fibroblasts isolated from tumoral (cancer-associated fibroblasts—CAFs) and non-tumoral (normal fibroblasts—NFs) area of one patient with colon cancer and analyzed for the expression of CD31 (green), cytocheratin (green), vimentin (green), and DAPI (blue). (Scale bars: 50 µm). One of three representative experiments, in which cells of three patients were used, is shown. (B) NFs and CAFs were evaluated for the expression of IL-34 by real-time PCR; levels were normalized to β-Actin and data were expressed as mean SEM of five patients. (C) Representative images of immunofluorescence ± staining of CAFs and NFs taken from tumoral and non-tumoral area, respectively, of one patient with colon cancer and one patient ulcerative colitis-associated colon cancer (CAC) and analyzed for the expression of IL-34 (green), and DAPI (blue). The example is representative of six separate experiments in which cells of three patients with colon cancer and three patients with CAC were analyzed. The scale bars are 75 µm. Cancers 2020, 12, 3537 4 of 15 Figure 2. Both normal fibroblasts (NFs) and cancer-associated fibroblasts (CAFs) express IL-34 receptors. A–B: NFs and CAFs were evaluated for the expression of macrophage colony-stimulating factor receptor (M-CSFR-1) (A) and PTP-ζ (B) RNA transcripts by real-time PCR; levels were normalized to β-Actin and data were expressed as mean SEM of six patients. (C) Representative images of immunofluorescence ± staining of NFs and CAFs taken from tumoral and non-tumoral area, respectively, of one patient with colon cancer and analyzed for the expression of M-CSFR-1 (green), PTP-ζ (green), and DAPI (blue). The example is representative of three separate experiments in which cells of three patients with colon cancer were analyzed. The scale bars are 75 µm. 2.2. Interleukin-34 Induces an Activated Phenotype in Intestinal Fibroblasts Comparative analysis of gene-expression profiles of CAFs and fibroblasts isolated from non-tumoral tissues showed that fibroblasts in tumor masses possess biological characteristics distinct Cancers 2020, 12, 3537 5 of 15 from those of normal fibroblasts [16,17]. Toassess whether IL-34 induces a cellular phenotype resembling that of CAFs, we initially assessed whether IL-34 induces in normal fibroblasts markers, which are over-expressed by CAFs [16]. RNA expression of α-SMA, vimentin and fibroblast activation protein (FAP) was increased in IL-34-treated normal fibroblasts as compared to untreated cells (Figure3A–C), while RNA transcript of each molecule was decreased in CAFs following IL-34 knockdown with an antisense oligonucleotide (AS) (Figure3D–G). It has long been recognized that CAFs proliferate in vitro at much higher rates than activated fibroblasts isolated from normal tissue or from tissue with acute injury or healing wounds [18]. Figure 3. IL-34 stimulates normal fibroblasts (NFs) to acquire a tumoral phenotype. (A–C). Serum-starved NFs were either left unstimulated (UNST) or treated with IL-34 (25–100 ng/mL) for 6 h, and then α-SMA (A), FAP (B), Vimentin (C) RNA transcripts were evaluated by real-time PCR; levels were normalized to β-Actin and data were expressed as mean SEM of six experiments in which cells ± of six patients were analyzed. (D) CAFs were transfected with either negative control antisense oligonucleotide (NCAS) or IL-34 antisense oligonucleotide (IL-34 AS) for 48 h. IL-34 and β-Actin were then analyzed by Western blotting. Uncropped Western Blot images are available in Figure S2. (E–G). CAFs were transfected with negative control antisense oligonucleotide (NCAS) or IL-34 antisense oligonucleotide (IL-34 AS) for 24 h and α-SMA (E), FAP (F), Vimentin (G) RNA transcripts were analyzed by real-time PCR; levels were normalized to β-Actin, and data were expressed as mean SEM ± of six experiments in which cells of six patients were analyzed. Therefore, we cultured normal intestinal fibroblasts with IL-34 and then evaluated the rate of proliferation (Figure4A). Basic-fibroblast growth factor (b-FGF) was used as a positive control [ 19,20]. Flow-cytometry analysis of CSFE-stained cells and BrdU analysis showed that IL-34 significantly enhanced proliferation of normal fibroblasts (Figure4A, Figure S2). Consistently, inhibition of IL-34 with the specific AS decreased CAFs proliferation (Figure4B, Figure S3). Cancers 2020, 12, 3537 6 of 15 Figure 4. IL-34 enhances fibroblast proliferation. (A) Serum-starved normal fibroblasts (NFs) were stimulated with IL-34 (50 ng/mL) or basic-fibroblast growth factor (b-FGF) (20 ng/mL) for 48 h. Cell proliferation was evaluated by flow cytometry, and proliferation index was calculated with Modfit LT. Data indicate mean SEM of six independent experiments in which cells of six patients ± were analyzed. Right insets: representative histograms showing the expression of carboxyfluorescein diacetate succinimidyl ester (CFSE) in NFs analyzed by flow cytometry. (B) CAFs were transfected with negative control antisense oligonucleotide (NCAS) or IL-34 antisense oligonucleotide (IL-34 AS) for 48 h. Cell proliferation was evaluated by flow cytometry, and proliferation index was calculated with Modfit LT. Data indicate mean SEM of six independent experiments in which cells of six patients ± were analyzed. Right insets: representative histograms showing the expression of CFSE in CAFs analyzed by flow cytometry. UNST= unstimulated. 2.3. Interleukin-34 Stimulates Cancer-Associated Fibroblasts to Promote Colon Cancer Cell Growth and Migration In co-culture experiments, CAFs enhance tumorigenesis of cancer cells when compared with normal fibroblasts [21]. Therefore, we assessed whether IL-34 produced by CAFs could enhance CRC cell growth and migration. To this end, we cultured DLD-1 cells in the presence or absence of IL-34 AS-treated CAFs-conditioned media and then examined the proliferation of these cells. DLD-1 were selected because these cells are known to proliferate vigorously in response to CAF-derived factors [22]. DLD-1 cells cultured in the presence of IL-34 AS-treated CAFs supernatants exhibited a significant reduction in proliferation as compared to DLD-1 cells cultured in the presence of supernatants of CAFs treated with the control AS (Figure5A). Moreover, a scratch test showed that the supernatants of IL-34-deficient CAFs had reduced ability to promote DLD-1 cell migration as compared to the supernatants of untreated CAFs (Figure5B). Similar results were seen when experiments were performed using HT-29 cells (Figure S4). Cancers 2020, 12, 3537 7 of 15 Figure 5. IL-34 produced by fibroblasts decreases DLD-1 cell proliferation and migration. (A) DLD-1 cells were incubated with supernatants of CAFs previously transfected with either negative control antisense oligonucleotide (NCAS) or IL-34 antisense oligonucleotide (IL-34 AS) for 24 h. DLD-1 proliferation was evaluated after 48 h by flow cytometry and proliferation index was calculated with Modfit LT. Data indicate mean SEM of six independent experiments in which cells of six patients were ± analyzed. Right insets: representative histograms showing the expression of CFSE in DLD-1 analyzed by flow cytometry. (B) Representative images of “pseudo” wound in monolayer of DLD-1 treated with supernatants of CAFs previously transfected with either negative control antisense oligonucleotide (NCAS) or IL-34 antisense oligonucleotide (IL-34 AS) for 24 h. Cells were photographed at the time of scratch (T0) and examined for cell migration after 24 h from the specific stimulation. Right panel shows the % of “pseudo” wound area in a monolayer of DLD-1 cells at the specific time point (T) with respect to area in T0 (defined as 100%), and the data are expressed as mean SEM of six independent ± experiments in which cells of six patients were analyzed. 2.4. Interleukin-34 Enhances Netrin-1 and b-FGF Expression in CAFs The above data prompted us to test the possibility that IL-34 could stimulate CAFs to produce factors promoting CRC cell growth and migration. To this end, we assessed the RNA transcripts for several molecules, which are known to stimulate CRC cell proliferation/migration. Among these factors, only netrin-1 and b-FGF RNA expression was significantly increased in normal fibroblasts stimulated with IL-34 (Figure6A). In line with such results, knockdown of IL-34 with the AS decreased netrin-1 and b-FGF RNA transcripts in CAFs (Figure6B). Cancers 2020, 12, 3537 8 of 15 Figure 6. IL-34 induces Netrin-1 and b-FGF RNA expression. (A) Serum-starved normal fibroblasts (NFs) were treated with IL-34 (50 ng/mL) for 6 h and Igf1; Igf2, Tgf-α, Hgf, Netrin-1 and b-FGF RNA transcripts were analyzed by real-time PCR; levels were normalized to β-Actin and data were expressed as mean SEM of six experiments in which cells of six patients were analyzed. ± (B) CAFs were transfected with either negative control antisense oligonucleotide (NCAS) or IL-34 antisense oligonucleotide (IL-34 AS) for 24 h and Igf1; Igf2, Tgf-α, Hgf, Netrin-1 and b-FGF RNA transcripts were analyzed by real-time PCR; levels were normalized to β-Actin and data were expressed as mean SEM of six experiments in which cells of six patients were analyzed. UNST = unstimulated. ± As expected, netrin-1 and b-FGF protein content was increased in normal fibroblasts treated with IL-34 (Figure7A,B), while suchproteinswere down-regulated in IL-34 AS-treated CAFs (Figure7C,D). Figure 7. IL-34 induces Netrin-1 and b-FGF protein expression. (A) Serum-starved normal fibroblasts (NFs) were treated with IL-34 (50 ng/mL) for 24 h. Netrin-1 and β-Actin were evaluated by Western Cancers 2020, 12, 3537 9 of 15 blotting. One of three independent experiments, in which cells of three patients were analyzed, is shown. Right panel shows the quantitative analysis of Netrin-1/β-Actin ratio. Values are expressed in arbitrary units (a.u.) and indicate mean SEM. Uncropped Western Blots images are available in Figure S5. ± (B) Serum-starved NFs were treated with IL-34 (50 ng/mL) for 48 h and b-FGF was evaluated in cell-free supernatants by ELISA. Values are expressed in arbitrary units (a.u.) and indicate mean SEM ± of six experiments in which cells of six patients were analyzed. C-D. CAFs were transfected with either negative control antisense oligonucleotide (NCAS) or IL-34 antisense oligonucleotide (IL-34 AS) for 24 h, and Netrin-1 and β-Actin (C) or b-FGF and β-Actin (Uncropped Western Blots images are available in Figure S6) (D) were evaluated by Western blotting. Right panels show the quantitative analysis of Netrin-1/β-Actin (C) or b-FGF /β-Actin (D) ratio, and values are expressed in arbitrary units (a.u.) and indicate mean SEM (Uncropped Western Blots images are available in Figure S7). ± One of three independent experiments, in which cells of three patients were analyzed, is shown. UNST = unstimulated. 3. Discussion This study was undertaken to examine whether IL-34, a cytokine highly expressed in CRC tissue, regulates the function of CAFs. Indeed, it has long been recognized that cytokines produced within the tumor environment contribute to the colon carcinogenesis process by targeting CAFs and, hence, regulating many aspects of tumor progression, from in situ growth of primary tumors to metastatic spread of cancer cells [8]. Data of the present study show that CAFs produce IL-34 and express the receptors for this cytokine. These data, together with our previous results showing that CRC cells can produce IL-34 [9,23], raise the possibility that IL-34 can regulate CAF functions in a paracrine and autocrine manner. Normal stroma in most organs contains a small number of quiescent or resting fibroblasts, whereas reactive tumor stroma is generally characterized by an increased number of activated fibroblasts that express αSMA, vimentin and FAP [17]. Notably, IL-34 enhanced expression of such markers in normal intestinal fibroblasts, while inhibition of IL-34 expression in CAFs decreased αSMA, vimentin and FAP.It is, however, known that such markers are not sufficient to identify CAFs with pro-tumorigenic activity, and some CAF markers may also be associated with cells with diverse, and possibly opposing, functions in the context of the specific tumor microenvironment [24]. Therefore, to further support the ability of IL-34 to promote differentiation of CAFs with tumorigenic properties, we performed functional studies and evaluated the effect of IL-34 stimulation on CAF proliferation. Indeed, it is known that CAFs proliferate vigorously and such a proliferation is regulated by cytokines released within the tumor microenvironment [21]. Flow-cytometry analysis revealed that IL-34 stimulated the growth of normal fibroblasts as well as inhibition of IL-34 was accompanied by reduced proliferation of CAFs. In recent years, evidence has been accumulated to show that in co-culture experiments, CAFs enhance tumorigenesis of cancer cells when compared with normal fibroblasts [19]. Pioneering studies showed that CAFs but not normal fibroblasts promoted the formation of tumors resembling prostatic cancer when inoculated into mice with Simian virus 40-transformed prostate epithelial cells [25]. Subsequently, similar results were obtained in other cancer systems where the ability of CAFs to influence tumor growth was partly dependent on the function of CAF-derived cytokines [26,27]. Our results fit with such observations and highlight the proliferative effect of IL-34 on cancer cells, as knockdown of IL-34 in CAFs attenuated the ability of culture supernatants of such cells to promote DLD-1 cell growth. Moreover, supernatants of IL-34-depleted CAFs exhibited reduced ability to promote in vitro DLD-1 cell migration. These findings confirm and expand on results of our previous studies showing a direct mitogenic effect of IL-34 on CRC cells [9,23]. Next, we explored the possibility that IL-34 can stimulate CAFs to produce factors that regulate CRC cell behavior. To this end, we analyzed the expression of several factors involved in the regulation of CRC cell growth and migration in normal fibroblasts stimulated with IL-34. IL-34 enhanced expression of netrin-1 and b-FGF, and this effect was evident at both RNA and protein level. Consistently, both netrin-1 and b-FGF were down-regulated in IL-34-depleted CAFs. Netrin-1 is a multifunctional secreted Cancers 2020, 12, 3537 10 of 15 glycoprotein involved in the control of several biological processes, such as angiogenesis, neuronal navigation, angiogenesis, and cell survival and migration and accumulating evidence suggests a role for this protein in many pathologies, including cardiovascular diseases, diabetes, and cancer [28–30]. Netrin-1 is highly expressed in CAFs in CRC tissue and regulates CRC cell stemness [31,32]. Similarly b-FGF stimulates acquisition of CAFs metastatic capacity [33] and positively regulates the growth of CRC cells [34]. The factors that control Netrin-1 and b-FGF induction in CRC remain, however, poorly characterized. Data of the present study indicate that IL-34 is a regulator of Netrin-1 and b-FGF in colon CAFs and suggest that the IL-34 promoting effect on CRC cell growth and migration can, at least in part, rely on the induction of these two proteins by CAFs. In conclusion, this study shows that CAFs produce and respond to IL-34 with the downstream 4. Materials and Methods 4.1. Patients and Samples Paired tissue samples were taken from the tumoral area and the macroscopically and microscopically unaffected, adjacent colonic mucosa of 9 patients who underwent colon resection for sporadic CRC at the Tor Vergata University Hospital (Rome, Italy). All patients received neither radiotherapy nor chemotherapy prior to undergoing surgery. An additional surgical sample was taken from the tumoral area of 3 patients with colitis-associated colon cancer (CAC). Each patient who took part in the study gave written informed consent, and the study protocol was approved by the local Ethics Committee (Tor Vergata University Hospital, Rome, Italy; protocol number: 171/16, received in 19 December 2016). 4.2. Isolation and Culture of Intestinal Fibroblasts All the reagents were purchased from Sigma-Aldrich (Milan, Italy) unless specified. Intestinal fibroblasts were isolated from the tumoral and non-tumoral area of 9 CRC patients as described 2 elsewhere [35,36]. Fibroblasts were maintained in 75 cm plastic flasks and incubated at 37 ◦C in a humidified atmosphere with 5% CO2 in D-MEM containing high glucose with Ultra Glutamine and supplemented with 10% fetal bovine serum (FBS), 1% of penicillin (100 U/mL), streptomycin (100 µg/mL) and 1% of non-essential amino acids (all from Lonza, Verviers, Belgium). Depending on the studies, fibroblasts were used either freshly isolated (for evaluating either the cell phenotype or the content of the cytokine and its receptors) or after 3–8 passages. To assess whether IL-34 controls cell proliferation, 5 104 normal fibroblasts were plated into × each well of a 12-well plate, left to adhere for 24 h, then starved for 6 h and finally either left unstimulated or stimulated with IL-34 (50 ng/mL, Miltenyi Biotec, Bologna, Italy) and b-FGF (20 ng/mL, Peprotech EC, Ltd., London, UK). After 48 h, cell proliferation was assessed by flow cytometry. In further experiments, normal fibroblasts were plated into each well of a 12-well plate, left to adhere for 24 h, then starved for 6 h and finally either left unstimulated or stimulated with recombinant human IL-34 for 6–48 h. At the end, cells were used for protein and gene expression analysis by Western blotting or Real time PCR, respectively, and cell-free supernatants were stored at 80 C until used. − ◦ CAFs (5 104) were plated and left to adhere as indicated above and after 24 h transfected with × an IL-34 antisense oligonucleotide (IL-34 AS) or negative control antisense oligonucleotide (NCAS) (both used a 200 nM, Integrated DNA Technologies, Inc. Leuven, Belgium) for 24–48 h using Opti-MEM medium and Lipofectamine 3000 reagent according to the manufacturer’s instructions (both from Life Technologies, Milan, Italy). Cells were used for analysis of RNA, protein and proliferation. Cell-free supernatants were used for assessing their ability to induce DLD-1 cell proliferation. 4.3. Real-Time PCR A constant amount of RNA (0.5 µg/sample) was retro-transcribed into complementary DNA (cDNA) and then 1 µL of cDNA/sample was amplified using the following conditions: denaturation 1 Cancers 2020, 12, 3537 11 of 15 min at 95 ◦C; annealing 30 s, at 57 ◦C for: TGF-α, at 58 ◦C for: M-CSFR-1, PTP-ζ, IGF2, FAP, Vimentin; at 60 ◦C for: β-Actin, IL-34, α-SMA, IGF1; HGF, b-FGF, and at 61 ◦C for Netrin-1, followed by 30 s of extension at 72 ◦C. The following primer sequences were used: IL-34: forward, 50-ACAGGAGCCG ACTTCAGTAC-30 and reverse, 50-ACCAAGACCCACAGATACCG-30; M-CSFR-1: forward, 50-CTGC TCAACTTTCTGCGAAG-30 and reverse, 50-CTCATCTCCACATAGGTGTC-30; PTP-ζ: forward, 50-ACTAACCGATCCCCAACAAG-30 and reverse, 50-CCACACATTTCCCTCCATAG-30; α-SMA: forward 50-TCTGGAGATGGTGTCACCCA-30 and reverse 30-ACCCACTGTGGTAGAGGTCT-50; FAP: forward, 50-TGTCCACCTTCCACAAGTAC-30 and reverse, 50-CTGTCCAAGTTGCTCATCAG-30; Vimentin: forward, 50-GGAGCAGCAGAATAAGATCC-30 and reverse, 50-CCAGAGACGCATTGT CAAC-3; IGF1: forward, 50-CTCCTCGCATCTCTTCTACC-30 and reverse, 50-CTCCAGCCTCCTTA GATCAC-30; IGF2: forward, 50-TCGTTGAGGAGTGCTGTTTC-30 and reverse, 50-GGGGTATCTGG GGAAGTTG-30; TGF-α: forward, 50-CTGTTCGCTCTGGGTATTG-30 and reverse, 50-ACTGAGTGT GGGAATCTGG-30; HGF: forward, 50-TCCAGAGGTACGCTACGAAG-30 and reverse, 50-GGTGT GGTGTCTGATGATCC-30; b-FGF: forward, 50-AGAGCGACCCTCACATCAAG-30 and reverse, 50-AGCCAGGTAACGGTTAGCAC-30; Netrin-1: forward, 50-GAAGACTGCGATTCCTACTGC-30 and reverse, 50-CCCTGCTTATACACGGAGATG-30; β-actin: forward, 50-AAGATGACCCAGATC ATGTTTGAGACC-30 and reverse 50-AGCCAGTCCAGACGCAGGAT-30. mRNA expression was calculated relative to the housekeeping β-Actin gene on the basis of the ∆∆Ct algorithm. 4.4. Total Protein Extraction and Western Blotting Fibroblasts were lysed on ice in buffer containing 10 mM HEPES (pH 7.9), 10 mM KCl, 0.1 mM EDTA, 0.2 mM EGTA and 0.5% Nonidet P40 supplemented with 1 mM dithiothreitol, 10 mg/mL aprotinin, 10 mg/mL leupeptin, 1 mM phenylmethylsulfonyl fluoride, 1 mM Na3VO4 and 1 mM NaF. Lysates were clarified by centrifugation at 4 ◦C for 30 min, and separated on 10% sodium dodecyl sulphate-polyacrylamide gel electrophoresis, and membranes were then incubated with the following antibodies: mouse anti human IL-34 (1:1000 Abcam, Cambridge, UK), rabbit anti-human Netrin-1 (1:1000 Abcam), rabbit anti-human b-FGF (final dilution 1:1000, Abcam), followed by horseradish peroxidase–conjugated secondary IgG monoclonal antibodies (all used at final dilution 1:20,000, Dako, Milan, Italy). The reaction was detected with a sensitive enhanced chemiluminescencekit(Pierce, Rockford, IL, USA). After the analysis, blots were stripped and incubated with the following internal loading control: mouse anti-human β-Actin (final dilution 1:5000 Sigma-Aldrich). Computer-assisted scanning densitometry (Image-Lab 5.2.1, Bio-Rad Laboratories, Milan, Italy) was used to analyze the intensity of the immunoreactive bands. 4.5. Immunofluorescence CAFs and normal fibroblasts were assessed by immunofluorescence as indicated elsewhere [13] using the following antibodies: mouse anti-human IL-34 (final dilution 1:200, Abcam), mouse anti-human Vimentin (final dilution 1:100, ThermoFisher Scientific, Milan, Italy), mouse anti-human CD31 (final dilution 1:100, ThermoFisher Scientific), mouse anti-human Cytocheratin (final dilution 1:100, Santa Cruz Biotechnology, Inc., Dallas, TX, USA), mouse anti-human M-CSFR-1 (final dilution 1:100, Novus Biological, CO, USA) or mouse anti-human PTP-ζ (final dilution 1:100, Abcam). Slides were then incubated for 1 h at RT with specific secondary antibodies coupled with Alexa Fluor Dyes (final dilution 1:2000; ThermoFisher Scientific). Coverslips were mounted on glass slides using ProLong Gold antifade reagent with DAPI (ThermoFisher Scientific) to counterstain the DNA. Samples were analyzed with a Leica DMI 4000 B fluorescence microscope (Leica, Wetzlar, Germany). 4.6. Flow Cytometry Cells were stained with the following monoclonal anti-human antibodies: PerCP 5.5 anti-EpCAM (both from Becton Dickinson, Milan, Italy), Pacific Blue anti-CD31 (eBioscience, San Diego, CA, USA), fluorescein isothiocyanate (FITC) anti-SMA, phycoerythrin (PE) anti-IL-34 (both from R&D Systems, Cancers 2020, 12, 3537 12 of 15 Minneapolis, MN, USA). In all experiments, appropriate isotype control IgG was used. All antibodies were used at 1:50 final dilution. For intracellular staining, cells were fixed and permeabilized using IC Fixation buffer and the permeabilization buffer (both from eBioscience) according to the manufacturer’s instruction. Cells were analyzed by flow cytometry (FACSVerse, Becton Dickinson) and data were analyzed by FlowJo ver. 10.7 (Becton Dickinson). 4.7. Analysis and Quantification of Cell Proliferation Cell proliferation was assessed by flow cytometry using carboxyfluorescein diacetate succinimidyl ester (CFSE; Molecular Probes, Life Technologies), which covalently binds cell components to yield a fluorescence that is divided equally between daughter cells at each division. Briefly, starved DLD-1 cells or normal fibroblasts or CAFs were incubated with CFSE according to the manufacturer’s instructions. After 30 min, the medium was removed, and fresh medium was added for the indicated time points. At the end of the specific treatment, cells were collected, washed twice with PBS and then incubated with PI (5 mg/mL, Life Technologies) for 15 min at 4 ◦C in the dark. CFSE- and/or PI-positive cells were determined by flow cytometry (FACSVerse BD Biosciences, San Jose, CA, USA), and the data were analyzed using ModFit LT 5.0 (Verity Software House, Inc., Topsham, ME, USA) and expressed as relative proliferation index with respect to unstimulated conditions. Cell growth was evaluated by using a commercially available 5-bromodeoxyuridine (BrdU) assay kit (Roche Diagnostics, Monza, Italy). Briefly, 3500 cells were cultured in 96-well microplates and allowed to adhere overnight. Five-bromodeoxyuridine was added to the cell cultures 6 h before the end of the experiments, and cell growth was evaluated by ELISA at 450 nm. 4.8. Enzyme-Linked Immunosorbent Assay Human b-FGF was measured using a sensitive commercial ELISA kit (R&D Systems) according to the manufacturer’s instructions. 4.9. Wound Healing Scratch Assay A confluent DLD-1 or HT-29 cell monolayer was artificially wounded by scratching with a 200 µL pipette tip (“pseudo” wound approximately 1 mm diameter). The wells were washed with PBS to remove debris, and then the cell-free supernatants of CAFs previously transfected with sense oligonucleotide or IL-34 AS for 24 h were added for further 24 h. Images were taken at time 0 and after 24 h, and the “pseudo” wound area was measured by Image-Lab software (Bio-Rad Laboratories). The wound healing ability of DLD-1 at 24 h was expressed as a percentage of “pseudo” wound area with respect to that at time 0. 4.10. Statistical Analysis Differences between two groups were compared using the Student’s t-test. All the analyses were performed using Graph-Pad 6 software (San Diego, CA, USA). 5. Conclusions This is the first study showing that, in colon cancer, IL-34 is produced by CAFs and targets these cell populations with the down-stream effect of enhancing the CAF pro-tumorigenic function. Supplementary Materials: The following are available online at http://www.mdpi.com/2072-6694/12/12/3537/s1, Figure S1: CAFs express interleukin-34 (IL-34). Figure S2: Uncropped Western Blot of Figure 3D, Figure S3: IL-34 enhances fibroblast proliferation. Figure S4: IL-34 produced by fibroblasts decreases HT-29 cell proliferation and migration, Figure S5: Uncropped Western Blot of Figure 7A, Figure S6: Uncropped Western Blot of Figure 7C, Figure S7: Uncropped Western Blot of Figure 7D. Author Contributions: E.F. performed experiments, analyzed data, wrote manuscript; A.D.G. and F.L. performed experiments; G.S.S. and L.B. provided biological samples; G.M. designed experiments and wrote the manuscript. All authors have read and agreed to the published version of the manuscript. Cancers 2020, 12, 3537 13 of 15 Funding: The study was supported by the Associazione Italiana per la Ricerca sul Cancro (IG2016–19223). Conflicts of Interest: G.M. has served as an advisory board member for ABBVIE. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. References 1. Quail, D.F.; Joyce, J.A. Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 2013, 19, 1423–1437. [CrossRef][PubMed] 2. Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018, 68, 394–424. [CrossRef] 3. Herrera, M.; Islam, A.B.; Herrera, A.; Martín, P.; García, V.; Silva, J.; Garcia, J.M.; Salas, C.; Casal, I.; De Herreros, A.G.; et al. 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https://docslib.org/doc/678254/interleukin-34-enhances-the-tumor-promoting-function-of-colorectal-cancer-associated-fibroblasts
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class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EErelel M, Cuhadaroglu C, Ece T, \u003Cem\u003Eet al.\u003C\/em\u003E The frequency of deep vein thrombosis and pulmonary embolism in acute exacerbations of chronic obstructive pulmonary disease. \u003Cspan class=\u0022cit-source\u0022\u003ERespir Med\u003C\/span\u003E \u003Cspan class=\u0022cit-pub-date\u0022\u003E2002\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E96\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E515\u003C\/span\u003E\u2013518.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca 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href=\u0022{openurl}?query=rft.jtitle%253DThorax%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fthx.2006.065557%26rft_id%253Dinfo%253Apmid%252F17101737%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToidGhvcmF4am5sIjtzOjU6InJlc2lkIjtzOjg6IjYyLzIvMTIxIjtzOjQ6ImF0b20iO3M6MTk6Ii9lcmovMzUvNi8xMjQzLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-abstract\u0022\u003EAbstract\u003C\/span\u003E\u003Cspan class=\u0022cit-sep cit-reflinks-variant-name-sep\u0022\u003E\/\u003C\/span\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\n \u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-8-1\u0022 title=\u0022View reference 8 in text\u0022 id=\u0022ref-8\u0022\u003E\u21b5\u003C\/a\u003E\n \n \u003Cdiv class=\u0022cit ref-cit ref-other\u0022 id=\u0022cit-35.6.1243.8\u0022 data-doi=\u002210.1159\/000029254\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003ESch\u00f6nhofer B, K\u00f6hler D. Prevalence of deep-vein thrombosis of the leg in patients with acute exacerbations of chronic obstructive pulmonary disease. \u003Cspan class=\u0022cit-source\u0022\u003ERespiration\u003C\/span\u003E \u003Cspan class=\u0022cit-pub-date\u0022\u003E1998\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E65\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E173\u003C\/span\u003E\u2013177.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DRespiration%253B%2Binternational%2Breview%2Bof%2Bthoracic%2Bdiseases%26rft.stitle%253DRespiration%26rft.aulast%253DSch%25C3%25B6nhofer%26rft.auinit1%253DB.%26rft.volume%253D65%26rft.issue%253D3%26rft.spage%253D173%26rft.epage%253D177%26rft.atitle%253DPrevalence%2Bof%2Bdeep-vein%2Bthrombosis%2Bof%2Bthe%2Bleg%2Bin%2Bpatients%2Bwith%2Bacute%2Bexacerbation%2Bof%2Bchronic%2Bobstructive%2Bpulmonary%2Bdisease.%26rft_id%253Dinfo%253Adoi%252F10.1159%252F000029254%26rft_id%253Dinfo%253Apmid%252F9670296%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1159\/000029254\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=9670296\u0026amp;link_type=MED\u0026amp;atom=%2Ferj%2F35%2F6%2F1243.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000074785700004\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\n \u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-9-1\u0022 title=\u0022View reference 9 in text\u0022 id=\u0022ref-9\u0022\u003E\u21b5\u003C\/a\u003E\n \n \u003Cdiv class=\u0022cit ref-cit ref-other\u0022 id=\u0022cit-35.6.1243.9\u0022 data-doi=\u002210.7326\/0003-4819-135-2-200107170-00010\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EWells PS, Anderson DR, Rodger M, \u003Cem\u003Eet al.\u003C\/em\u003E Excluding pulmonary embolism at bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and D-dimer. \u003Cspan class=\u0022cit-source\u0022\u003EAnn Intern Med\u003C\/span\u003E \u003Cspan class=\u0022cit-pub-date\u0022\u003E2001\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E135\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E98\u003C\/span\u003E\u2013107.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DAnnals%2Bof%2BInternal%2BMedicine%26rft.stitle%253DANN%2BINTERN%2BMED%26rft.issn%253D0003-4819%26rft.aulast%253DWells%26rft.auinit1%253DP.%2BS.%26rft.volume%253D135%26rft.issue%253D2%26rft.spage%253D98%26rft.epage%253D107%26rft.atitle%253DExcluding%2BPulmonary%2BEmbolism%2Bat%2Bthe%2BBedside%2Bwithout%2BDiagnostic%2BImaging%253A%2BManagement%2Bof%2BPatients%2Bwith%2BSuspected%2BPulmonary%2BEmbolism%2BPresenting%2Bto%2Bthe%2BEmergency%2BDepartment%2Bby%2BUsing%2Ba%2BSimple%2BClinical%2BModel%2Band%2BD-dimer%26rft_id%253Dinfo%253Adoi%252F10.7326%252F0003-4819-135-2-200107170-00010%26rft_id%253Dinfo%253Apmid%252F11453709%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.7326\/0003-4819-135-2-200107170-00010\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=11453709\u0026amp;link_type=MED\u0026amp;atom=%2Ferj%2F35%2F6%2F1243.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000169842300003\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\n \u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-10-1\u0022 title=\u0022View reference 10 in text\u0022 id=\u0022ref-10\u0022\u003E\u21b5\u003C\/a\u003E\n \n \u003Cdiv class=\u0022cit ref-cit ref-other\u0022 id=\u0022cit-35.6.1243.10\u0022 data-doi=\u002210.1001\/archinte.161.1.92\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EWicki J, Perneger TV, Funod AF, \u003Cem\u003Eet al.\u003C\/em\u003E Assessing clinical probability of pulmonary embolism in the emergency ward. \u003Cspan class=\u0022cit-source\u0022\u003EArch Intern Med\u003C\/span\u003E \u003Cspan class=\u0022cit-pub-date\u0022\u003E2001\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E161\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E92\u003C\/span\u003E\u201397.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DArchives%2Bof%2BInternal%2BMedicine%26rft.stitle%253DArch%2BIntern%2BMed%26rft.issn%253D0003-9926%26rft.aulast%253DWicki%26rft.auinit1%253DJ.%26rft.volume%253D161%26rft.issue%253D1%26rft.spage%253D92%26rft.epage%253D97%26rft.atitle%253DAssessing%2BClinical%2BProbability%2Bof%2BPulmonary%2BEmbolism%2Bin%2Bthe%2BEmergency%2BWard%253A%2BA%2BSimple%2BScore%26rft_id%253Dinfo%253Adoi%252F10.1001%252Farchinte.161.1.92%26rft_id%253Dinfo%253Apmid%252F11146703%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1001\/archinte.161.1.92\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=11146703\u0026amp;link_type=MED\u0026amp;atom=%2Ferj%2F35%2F6%2F1243.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000166124200010\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\n \u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-11-1\u0022 title=\u0022View reference 11 in text\u0022 id=\u0022ref-11\u0022\u003E\u21b5\u003C\/a\u003E\n \n \u003Cdiv class=\u0022cit ref-cit ref-other\u0022 id=\u0022cit-35.6.1243.11\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EBaum GL, Fisher FD. The relationship of fatal pulmonary insufficiency with cor pulmonale, right sided mural thrombi, and pulmonary emboli: a preliminary report. \u003Cspan class=\u0022cit-source\u0022\u003EAm J Med Sci\u003C\/span\u003E \u003Cspan class=\u0022cit-pub-date\u0022\u003E1960\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E240\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E609\u003C\/span\u003E\u2013612.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DThe%2BAmerican%2Bjournal%2Bof%2Bthe%2Bmedical%2Bsciences%26rft.stitle%253DAm%2BJ%2BMed%2BSci%26rft.aulast%253DBaum%26rft.auinit1%253DG.%2BL.%26rft.volume%253D240%26rft.spage%253D609%26rft.epage%253D612%26rft.atitle%253DThe%2Brelationship%2Bof%2Bfatal%2Bpulmonary%2Binsufficiency%2Bwith%2Bcor%2Bpulmonale%252C%2Brightsided%2Bmural%2Bthrombi%2Band%2Bpulmonary%2Bemboli%253A%2Ba%2Bpreliminary%2Breport.%26rft_id%253Dinfo%253Apmid%252F13687964%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=13687964\u0026amp;link_type=MED\u0026amp;atom=%2Ferj%2F35%2F6%2F1243.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=A1960WB87700009\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\n \u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-12-1\u0022 title=\u0022View reference 12 in text\u0022 id=\u0022ref-12\u0022\u003E\u21b5\u003C\/a\u003E\n \n \u003Cdiv class=\u0022cit ref-cit ref-other\u0022 id=\u0022cit-35.6.1243.12\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EMitchell RS, Silvers GW, Dart GA, \u003Cem\u003Eet al.\u003C\/em\u003E Clinical and morphologic correlations in chronic airway obstruction. \u003Cspan class=\u0022cit-source\u0022\u003EAspen Emphysema Conf\u003C\/span\u003E \u003Cspan class=\u0022cit-pub-date\u0022\u003E1968\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E9\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E109\u003C\/span\u003E\u2013123.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DAspen%2BEmphysema%2BConf%26rft.volume%253D9%26rft.spage%253D109%26rft_id%253Dinfo%253Apmid%252F5722654%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=5722654\u0026amp;link_type=MED\u0026amp;atom=%2Ferj%2F35%2F6%2F1243.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\n \u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-13-1\u0022 title=\u0022View reference 13 in text\u0022 id=\u0022ref-13\u0022\u003E\u21b5\u003C\/a\u003E\n \n \u003Cdiv class=\u0022cit ref-cit ref-other\u0022 id=\u0022cit-35.6.1243.13\u0022 data-doi=\u002210.1378\/chest.08-1516\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003ERizkallah J, Man SF, Sin DD. Prevalence of pulmonary embolism in acute exacerbations of chronic obstructive pulmonary disease. \u003Cspan class=\u0022cit-source\u0022\u003EChest\u003C\/span\u003E \u003Cspan class=\u0022cit-pub-date\u0022\u003E2009\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E135\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E786\u003C\/span\u003E\u2013793.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DChest%26rft_id%253Dinfo%253Adoi%252F10.1378%252Fchest.08-1516%26rft_id%253Dinfo%253Apmid%252F18812453%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1378\/chest.08-1516\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=18812453\u0026amp;link_type=MED\u0026amp;atom=%2Ferj%2F35%2F6%2F1243.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000264310500028\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\n \u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-14-1\u0022 title=\u0022View reference 14 in text\u0022 id=\u0022ref-14\u0022\u003E\u21b5\u003C\/a\u003E\n \n \u003Cdiv class=\u0022cit ref-cit ref-other\u0022 id=\u0022cit-35.6.1243.14\u0022 data-doi=\u002210.1056\/NEJM199205073261902\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003ECarson JL, Kelley ML, Duff AE, \u003Cem\u003Eet al.\u003C\/em\u003E The clinical course of pulmonary embolism. \u003Cspan class=\u0022cit-source\u0022\u003EN Engl J Med\u003C\/span\u003E \u003Cspan class=\u0022cit-pub-date\u0022\u003E1992\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E326\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E1240\u003C\/span\u003E\u20131245.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca 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class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003ECarson JL, Terrin ML, Duff A, \u003Cem\u003Eet al.\u003C\/em\u003E Pulmonary embolism and mortality in patients with COPD. \u003Cspan class=\u0022cit-source\u0022\u003EChest\u003C\/span\u003E \u003Cspan class=\u0022cit-pub-date\u0022\u003E1996\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E110\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E1212\u003C\/span\u003E\u20131219.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca 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class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EMonreal M, Munoz-Torrero JFS, Naraine VS, \u003Cem\u003Eet al.\u003C\/em\u003E Pulmonary embolism in patients with chronic obstructive pulmonary disease or congestive heart failure. \u003Cspan class=\u0022cit-source\u0022\u003EAm J Med\u003C\/span\u003E \u003Cspan class=\u0022cit-pub-date\u0022\u003E2006\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E119\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E851\u003C\/span\u003E\u2013858.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca 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Axioms | Free Full-Text | A New Equilibrium Version of Ekeland& rsquo;s Variational Principle and Its Applications In this note, a new equilibrium version of Ekeland’s variational principle is presented. It is a modification and promotion of previous results. Subsequently, the principle is applied to discuss the equilibrium points for binary functions and the fixed points for nonlinear mappings. A New Equilibrium Version of Ekeland’s Variational Principle and Its Applications by Yuqiang Feng 1,2,* , Juntao Xie 1 and Bo Wu 3 1 School of Science, Wuhan University of Science and Technology, Wuhan 430065, China 2 Hubei Province Key Laboratory of Systems Science in Metallurgical Process, Wuhan 430065, China 3 State Key Laboratory of Environment-Friendly Energy Materials, Mianyang 621010, China * Author to whom correspondence should be addressed. Axioms 2022 , 11 (2), 68; https://doi.org/10.3390/axioms11020068 Received: 8 December 2021 / Revised: 28 January 2022 / Accepted: 1 February 2022 / Published: 9 February 2022 (This article belongs to the Special Issue Calculus of Variations and Nonlinear Partial Differential Equations ) Abstract In this note, a new equilibrium version of Ekeland’s variational principle is presented. It is a modification and promotion of previous results. Subsequently, the principle is applied to discuss the equilibrium points for binary functions and the fixed points for nonlinear mappings. Keywords: Ekeland-type variational principle ; bi-function ; equilibrium point ; fixed point MSC: 47H10; 49J40; 54H25 1. Introduction Ekeland’s variational principle (abbrev. EVP ), which is considered to be the basis of modern calculus of variations, was presented in 1974 (see, for instance [ 1 , 2 ]). It is widely used in many fields, such as differential equations, optimization, fixed point theory, etc. It is precisely the wide application of this theorem that it has attracted the attention of a large number of scholars, and has been promoted from all directions. For example, Zhong [ 3 ] extended the form of EVP in metric space; we rewrite the result as follows. Theorem 1 (EVP of Zhong-type [ 3 ]). Let ( X , d ) be a complete metric space and x 0 ∈ X fixed. The function f : X → R ∪ { + ∞ } is bounded from below, lower semi-continuous, and not identically + ∞ . If g : [ 0 , + ∞ ) → [ 0 , + ∞ ) is a continuous non-decreasing function such satisfying ∫ 0 + ∞ 1 1 + g ( r ) d r = + ∞ , then, for any ε > 0 , y ∈ M such that f ( y ) < inf x ∈ X f ( x ) + ε and, for any λ > 0 , there exists z ∈ X satisfying f ( z ) ≤ f ( y ) d ( z , x 0 ) ≤ r ¯ + r 0 and f ( x ) ≥ f ( z ) − ε λ ( 1 + g ( d ( x 0 , z ) ) ) d ( x , z ) ∀ x ∈ M where r 0 = d ( x 0 , y ) and r ¯ is such that ∫ r 0 r ¯ + r 0 1 1 + g ( r ) d r ≥ λ . Oettli and Théra [ 4 ] and Blum and Oettli [ 5 ] investigated the equilibrium versions of EVP. In [ 6 ], Bianchi et al. presented equilibrium versions of EVP as follows Let X be an Euclidean space, C ⊆ X be a closed set and f : C × C → R . Theorem 2 ([ 6 ]). Assume the following assumptions are satisfied: (i) f ( x , · ) is lower bounded and lower semicontinuous, for every x ∈ C ; (ii) f ( t , t ) = 0 , for every t ∈ C ; (iii) f ( z , x ) ≤ f ( z , t ) + f ( t , x ) for every x , t , z ∈ C . Then, for every ε > 0 and for every x 0 ∈ C , there exists x ¯ ∈ C such that (a) f ( x 0 , x ¯ ) + ε ∥ x 0 − x ¯ ∥ ≤ 0 ; (b) f ( x ¯ , x ) + ε ∥ x ¯ − x ∥ > 0 , ∀ x ∈ C , x ≠ x ¯ . Farkas and Molnar [ 7 ] improved the conclusion in [ 6 ], and obtained a Zhong-type variational principle for bi-functions as follows: Theorem 3 ([ 7 ]). Let ( X , d ) be a complete metric space, C ⊂ X be a closed set, and f : C × C → R + be a mapping. Let g : [ 0 , + ∞ ) → ( 0 , + ∞ ) be a continuous nondecreasing function such that ∫ 0 + ∞ 1 g ( s ) d s = + ∞ Let x 0 ∈ C be fixed. Assume that the following assumptions be satisfied: (i) f ( x , · ) is bounded from below and lower semicontinuous, for every x ∈ C ; (ii) f ( z , z ) = 0 , for every z ∈ C ; (iii) f ( z , x ) ≤ f ( z , t ) + f ( t , x ) for every x , t , z ∈ C ; Then, for every ε > 0 and y ∈ C for which we have inf z ∈ C f ( y , z ) > − ε (1) and for every λ > 0 , there exists x ε such that (a) d ( x 0 , x ε ) < r + r ¯ ; (b) f ( x ε , x 0 ) + ε λ ( 1 + g ( d ( x 0 , x ε ) ) ) d ( x ε , x 0 ) ≤ 0 ; (c) f ( x ε , x ) + ε λ ( 1 + g ( d ( x 0 , x ε ) ) ) d ( x , x ε ) > 0 , ∀ x ∈ C , x ≠ x ε ; where r 0 = d ( x 0 , y ) and r ¯ are chosen such that ∫ r 0 r 0 + r ¯ 1 1 + g ( r ) d r ≥ λ . However, when proving (a), there are some errors in [ 7 ]. In the process of proving { d ( x 0 , x n ) < r 0 + r ¯ } ( 14 ) , they presented the following inequality, ∑ n = 1 k − 1 d ( x n , x n + 1 ) 1 + g ( d ( x 0 , x n + 1 ) ) ≥ ∑ n = 1 k − 1 d ( x 0 , x n + 1 ) − d ( x 0 , x n ) 1 + g ( d ( x 0 , x n + 1 ) ) ≥ ∑ n = 1 k − 1 ∫ d ( x 0 , x n ) d ( x 0 , x n + 1 ) 1 1 + g ( r ) d r = ∫ d ( x 0 , x 1 ) d ( x 0 , x k ) 1 1 + g ( r ) d r But in fact, by the continuity and monotonicity of g and the definition of W ( x n ) , we have d ( x 0 , x n ) < d ( x 0 , x n + 1 ) , then for d ( x 0 , x n ) ≤ r ≤ d ( x 0 , x n + 1 ) , 1 1 + g ( r ) ≥ 1 1 + g ( d ( x 0 , x n + 1 ) ) Hence, ∑ n = 1 k − 1 ∫ d ( x 0 , x n ) d ( x 0 , x n + 1 ) 1 1 + g ( r ) d r ≥ ∑ n = 1 k − 1 ∫ d ( x 0 , x n ) d ( x 0 , x n + 1 ) 1 1 + g ( d ( x 0 , x n + 1 ) ) d r = ∑ n = 1 k − 1 d ( x 0 , x n + 1 ) − d ( x 0 , x n ) 1 + g ( d ( x 0 , x n + 1 ) ) , which contradicts their conclusion. In this note, we aim at modifying the result of [ 7 ], and establish a new equilibrium form of the Ekeland’s variational principle for bi-function. Then, the conclusions are used to discuss the equilibrium point problem and fixed point problem. Some recent advances in Ekeland’s variational principles and applications can be seen in [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ] and references therein. This paper is organized as follows: In Section 2 , we state a new version of Ekeland’s variational principle for bi-functions. In Section 3 , as applications of the main result, we discuss a equilibrium problem and a fixed point problem. 2. A New Equilibrium Version of EVP In this section, we establish a new equilibrium version of EVP. Theorem 4. Let ( X , d ) be a complete metric space, C ⊂ X be a closed set, x 0 ∈ C fixed, and g : [ 0 , + ∞ ) → ( 0 , + ∞ ) be a continuous nondecreasing function such that ∫ 0 + ∞ 1 g ( s ) d s = m , ( 0 < m ≤ + ∞ ) . If f : C × C → R satisfies: (i) f ( x , · ) is bounded from below and lower semi-continuous, ∀ x ∈ C ; (ii) f ( y , y ) = 0 , ∀ y ∈ C ; (iii) f ( x , z ) ≤ f ( x , y ) + f ( y , z ) , ∀ x , y , z ∈ C . Then, for any ε > 0 , 0 < α < m fulfilling inf z ∈ C f ( x 0 , z ) > − α ε (2) there is x ε ∈ C such that (a) f ( x 0 , x ε ) + ε g ( d ( x 0 , x 0 ) ) d ( x 0 , x ε ) ≤ 0 (b) f ( x ε , x ) + ε g ( d ( x 0 , x ε ) ) d ( x ε , x ) > 0 , ∀ x ∈ C , x ≠ x ε ; (c) d ( x 0 , x ε ) ≤ l , where l satisfies ∫ 0 l 1 g ( s ) d s = α . Proof. Let T ( x ) = { y ∈ C \ B ( x 0 , d ( x 0 , x ) ) | f ( x 0 , x ) + ε g ( d ( x 0 , x ) ) d ( x 0 , x ) ≤ 0 } . In the same manner as the proof of Theorem 2.1 in [ 7 ], we can construct a sequence { x n } n = 0 ∞ ⊆ C such that (1) x n + 1 ∈ T ( x n ) , T ( x n + 1 ) ⊂ T ( x n ) , n = 0 , 1 , 2 , ⋯ ; (2) diam T ( x n ) → 0 . Due to the completeness of X and the closeness of C , there is a unique x ε ∈ C such that lim n → ∞ x n = x ε , ⋂ n = 0 ∞ T ( x n ) = { x ε } . As x ε ∈ T ( x 0 ) , we have f ( x 0 , x ε ) + ε g ( d ( x 0 , x 0 ) ) d ( x 0 , x ε ) ≤ 0 . This verifies assertion (a). Due to x ε ∈ T ( x n ) , n = 0 , 1 , 2 , ⋯ , we obtain T ( x ε ) ⊂ T ( x n ) , n = 0 , 1 , 2 , ⋯ . Hence T ( x ε ) ∈ ⋂ n = 0 ∞ T ( x n ) . and T ( x ε ) = { x ε } . Therefore, the assertion ( b ) f ( x ε , x ) + ε g ( d ( x 0 , x ε ) ) d ( x ε , x ) > 0 , ∀ x ∈ C , x ≠ x ε , holds. In what follows, let us verify conclusion (c). As x n + 1 ∈ T ( x n ) , f ( x n , x n + 1 ) + ε g ( d ( x 0 , x n ) ) d ( x n , x n + 1 ) ≤ 0 , ( n = 0 , 1 , 2 , ⋯ ) Hence, ∑ j = 0 n f ( x j , x j + 1 ) + ∑ j = 0 n ε g ( d ( x 0 , x j ) ) d ( x j , x j + 1 ) ≤ 0 . Noting that ∑ j = 0 n f ( x j , x j + 1 ) ≥ f ( x 0 , x n + 1 ) , (3) we obtain ∑ j = 0 n ε g ( d ( x 0 , x j ) ) d ( x j , x j + 1 ) ≤ − ∑ j = 0 n f ( x j , x j + 1 ) ≤ − f ( x 0 , x n + 1 ) < α ε , which means ∑ j = 0 ∞ 1 g ( d ( x 0 , x j ) ) d ( x j , x j + 1 ) < α We assert d ( x 0 , x ε ) ≤ l . Contrarily, assume d ( x 0 , x ε ) > l . Take { n i } as a subsequence of { n } such that { d ( x 0 , x n i ) } is monotone increasing, converges to d ( x 0 , x ε ) and d ( x 0 , x k ) ≤ d ( x 0 , x n i − 1 ) ( k = n i − 1 + 1 , n i − 1 + 2 , ⋯ , n i − 1 ) , then ∑ k = n i − 1 n i − 1 d ( x k , x k + 1 ) g ( d ( x 0 , x k ) ) ≥ ∑ k = n i − 1 n i − 1 d ( x k , x k + 1 ) g ( d ( x 0 , x n i − 1 ) ) ≥ d ( x n i − 1 , x n i ) g ( d ( x 0 , x n i − 1 ) ) ≥ d ( x 0 , x n i ) − d ( x 0 , x n i − 1 ) g ( d ( x 0 , x n i − 1 ) ) ≥ ∫ d ( x 0 , x n i − 1 ) d ( x 0 , x n i ) 1 g ( s ) d s which implies α > ∑ n = 0 ∞ d ( x n , x n + 1 ) g ( d ( x 0 , x n ) ) ≥ ∫ 0 d ( x 0 , x ε ) 1 g ( s ) d s > ∫ 0 l 1 g ( s ) d s = α , a contradiction. This completes the proof of conclusion (c). □ If there exists φ : X → R + such that f ( x , y ) = φ ( y ) − φ ( x ) , we have the following corollary. Corollary 1. Let ( X , d ) be a complete metric space, C ⊂ X be a closed set, x 0 ∈ C fixed and φ : C → R + be a bounded from below and lower semi-continuous mapping, g : [ 0 , + ∞ ) → ( 0 , + ∞ ) be a continuous nondecreasing function such that ∫ 0 + ∞ 1 g ( s ) d s = m , ( 0 < m ≤ + ∞ ) If and ε > 0 , 0 < α < m satisfy φ ( x 0 ) ≤ inf x ∈ C φ + α ε , then there exists x ε such that (a) φ ( x ε ) ≤ φ ( x 0 ) ; (b) φ ( x ) > φ ( x ε ) − ε g ( d ( x 0 , x ε ) ) d ( x , x ε ) ∀ x ∈ C w i t h x ≠ x ε ; (c) d ( x 0 , x ε ) ≤ l ; where l satisfies ∫ 0 l 1 g ( s ) d s = α Remark 1. Corollary 1 can be seen as an extension of Theorem 2.1 in [ 8 ]. 3. Applications As applications of Theorem 4, we first discuss the existence of equilibrium point for a bi-function. By an equilibrium problem (abbrev. EP), we understand the problem of finding x ¯ ∈ X s u c h t h a t f ( x ¯ , x ) ≥ 0 , ∀ x ∈ C . where C is a given subset of a metric space X and f : C × C → R is a given bi-function. Theorem 5. Let ( X , d ) be a complete metric space, C ⊂ X be a compact set. Assume f : C × C → R satisfies (i) f ( x , · ) is bounded from below and lower semi-continuous, for every x ∈ C ; (ii) f ( z , z ) = 0 , for every z ∈ C ; (iii) f ( z , x ) ≤ f ( z , t ) + f ( t , x ) for every x , t , z ∈ C ; (iv) f ( · , y ) is upper semi-continuous, for every y ∈ C . Then, the equilibrium problem (EP) has a solution. Proof. Let g ( s ) ≡ 1 . It is a continuous nondecreasing function such and ∫ 0 + ∞ 1 g ( s ) d s = + ∞ Let x 0 ∈ C be fixed, for every ε n = 1 n and α = n ( b − 1 ) , where b = inf z ∈ C f ( x 0 , z ) . Then, by Theorem 4 (b), there exists x n ∈ C such that f ( x n , x ) + 1 n d ( x n , x ) ≥ 0 , ∀ x ∈ C Due to compactness of C , there is a subsequence { x n k } of { x n } which is convergent, i.e., there exists x ¯ ∈ C , such that lim k → ∞ x n k = x ¯ . Hence, we have f ( x ¯ , x ) ≥ lim k → ∞ sup [ f ( x n k , x ) + 1 n k d ( x n k , x ) ] ≥ 0 , ∀ x ∈ C This implies that x ¯ is a solution to the equilibrium problem (EP). □ Then, we establish the following Caristi type fixed point theorem. Theorem 6. Let ( X , d ) be a complete metric space, x 0 ∈ X fixed, and φ : X → R + be a bounded from below and lower semicontinuous mapping, g : [ 0 , + ∞ ) → ( 0 , + ∞ ) be a continuous nondecreasing function such that ∫ 0 + ∞ 1 g ( s ) d s = m where m ∈ R + ⋃ { + ∞ } . If a mapping K : X → X satisfies: for some ε > 0 , ε d ( x , K ( x ) ) g ( d ( x 0 , x ) ) ≤ φ ( x ) − φ ( K ( x ) ) ∀ x ∈ X , (4) then K has a fixed point in X . Proof. Let f ( x , y ) = φ ( y ) − φ ( x ) , C = X . By the proof of Theorem 4, for each ε > 0 , there exists a sequence { x n } n ∈ N ⊂ X and x ε ∈ X , such that x n → x ε as n → ∞ and φ ( x ) > φ ( x ε ) − ε g ( d ( x 0 , x ε ) ) d ( x , x ε ) ∀ x ∈ C , x ≠ x ε (5) In what follows, we will prove that x ε is a fixed point of K . Conversely, suppose that x ε ≠ K ( x ε ) . Let x = K ( x ε ) and substitute it into (5), we find φ ( K ( x ε ) ) ≥ φ ( x ε ) − ε g ( d ( x 0 , x ε ) ) d ( K ( x ε ) , x ε ) . (6) Taking x ε instead of x in (4), we have that ε d ( x ε , K ( x ε ) ) g ( d ( x 0 , x ε ) ) ≤ φ ( x ε ) − φ ( K ( x ε ) ) (7) Combing the inequalities (6) with (7), we know ε d ( x ε , K ( x ε ) ) g ( d ( x 0 , x ε ) ) ≤ φ ( x ε ) − φ ( K ( x ε ) ) < ε d ( x ε , K ( x ε ) ) g ( d ( x 0 , x ε ) ) which is a contradiction. Thus x ε = K ( x ε ) , i.e., x ε is a fixed point of K . □ Author Contributions Methodology, Y.F. and J.X.; writing—original draft preparation, Y.F. and J.X.; writing—review and editing, Y.F.; funding acquisition, B.W. All authors have read and agreed to the published version of the manuscript. Funding This research is partially supported by the Open Project of State Key Laboratory of Environment-friendly Energy Materials (19kfhg08). Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable. Data Availability Statement Not applicable. Acknowledgments The authors thank the anonymous referees for their valuable constructive comments and suggestions, which improved the quality of this paper in the present form. Conflicts of Interest The authors declare no conflict of interest. References Ekeland, I. On the variational principle. J. Math. Anal. Appl. 1974 , 4 , 324–353. [ Google Scholar ] [ CrossRef ][ Green Version ] Ekeland, I. Nonconvex minimization problems. Bull. Am. Math. Soc. 1979 , 1 , 443–474. [ Google Scholar ] [ CrossRef ][ Green Version ] Zhong, C.-K. 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An equilibrium version of set-valued Ekeland variational principle and its applications to set-valued vector equilibrium problems. Acta Math. Sin. (Engl. Ser.) 2017 , 33 , 210–234. [ Google Scholar ] [ CrossRef ] Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/ ). MDPI and ACS Style Feng, Y.; Xie, J.; Wu, B. A New Equilibrium Version of Ekeland’s Variational Principle and Its Applications. Axioms 2022, 11, 68. https://doi.org/10.3390/axioms11020068 AMA Style Feng Y, Xie J, Wu B. A New Equilibrium Version of Ekeland’s Variational Principle and Its Applications. Axioms. 2022; 11(2):68. https://doi.org/10.3390/axioms11020068 Chicago/Turabian Style Feng, Yuqiang, Juntao Xie, and Bo Wu. 2022. "A New Equilibrium Version of Ekeland’s Variational Principle and Its Applications" Axioms11, no. 2: 68. https://doi.org/10.3390/axioms11020068 Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here . Article Metrics No Article Access Statistics Export citation file: BibTeX | EndNote | RIS MDPI and ACS Style Feng, Y.; Xie, J.; Wu, B. A New Equilibrium Version of Ekeland’s Variational Principle and Its Applications. Axioms 2022, 11, 68. https://doi.org/10.3390/axioms11020068 AMA Style Feng Y, Xie J, Wu B. A New Equilibrium Version of Ekeland’s Variational Principle and Its Applications. Axioms. 2022; 11(2):68. https://doi.org/10.3390/axioms11020068 Chicago/Turabian Style Feng, Yuqiang, Juntao Xie, and Bo Wu. 2022. 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Distributions of R 490/435 values of single cells of L. monocytogenes... | Download Scientific Diagram Download scientific diagram | Distributions of R 490/435 values of single cells of L. monocytogenes 4140 cells immobilized on a filter membrane and measured by FRIM upon exposure to leucocin 4010 at concentrations of 0 (a), 9,600 (b), and 24,000 (c) AU/ml. from publication: Two Subpopulations of Listeria monocytogenes Occur at Subinhibitory Concentrations of Leucocin 4010 and Nisin | In situ analyses of single Listeria monocytogenes cells at subinhibitory concentrations of leucocin 4010 and nisin revealed two subpopulations when measured by fluorescence ratio imaging microscopy (FRIM) after staining with 5(6)-carboxyfluorescein diacetate succinimidyl... | Nisin, Listeria monocytogenes and Bacteriocins | ResearchGate, the professional network for scientists. Distributions of R 490/435 values of single cells of L. monocytogenes 4140 cells immobilized on a filter membrane and measured by FRIM upon exposure to leucocin 4010 at concentrations of 0 (a), 9,600 (b), and 24,000 (c) AU/ml. Two Subpopulations of Listeria monocytogenes Occur at Subinhibitory Concentrations of Leucocin 4010 and Nisin In situ analyses of single Listeria monocytogenes cells at subinhibitory concentrations of leucocin 4010 and nisin revealed two subpopulations when measured by fluorescence ratio imaging microscopy (FRIM) after staining with 5(6)-carboxyfluorescein diacetate succinimidyl ester. One subpopulation consisted of cells with a dissipated pH gradient (ΔpH... Contexts in source publication Context 1 ... A novel statistical method was developed to describe the dissipation of pH for single cells of L. monocytogenes exposed to the bacterio- cins. Statistical analyses were carried out by using R 490/435 values. In all experi- ments, single-cell analysis of R 490/435 values revealed a bimodal distribution (i.e., two subpopulations) as outlined in Fig. 2: one subpopulation showed an average R 490/435 of ca. 2.5 (subpopulation 1), and the other subpopulation showed an average R 490/435 of ca. 9 (subpopulation 2). For each of the different combina- tions of bacteriocin and meat additive, the following order of procedures was used (each step of the statistical procedure is explained in ... Context 2 ... detailed information on the distributions of the mea- sured R 490/435 values shown as bars, as well as the fitted curves of the binomial distributions of the R 490/435 values (estimated according to steps i and ii of the statistical procedure), are shown in Fig. 2 and 3 for L. monocytogenes exposed to leucocin 4010 and nisin, respectively. In the absence of bacteriocins, all L. monocytogenes cells were designated as subpopulation 2, showing R 490/435 values with an average of ca. 9.0 ( Fig. 2a and 3a). Exposure of L. monocytogenes to subinhibitory con- centrations of leucocin 4010 (9,600 AU/ml) or ... Context 3 ... of the R 490/435 values (estimated according to steps i and ii of the statistical procedure), are shown in Fig. 2 and 3 for L. monocytogenes exposed to leucocin 4010 and nisin, respectively. In the absence of bacteriocins, all L. monocytogenes cells were designated as subpopulation 2, showing R 490/435 values with an average of ca. 9.0 ( Fig. 2a and 3a). Exposure of L. monocytogenes to subinhibitory con- centrations of leucocin 4010 (9,600 AU/ml) or nisin (400 IU/ml) revealed two subpopulations ( Fig. 2b and 3b). One subpopulation showed low values of R 490/435 , with an aver- age of ca. 2.5, and these cells were designated as subpopu- lation 1, and the other cells with high values of ... Context 4 ... 4010 and nisin, respectively. In the absence of bacteriocins, all L. monocytogenes cells were designated as subpopulation 2, showing R 490/435 values with an average of ca. 9.0 ( Fig. 2a and 3a). Exposure of L. monocytogenes to subinhibitory con- centrations of leucocin 4010 (9,600 AU/ml) or nisin (400 IU/ml) revealed two subpopulations ( Fig. 2b and 3b). One subpopulation showed low values of R 490/435 , with an aver- age of ca. 2.5, and these cells were designated as subpopu- lation 1, and the other cells with high values of R 490/435 (average of ca. 9.0) were designated as subpopulation 2 (Fig. 2b and 3b). However, the histograms in Fig. 2b and 3b also show that a minor fraction of ... Context 5 ... of leucocin 4010 (9,600 AU/ml) or nisin (400 IU/ml) revealed two subpopulations ( Fig. 2b and 3b). One subpopulation showed low values of R 490/435 , with an aver- age of ca. 2.5, and these cells were designated as subpopu- lation 1, and the other cells with high values of R 490/435 (average of ca. 9.0) were designated as subpopulation 2 (Fig. 2b and 3b). However, the histograms in Fig. 2b and 3b also show that a minor fraction of cells exhibited R 490/435 values in between the typical low value ( low ) and the typical high value ( high ) calculated as explained in step i of the statis- tical procedure. These cells were assigned to subpopulation 1 or 2 according to the weighting scheme ... Context 6 ... (400 IU/ml) revealed two subpopulations ( Fig. 2b and 3b). One subpopulation showed low values of R 490/435 , with an aver- age of ca. 2.5, and these cells were designated as subpopu- lation 1, and the other cells with high values of R 490/435 (average of ca. 9.0) were designated as subpopulation 2 (Fig. 2b and 3b). However, the histograms in Fig. 2b and 3b also show that a minor fraction of cells exhibited R 490/435 values in between the typical low value ( low ) and the typical high value ( high ) calculated as explained in step i of the statis- tical procedure. These cells were assigned to subpopulation 1 or 2 according to the weighting scheme described in step ii of the ... Context 7 ... i of the statis- tical procedure. These cells were assigned to subpopulation 1 or 2 according to the weighting scheme described in step ii of the statistical analysis. After exposure to sufficiently high concentrations of leucocin 4010 (24,000 AU/ml) and nisin (1,800 IU/ml), all L. monocytogenes cells examined were designated as subpopulation 1 (Fig. 2c and ... [...] B. Davis Use of Antimicrobial Food Additives as Potential Dipping Solutions to Control Pseudomonas spp. Contamination in the Frankfurters and Ham Oct 2014 Mi-Hwa Oh Beom-Young Park Hyunji Jo [...] Yohan Yoon This study evaluated the effect of sodium diacetate and sodium lactate solutions for reducing the cell count of Pseudomonas spp. in frankfurters and hams. A mixture of Pseudomonas aeruginosa (NCCP10338, NCCP10250, and NCCP11229), and Pseudomonas fluorescens (KACC10323 and KACC10326) was inoculated on cooked frankfurters and ham. The inoculated samp... Inactivation of Listeria mono-cytogenes during Reheating of Frankfurters with Hot Water before Consumption Mawill Rodriguez Patricia Kendall Keith E Belk John N. Sofos Hot water may be used to kill Listeria monocytogenes on frankfurters immediately before consumption. This study evaluated the effectiveness of different time and water temperature combinations in destroying L. monocytogenes on frankfurters formulated with or without potassium lactate and sodium diacetate (PL/SD). Frankfurters were inoculated (1–2 l... Citations ... This technique, based on the linear response between the ratiometric intensity of fluorescence emitted by the probe and the pHi of the cells, gives information at the single-cell level, which allows determining the pHi of different subpopulations of cells simultaneously. Several authors (Hornbaek et al., 2002; Mortensen et al., 2006Mortensen et al., , 2008Smigic et al., 2009;Vindelov and Arneborg, 2002) used the fluorescent probe 5(6)-carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) to measure the pHi of bacteria and yeast cells at a pH ranging from 5.5 to 8. However, CFDA-SE is not adequate for pHi measurements of cells under acidic conditions, like in the case of wine fermentations where the pH of the medium ranges from 3 to 3.5, since they are not sensitive to pH values lower than 5.5. ... Antimicrobial peptides (AMPs) produced by Saccharomyces cerevisiae induce alterations in the intracellular pH, membrane permeability and culturability of Hanseniaspora guilliermondii cells Article Apr 2015 INT J FOOD MICROBIOL Patrícia Branco Tiago Viana Helena Albergaria Nils Arneborg Saccharomyces cerevisiae produces antimicrobial peptides (AMPs) during alcoholic fermentation that are active against several wine-related yeasts (e.g. Hanseniaspora guilliermondii) and bacteria (e.g. Oenococcus oeni). In the present study, the physiological changes induced by those AMPs on sensitive H. guilliermondii cells were evaluated in terms of intracellular pH (pHi), membrane permeability and culturability. Membrane permeability was evaluated by staining cells with propidium iodide (PI), pHi was determined by a fluorescence ratio imaging microscopy (FRIM) technique and culturability by a classical plating method. Results showed that the average pHi of H. guilliermondii cells dropped from 6.5 (healthy cells) to 5.4 (damaged cells) after 20min of exposure to inhibitory concentrations of AMPs, and after 24h 77.0% of the cells completely lost their pH gradient (∆pH=pHi-pHext). After 24h of exposure to AMPs, PI-stained (dead) cells increased from 0% to 77.7% and the number of viable cells fell from 1×10(5) to 10CFU/ml. This means that virtually all cells (99.99%) became unculturable but that a sub-population of 22.3% of the cells remained viable (as determined by PI staining). Besides, pHi results showed that after 24h, 23% of the AMP-treated cells were sub-lethally injured (with 0<∆pH<3). Taken together, these results indicated that this subpopulation was under a viable but non-culturable (VBNC) state, which was further confirmed by recuperation assays. In summary, our study reveals that these AMPs compromise the plasma membrane integrity (and possibly also the vacuole membrane) of H. guilliermondii cells, disturbing the pHi homeostasis and inducing a loss of culturability. Copyright © 2015 Elsevier B.V. All rights reserved. ... Nevertheless, the twopopulation model is promising and should be further explored. The existence of different L. monocytogenes subpopulations under unfavorable environmental conditions has been previously reported for L. monocytogenes in both food-and clinical microbiology settings (Hornbaek et al., 2006; Knudsen et al., 2013). ... Bi-phasic growth of Listeria monocytogenes in chemically defined medium at low temperatures Jun 2014 INT J FOOD MICROBIOL Nikolaos A Tyrovouzis Apostolos S Angelidis Nikolaos G Stoforos The present work reports a novel observation regarding the growth of L. monocytogenes in modified Welshimer's broth (MWB) at low temperatures. Specifically, the direct monitoring of the growth of L. monocytogenes Scott A using plate count data revealed that the pathogen displays a bi-phasic growth pattern in MWB at 7°C. This bi-phasic growth pattern is masked (not observed) when optical density (OD) measurements are used to monitor growth due to the inability of OD readings to detect L. monocytogenes population density increases up to 10(7)CFU/mL. This bi-phasic growth phenomenon was further investigated as a function of growth temperature (4°C, 7°C, 10°C, 14°C and 18°C), medium composition (by altering the MWB composition by ten-fold increases in different sets of medium constituents), inoculum level (10(2), 10(3), 10(4), 10(5), 10(6), and 10(7)CFU/mL) and L. monocytogenes strain (10 strains). The growth of L. monocytogenes Scott A in MWB at 7°C, 10°C and 14°C was consistently bi-phasic and independent of growth rate; at 18°C, growth was consistently mono-phasic (single-phase, typical sigmoid growth curves), whereas no growth was observed at 4°C. The tested modifications in the composition of MWB did not influence the bi-phasic nature of L. monocytogenes Scott A growth at 7°C, and, overall, we could not point out any strain-, or serotype-specific effects. On the other hand, the initial inoculum level appears to affect the form of the growth curve, as there was a shift towards mono-phasic growth in trials with increasing initial inocula. A mathematical model, based on a stepwise response and described through two sequential sigmoid curves, was used to describe bi-phasic growth and estimate the kinetic parameters of L. monocytogenes growth. An alternative hypothesis, based on the assumption of the existence of two subpopulations, possessing different growth kinetics, materialized under the stress imposed on L. monocytogenes cells due to the combined effect of three factors (defined medium, low temperature and low initial inoculum) was also proposed and formulated. ... (Singh et al., 2001; Mahadeo and Tatini, 1994; Ming et al., 1997). The efficacy of bacterocins is concentration dependent, endogenous enzymes and other meat and non meat additives ( Horbaek et al., 2006 ). Therefore, it is imperative to evaluate its effectiveness in-vitro conditions. ... The effect of nisin on Listeria monocytogenes in chicken burgers Jun 2014 Veli Gok In this study, the effect of nisin on the growth and survival of L. monocytogenes has been investigated in chicken burger samples. Chicken burger samples inoculated with L. monocytogenes(ATCC 7644) (L.m.) at the levels of 4 log cfu/g and 6 logcfu/g and were added nisin at the amounts of 25 μg/g, 50 μg/g and 100 μg/g to form eight experimental groups (C-1: 4 log cfu/g L.m.,A-1: 4 log cfu/g L.m.+ 25 ppm nisin, A-2: 4 log cfu/g L.m. + 50 ppm nisin, A-3: 4 log cfu/g L.m. + 100 ppm nisin, C-2: 6 logcfu/g L.m., B-1: 6 logcfu/g L.m. + 25 ppm nisin, B-2: 6 logcfu/g L.m. + 50 ppm nisin, B-3: 6 logcfu/g L.m. + 100 ppm nisin). No nisin was added into the control group. They were stored at 4oC for 7 days.At the present study, although the amounts of nisin used did not totally inhibitL. monocytogenes, the numbers of L. monocytogenes were reduced average 1-2 log cfu/g in the experimental chicken burgers. Therefore, it might be necessary to explore other different amounts of nisin to ensure possibilities of using nisin in meat and meat products View ... In the present study, huge variations in pH i were observed between the individual cells of both L. plantarum UFLA CH3 and L. brevis UFLA FFC199 upon passing through the GIT model. Heterogeneity in pH i among single cells has been previously reported in other systems [21, 43] . The heterogenic response found in the present work is likely related to the presence of naturally resistant cells in better physiological condition [38]. ... Effect of the gastrointestinal environment on pH homeostasis of Lactobacillus plantarum and L.brevis cells as measured by real-time fluorescence ratio-imaging microscopy Apr 2014 RES MICROBIOL Cíntia Lacerda Ramos Line Thorsen Mia Ryssel Dennis S. Nielsen Lene Jespersen In the present work, an in vitro model of the gastrointestinal tract (GIT) was developed to obtain real-time observations of the pH homeostasis of single cells of probiotic Lactobacillus spp. strains as a measure of their physiological state. Changes in the intracellular pH (pHi) were determined using fluorescence ratio imaging microscopy (FRIM) for potential probiotic strains of L. plantarum UFLACH3 and L. brevis UFLAFFC199. Heterogeneous populations were observed, with pHi values ranging from 6.5-7.5, 3.5-5.6 and 6.5-8.0 or higher during passage of saliva (pH 6.4), gastric (pH 3.5) and intestinal juices (pH 6.4), respectively. When nutrients were added to gastric juice, the isolate L. brevis significantly decreased its pHi closer to the extracellular pH (pHex) than in gastric juice without nutrients. This was not the case for L. plantarum. This study is the first to produce an in vitro GIT model enabling real-time monitoring of pH homeostasis of single cells in response to the wide range of pHex of the GIT. Furthermore, it was possible to observe the heterogeneous response of single cells. The technique can be used to determine the survival and physiological conditions of potential probiotics and other microrganisms during passage through the GIT. ... (Singh et al., 2001; Mahadeo and Tatini, 1994; Ming et al., 1997). The efficacy of bacterocins is concentration dependent, endogenous enzymes and other meat and non meat additives ( Horbaek et al., 2006 ). Therefore, it is imperative to evaluate its effectiveness in-vitro conditions. ... The effect of nisin on Listeria monocytogenes in chicken burgers Apr 2014 Recep Kara Hilmi Yaman (Hornbaek et al., 2006) (12) (12)
https://www.researchgate.net/figure/Distributions-of-R-490-435-values-of-single-cells-of-L-monocytogenes-4140-cells_fig2_7312062
A Summary of the 2018-19 US Flu Season The 2018-19 US flu season lasted 21 weeks, marking the longest season in a decade. A Summary of the 2018-19 US Flu Season The 2018-19 US flu season lasted 21 weeks, marking the longest season in a decade. The 2018-2019 United States flu season was the longest season in a decade, the US Centers for Disease Control and Prevention (CDC) has announced. Influenza The report, published in the CDC’s Morbidity and Mortality Weekly Report ,notes that although the United States experienced a lengthy flu season, overall the season was of moderate severity. Illnesses attributed to influenza A viruses predominated, with very little influenza B activity. According to surveillance data, among 80,993 specimens tested at public health laboratories throughout the season, 42,303 (52.2%) were positive for influenza viruses—40,624 (96.0%) were positive for influenza A and 1679 (4%) for influenza B. Subtype information was available for 38,995 cases of influenza A, with 22,084 (56.6%) cases of A(H1N1)pdm09 and 16,991 (43.6%) cases of A(H3N2). The report documents that there were 2 notable waves of influenza A activity: from October to mid-February there was an influx of the A(H1N1)pdm09 cases and from mid-February to mid-May there was an increase in A(H3N2) cases. Influenza B subtypes were available for 1105 (65.8%) influenza B viruses; 406 (36.7%) were B/Yamagata lineage; and 699 (63.3%) were B/Victoria lineage. Most of the A(H1N1)pdm09 viruses were antigenically similar to the cell culture-propagated reference virus representing the 2018-2019 Northern Hemisphere influenza vaccine virus, but considerable genetic diversity among currently circulating A(H1N1)pdm09 viruses belonging to clade 6B,1A was observed. Additionally, the increased circulation of clade 3C.3a viruses strongly contributed to the increasing proportion of A(H3N2) viruses that were antigenically distinct from the reference virus representing the A(H3N2) component of the 2018-2019 Northern Hemisphere vaccines. The investigators also noted that the severity assessment was moderate across all age groups. The rate of hospitalization was lower for adults compared with the 2017-2018 influenza season, but similar for children. Between September 30, 2018, and May 18, 2019, 116 laboratory-confirmed influenza-associated pediatric deaths were reported. More than 99% of influenza virus tested since October 1, 2018, were susceptible to oseltamivir and peramivir, and all tested viruses were susceptible to zanamivir and baloxavir. The CDC warns that although the United States has entered the summer months and seasonal influenza activity is currently below baseline, influenza illnesses are often reported outside of flu season. Influenza should be considered as a possible diagnosis in ill travelers returning from countries with ongoing influenza activity. When variant influenza infection is suspected, clinicians should make referrals to state health departments for testing. The authors of the report imply that receiving a seasonal influenza vaccine each year remains the best way to protect against seasonal influenza and its potentially severe consequences. Vaccine recommendations for the 2019-20 influenza season as made by the World Health Organization and US Food and Drug Administration’s Vaccines and Related Biologic Products Advisory Committee suggest “that influenza trivalent vaccines contain an A/Brisbane/02/2018 A(H1N1)pdm09-like virus, an A/Kansas/14/2017 A(H3N2)-like virus, and a B/Colorado/06/2017-like (B/Victoria lineage) virus. The quadrivalent vaccine recommendation included the trivalent vaccine viruses and a B/Phuket/3073/2013-like (B/Yamagata lineage) virus.” This study determined the efficacy of face masks at reducing exhaled particles in children, as well as whether the type of activity affected the concentration and size of particles. Children have notoriously high rates of circulating viruses. Respiratory viruses, likeCOVID-19, are transmitted through respiratory droplets and aerosols, which are expelled via breaking, talking, singing, coughing, and sneezing. With this knowledge, the outbreak of the COVID-19 pandemic led to myriad recommendations or requirements for face masks. When masking was widely implemented, public health agencies noted significantly lower rates of viral respiratory infections. However, there has been little investigation into the production of exhaled particles during common activities, and the effectiveness of face masks in children. Arecent pediatric investigation, published in Wiley Online Library, sought to determine the effect of type of activity and mask usage on exhaled particle production in children. The prospective crossover study included 22 children 3-17 years of age, averaging 10.2 years old and 59.1% female. The children were asked to perform activities that expel particles, including breathing quietly, speaking, singing, coughing, and sneezing, while wearing either no mask, a cloth mask, or a surgical mask. During each activity, the investigators examined the effect of face mask used on the concentration and size of exhaled particles produced. Concentration (number of particles/cm3) and size of particles were monitored in real-time and recorded with an Aerodynamic Particle Sizer (APS) Model 3321. Predictably, the average exhaled particle concentration increased based on the activity’s intensity. The lowest particle concentration was recorded during tidal breathing (1.285 particles/cm3 [95% CI 0.943, 1.627]), while the highest concentration of particles was expelled during sneezing (5.183 particles/cm3 [95% CI 1.911, 8.455]). High intensity activities were also associated with an increase in the size of respirable particles (particles ≤ 5 µm are respirable size). Surgical and cloth masks were associated with lower average particle concentrations, compared to not wearing a mask. Surgical masks performed better than cloth masks across all the activities, and especially helped to reduce the size of the respirable particles. For sneezing, the highest intensity activity, cloth masks reduced total exhaled particle release by 45.6%. Surgical masks reduced the total particles exhaled during sneezing by 54.1%. Notably, the children were surveyed after the study to rate their experiences wearing each type of mask. At 64%, most children indicated they would prefer to wear cloth masks over surgical masks in school, and 72.7% reported their favorite mask type was cloth. The participants reported an overall better experience wearing the cloth mask compared to the surgical mask, but rated the breathability of surgical masks better than the cloth masks. The investigators concluded that children produce exhaled particles, varying in size and concentration, at rates similar to adults. Coughing and sneezing were associated with a higher production of exhaled particles, with the study authors writing, “Higher production was particularly observed in the respirable size fraction, reflecting the formation of smaller exhaled particles during activities with a greater expiratory flow.” Average particle concentration increased more significantly during high-intensity activities in older children than in younger children. The investigators emphasized their findings that face masks work equally well to reduce exhaled particles across all ages.
https://www.contagionlive.com/view/a-summary-of-the-201819-us-flu-season
The Oxford Oratory A sanctuary in the midst of the city The Oxford Oratory is a vibrant centre of Catholic life. Our church is open every day: join us for Mass, pop in for some quiet prayer, or come and discover more at one of our groups. Our historic church of St Aloysius has been a key feature in the lives of the city’s Catholics for 150 years, attracting people of all ages and from every walk of life. We use beauty to raise hearts and minds to God, faithful to the traditions of St Philip Neri and St John Henry Newman. The Oratory Prayer Book is now shipping internationally! We’ve made it even easier to buy the Oratory Prayer Book from anywhere in the world. And we’ve made it easier to order multiple copies too — in the UK and worldwide. Order your copy here:https://tinyurl.com/opb-buy If you have one, we’d love to hear what you think about it. Let us know in the comments, or tag a photo of your prayer book in the wild with #oratoryprayerbook Thanks to @acatholicinoxford for the photo. #oxfordoratory Worship What does it actually mean to worship God? In the New Testament, the word we most often translate as ‘worship’ doesn’t mean to reverence another in some abstract sense. It always involves some kind of bodily action. When we think about the magi visiting the Holy Family, we sometimes convey this motion by describing them — after they fall to their knees — as ‘doing homage’. But it’s actually that same word here we might translate elsewhere as ‘worship’. It’s just that we recognise the need to describe the bodily sign of their submission and adoration of the new born King with something that sounds a bit more physical. The word we usually translate as ‘worship’ ( proskuneo) comes literally from a root meaning ‘to make yourself like a dog before the other person’. It originally meant prostrating yourself on the floor to show your humble submission before another. By the time of the New Testament, people wouldn’t necessarily have had the root of this word in mind whenever they used it,* but the word still carries with it the idea of doing something with your body to express your worship. The feast of Corpus Christi is all about this kind of bodily worship. It’s tied to the fact that we are not pure spirits, but that we are human beings, body and soul. To worship God is not just a spiritual act. The right worship of God does not consist in simply having the right kinds of thoughts towards him. But the worship of God involves the humble submission of our entire human being, body and soul, before the God who is greater than all of us. And ever since the Incarnation, we do this not just before an abstract spirit. Because, from the moment of the Incarnation, God really does have a human body, that we can worship, that we fall down on our knees before, like the magi and the Canaanite woman, and so many others in the Gospel who kneel down and worship Christ. When we worship God, we kneel before God who is present in the flesh, under the appearances of bread and wine, in our churches all over the world. Corpus Christi is a joyful celebration of Christ’s presence among us, and it gives us an opportunity to think about how we respond to that gift. All this talk of kneeling and worship might not sound so joyful, but one of the great paradoxes of Christianity is that we find our greatest freedom in the humble service of God. Our greatest joy really should be found in finding ways to express this loving worship. So at least once a year, it is no bad thing to think about how we express with our own bodies that worship of God’s body, and what ways we can find to worship him even more perfectly. This Sunday, we will carry Christ’s Body through the streets of our city. We have a chance to demonstrate to the world our love, our joyful service, our worship of him, through our presence. The procession leaves our church at 2:30pm. Make sure you are there. But we should also think about the more ordinary things, like making sure we show that worship whenever we are in his presence. We should show through our behaviour in church that we believe him to be there: by genuflecting before him in the tabernacle of the church, and by keeping the church quiet and prayerful. We show our worship above all by kneeling down before him — like all those people in the Gospel — for the moment of Holy Communion. And we allow the priest to place the Host on our tongues, so that we don’t handle unnecessarily what is holy and precious, and no particles of Our Lord’s Body are ever dropped or lost through carelessness. We continue that worship in our prayers of thanksgiving after Communion and once the Mass has ended. We certainly never leave church during Communion. And we might think of ways of extending the time we spend with Christ present in the Blessed Sacrament: by attending Mass during the week sometimes, or visiting him during the times each week when his Body is exposed solemnly on the altar for Adoration, or even just by visiting an empty church, where he is waiting for us to show him our worship. Our Lord is hidden there, waiting for us to come and visit him, and make our request to him. See how good he is! He is there in the Sacrament of his love, sighing and interceding incessantly with his Father for sinners. To what outrages does he not expose himself, that he may remain in the midst of us! He is there to console us; and therefore we ought often to visit him. How pleasing to him is the short quarter of an hour that we steal from our occupations, from something of no use, to come and pray to him, to visit him, to console him for all the outrages he receives! When he sees pure souls coming eagerly to him, he smiles upon them. They come with that simplicity which pleases him so much, to ask his pardon for all sinners, for the outrages of so many ungrateful men. What happiness do we not feel in the presence of God, when we find ourselves alone at his feet before the holy tabernacles! ‘Come, my soul, redouble thy fervour; thou art alone adoring thy God. His eyes rest upon thee alone.’ — St John Mary Vianney * One exception is that I do think Christ had this root meaning in mind when he spoke to the Canaanite woman in Matthew 15:21–28. He wasn’t randomly insulting her by comparing her to a dog, but drawing attention to the fact that she was making herself like a dog before him — i.e. worshipping him — because she recognised him to be God. In other words, he was acknowledging her worship as proof of her faith and humility. On Saturday, Fr Rupert led Men’s Oratory on a walking pilgrimage to Islip, birthplace of St Edward the Confessor. #oxfordoratory Congratulations to Elizabeth who was received into the Church yesterday evening on the Feast of the Visitation. #oxfordoratory Congratulations to Livi, baptised on the vigil of Pentecost. “Therefore, Lord, we pray: graciously accept this oblation of our service, that of your whole family, which we make to you also for those to whom you have been pleased to give the new birth of water and the Holy Spirit, granting them forgiveness of all their sins; order our days in your peace, and command that we be delivered from eternal damnation and counted among the flock of those you have chosen. Through Christ our Lord. Amen.” #oxfordoratory Courtesy I recall how, as a child at school, we were sometimes made to learn poetry. At the time I hated it, and baulked at the idea of having to commit to memory The Ancient Mariner, and in fact, never did. But one poem which did touch me, was Belloc’s Courtesy. It began: Of Courtesy, it is much lessThan Courage of Heart or Holiness,Yet in my Walks it seems to meThat the Grace of God is in Courtesy. The poet goes on to tell us how, on one occasion he visited the ‘monks’ at Storrington in Sussex, and that ‘They took me straight into their Hall’where he ‘saw Three Pictures on a wall, And Courtesy was in them all.’ He then tells us the subject of those paintings: The first the Annunciation;The second the Visitation;The third the Consolation,Of God that was Our Lady’s Son. The first was of St. Gabriel;On Wings a-flame from Heaven he fell;And as he went upon one kneeHe shone with Heavenly Courtesy. Our Lady out of Nazareth rode —It was Her month of heavy load;Yet was her face both great and kind,For Courtesy was in Her Mind. The third it was our Little Lord,Whom all the Kings in arms adored;He was so small you could not seeHis large intent of Courtesy. Today is the feast of the Visitation, when we celebrate how our Lady made the long and uncomfortable journey to see her older kinswoman, Elizabeth, and her husband Zachariah, who lived in the hill country of Judah. Courtesy seems to me to be a perfect description of what this moment is all about. Imagine the cordial welcome extended to Mary by the older woman, solicitous for her health and how both women were eager to share with one another the joy of the forthcoming births of their sons. Our Lady had herself gone to visit her older cousin, not simply because she wanted to ‘be there’ for her, but because she wanted to share her own good news, which was not hers alone but for her people and, ultimately for the entire world. This is something Elizabeth seemed to know already! Her enthusiastic greeting is wonderful when she cries out ‘Oh that I should be visited by the Mother of my Lord’. Her unborn son joins in the greeting, kicking and letting his mother know that he too is part of this exciting thing that is happening. Elizabeth’s gracious words: ‘Blessed art thou among women and blessed is the fruit of thy womb’ have been enshrined in our prayer to the Virgin, incorporated with the Angelic Salutation: ‘Hail Mary, full of grace!’ And if today’s feast is about courtesy (so much more than stiff politeness or polished manners, but a warm and real concern for the wellbeing and interest of the other) then it is also about joy. Mary’s presence, together with that of her Divine Son, transformed the home of Elizabeth and Zachariah. ‘Elizabeth was filled with the Holy Spirit’ because of it. St Jose Maria puts it thus: ‘Mary brought joy to her cousin’s home, because she “brought” Christ’. Dame Julian liked to call Jesus ‘our courteous Lord,’ no doubt on account of his gracious dealings with us, flowing from his ‘large intent of Courtesy’! Julian writes in her Showings: And this is a supreme friendship of our courteous Lord, that he protects us so tenderly whilst we are in our sins; and furthermore he touches us most secretly, and shows us our sins by the sweet light of mercy and grace. But when we see ourselves so foul, then we believe that God may be angry with us because of our sins. Then we are moved by the Holy Spirit through contrition to prayer, and we desire with all our might an amendment of ourselves to appease God’s anger, until the time that we find rest of soul and ease of conscience. And then we hope that God has forgiven us our sin; and this is true. And then our courteous Lord shows himself to the soul, happily and with the gladdest countenance, welcoming it as a friend, as if it had been in pain and in prison, saying: My dear darling, I am glad that you have come to me in all your woe. I have always been with you, and now you see me loving, and we are made one in bliss. So sins are forgiven by grace and mercy, and our soul is honourably received in joy, as it will be when it comes into heaven, as often as it comes by the operation of grace of the Holy Spirit and the power of Christ’s Passion. Even though we have just changed all the light bulbs, our church looks its best when we don’t need to use them. #oxfordoratory The flag goes up on feast days! #oxfordoratory Blessings with St Philip’s relic after Vespers on Thursday. #oxfordoratory Look down from heaven, Holy Father, from the loftiness of that mountain to the lowliness of this valley; from that harbour of quietness and tranquillity to this calamitous sea. And now that the darkness of this world hinders no more those benignant eyes of thine from looking clearly into all things, look down and visit, O most diligent keeper, this vineyard which thy right hand planted with so much labour, anxiety and peril. To thee then we fly; from thee we seek for aid; to thee we give our whole selves unreservedly. Thee we adopt for our patron and defender; undertake the cause of our salvation, protect thy clients. To thee we appeal as our leader; rule thine army fighting against the assaults of the devil. To thee, kindest of pilots, we give up the rudder of our lives; steer this little ship of thine, and, placed as thou art on high, keep us off all the rocks of evil desires, that with thee for our pilot and our guide, we may safely come to the port of eternal bliss. #oxfordoratory Our celebrations for St Philip began with First Vespers last night and continue with Masses today. Here St Philip’s relic and altar are incensed during Vespers. #oxfordoratory Our new longer term temporary digital organ was hoisted up to the gallery this week in time for First Vespers of Our Holy Father St Philip. Catch up on our YouTube channel if you missed it, and join us for the Solemn Mass at 6pm this Friday. #oxfordoratory Vessel of the Holy Spirit This year the novena in preparation for the feast of Our Holy Father St Philip corresponds almost exactly with the novena of novenas, the first novena, the nine days of prayer between the Ascension and Pentecost when we wait once more with the Apostles for the outpouring of the Holy Spirit. And this is most appropriate, as St Philip was, more than anything else, a man of the Spirit — as we say in his litany, he is the “vessel of the Holy Spirit”. The story of his life, which we read during the novena, really begins with his singular experience of the Spirit on the Vigil of Pentecost 1544 in the catacomb of St Sebastian when the Spirit descended like a ball of fire, entering his mouth and then into his heart. After that experience — Philip’s own Pentecost — his life would never be the same again. Behind his holiness of life, and his preaching, and his miracles, and his founding of our Institute, there is something fundamental we can learn from St Philip — conveniently for this time in the Church’s liturgical calendar, something about the Holy Spirit. St Philip’s life shows us what happens when we do not simply possess the Holy Spirit, but allow ourselves to be possessed by him. We all have the Holy Spirit dwelling in us — all of us who have been baptised and confirmed. He is in us as much as he was in St Philip Neri, as much as he was in the Apostles at Pentecost. But we are very good at closing ourselves to the Spirit — we, through our sins and our selfishness, our attachments and our self-will, block him out; we ignore his prompting and are deaf to his call, we partition him away into a little forgotten compartment in our souls. Or we make of him a very petty little thing indeed, our God — a God who always agrees with what we say, who wants us to do precisely what we want to do, and makes me right and everyone else wrong. But this is not the Holy Spirit whom we worship; this is not the awesome power of Almighty God, who hovered over the waters at creation, who raised Jesus from the dead, who came down on the Apostles and Our Lady in the Upper Room, who wonderfully penetrated the heart of St Philip, and who gives power and authority to the Church. The Holy Spirit blows where he wills; his ways are not always our ways; and if we give ourselves to him and allow him to possess us completely — as St Philip did — then we will find that he will do more for us than we ask or even imagine; do more through us and with us. St Philip wanted to be a layman — the Spirit called him to the priesthood; he wanted to be a martyr, the Spirit made him a martyr not of blood, but of charity; Philip wanted to preach the Gospel to the pagans in the Indies, the Holy Spirit had other plans. He wanted to be a humble, hidden servant of the Church, living at San Girolamo and doing what good he could, but the Spirit gave him the gift of preaching and teaching and working miracles and reading men’s hearts and winning souls, and brought him to the Vallicella, and through him founded the Congregation of the Oratory, spread, as it now is, across the world. St Philip loved to be unknown — the Holy Spirit moulded and fashioned and transformed him into one of the most popular saints, the Apostle of Rome. St Philip wanted to reform the hearts and souls of those men and women he met — the Spirit used him to reform the very heart of the Church herself. It is not enough to have the Holy Spirit — it is not enough even to think we are serving God or doing great things in his honour. We must allow ourselves to be led by the Spirit, formed and transformed by the Spirit. We must be prepared to give up our own desires and plans — even the good ones — and be taken over by the Holy Spirit to be used for his own purposes. If we do this, if we open up to the Spirit who dwells in our hearts, then the life of St Philip Neri, and indeed of all the saints, shows us that the Spirit will do great things for, in, and through us. St Philip, Vessel of the Holy Spirit and Sweetest of Fathers. Pray for us. A Prayer of Our Holy Father St Philip: My Lord Jesus, I want to love you but you cannot trust me. If you do not help me, I will never do any good. I do not know you; I look for you but I do not find you. Come to me, O Lord. If I knew you, I would also know myself. If I have never loved you before, I want to love you truly now. I want to do your will alone; putting no trust in myself, I hope in you, O Lord. The Paschal Candle has been lit for Masses since the Easter Vigil to represent Christ’s presence among us, as with his disciples for forty days. After the Gospel of the Solemn Mass yesterday, it is extinguished to symbolise his ascension into heaven. #oxfordoratory Look up to heaven On Monday this week some of the Fathers and Brothers spent the day erecting and moving scaffolding — with all due health and safety measures observed — in order to change and improve the lighting on the sanctuary of our church. It is already a great boon for us to see more clearly the beautiful decoration which adorns that focal point of the whole building, as well as being a great help for the priest reading from the missal. Tomorrow as we celebrate the feast of the Ascension, our eyes are directed upwards once more as Our Risen Lord ascends to heaven and for a moment like the Apostles we gaze upwards as he is taken from our sight. How very much more clearly do we see when we make that effort to lift up our eyes towards the Lord. We not only contemplate his glory but from that vantage point are able to see all things in their fullness, seeing them from the perspective of heaven. Prayer, the lifting of the mind and heart to God, enables us to understand and to see clearly, all those other things of life in which we are otherwise immersed. That daily shifting our focus from the things of this world to the vantage point of heaven is that great encouragement for our daily striving for God, so that where Christ goes we too may follow him. It is often an effort for us to pull ourselves out of the daily round in order to lift up our heads and our hearts to the things of heaven, but if we are to have the desire for heaven to drive us on, it is essential that we always keep our goal before us. Not only in prayer, but all those things which form the way we see things must have heaven as their vantage point and aim. Monsignor Knox wrote: In all ages, in all countries, the world acts as a solvent to Catholic piety; breathes an air in which Catholic piety languishes. Man’s intellect always wants to approach things from the human side, from the side from which they can be known by man; shirks and burkes discussion of things from the side of reality, from the side which relates them to God. Man’s art and literary genius is constantly concerned with man at his most human level, his passions, his craven fears, the rebellion of his will against the order in which he lives. All that breathes a poison, for which writers who care about the truth as it is in God have to provide an antidote; they must fight, they must react, but still more they must see things, they must record things, from that higher standpoint which is God’s. You must, sometimes, give the lungs of your soul an airing on these heights, even if the atmosphere of it is more rare, is breathed with more effort, than the other. Or else, the miasma of the modern world will get you down, will weaken your resistance; you will be a prey to the germs of infidelity, to the infection of bad example. And you will forget your Friend. As the Church invites us then on the Ascension to gaze up towards heaven, to contemplate Our Lord, Risen and Ascended, it is perhaps a good time for us to think on the place we give to the things of heaven in our life each day — not only in terms of the time we give to heaven, but also in terms of what we strive for, on what really all our efforts are in fact based. And from our gazing upon heaven, we can then go on like the Apostles, down from that mountain and into the world — to teach the Good News and make disciples of all nations, keeping ever in mind that he whom we meet on those heights of prayer is with us always, even to the end of time. Q: How many Oratorians does it take to change a lightbulb?A: “Change”? Actually the real answer turns out to be three, plus one very helpful volunteer and a lot of scaffolding. The sanctuary lighting is all working at full brightness again! #oxfordoratory Monday 15 May 2023 Congratulations to David who was baptised on Saturday! #oxfordoratory Saturday 13 May 2023 One of this month’s relics on display is St Philip’s own copy of Jacapone da Todi’s “Laude”, which St Philip has written his name in. The story of how it was rediscovered in our church — only days before the first Fathers of the Oratory arrived here from Birmingham — is extraordinary. You might find it hard to believe, unless you heard it straight from the priest who found them, who is now the Bishop of Leeds. Read his account from his St Philip’s day sermon on our website: www.oxfordoratory.org.uk/blog/post/1335-solemnity-of-our-holy-father-saint-philip The novena to St Philip begins on Tuesday after the evening Mass. You will be able to place your own prayer intentions for the novena in St Philip’s chapel over the weekend. There will be Solemn Choral Vespers on Thursday 25 May at 6:30pm. We will welcome Fr Robert Ombres OP from Blackfriars to preach at the Solemn Mass for the feast day itself on Friday 26 May at 6pm. #oxfordoratory Friday 12 May 2023 May Music Sunday 7 MaySolemn Mass 11:005th Sunday of EasterMissa Simile est regnum caelorum LoboJubilate Deo universa terra PalestrinaCaro mea vere est cibus Guerrero Sunday 14 MaySolemn Mass 11:006th Sunday of EasterMissa Regina caeli PalestrinaBenedicite gentes PalestrinaPortio mea White Thursday 18 MaySolemn Mass 18:00The Ascension of the LordMissa Ascendens Christus VictoriaAscendit Deus PhilipsO Rex gloriae Marenzio Sunday 21 MaySolemn Mass 11:007th Sunday of EasterMissa Jam Christus astra ascenderat PalestrinaViri Galilaei PalestrinaEgo sum panis vivus Palestrina Thursday 25 MaySolemn Vespers 18:30Our Holy Father St Philip NeriDeus in adjutorium PadillaMagnificat primi toni VictoriaPangamus Nerio SewellO salutaris hostia LalouxTantum ergo WidorAlleluia GabrieliRespice de caelo Sewell Friday 26 MaySolemn Mass 18:00Our Holy Father St Philip NeriMissa Papae Marcelli PalestrinaIn spiritu humilitatis CroceJubilate Deo a8 G Gabrieli Sunday 28 MaySolemn Mass 11:00PentecostMissa De la Batalla GuerreroConfirma hoc deus LassusLoquebantur variis linguis Palestrina The Oratory 25 Woodstock Road © 2023 Oxford Oratory. All rights reserved. The Oxford Oratory of St Philip Neri is a Registered Charity number 1018455
https://www.oxfordoratory.org.uk/tour/blog/post/9897-9897/blog/post/9916-look-up-to-heaven/reflections.php
Regulations of Harris County, Texas for the Approval and Acceptance of Infrastructure - DocsLib REGULATIONS OF HARRIS COUNTY, TEXAS FOR THE APPROVAL AND ACCEPTANCE OF INFRASTRUCTURE AS ADOPTED: AUGUST 11, 2009 EFFECTIVE: SEPTEMBER 1, 2009 AMENDED: 1 REGULATIONS OF HARRIS COUNTY, TEXAS FOR THE APPROVAL AND ACCEPTANCE OFINFRASTRUCTURE AS ADOPTED: AUGUST 11, 2009 EFFECTIVE: SEPTEMBER 1, 2009 AMENDED: 1 MAY 2011 HARRIS COUNTY PUBLIC INFRASTRUCTURE DEPARTMENTARCHITECTURE& ENGINEERING DIVISION ARTHUR L. STOREY, JR. PE COUNTY ENGINEER JOHN R. BLOUNT, PE ARCHITECTURE & ENGINEERING DIVISION DIRECTOR PERMIT OFFICE 10,555 NORTHWEST FRWY, STE 120 HOUSTON, TEXAS 77092-8620 (713) 956-3000 TABLE OF CONTENTS PAGE SECTION 1 - PRELIMINARY PROVISIONS ...... 1 Section 1.01 - Authority ...... 1 Section 1.02 - Area Covered by Regulations ...... 1 Section 1.03 - Purpose ...... 1 SECTION 2 - USE OF TERMS ...... 2 Section 2.01 - Accredited Laboratory ...... 2 Section 2.02 - BaseFlood...... 2 Section 2.03 - Base Flood Elevation ...... 2 Section 2.04 - Coastal Areas ...... 2 Section 2.05 - Conduit ...... 2 Section 2.06 - County Engineer ...... 3 Section 2.07 -Curband Gutter Sections ...... 3 Section 2.08 - DesignStormEvent ...... 3 Section 2.09 -DrainageArea Map ...... 3 Section 2.10 - Elevation ...... 3 Section 2.11- Extreme Event ...... 4 Section 2.12 - FEMA ...... 4 Section 2.13 - Geotechnical Engineer ...... 4 Section 2.14 - HCFCD ...... 4 Section 2.15 - Hydraulic Grade Line ...... 4 Section 2.16 - In-Fill Development ...... 4 Section 2.17 Latent Defects………………………………………………..4 Section 2.18 - Mean Sea Level ...... 5 Section 2.19 - Person…...... 5 Section 2.20 - Rainfall Frequency ...... 5 Section 2.21 - Redevelopment ...... 6 Section 2.22 - RoadsideDitchSections ...... 6 Section 2.23 - Sheet Flow ...... 6 Section 2.24 - Subdivision ...... 6 Section 2.25 - Unincorporated Area ...... 6 SECTION 3 - GENERAL PROVISIONS ...... 8 Section 3.01 - Administration by the County Engineer ...... 8 Section 3.02 - Responsibility of Other Officials ...... 8 SECTION 4 - ADMINISTRATIVE PROCEDURES FOR THE REVIEW OF PLATS ...... 9 Section 4.01 - Approval Required ...... 9 Section 4.02 - Enforcement ...... 9 Section 4.03 - Plat Criteria ...... 9 Section 4.04 - Exceptions ...... 10 Section 4.05 - Review Procedures ...... 12 Section 4.06 - Recordation Requirements ...... 12 Section 4.07 - Certificates Required on Plats of Property Located in the Unincorporated Area of Harris County ...... 16 SECTION 5 - ADMINISTRATIVE PROCEDURES FOR THE ... 17 REVIEW OFCONSTRUCTIONDRAWINGS Section 5.01 - Submittal Procedures ...... 17 Section 5.02 - Construction Drawings - General ...... 17 Section 5.03 - Drawing Layout Requirements ...... 18 Section 5.04 - Standard Detail Sheets ...... 19 Section 5.05 - Standard Note Requirements ...... 19 SECTION 6 - DRAINAGE REQUIREMENTS ...... 21 Section 6.01 - Drainage Policy ...... 21 Section 6.02 - Design Requirements ...... 22 Section 6.03 - Storm Water Detention ...... 36 Section 6.04 - Ownership and Easements ...... 41 Section 6.05 - Submerged Storm Sewers ...... 43 Section 6.06 - Low Impact Development………………………………..45 SECTION 7 - PAVING ...... 46 Section 7.01 - Paving Design Requirements ...... 46 Section 7.02 - Design Requirements ...... 46 Section 7.03 - Materials Requirements ...... 52 Section 7.04 - Specification Requirements ...... 54 Section 7.05 - Geometric Requirements ...... 56 SECTION 8 - STRUCTURES ...... 63 SECTION 9 - TESTING REQUIREMENTS ...... 65 Section 9.01 - General ...... 65 Section 9.02 - Bedding and Backfill ...... 65 Section 9.03 - Subgrade Testing ...... 66 Section 9.04 - Flexible Base ...... 66 Section 9.05 - Surface Course ...... 67 Section 9.06 -ConcretePavement ...... 67 Section 9.07 - Concrete Cores ...... 68 Section 9.08 - Structures ...... 68 SECTION 10 - INSPECTIONS ...... 69 Section 10.01 - Construction Inspections ...... 69 Section 10.02 - Notice of Start ...... 69 SECTION 11 - ACCEPTANCE OF IMPROVEMENTS ...... 70 WITHIN SUBDIVISIONS Section 11.01 - Acceptance Procedures ...... 70 Section 11.02 - Inspection and Re-Inspection Fees ...... 72 SECTION 12 -TRAFFIC...... 74 Section 12.01 - Traffic Definitions ...... 74 Section 12.02 - Left TurnLanes...... 75 SECTION 13 – LANDSCAPE AND MONUMENTATION ...... 77 Section 13.01 - Landscape Policy ...... 77 Section 13.02 - Use of Terms ...... 77 Section 13.03 - Construction Activity ...... 77 Section 13.04 - Prohibited Activity ...... 78 Section 13.05 - Treescape and Screening Requirements for Commercial Establishments and Public Buildings ...... 78 Section 13.06 - Tree Planting Requirements for Single Family Residential Lots ...... 80 Section 13.07 - Preservation of Existing Trees ...... 81 SECTION 14 – VARIANCES ...... 82 SECTION 15 – SEVERABILITY ...... 83 APPENDICES Certificates Required on Plats of Property Located………………………………….A in the Unincorporated Area of Harris County Notary Formats……………………………………………………………………………….B Intensity Duration Curve…………………………………………………………………..C Construction Notes to be On All Projects……………………………………………...D Construction Notes Involving …………………………………………………………….E Utilities and Paving Work Located Within a Public Right-of-Way Construction Notes forEsplanadeOpenings ………………………………………….F and Left Turn Lanes Construction Notes for All Projects Located ………………………………………….G in the 10% (10-Year) 1% (100-Year) Flood Plain and .2% (500-Year) Flood Plain Below the Base Flood Elevation Graphic Requirements ……………………………………………………………………..H Detention Rate Chart ……………………………………………………………………….I Joint Detail For: Knuckle Configuration………………………………………………..J REGULATIONS OF HARRIS COUNTY, TEXAS FOR THE APPROVAL AND ACCEPTANCE OF INFRASTRUCTURE SECTION 1 - PRELIMINARY PROVISIONS SECTION 1.01 - AUTHORITY These Regulations are adopted by the Commissioners' Court of Harris County, Texas, acting in its capacity as the governing body of Harris County and the Harris County Flood Control District. The authority of Harris County to adopt these Regulations and for the contents hereof is derived from the following statutes: Chapter 232 of the Texas Local Government Code, Texas Local Government Code Section 240.901, as amended; Texas Transportation Code Section 251.001 – 251.05 and Section 254.001 – 254.019, as amended; the Harris CountyRoadLaw, as amended, (Special Laws of the 33rd Texas Legislature, Regular Session, 1913, Chapter 17, as amended), and the Flood Control and Insurance Act, as amended. These Regulations may be amended at any time by a majority of Commissioners' Court. SECTION 1.02 - AREA COVERED BY REGULATIONS These Regulations apply in all unincorporated areas of Harris County, Texas, and those areas where Harris County maintains the rights-of-way. SECTION 1.03 - PURPOSE The purpose of these Regulations is to ensure that the construction of infrastructure within the County’s rights-of-way perform their intended function with limited maintenance and repair. 1 SECTION 2 - USE OF TERMS SECTION 2.01 - ACCREDITED LABORATORY An “Accredited Laboratory” is a laboratory that is accredited by the American Association for Laboratory Accreditation (A2LA) or American Association of StateHighwayand Transportation Officials (AASHTO) in the field of construction materials testing. SECTION 2.02 - BASE FLOOD A “Base Flood” is the national standard on which the floodplain management and insurance requirements of the National Flood Insurance Program (NFIP) are based. Special Flood Hazard Areas (SFHAs) are depicted on Federal Emergency Management Agency (FEMA) Flood Insurance Rate Maps (FIRMs) and are areas subject to inundation by the base flood having a one-percent or greater probability of being equaled or exceeded during any given year (this is also known as a 1% or 100- year flood event). SECTION 2.03 - BASE FLOOD ELEVATION “Base Flood Elevation” (BFE) means the calculated elevation or level above mean sea level that flood waters may reach during the base flood. SECTION 2.04 - COASTAL AREAS “Coastal Areas” means areas which border on bays or estuaries or other waterways subject to tidal action which are subject to possible flooding or increased flood levels because of tidal action, hurricane surge or rising water due tostorms, hurricanes or tsunamis. A “coastal area” is not necessarily in a “V” Zone. In cases where there is a question as to whether an area is a coastal area, the Harris County Public Infrastructure Department shall refer to the FEMA Flood Insurance Study. SECTION 2.05 - CONDUIT A “Conduit” is any open or closed device for conveying flowing water. 2 SECTION 2.06 - COUNTY ENGINEER “County Engineer” means the holder of the statutory position of the County Engineer for Harris County or the employee designated by the County Engineer to perform a task required by these Regulations. The Executive Director of the Harris County Public Infrastructure Department holds the position of County Engineer of Harris County. SECTION 2.07 - CURB AND GUTTER SECTIONS A “Curb and Gutter Section” is a full width concrete pavement with curb, either doweled on six-inch (6”)curbsor monolithic or doweled four-inch (4”) by twelve-inch (12”) curb or monolithic curb and gutter sections forasphalt concretepavement. SECTION 2.08 - DESIGN STORM EVENT “Design Storm Event” means the rainfall intensity upon which the drainage facility will be sized. References to rainfall conditions in these specifications shall apply to “Technical Paper No. 40, U. S. Weather Bureau”, published by the U. S. Department of Agriculture, Soil Conservation Service. SECTION 2.09 - DRAINAGE AREA MAP “Drainage Area Map” means the area map of a watershed, which is subdivided to show the area served by each subsystem. SECTION 2.10 - ELEVATION “Elevation” means height above mean sea level. The vertical control system (benchmarks) referenced in the most current Flood Insurance Study shall be used except in coastal areas where subsidence has occurred. The most recent re-leveling of the vertical control system by the Harris-Galveston Subsidence District shall be used in the coastal areas. Any future studies changing the Flood Insurance Rate Map (FIRM), which is referenced to a later re-leveling of the vertical control system shall be used whenever a revised FIRM becomes effective. 3 SECTION 2.11 - EXTREME EVENT “Extreme Event” means a rainfall event, which exceeds the Design Storm Event up-to and including the 100-year frequency resulting in surcharge of the underground storm sewer system and overland sheet flow. SECTION 2.12 - FEMA “FEMA” means the Federal Emergency Management Agency. SECTION 2.13 - GEOTECHNICAL ENGINEER A “Geotechnical Engineer” is a licensed engineer within the State of Texas who works for a company registered in the State of Texas that has been accredited by the American Association for Laboratory Accreditation (A2LA) in geotechnical testing. SECTION 2.14 - HCFCD “HCFCD” means the Harris County Flood Control District. SECTION 2.15 - HYDRAULIC GRADE LINE “Hydraulic Grade Line” means the line representing the pressure head available at any given point within the drainage system. SECTION 2.16 - IN-FILL DEVELOPMENT “In-fill Development” means the development of open tracts of land in areas where the storm drainage infrastructure is already in place and takes advantage of the existing infrastructure as a drainage outlet. SECTION 2.17 – LATENT DEFECTS “Latent Defects” means a defect or condition of construction which does not comply with the construction documents or designs intent which is generally a hidden or concealed defect which cannot be discovered by reasonable or customary inspection, 4 examination or observation at either the time of construction or substantial completion, but which manifests over time. SECTION 2.18 - MEAN SEA LEVEL “Mean Sea Level” means the average height of the surface of the sea for all states of the tide as was established by theUnited StatesCoastal and Geodetic Survey in 1929. SECTION 2.19 - PERSON “Person” includes any individual or group of individuals, corporation, partnership, association, or any other organized group of persons, including State and Local governments and agencies thereof. SECTION 2.20 - RAINFALL FREQUENCY “Rainfall Frequency” means the probability of a rainfall event of defined characteristics occurring in any given year. Information on rainfall frequency is published by the National Weather Service. For the purpose of storm drainage design, the following frequencies are applicable: 1. 2-year frequency – a rainfall intensity having a 50% probability of occurrence in any given year, or nominally likely to occur once every two years. 2. 3-year frequency – a rainfall intensity having a 33% probability of occurrence in any given year, or nominally likely to occur once every three years. 3. 5-year frequency – a rainfall intensity having a 20% probability of occurrence in any given year, or nominally likely to occur once every five years. 4. 10-year frequency – a rainfall intensity having a 10% probability of occurrence in any given year, or nominally likely to occur once every ten years. 5. 25-year frequency – a rainfall intensity having a 4% probability of occurrence in any given year, or nominally likely to occur once every twenty-five years. 6. 100-year frequency – a rainfall intensity having a 1% probability of occurrence in any given year, or nominally likely to occur once every one hundred years. 5 7. 500-year frequency – a rainfall intensity having a 0.2% probability of occurrence in any given year, or nominally likely to occur once every five hundred years. SECTION 2.21 - REDEVELOPMENT “Redevelopment” means a change in land use that alters the impervious cover from one type of development to either the same type or another type and takes advantage of the existing infrastructure in place as a drainage outlet. SECTION 2.22 - ROADSIDE DITCH SECTIONS “Roadside Ditch Sections” are ditch sections adjacent to either full widthreinforced concretepavement or asphaltic concrete pavement. SECTION 2.23 - SHEET FLOW “Sheet Flow” means the overland storm runoff that is not conveyed in a defined conduit and is typically in excess of the capacity of the conduit or roadside ditch. SECTION 2.24 - SUBDIVISION “Subdivision” means a division of any tract of land into two (2) or more parts for the purpose of laying out any subdivision or any tract of land or any addition to thecity, or for laying out suburban lots or buildings lots, or any lots, andstreets, alleys or parts of other portions intended for public use or the use of the purchasers or owners of lots fronting thereon or adjacent thereto. A subdivision includes re-subdivision (replat), but it does not include the division of land in parcels or tracts of ten (10) acres or more and not involving any new streets, alleys or easements of access. This definition is based on current state statutes and should the statutes be changed its new definition would govern. SECTION 2.25 - UNINCORPORATED AREA “Unincorporated Area” means the area in Harris County, Texas, which is not within an incorporated area of a city, town, and village or within the “jurisdiction of the Port of Houston Authority of Harris County, Texas,” being that area within 2,500 feet of the 6 thread of the Houston Ship Channel that is eligible for limited purpose annexation pursuant to Texas Local Government Code §43.136. 7 SECTION 3 - GENERAL PROVISIONS SECTION 3.01 - ADMINISTRATION BY THE COUNTY ENGINEER The Executive Director of the Harris County Public Infrastructure Department, in his capacity as the Harris County Engineer, , is responsible for the administration of these Regulations, approval of plans required by these Regulations, and enforcement of these Regulations and maintaining proper records. The Executive Director of the Harris County Public Infrastructure Department, in his role of County Engineer, may delegate particular authority given to the County Engineer under these Regulations to another member of the Harris County Public Infrastructure Department and an action by such delegated person under such granted authority shall be deemed an action of the County Engineer. SECTION 3.02 - RESPONSIBILITY OF OTHER OFFICIALS Under these regulations the Harris County Public Infrastructure Department is responsible for all administrative decisions, determinations and duties. The Harris County Public Infrastructure Department may seek and secure the assistance of other officials of Harris County and of the Harris County Flood Control District in making its decisions, determinations and in performing duties but is not required to conform to the recommendations of others. 8 SECTION 4 - ADMINISTRATIVE PROCEDURES FOR THE REVIEW OF PLATS SECTION 4.01 - APPROVAL REQUIRED All development within the unincorporated areas of Harris County is prohibited without first securing approved plans or plat, if required, and a development permit issued under the Regulations of Harris County, Texas, for Flood Plain Management. SECTION 4.02 - ENFORCEMENT It shall be unlawful for any person to lay out, subdivide or plat any land into lots, blocks, tracts or streets within the unincorporated area of Harris County if the land has not been laid out, subdivided and platted in accordance with these rules and regulations. SECTION 4.03 - PLAT CRITERIA For tracts of land located within the extraterritorial jurisdiction (ETJ) of an incorporated city or town and subject to the jurisdiction of the Planning Commission or other governing body of that city or town, general subdivision and layout requirements as established by the applicable Commission or other governing body shall apply. In the circumstance where any rule, regulation, procedure or policy lawfully or officially adopted by the governing body of any city or town exercising jurisdiction within its extraterritorial jurisdiction is less restrictive than that contained herein, the standards adopted by these rules and regulations and applicable State law shall apply. For all other tracts not located within a municipality’s extraterritorial jurisdiction or for which the municipality has issued a written certification stating that a plat is not required to be filed for that subdivision of land in accordance with Chapter 212 of the Texas Local Government Code, the following rules and design requirements shall apply: 1. Lots shall be of sufficient acreage to meet minimum requirements for on-sitesewageservice. 2. Public road rights-of-way shall be a minimum fifty feet (50’) in width and in conformance with the Geometric Design Guidelines as adopted by Harris County Commissioners’ Court. 9 3. A building setback line of not less than twenty-five feet (25’) from the road right-of-way shall be imposed on tracts intended for construction of a single- family structure or structures. However, twenty-foot (20’) building setback lines will be permitted for single-family residential lots on cul-de-sacs and knuckles. A ten-foot (10’) building setback line will be permitted on side lots of single-family residential lots. A building setback line of no less than ten feet (10’) shall be imposed on all other tracts. 4. Construction of road and appurtenant drainage facilities shall be in conformance with specifications as set out in these rules and regulations. 5. Financial Surety: A cash deposit, bond, or letter of credit made in accordance with the Texas Local Government Code ß232.004 or ß232.0045 and these regulations. SECTION 4.04 - EXCEPTIONS Exceptions to platting requirements are established in Section 232.0015 of the Texas Local Government Code. A brief description follows: 1. A county may not require the owner of a tract of land located outside the limits of a municipality who divides the tract into two or more parts to have a plat of the subdivision prepared if the owner does not lay out a part of the tract as streets, alleys, squares, parks, or other parts of the tract to be dedicated to public use or for lots fronting on or adjacent to the streets, alleys, squares, or other parts, and the land is to be used primarily for agricultural use or farm, ranch, wildlife management, or timber production. 2. A county may not require the owner of a tract of land located outside the limits of a municipality who divides the tract of land into four or fewer parts and does not lay out a part of the tract as streets, alleys, squares, parks, or other parts of the tract to be dedicated to public use or for lots fronting on or adjacent to the streets, alleys, squares, or other parts to have a plat of the subdivision prepared if each of the lots is to be sold, given, or otherwise transferred to an individual who is related to the owner within the third degree of consanguinity or affinity. 3. A county may not require the owner of a tract of land located outside the limits of a municipality who divides the tract into two or more parts to have a plat of the subdivision prepared if all the lots of the subdivision are more than 10 10 acres in area and the owner does not lay out a part of the tract as streets, alleys, squares, parks, or other parts of the tract to be dedicated to public use or for lots fronting on or adjacent to the streets, alleys, squares, or other parts. 4. A county may not require the owner of a tract of land located outside a municipality to have a plat of the subdivision prepared if all the lots are sold to veterans through the Veterans’ Land Board program. 5. A county may not require the owner of a tract land to have a plat prepared if the owner is the state or any state agency, board, or commission or owned by the permanent school funds of the state unless the subdivision lays out a part of the tract as streets, alleys, squares, parks, or other parts of the tract to be dedicated to public use or for lots fronting on or adjacent to the streets, alleys, squares, or other parts. 6. A county may not require the owner of a tract of land located outside the limits of a municipality who divides the tract into two or more parts to have a plat of the subdivision prepared if the owner of the land is a political subdivision of the state, the land is situated in the floodplain, and the lots are sold to adjoining landowners. 7. A county may not require the owner of a tract of land outside the limits of a municipality who divides the tract into two parts to have a plat of the subdivision prepared if the owner does not lay out a part as streets, alleys, squares, parks, or other parts of the tract to be dedicated to public use or for lots fronting on or adjacent to the streets, alleys, squares, or other parts and one part is to be retained by the owner, and the other new part is to be transferred to another person who will further subdivide the tract subject to the plat approval requirements. 8. A county may not require the owner of a tract of land located outside the limits of a municipality who divides the tract into two or more parts to have a plat of the subdivision prepared if the owner does not lay out a part of the tract as streets, alleys, squares, parks, or other parts of the tract to be dedicated to public use or for lots fronting on or adjacent to the streets, alleys, squares, or other parts and all parts are transferred to persons who owned an undivided interest in the original tract and a plat is filed before any further development of any part of the tract. 11 SECTION 4.05 - REVIEW PROCEDURES Municipalities in Harris County exercising their extraterritorial jurisdiction in the unincorporated area of Harris County have developed specific and unique procedures in processing plats. Therefore, it shall be the responsibility of the owner of the tract being platted to ensure that the Harris County Flood Control District and the Engineering Division of the Harris County Public Infrastructure Department receive copies of a proposed plat for review and comment. Required dedicatory language and plat certificates are included in Appendix “A”. The original mylar of the plat fully executed by the owners and approved by the appropriate Planning Commission or governing body accompanied by the required information described in Recordation Requirements is to be submitted to the Harris County Flood Control District. Upon the District’s final review and approval, the plat will be forwarded to the Engineering Division of the Public Infrastructure Department. Upon satisfactory completion of the review, the plat will be forwarded for the signature of the County Engineer. The plat will be processed and placed on the next available Commissioners’ Court agenda for approval. The County Clerk shall calculate the required recording fees and notify the applicant or designee of the same. Upon receipt of those fees, the plat will be filed and recorded in the Official Public Records of Real Property of Harris County, Texas. SECTION 4.06 - RECORDATION REQUIREMENTS The following documentation is required to be submitted along with any original plat that is to be reviewed by the Harris County Public Infrastructure Department, submitted to Harris County Commissioners’ Court for approval, and filed with the Harris County Clerk. Harris County will accept for recordation only those plats printed on the front side of the mylar or other reproducible material. 1. A title report, or opinion, title policy or certificate or letter from a title company authorized to do business in the State of Texas must be provided indicating ownership of the property, all liens against same, and any existing easements. The title report shall not have been executed more than sixty (60) days prior to the time the final plat is received by the Harris County Public Infrastructure Department and may require updating at the request of Harris County personnel. Owners of property located within the plat must either sign the plat or execute an Owner’s Ratification of Plat document, as promulgated by the County Engineer. Furthermore, liens against the property shall be subordinate to all dedication of streets, rights-of-ways, easements and terms and conditions referred to on the plat. Lienholders must either sign the plat or 12 execute a Lienholder’s Subordination to Dedication document as promulgated by the Harris County Engineer. See Appendix “B” for notary formats. 2. An original tax certificate from the tax collector of each political subdivision in which the property is located showing that all taxes owed to the County, School District, Utility District, and/or any other political subdivision have been paid in full. If the plat or replat is filed after September 1 of a year, the plat or replat must also have attached to it a tax receipt issued by the collector for each taxing unit with jurisdiction of the property indicating that the taxes imposed by the taxing unit for the current year have been paid or, if the taxes for the current year have not been calculated, a statement from the collector for the taxing unit indicating that the taxes to be imposed by that taxing unit for the current year have not been calculated. If the tax certificate for a taxing unit does not cover the preceding year, the plat or replat must also have attached to it a tax receipt issued by the collector for the taxing unit indicating that the taxes imposed by the taxing unit for the preceding year have been paid. This requirement does not apply to the extent of the applicability of exceptions in Texas Property Code ß 12.002(e) in regard to certain real property acquired by will or inheritance or to certain property acquired by eminent domain. 3. A completed Utility Service Plan, as promulgated by the County Engineer, shall be submitted. In no case shall a plat be recorded prior to assurances being given that all applicable State and County reviews and/or permit(s) have been obtained. 4. A letter from the County Tax Assessor-Collector certifying that the name of the subdivision to be presented to Commissioners’ Court is not in conflict with any other previously recorded subdivision. This requirement applies to the first section of multi-section subdivisions, all re-plats, and amending plats and is not applicable tostreetdedication plats designated by a street name. 5. A copy of the current Federal Emergency Management Agency’s Flood Insurance Rate Map (FIRM) with the boundaries of the subdivision delineated. 6. Two (2) sets of approved drawings are to be on file with the Public Infrastructure Department at the time the plat is submitted to Commissioners’ Court. However, if the tract of land is being platted to create reserves for the purpose of sale only and there are no immediate plans for construction of 13 improvements on said reserves, then a note shall be placed on the face of the plat stating: “Site drainage plans for the future development of this reserve must be submitted to the Harris County Flood Control District and Engineering Division of Harris County Public Infrastructure Department.” 7. A letter, statement or other instrument from the owner of any privately owned easement within the plat boundaries where such easement is to be crossed by streets (either public or private) or public utility or drainage easements, stating that the owner of such easement approves such crossing of the private easement for the purposes intended and depicted on the plat, if such approval is not granted in the original document conveying the easement. 8. A plat review fee as established by Commissioners’ Court is required prior to setting a plat on an agenda. 9. For plats of lots and/or reserves requiring plan review and not dedicating any public rights-of-way, an administrative fee is assessed in the amount of $10.00 per lot. Reserves are assessed an administrative fee of $20.00 per 100 feet of plat boundary adjoining road right-of-way rounded to the next highest increment of $20.00. Fees made payable to the County Treasurer are due upon plan or plat approval as applicable. 10. For plats proposing the dedication of a public street(s) and construction of paving and appurtenant drainage, a Financial Surety is required prior to plat approval and shall be: A. Made payable to the County Judge and the Judge’s successor in office, unless cash; and B. In a total amount based upon the following schedule: 14 FINANCIAL SURETY SCHEDULE * RESIDENTIAL SUBDIVISIONS COMMERCIAL SUBDIVISIONS $50 per lot with average road frontage $75 per 100 feet of proposed less than 100 feet. pavement. The fee shall be rounded to the next 100 feet. $75 per lot with average road frontage 100 feet or greater. * NOTE: The minimum financial surety posted in any case shall be $2,500.00. Included is the non-refundable administrative fee of $10 per lot for residential subdivisions or $20 per 100 ft of pavement in commercial subdivisions. 11. For properties being platted in the unincorporated areas of Harris County, where there is not Extraterritorial Jurisdiction being exercised for water and sewer facilities the following requirements for water and sewage facilities apply: A. The drinking water supply shall meet the minimum requirements established by Chapter 341 of the Health and Safety Code and any other minimum requirements established by the Texas Commission on Environmental Quality applicable to drinking water. B. Any onsiteseweragedisposal systems shall be constructed in accordance with Chapter 366 of the Health and Safety Code and the Revised Rules of Harris County for On-Site Sewerage Facilities. C. Any sewerage facility other than a properly permittedonsite sewage facilityshall be constructed and operated under a valid permit issued by the Texas Commission on Environmental Quality. 12. Additional information may be required by the Public Infrastructure Department to clarify or support any of the aforementioned recordation requirements. 15 SECTION 4.07 - CERTIFICATES REQUIRED ON PLATS OF PROPERTY LOCATED IN THE UNINCORPORATED AREA OF HARRIS COUNTY 1. Dedicatory language on the plats must include the following paragraphs: A. “FURTHER, Owners do hereby dedicate to the public a strip of land fifteen (15) feet wide on each side of the center line of any and all bayous, creeks,gullies, ravines, draws, sloughs, or other natural drainage courses located in said plat, as easements for drainage purposes, giving the City of (name of city), Harris County, or any other governmental agency, the right to enter upon said easement at any and all times for the purpose of construction and maintenance of drainage facilities and structures.”; B. “FURTHER, Owners do hereby covenant and agree that all of the property within the boundaries of this plat and adjacent to any drainage easement, ditch,gully, creek or natural drainage ways shall hereby be restricted to keep such drainage ways and easements clear of fences, buildings, planting and other obstructions to the operations and maintenance of the drainage facility and that such abutting property shall not be permitted to drain directly into this easement except by means of an approved drainage structure.”; and C. “FURTHER, Owners certify and covenant that they have complied with or will comply with existing Harris County Road Law, Section 31-C as amended by Chapter 614, Acts of 1973, 63rd Legislature and all other regulations heretofore on file with the Harris County Engineer and adopted by the Commissioners’ Court of Harris County.” 2. Approved Certificate Language may be found in Appendix “A” to these regulations. 16 SECTION 5 - ADMINISTRATIVE PROCEDURES FOR THE REVIEW OF CONSTRUCTION DRAWINGS SECTION 5.01 - SUBMITTAL PROCEDURES 1. A preliminary set of drawings shall be submitted to the County Engineer for review along with a County issued Routing Slip. Upon review, the drawings will be returned to the consultant with any necessary comments. 2. Upon addressing all the comments, a final review will be conducted by submitting the marked-up preliminary set, a reproducible set, a blue line set, and the routing slip to the County Engineer. The plans will be approved or additional comments will be made and the sets returned. SECTION 5.02 - CONSTRUCTION DRAWINGS - GENERAL For all construction drawings submitted to the Harris County Public Infrastructure Department pursuant to these regulations the following requirements shall apply: 1. A Professional Engineer, licensed in the State of Texas, is required to seal, date and sign each sheet of the drawings in accordance with rules set forth by the Texas State Board for Professional Engineers. The seal must reproduce on all sheets. 2. A cover sheet shall be required for all projects involving three or more plan and profile sheets. All plan sheet numbers should be included on the cover sheet or area map. A vicinity map should always be included to show the project location. 3. Drawings for street and/or public improvements shall be standard twenty-three inch by thirty-six inch (23” x 36”) Federal Aid Sheets or twenty-four inch by thirty-six inch (24” x 36”) overall dimensions for all design in rights-of-way or easements. Site drawings may be submitted on larger sheets when practical. 4. Drawings submitted for Harris County Public Infrastructure Department approval shall be on a reproducible material. 5. A North arrow is required on all sheets and should be generally oriented either upward or to the right. 6. All projects shall be tied to the datum adjustment that matches the FIRMs or the most current datum available in coastal areas. Equations may be used to translate other datum adjustments to the required adjustment. 17 7. Graphic standards for construction drawings submitted shall be in accordance with those outlined in Appendix “C” to these regulations. 8. If the property lies below the base flood level, the flood plain must be delineated graphically on all plan sheets. SECTION 5.03 - DRAWING LAYOUT REQUIREMENTS Drawings submitted to the Harris County Public Infrastructure Department pursuant to these regulations shall have the following items: 1. General construction layouts shall be submitted for all paving and utility projects involving more than three plan and profile sheets. For the purpose of fulfilling this requirement, paving and drainage layouts may be combined and water andsanitary sewerlayouts may be combined. 2. A drainage area map shall be submitted and shall include drainage computations with drainage area and storm water flow labeled. 3. A lot grading plan shall be submitted for residential lots on which earthwork is proposed that will change the natural topography. 4. A drawing showing existing natural contours at one-foot (1’) intervals of the land to be developed. 5. A graphical sheet index shall be included on the general construction layout or on a separate index sheet showing the plan and profile sheet location and sheet number. 6. Match lines in appropriate locations and not in the intersections of two streets or cul-de-sac knuckles shall be provided. 7. If a roadway exists where drawings are being prepared to improve the roadway or construct new pavement or to construct a utility, this roadway should be labeled as to its existing width, type of surfacing and base thickness if available without destruction of pavement. 8. All improvements shall be labeled as “Proposed” or “Existing” in both Plan and Profile Views. 9. Include a firelanedesigned in accordance with the current Harris County Fire Code for approval with all commercial site plans. 18 10. Include a landscape plan designed in accordance with these regulations for approval with all commercial site plans. SECTION 5.04 - STANDARD DETAIL SHEETS For all construction drawings submitted to the Harris County Public Infrastructure Department pursuant to these regulations, the following requirements shall apply: 1. The Harris County standard paving and detail sheets shall be incorporated by reference in the project specifications and by construction notes on the drawings. 2. The details of special structures not covered by approved standard drawings, such as stream and gully crossings, specialmanholes, etc., should be included. The details shall be drawn on the detail sheets with the horizontal and vertical scales equal. 3. The Harris County Public Infrastructure “Express Review Sheet” shall be submitted with each set of drawings and be completed including Harris County Appraisal District account number. SECTION 5.05 - STANDARD NOTE REQUIREMENTS The following standard notes shall be included in the drawings, where applicable, as specified below: 1. All projects shall include the notes in Appendix “D” to these regulations. 2. All projects involving paving or utilities located in a public right-of-way shall include notes in Appendix “E” to these regulations. 3. All projects involving esplanade openings and left turn lanes shall include the notes in Appendix “F” to these regulations. 4. All projects located within the 10% (10-year) floodplain, the 1% (100-year) flood plain, or 0.2% (500-year) floodplain shall include notes in Appendix “G” to these regulations. 19 20 SECTION 6 - DRAINAGE REQUIREMENTS SECTION 6.01 - DRAINAGE POLICY 1. Design Requirements A. The drainage criteria administered by Harris County and complemented by the City of Houston and the Harris County Flood Control District Criteria for newly designed areas provides protection from structural flooding from a 1% (100-year) base flood storm event. This is accomplished with the application of various drainage enhancements such as storm sewers, roadsideditches, open channels, detention and overland (sheet) run-off. This combined system attempts to prevent structural flooding for extreme events up to a 1% (100-year) storm. B. Recognizing that each site has unique characteristics that may enhance the opportunity to provide proper drainage, the intent of these criteria is to specify minimum requirements. These minimums may be modified with prior consent of the Harris County Public Infrastructure Department provided that the objective for the minimum drainage standards is maintained. 2. Street Drainage Design - Street ponding of short duration is anticipated and designed to contribute to the overall drainage capability of the system. Storm sewers and roadside ditch conduits are designed as a balance of capacity and economics. These conduits are designed to convey less intense, more frequent rainfalls while attempting to allow traffic movement during these events. When rainfall events exceed the capacity of the storm sewer system, the additional run- off is intended to be stored or conveyed overland in a manner that reduces the threat of flooding to structures. 3. Flood Control Design – Harris County is a participant in the National Flood Insurance Program. The flood insurance program attempts to make flood insurance available at low cost by providing for measures that reduce the likelihood of structural flooding. 4. Relationship to the Platting Process – The approval of storm drainage systems, detention facilities, and flood channel improvements is a part of the review process for planning and platting of new development. 21 SECTION 6.02 - DESIGN REQUIREMENTS All designs of drainage facilities, manholes, inlets, bedding and backfill shall meet the requirements of Standard Specifications, Standard Drawings and Harris County Regulations. The City of Houston design guidelines in effect on September 1, 2005 will apply for all projects located within Harris County and the City of Houston ETJ. The most stringent design details shall apply in the event of any discrepancy. Note: With prior approval, products listed in the Harris County Special Specifications 8013 may be used. Alternative types ofpipeproposed for use in storm sewer applications must receive prior approval of the County Engineer. 1. Method of Determining Runoff A. Area runoff shall be determined using the Rational Formula which is defined as: Q = CiA Where Q = amount of runoff in cubic feet per second (cfs) C = watershed imperviousness coefficient. See Figure 1: Minimum “C” Values for Land Use Types for suggested typical values. i = rainfall intensity in inches per hour Implicit in the determination of “i” is when the entire watershed under consideration is contributing runoff, a concept known as the Time-of Concentration (Tc) ratio, which are expressed in minutes. Tc represents the time in minutes required for the runoff to flow through the drainage area to the point of consideration. This is defined as: 0.1761 Tc = 10 A + 15 (in minutes) A = acres of subarea under consideration in the watershed area Note: See Appendix “H” for intensity duration 22 B. Design Storm Events for typical storm sewer design will consist of a 2-year storm. Design rainfall pattern shall follow the requirements specified in the most current edition of the HCFCD Criteria Manual. Figure 1: Minimum “C” Values for Land Use Types Runoff Land Use Type Coefficient Residential Districts Lots more than ¾ acres 0.35 Lots ¼ - ¾ acre 0.45 Lot less than ¼ acre 0.55 Multi-Family Areas Less than 20 DU/AC 0.65 20 DU/AC or Greater 0.80 Business Districts 0.80 Industrial Districts Light Areas 0.65 Heavy Areas 0.75 Railroad Yard Areas 0.30 Parks / Open Acres 0.18 C. Application of Runoff Calculation Models (1). The Rational Method shall be used for designs on all areas served by storm sewer up to 600 acres in size. (2). Rainfall runoff modeling shall be applied to areas greater than 600 acres in size or any areas that are drained by an open channel provided the model takes into account the storage and ponding in streets. Models must be acceptable to FEMA if they are to support a submittal for a map change. D. Coefficients for the Rational Method. (1). The runoff coefficient “C” values in the Rational Method formula will vary based on the land use. Minimum to be used is shown in Figure 1: Minimum “C” Values for Land Use Types. 23 (2). Alternatively, when the area is not outlined in Figure 1, the runoff coefficient “C” in the Rational Method formula can be calculated from the equation: C = 0.6Ia + 0.2 Where C = Watershed coefficient Ia = percent impervious area (3). If the alternate form is to be submitted, a calculation of the computation of C is to be provided as part of the drainage calculations. 2. Design of Storm Sewers 1. Storm sewers shall be designed using the Manning Equation in combination with the Continuity Equation. Proper consideration will be given to the units of measure, whether English or metric. 2. The Manning Equation is defined as: 2/3 V = (K/n)R Sf ½ Where K = 1.49 for English units and 1.0 for metric units n = 0.013 for concrete pipes and 0.024 for CMP pipes V = velocity in feet per second R = hydraulic radius of the conduit in feet which equals area/wetted perimeter Sf = friction slope as headloss per length 3. The Continuity Equation is defined as: Q = VA Where Q = Discharge or runoff in cfs V = velocity in feet per second A = Cross-sectional area of conduit in square feet 4. Design Frequency 24 (1). Newly Developed Areas – The design storm event for sizing storm sewers in newly developing areas shall be a two (2) year rainfall. (2). Redevelopment or In-Fill Development with Increased Rate of Runoff – The existingstorm drainserving redevelopment or infill development shall be evaluated in accordance with conditions outlined below, using a 2-year rainfall, assuming existing development conditions. Afterwards the storm drain shall be re- evaluated with the proposed re-development, or in-fill development, in place. (a). If the hydraulic gradient is twelve inches (12”) or less above the top of curb with the flow in the receiving channel at the top of theoutfallpipe and no structures are threatened by the project, then no improvements to the existing storm drain are required. (b). If the extreme event analysis indicates that structures are threatened by flooding, the applicant has the option of either making improvements to the existing storm drain or providing detention or improving the receiving stream and not impacting downstream conditions. 5. Velocity Considerations (1). Storm sewers should be constructed to convey the design flow in sub critical hydraulic conditions if possible. (2). Minimum 2-year flow velocities should not be less than three feet (3’) per second with the pipe flowing full, under the design conditions. (3). Maximum 2-year flow velocities should not exceed eight feet (8’) per second. 6. Pipe Sizes and Placement (1). Soil boring with logs shall be made along the alignment of all storm sewers having a cross section equal to or greater than seventy-two inches (72”) in diameter or equivalent cross sectional area. Each boring shall be taken at intervals not to exceed five hundred (500) 25 linear feet and at a depth of less than three feet (3’) below the flow line of the sewer. The required bedding will be determined from the soil boring. (2). The storm sewer and inletleadshall be designed with a minimum of twenty-four inch (24”) inside diameter or equivalent cross sectional area. Box conduits shall be a minimum of two feet (2’) by two feet (2’). Closed conduits, either circular, elliptical, or box, shall be selected based on hydraulic principles and economy of size and shape. (3). Larger pipes upstream should not flow into smaller pipes downstream unless construction constraints prohibit the use of a larger pipe downstream, or the improvements are outfalling into an existing system, or the upstream system is intended for use in detention. (4). Match crowns of trunk storm sewer pipe at any change in pipe size unless severe depth constraints prohibit the matching of crowns. Severe depth constraints include any system in which the outfall system exists and the designed storm system cannot achieve 2 feet or more of cover at the point of lowest cover without additional fill. This includes: (a). Any system that includes a lake or detention pond, and the depth of the storm sewers is constrained by that lake or detention pond, and the designed storm sewer system cannot achieve 2 feet or more cover at the point of lowest cover without additional fill. (b). Any time there is a conflict with the existing utility system which cannot be reasonably relocated. This includes large diameter water lines, underground electrical conduits, underground telecommunication conduits, petrochemical pipelines, or sanitary sewers. (c). Any time there is a conflict with a proposed sanitary sewer system which cannot be avoided due to design criteria constraints. This includes but may not be limited to sanitary sewers and their serviceleads. 26 (d). The saving of specimen trees which would be harmed by fill on lots with a minimum lot size of 8400 sf. A tree survey must be provided showing location, size and species of trees proposed to be saved. (5). Locate storm sewers in public street rights-of-way or in approved easements. (6). All precast, reinforced, concrete conduits must be laid in a straight line. Deflection in accordance with manufacturer’s specifications will be allowed if on approved drawings. (7). All public side lot or back lot drainage facilities shall be underground storm sewer systems designed in accordance with these Harris County standards. Drainage swales are permitted for off-site sheet flow only. Private, individual lot drainage is exempt from this requirement except when discharging into a public right- of-way. (8). In all easements restricted to storm sewers, the conduit shall be centered within the limits of the easement. The width of the easement shall be two (2) times the depth plus the diameter of the pipe rounded up to the next highest five foot (5’) increment. The minimum shall never be less than twenty feet (20’). (9). For storm sewers located in easements adjacent to public street rights-of-way, the minimum width shall be increased for larger pipe or conduit by requiring that a minimum distance of five feet (5’) shall be maintained between the easement line and the outside edge of the sewer, and a minimum distance of two feet (2’) shall be maintained from the right-of-way line to the outside edge of the sewer pipe or conduit. 7. Starting Water Surface and Hydraulic Gradient (1). The hydraulic gradient shall be calculated using the top of the outfall pipe as the starting water surface elevation. (2). Should the upstream pipe be higher than the hydraulic grade line at drop in pipes invert, then the hydraulic grade line shall be recalculated assuming the starting water surface to be at the top of the pipe at that point. 27 (3). For the design storm (a two year frequency), the hydraulic gradient shall at all times be below the gutter line. 8.ManholeLocations (1). Use manholes for precast conduits at the following locations: (a). Size or cross section changes. (b). Inlet lead and conduit intersections. (c). Changes in pipe grade. (d). At a maximum space of seven hundred feet (700’) along a conduit run. (2). Use manholes for monolithic concrete storm sewers at the same locations as precast conduits, except they are not required at theintersectionof inlet leads unless needed to provide maintenance access. 9. Inlets (1). Locate inlets at all low points in gutter or at intermediate points in the profile grade to provide proper drainage. (2). Inlets should not be placed withindrivewaylocations/limits but should be placed in the center of the lot. (3). Valley gutters across intersections are not permitted. (4). Inlet spacing is a function of gutter slope and should be designed to conform with the Pavement Design Requirements and Drainage Design Requirements of these design guidelines. (a). Local and collector street section: For minimum gutter slopes, the maximum inlet spacing shall be a gutter run of seven hundred feet (700’) at high point in pavement or the adjacent inlet, with a maximum of one thousand four hundred feet (1400’) of pavement draining towards any one inlet location. 28 (b). On cul-de-sac or partial cul-de-sac sections, gutter runs shall be limited to four hundred feet (400’). (c). On major thoroughfares, gutter runs shall be limited to three hundred feet (300’). (5). Use only Harris County and City of Houston Standard Inlets shown in Figure 3, “City of Houston Standard Inlets Acceptable to Harris County.” (6). Storm sewer leads, twenty-four inches (24”) or larger, must be tied directly into the face or back of “B-B” or “H-2” inlet box and shall not be tied into the short side of “B-B” or “H-2” inlets. (7). Do not use “Beehive” grate inlets or other “specialty” inlets. (8). Do not use unprotected grate-top inlets in unlined roadside ditch. (9). Do not place inlets in circular portion of cul-de-sac streets unless special conditions warrant otherwise and are included on approved plans and are approved prior to placement. (10). If drainage will enter or leave proposed pavement then inlets must be located at the end of proposed pavement. (11). Do not locate inlets adjacent to esplanade openings. (12). Place inlets on side streets intersecting major streets, unless special conditions warrant otherwise and are included on approved plans. FIGURE 3: City of Houston Standard Inlets Acceptable to Harris County Inlet Application Capacity City of Houston Type Drawing Number A Parking Lots / Small Areas 2.5 cfs 02632-01 B-B Residential / Commercial 5.0 cfs 02632-04 C Residential / Commercial 5.0 cfs 02632-06 29 FIGURE 3: City of Houston Standard Inlets Acceptable to Harris County Inlet Application Capacity City of Houston Type Drawing Number C-1 Commercial 10.0 cfs 02632-06 C-2 Commercial 15.0 cfs 02632-06 C-2A Commercial 20.0 cfs 02632-06 D Parking Lots 2.0 cfs 02632-07 D-1 Small Areas 2.5 cfs 02632-08 E Roadside Ditches 20.0 cfs 02632-09 & 02632-10 H-2 Residential / Commercial 5.0 cfs 02633-01 & 02633-02 30 3. Consideration of Overland Flow A. Extreme Event Analysis – The design frequency for consideration of overland sheet flow will consider extreme storm events. These events, which exceed the capacity of the underground storm sewer system and result in ponding and overland sheet flow, shall be routed to drain along street rights-of-way or open areas and through the development to a primary outlet. B. Relationship of Structures to Street (1). All structures shall be higher than the ponding anticipated in areas immediately adjacent to the structure as anticipated by the extreme event analysis. (2). In those cases where the design engineer has determined that the sheet flow ponding will encroach within a ten-foot (10’) radius of any point of the structure’s building pad, the engineer shall show the proposed structure’s minimum slab elevation at eighteen inches (18”) above the 1% (100-year) flood plain, or, one-foot (1’) above the ponding depth, whichever is greater. (3). Slab and drainage elevations, conduit locations, and grading for the extreme event shall be shown on a specifically designated page of construction plans. C. Calculation of Flow (1). Streets will be designed so that consecutive high points in the street will provide for a gravity flow of drainage to the ultimate outlet. (2). The maximum depth of ponding at high points will be six inches (6”) above top of curb during an extreme event condition. (3). The maximum depth of ponding at low points will be eighteen inches (18”) above the top of curb during an extreme event condition. (4). Along major thoroughfares and principal arterial streets, the depth of water along the median gutter section shall not exceed three inches (3”) in depth under the extreme event condition. 31 (5). Sheet flow between lots may be provided only in connection with a defined drainage easement. (6). A map shall be provided which delineates extreme event flow direction for both offsite, and through a proposed development. The map shall also show the method of discharge to the primary drainage outlet. Positive drainage must be provided to intercept offsite sheet flow. (7). In areas where ponding occurs and where no sheet flow path exists, a calculation must be provided which demonstrates how the runoff from a 100-year event will be conveyed and remain in compliance with the other terms of this Section. D. Interim off-site sheet flow: Drainage swales may be used for interim offsite sheet flow in lieu of closed conduits in phased projects and for projects adjacent to existing development. This is required any time the proposed development will cause ponding on an adjacent owner’s property. 4. Design of Open Channels A. Design Frequency (1). Open channel design and construction standards shall follow the requirements specified in the HCFCD Criteria Manual. (2). Design standards foroutfallsinto channels shall conform to those standards delineated in the HCFCD Criteria Manual. B. Determination of Water Surface Elevation (1). Water surface elevations shall be calculated using Manning’s Equation and the Continuity Equation. (2). For the design storm event, the water surface must be calculated to remain within banks. C. Design ofCulverts 32 (1). Head losses in culverts shall conform to Texas Department of Transportation Hydraulic Manual, Chapter 4 – Culverts. (2). Corrugated metal pipe will not be approved for permanent culverts in Harris County rights-of-way except at railroad crossings, and if used underneath the railroad crossing, theculvertshall be designed to railroad loadings. D. Design of Outfalls (1). All outfall designs shall conform to HCFCD Standards. 5. Design of Roadside Ditches A. Design Frequency (1). Roadside ditch design is permissible only for commercial areas equal to or less than one (1) acre or for single-family residential lots. Detention is required in accordance with Section 6.03 for all other conditions. (2). The design storm event for the roadside ditches shall be a two (2) year rainfall. (3). Design capacity under the two (2) year storm event for a roadside ditch shall be no less than 0.5 feet below the edge of pavement or the natural ground at the right-of-way line, whichever is lower. (4). The design shall include an extreme event analysis to indicate that the proposed structures will not be flooded. (5). Outfall drainage to existing roadside ditches shall be limited to tracts with frontage along the roadside ditch. If no frontage to the roadside ditch exists, but it can be shown with detail topographic surveys that the tract ultimately drains to the roadside ditch, then outfall will only be considered with full retention of the storm water during the design rainfall event. B. Velocity Considerations 33 (1). For grass-lined sections, the maximum design velocity shall be four feet (4’) per second during the design event. (2). A grass-lined or unimproved roadside ditch shall have side slopes no steeper than three (3) horizontal to one (1) vertical (3:1) or as soil conditions will permit. Steeper slopes will be allowed when the existing right-of-way is limited or other construction features dictate the design. The steepest slope shall not exceed two (2) horizontal to one (1) vertical (2:1). (3). The minimum grade for roadside ditches shall be 0.1 foot per 100 feet. (4). Calculation of velocity shall use a Manning’s roughness coefficient of 0.04 for earthen sections and 0.025 for ditches for paved inverts. (5).Erosion controlmethods shall be used when design velocities are expected to be greater than four feet (4’) per second or where erodible soil conditions are indicated in the geotechnical report. C. Culverts (1). Culvert length shall be determined by measuring the width of the crossing and adding a one-foot (1’)shoulderto each edge of radius of the crossing and the intersection length from the edge of the shoulder to the flow line of the ditch. The slope will not be steeper than a three (3) horizontal to one (1) vertical (3:1) at each end. (2). Culverts shall be placed at all driveway and roadway crossings and other locations where deemed necessary. The size and grade of the culvert(s) shall be provided for each lot. (3). Pipe culverts shall conform to ASTM Specification C-76, Class III, for reinforced concrete pipe. (4). The size of roadside culverts is to be based upon drainage area. Notwithstanding this requirement, the minimum culvert size shall be eighteen inches (18”) for residential and commercial driveways. (5). All proposed and reasonably expected future culverts shall be included in the hydraulic profile. The culvert used shall not create a 34 headloss of more than 0.20 feet greater than the normal water surface profile without the culvert. (6). Storm water discharging from a ditch into a storm sewer system must be intercepted by use of an appropriate structure (i.e., stubs with ring grates or type “E” manholes). D. Invert Protection (1). Ditch invert protection shall be used when velocities exceed four feet (4’) per second. (2). Ditch invert protection will be used at the upstream and downstream ends of all culverts. E. Depth and Size Limitations for Roadside Ditches (1). The maximum depth for a roadside ditch shall not exceed four feet (4’) below the adjacent road centerline top of pavement. There may be instances where extreme conditions may warrant a deeper ditch. In those cases, specific written prior approval must be obtained from the Harris County Public Infrastructure Department. (2). Roadside ditch bottoms shall be at least two feet (2’) wide, unless design analysis supports a narrower width and prior written approval is obtained from the Harris County Public Infrastructure Department. (3). A minimum distance of two feet (2’) shall be established and maintained between the right-of-way line and the adjacent edge of the bank of a ditch. 35 SECTION 6.03 - STORM WATER DETENTION 1. Application of Detention A. If new development or redevelopment has the opportunity to drain directly into a channel maintained by HCFCD, then HCFCD criteria shall prevail. (1). If the drainage system for a development project outfalls directly into a channel maintained by the HCFCD, and the requirements of the HCFCD include payment of an impact fee, then no further impact fees or detention will be required by Harris County Public Infrastructure Department. (2). If redevelopment occurs without increasing the overall impervious character of the site, or without increasing the drainage outfall capacity from the site, then no detention will be required. (3). If the development involves only one single family residence where no major changes in existing drainage are proposed and the tract is not part of a larger development project, then no detention will be required. (4). If development involves only lots fronting on Countyroads, no detention is required if the developed area is contained within the 150 foot lot depth fronting the road or the total impervious area does not exceed the area calculated by multiplying the 150 foot lot depth by the lot width adjacent to the County road. This provision is only applicable for single-family residential lots where no changes in existing drainage patterns are proposed for the remainder of the lot. B. Use of on-site detention is required under these regulations when either: (1) It is proposed that commercial development outfall into a Harris County roadside ditch, and the depth of the tract or development is greater than one hundred-fifty feet (150’) or the development is for a tract larger than one acre in size; or (2) It is proposed that the tract or development outfall to a Harris County storm sewer system and the capacity allocated to the tract in the original design calculations is less than projected for the 36 proposed development. This shall be evaluated using either the methodology documented in the original design calculations or that outlined in these regulations. 2. Calculations of Detention Volume A. Design rainfall shall follow the requirement specified in the current HCFCD Criteria Manual. B. Detention volume for new development areas is to be calculated based on the gross area of the tract being developed. However, the County Engineer may grant phased detention for phased commercial projects based on the portion of the tract being developed at the time. All future development will require approval from HCPID and HCFCD. C. Detention volume for redevelopment areas is to be calculated on the basis of the amount of area of increased impervious cover. D. Detention volume for areas proposed for gravity outfall shall be: (1). Roadside ditch outfall – Minimum storage rate of 1.0 acre feet per acre unless a Method 2 hydrologic and hydraulic analysis, as defined by the current Harris County Flood Control District Design Criteria Manual, shows a lower rate and volume is acceptable. The discharge rate shall be limited to the capacity of as outlined in Section 6.03 (4)(A). NOTE: If a method 2 analysis is performed, the minimum detention volume shall not be less than 0.75 acre-feet per acre. (2). Storm sewer outfall – Minimum storage rate of 0.65 acre-feet per acre unless a formal Method 2 hydrologic and hydraulic analysis, as defined by the current Harris County Flood Control District Design Criteria Manual, shows a lower rate and volume is acceptable. The discharge rate shall be limited to the existing storm sewer capacity allocated to the tract. E. For the areas proposed for pumped/gravity combination outfall, the following criteria shall apply: 37 (1). The detention volume shall be the same as D(1) and D(2), EXCEPT THAT the volume of pumped flow shall be limited to 75% of total basin capacity. NOTE: The minimum detention volume shall not be less than 1.0 acre-feet per acre for a pumped/gravity combination system that outfalls into a roadside ditch. (2). Automatic controls shall be incorporated to shut off all pumping when outfall system capacity is reached. Additionally, a gravity return line to the detention facility must be provided for additional head control in the event of failure of automatic level controls. Pumping cannot be resumed until the outfall has receded to one- half (½) the depth of the roadside ditch. (3). Drain Time – Maximum drain time is seven days. If the maximum discharge rate from the detention facility to a roadside ditch is insufficient to allow the facility to drain within seven days, this is likely an indication that the proposed area to be developed is too large to be accommodated within the existing roadside ditch. In this case, an alternative drainage solution may be required which could include acquisition of off-site drainage easements and construction of open channel ditches to serve the development. If the calculated drain time exceeds seven days, consult with the County Engineer. F. When parking areas are used for detention, the maximum depth of ponding in parking areas shall be nine inches (9”) directly over the inlet grate. G. Outfall drainage to existing roadside ditches shall be limited to those tracts with frontage along the roadside ditch. In cases where no frontage on roadside ditch exists, but where it can be shown with detail topographic surveys that the tract ultimately drains to the roadside ditch, the minimum detention volume shall not be less than 1.0 acre-feet per acre. The allowable discharge rate to a roadside ditch shall be limited to the pro- rata share of the existing capacity of the roadside ditch at the point of outfall or any location downstream, whichever is less as outlined in Section 6.03 (4)(A). 3. Design of Basin 38 The following requirements shall apply for basins designed under these Regulations: A. The side slope ratio shall be 3:1 or flatter depending on local soil conditions. B. The design must either prevent sheet flow down the basin side slopes or provide for adequate erosion control through the back slope drains, concrete slopes, or other acceptable methods. C. Dry bottom basins shall be sloped to drain and dry out between storm events in order to accommodate maintenance. The minimum bottom traverse slope shall be three-fourths of one percent (0.75%), and the minimum pilot channel slope shall be one-tenth of one percent (0.1%). D. Wet bottom basins shall meet the following criteria: (1). A minimum of six feet (6’) of permanent water depth is required unless the wet bottom is for purposes of wetlands. (2). A six-foot (6’) width minimum shelf, one-foot (1’) above static waters surface elevation is required. (3). Side slopes must meet the following criteria: (a). A ratio of 3:1 from shelf to bottom of basin; or (b). A ratio of 3:1 or flatter depending on local soil conditions from above shelf to natural ground. (4). Alternatives to items D(2) and D(3) above may be approved provided the facility design demonstrates that it can be easily maintained with due consideration of public safety. 4. Detention Outfall Facilities A. The maximum discharge rate for detention facilities shall be limited to the capacity allowed to the subject tract of the receiving storm sewer. In the case of a roadside ditch outfall, the rate of runoff from the front one hundred-fifty feet (150’) of the tract calculated is defined in Section 6.02 (1) of these regulations, assuming a runoff coefficient “C” of 0.2. Alternatively, the allowable discharge rate to a roadside ditch can be calculated based upon the pro-rata share of the existing capacity of the 39 roadside ditch at the point of outfall or any location downstream, whichever is less. Capacity of the roadside ditch shall be computed using detailed topographic survey of the ditch and Manning’s Equation as outlined in Section 6.02 (2) (B). Pro-rata share of capacity shall be computed as the ratio of the detention pond service area (including the detention pond) that naturally drains to the roadside ditch divided by the total drainage area of the roadside ditch upstream of the outfall location. B. The outfall orifice shall be designed using the following equation: ______Q = CA  2gh D = Q ½ / 2.25 h ¼ Where Q = outflow discharge in cfs C = 0.8 A = orifice area h = head – water surface differential – typically two feet (2’), but no less than 0.5 feet g = gravity – 32.2 feet / sec 2 D = diameter of orifice (inches) C. Restrictor Criteria (1). The minimum restrictor size shall be six inches (6”). (2). The outfall pipe containing the restrictor shall be a minimum of eighteen inches (18”) or six inches (6”) greater than the restrictor pipe size, whichever is larger. (3). The restrictor shall be located in the upstream end of the outfall pipe. D. Outfall Method 40 (1). The outfall pipe shall be Class III Reinforced Concrete. (2). The restrictor shall be PVC or other material acceptable to the Harris County Public Infrastructure Department. (3). All gravity discharges shall be designed to prevent erosion of the roadside ditch. (4). Pump systems: (a). An outfall from a pumped discharged system shall not discharge directly into the roadside ditch but shall provide a stilling manhole or basin for pump system energy dissipation prior to a gravity discharge. (b). The entrance velocity into the roadside ditch shall not exceed three feet (3’) per second. (c). A maximum level control and return line to thedetention basinshall be provided to limit head build up and control outflow into the roadside ditch during a flooding event. E. A gravity spillway must be provided in addition to the pipe outlet to protect structures from flooding in the event the capacity of the basin is exceeded. SECTION 6.04 - OWNERSHIP AND EASEMENTS 1. Private Facilities A. Submission of pump system specifications and a written operating plan that defines how the pump(s) will be controlled to avoid overloading the existing system is required when pump discharge outfalls into a roadside ditch. This information shall be included in the plan detail sheets. B. A maintenance work area of twenty feet (20’) in width surrounding the extent of the detention area shall be provided. Permanent access easements and necessary utility easements and parking lots 41 may be included as a portion of this twenty-foot (20’) width as determined by the County Engineer. C. Notice of Detention Requirements Form (1). Blank forms are available upon request. (2). The “Notice of Detention Requirements” forms shall indicate the party responsible for maintenance of the detention facility. (3). A signed and notarized “Notice of Detention Requirements” shall be filed in the Harris County Clerk’s Office, Real Property Records. (4). Once filed, the form becomes a legal document attached to the property in perpetuity. (5). If conditions change and the detention system is no longer required, the Harris County Public Infrastructure Department will notify, in writing, the Harris County Clerk’s Office, Real Property Records. Such notice shall unencumber the property from the previously recorded “Notice of Detention Requirements” form. D. Any facility serving a single-family residential subdivision with 14 or more lots and private streets, shall have the detention facility maintained by a political subdivision of the state. 2. Public Facilities. A. Detention facilities will be accepted for maintenance by Harris County or the Harris County Flood Control District in cases where public drainage is being provided and the facilities meet minimum requirements for acceptance. B. A maintenance work area of thirty feet (30’) in width surrounding the detention area must be provided. Up to 10 feet of public right-of-way may be included as a portion of the 30-foot width. 42 C. A dedication of easement shall be provided by plat or by separate instrument. D. For wet bottom basins, the minimum wet surface area shall be one (1) acre unless it incorporates storm water quality features such as wetland areas. E. Any facility draining water from public streets shall be maintained by a governmental body such as a municipal utility district or HCFCD. SECTION 6.05 – SUBMERGED STORM SEWERS The use of submerged storm sewers should be avoided unless it is part of a storm water quality feature/amenity lake system. For the purpose of these regulations, storm sewer systems are not considered submerged where only the outlet pipe from the last manhole entering a storm water quality/amenity lake system is below static water surface. In this case, storm sewers shall meet the following conditions: Permanent Access Easements/Private Streets/Storm Sewers 1. Incorporate methods to drain the system in case of repairs. Methods include specifying locations of cofferdams, specifying portable pump equipment, and providing a sequence that would result in being able to drain any portion of the storm sewer within 3 days with the longest allowable time being 5 days. 2. In order to reduce the possibility of mosquito breeding, a system shall be designed such that sections of storm sewer are dry or hold a minimum of 3 inches of water and are continuously connected to the lake feature. Public Streets/Storm Sewers 1. Incorporate a sluice gate system into design so that the lake can be drained by gravity. If desired, an additional sluice gate may be added to isolate the storm sewer system from the lake. 2. Design the sluice gate system such that upon opening, the lowest portion of the storm sewer will drain dry by gravity within 3 days with the longest allowable time being 5 days. 43 3. If equipped with a sluice gate designed to isolate the storm sewer, the manhole adjacent and upstream of the sluice gate must have asumpof sufficient depth to allow for pumping the system dry. 4. Provide an Interlocal Agreement, in a form acceptable to the County Attorney, between the utility district or other political subdivision of the State and the County indicating the following: a) The entire system shall be covered by a drainage easement dedicated to the public. b) The utility district will accept the dedication of the sluice gate system for maintenance. c) The utility district will make available to the County all complaints regarding the storm sewer system and the utility district’s repair and maintenance records. d) The utility district agrees not to damage any pavement or storm sewer in its maintenance of the sewer system. 5. In order to reduce the possibility of mosquito breeding, a system shall be designed such that sections of storm sewer are dry or hold a minimum of 3 inches of water and are continuously connected to the lake feature. The following additional design requirements apply to submerged storm sewer systems. a) The hydraulic gradient shall be calculated using the static lake level as the starting water surface elevation. b) All storm sewer pipe shall be reinforced concrete pipe ASTM, C-76, Class III with joint conforming to ASTM C-361 with rubber gaskets conforming to ASTM, C-443. c) All storm sewers shall be encased in cement stabilized sand in conformity with City of Houston drawings, 02317-02, 02317-03, 02317-05, 02317-06, and 02317-07, as appropriate. 44 SECTION 6.06 – LOW IMPACT DEVELOPMENT andGREEN INFRASTRUCTURE A Low Impact Development (LID) or Green Infrastructure (GI) technique may be utilized to address drainage and storm water quality requirements provided: 1. The proposed LID or GI technique conforms to the Harris County Low Impact Development & Green Infrastructure Design Criteria for Storm Water Management (Design Criteria) as adopted by Commissioners’ Court; and 2. Prior to submitting plans for acceptance, the proposed LID or GI technique must be reviewed in a pre-project meeting in accordance with the Design Criteria.. 45 SECTION 7 - PAVING SECTION 7.01 – PAVING DESIGN REQUIREMENTS The following design requirements are applicable to all pavement that is designed and constructed under Harris County jurisdiction by the development community. SECTION 7.02 - DESIGN REQUIREMENTS The following design requirements are applicable to pavement within the Harris County street right-of-way: 1. PAVEMENT WIDTH– The width shall be in accordance with the following Table 7.1, “Roadway Classifications and Section Requirements” and the “Geometric Design Guidelines for Subdivision Streets, Harris County and City of Houston” as adopted by Harris County Commissioners’ Court on July 28, 2009. Comment [SW1]: Confirm date with Loyd 46 Table 7.1 Roadway Classifications and Section Requirements Land Use on Both Sides of Roadway Portland Cement Concrete Right-of-Way (R.O.W.) Classificatio Single Double Paving Section Major Thoroughfare n on Table Paving IV.1 Section Width Curb Width Curb Width Curb Single family Residential on Local 28’ (B-B) 6” or 4” x 12 2/25’ 6” or 4” x 12 both sides of R.O.W. Single Family Residential Local 28’ (B-B) 6” or 4” x 12 2/25’ 6” or 4” x 12 Reserve Restricted to Landscape or pocket parks less than one acre Single Family Residential Collector 28’ (B-B) 6” or 4” x 12 2/25’ 6” or 4” x 12 Detention Pond or Amenity Lake Single Family Residential Collector 41’ (B-B)* 6” or 4” x 12 2/25’ 6” or 4” x 12 Reserve Restricted to Recreation/Open Single Family Residential Thoroughfare 41’ (B-B) 6” or 4” x 12” 2/25’ 6” or 4 ”x 12” 25’ (B-B) 6” only Unrestricted or Restricted to Commercial or Industrial Restricted Reserve to Thoroughfare 41’(B-B) 6” 2/25’ 6” 25’ (B-B) 6” only Commercial or Industrial on both sides of R.O.W. *A waiver to this requirement may be requested if onsite parking is proposed. A site plan for the reserve development indicating the type of facilities and number of parking spaces proposed is required to be submitted with the preliminary infrastructure drawing submittal. Harris County will make a determination if the proposal is satisfactory. If acceptable, a letter of certification from the developer stating that the required number of parking spaces will be provided in connection with the development of the reserve is required as a condition of signature and approval of the infrastructure drawings. Notes: 1. 4x12 curb section shall only be approved on streets where single family structures are taking direct primary access. 2. Alternative paving sections may be considered and approved by the County Engineer for master planned, mixed-use developments. Table 7.1 Continued below: 47 Land Use on Both Sides of right-of Asphaltic Concrete Way (R.O.W.) Roadway Double Paving Section ______Single Paving Classification with Roadside Ditches _ Section with on Table IV.1 Single Paving Section Roadside Ditches with Roadside Ditches Width Width Width Single family Residential on both Local 22’ (E-E) with 6’ 2/24’ (E-E) with 6’ 22’ (E-E) with 6’ sides of R.O.W. shoulders shoulders shoulders Single Family Residential Local 22’ (E-E) with 6’ 2/24’ (E-E) with 6’ 22’ (E-E) with 6’ shoulders shoulders shoulders Reserve Restricted to Landscape or pocket parks less than one acre Single Family Residential Collector 22’ (E-E) with 6’ 2/24’ (E-E) with 6’ 22’ (E-E) with 6’ shoulders shoulders shoulders Detention Pond or Amenity Lake Single Family Residential Collector 41’ (E-E) with 6’ 2/24’ (E-E) with 6’ 41’ (E-E) with 6’ shoulders shoulders shoulders Reserve Restricted to Recreation/Open Single Family Residential Thoroughfare 41’ (E-E) with 6’ 2/24’ (E-E) with 6’ 41’ (E-E) with 6’ shoulders shoulders shoulders Unrestricted or Restricted to Commercial or Industrial Restricted Reserve to Commercial Thoroughfare 41’ (E-E) with 6’ 2/24’ (E-E) with 6’ 41’ (E-E) with 6’ or Industrial on both sides of shoulders shoulders shoulders R.O.W. 48 PAVEMENT THICKNESS A. Local, Collector, Thoroughfare (1). Concrete - The requirements presented in Table 7.2 below shall be the minimum allowable local, collector, thoroughfare thicknesses utilizing Portland cement concrete. These thicknesses were developed considering both the Portland Cement Association (PCA) design method (“Design of Concrete Pavement for City Streets”, 1974) and the American Association of State Highway and Transportation Officials (AASHTO) method (“AASHTO Guide for Design of Pavement Structures”, 1993). Table 7-2. Concrete Thickness for 30-Year Design Life Roadway Concrete Pavement 28-day Minimum Required Depth Classification Thickness, in. Compressive of Stabilization, in. Strength, fc’, psi Local2 6 3000 6 Collector2 6 3000 6 Thoroughfare2 7 3000 8 Principal 81 4500 8 Thoroughfare2 101 3000 8 Notes: 1. For principal thoroughfares in excess of 30,000 VPD (see criteria below). 2. For paving design purposes, see definitions for local, collector, and thoroughfare as described in “Section 12 – Traffic” of these regulations. (2). Asphalt, Flexible Base – roads shall use a minimum of a six-inch (6”) stabilized subgrade, eight inches (8”) of base course, one and one-half inches (1½) hot mixed, hot laid asphalt. Alternative pavement design may be considered provided the equivalent 49 structural number is met or exceeded. Flexible base pavement for all developments, other than low density, single-family, shall be designed in accordance with the design parameters in Section 2, below. B. Principal Thoroughfares (in excess of 30,000 VPD on year 15 of design life). A licensed engineer shall design the pavement thickness and reinforcement using the AASHTO method and Harris County Public Infrastructure Department specified design parameters. The pavement thickness and reinforcement design shall be based on a current soil analysis, stabilized subgrade, roadway use (including the design lane traffic volume) and life span of the proposed pavement. Harris County Public Infrastructure Department specified design parameters for reinforced concrete designs for Principal Thoroughfares are: AASHTO Design Design Value Comments Parameter Drainage Coefficient, Cd 1.2 Good to excellent, 1% Excellent, 1% to 5% Load Transfer Coefficient, J 3.2 Jointed, reinforced pavement with load transfer such as dowels, specified by detail Loss of Support, LS 1 Modulus of Rupture, S’c See comment Dependent on required concrete compressive strength Mr=570 psi for f’c =3000 psi Mr=620 psi for f’c =3500 psi Mr=660 psi for f’c =4000 psi Mr=710 psi for f’c =4500 psi Reliability, R 95% Initial Serviceability Index, po 4.5 Terminal Serviceability Index, 2.5 pt Elastic Modulus, Ec See comment Dependent upon required concrete strength 6 Ec=3.6x10 psi for f’c =3000 psi 6 Mr=3.8x10 psi for f’c =3500 psi 6 Mr=4.0x10 psi for f’c =4000 psi 50 AASHTO Design Design Value Comments Parameter 6 Mr=4.2x10 psi for f’c =4500 psi Friction Factor, F 1.8 Lime, lime-fly ash, asphalt or cement stabilized subgrade Harris County Public Infrastructure Department specified design parameters for flexible paving designs based on available traffic data are: AASHTO Design Parameter Design Value Comments Reliability, R 95% Standard Deviation, So 0.45 Soil Resilient Modulus, Mr 30,000 psi Mr = 1500 X CBR; CBR estimated as 20 for stabilized subgrade Drainage Coefficient, m2 m3 1.25 AASHTO Table .24 – good quality drainage (1% - 5%) – drains within 1 day Initial serviceability index, po 4.2 Terminal serviceability index, 2.5 pt Structural layer Coefficients Hot-mixed hot-laid asphalt surface material 0.44 Black base 0.34 Cement-stabilized limestone 0.23 Lime-stabilized limestone 0.17 Crushed recycled concrete 0.14 Raw limestone 0.14 Cement-stabilized earth 0.15 Lime-stabilized or lime-fly 0.11 ash stabilized earth Minimum acceptable recommended thickness Surface course 2 in. 51 AASHTO Design Parameter Design Value Comments Base course 4 in. Sub-base course 4 in. SECTION 7.03 – MATERIALS REQUIREMENTS The following requirements shall apply to paving subject to the jurisdiction of the Harris County Public Infrastructure Department:
https://docslib.org/doc/7088158/regulations-of-harris-county-texas-for-the-approval-and-acceptance-of-infrastructure
OCEANIC WIRELESS NETWORK v. CIR GR NO. 148380, (2005-12-09) Digest Add to Casebook Share Add TAGS to your cases to easily locate them or to build your SYLLABUS . Please SIGN IN to use this feature. https://lawyerly.ph/juris/view/ca2c7?user=fbGU2WFpmaitMVEVGZ2lBVW5xZ2RVdz09 [OCEANIC WIRELESS NETWORK v. CIR](https://lawyerly.ph/juris/view/ca2c7?user=fbGU2WFpmaitMVEVGZ2lBVW5xZ2RVdz09) {case:ca2c7} Highlight text as FACTS , ISSUES , RULING , PRINCIPLES to generate case DIGESTS and REVIEWERS . Please LOGIN use this feature. Show as cited by other cases (1 times) Show printable version with highlights × DIVISION [ GR NO. 148380, Dec 09, 2005 ] OCEANIC WIRELESS NETWORK v. CIR + DECISION 513 Phil. 317 FIRST DIVISION [ G.R. NO. 148380, December 09, 2005 ] OCEANIC WIRELESS NETWORK, INC., PETITIONER, VS. COMMISSIONER OF INTERNAL REVENUE, THE COURT OF TAX APPEALS, AND THE COURT OF APPEALS, RESPONDENTS. D E C I S I O N AZCUNA, J.: This is a Petition for Review on Certiorari seeking to reverse and set aside the Decision of the Court of Appeals dated October 31, 2000, and its Resolution dated May 3, 2001, in "Oceanic Wireless Network, Inc. v. Commissioner of Internal Revenue" docketed as CA-G.R. SP No. 35581, upholding the Decision of the Court of Tax Appeals dismissing the Petition for Review in CTA Case No. 4668 for lack of jurisdiction. Petitioner Oceanic Wireless Network, Inc. challenges the authority of the Chief of the Accounts Receivable and Billing Division of the Bureau of Internal Revenue (BIR) National Office to decide and/or act with finality on behalf of the Commissioner of Internal Revenue (CIR) on protests against disputed tax deficiency assessments. The facts of the case are as follows: On March 17, 1988, petitioner received from the Bureau of Internal Revenue (BIR) deficiency tax assessments for the taxable year 1984 in the total amount of P8,644,998.71, broken down as follows: Kind of Tax Assessment No. Amount Deficiency Income Tax FAR-4-1984-88-001130 P8,381,354.00 Penalties for late payment of income and failure to file quarterly returns FAR-4-1984-88-001131 3,000.00 Deficiency Contractor's Tax FAR-4-1984-88-001132 29,849.06 Deficiency Fixed Tax FAR-4--88-001133 12,083.65 Deficiency Franchise Tax FAR-4--84-88-001134 227,712.00 T o t a l ---------------------- P8,644,998.71 Petitioner filed its protest against the tax assessments and requested a reconsideration or cancellation of the same in a letter to the BIR Commissioner dated April 12, 1988. Acting in behalf of the BIR Commissioner, then Chief of the BIR Accounts Receivable and Billing Division, Mr. Severino B. Buot, reiterated the tax assessments while denying petitioner's request for reinvestigation in a letter [1] dated January 24, 1991, thus: "Note: Your request for re-investigation has been denied for failure to submit the necessary supporting papers as per endorsement letter from the office of the Special Operation Service dated 12-12-90." Said letter likewise requested petitioner to pay the total amount of P8,644,998.71 within ten (10) days from receipt thereof, otherwise the case shall be referred to the Collection Enforcement Division of the BIR National Office for the issuance of a warrant of distraint and levy without further notice. Upon petitioner's failure to pay the subject tax assessments within the prescribed period, the Assistant Commissioner for Collection, acting for the Commissioner of Internal Revenue, issued the corresponding warrants of distraint and/or levy and garnishment. These were served on petitioner on October 10, 1991 and October 17, 1991, respectively. [2] On November 8, 1991, petitioner filed a Petition for Review with the Court of Tax Appeals (CTA) to contest the issuance of the warrants to enforce the collection of the tax assessments. This was docketed as CTA Case No. 4668. The CTA dismissed the petition for lack of jurisdiction in a decision dated September 16, 1994, declaring that said petition was filed beyond the thirty (30)-day period reckoned from the time when the demand letter of January 24, 1991 by the Chief of the BIR Accounts Receivable and Billing Division was presumably received by petitioner, i.e. , "within a reasonable time from said date in the regular course of mail pursuant to Section 2(v) of Rule 131 of the Rules of Court." [3] The decision cited Surigao Electric Co., Inc. v. Court of Tax Appeals [4] wherein this Court considered a mere demand letter sent to the taxpayer after his protest of the assessment notice as the final decision of the Commissioner of Internal Revenue on the protest. Hence, the filing of the petition on November 8, 1991 was held clearly beyond the reglementary period. [5] The court a quo likewise stated that the finality of the denial of the protest by petitioner against the tax deficiency assessments was bolstered by the subsequent issuance of the warrants of distraint and/or levy and garnishment to enforce the collection of the deficiency taxes. The issuance was not barred by prescription because the mere filing of the letter of protest by petitioner which was given due course by the Bureau of Internal Revenue suspended the running of the prescription period as expressly provided under the then Section 224 of the Tax Code: SEC. 224. Suspension of Running of the Statute of Limitations . The running of the Statute of Limitations provided in Section 203 and 223 on the making of assessment and the beginning of distraint or levy or a proceeding in court for collection, in respect of any deficiency, shall be suspended for the period during which the Commissioner is prohibited from making the assessment or beginning distraint or levy or a proceeding in court and for sixty (60) days thereafter; when the taxpayer requests for a reinvestigation which is granted by the Commissioner; when the taxpayer cannot be located in the address given by him in the return files upon which a tax is being assessed or collected: Provided, That if the taxpayer inform the Commissioner of any change of address, the running of the statute of limitations will not be suspended; when the warrant of distraint and levy is duly served upon the taxpayer, his authorized representative, or a member of his household with sufficient discretion, and no property could located; and when the taxpayer is out of the Philippines. [6] (Underscoring supplied.) Petitioner filed a Motion for Reconsideration arguing that the demand letter of January 24, 1991 cannot be considered as the final decision of the Commissioner of Internal Revenue on its protest because the same was signed by a mere subordinate and not by the Commissioner himself. [7] With the denial of its motion for reconsideration, petitioner consequently filed a Petition for Review with the Court of Appeals contending that there was no final decision to speak of because the Commissioner had yet to make a personal determination as regards the merits of petitioner's case. [8] The Court of Appeals denied the petition in a decision dated October 31, 2000, the dispositive portion of which reads: "WHEREFORE, the petition is DISMISSED for lack of merit. SO ORDERED." Petitioner's Motion for Reconsideration was likewise denied in a resolution dated May 3, 2001. Hence, this petition with the following assignment of errors: [9] I THE HONORABLE RESPONDENT CA ERRED IN FINDING THAT THE DEMAND LETTER ISSUED BY THE (THEN) ACCOUNTS RECEIVABLE/BILLING DIVISION OF THE BIR NATIONAL OFFICE WAS THE FINAL DECISION OF THE RESPONDENT CIR ON THE DISPUTED ASSESSMENTS, AND HENCE CONSTITUTED THE DECISION APPEALABLE TO THE HONORABLE RESPONDENT CTA; AND, II THE HONORABLE RESPONDENT CA ERRED IN DECLARING THAT THE DENIAL OF THE PROTEST OF THE SUBJECT ALLEGED DEFICIENCY TAX ASSESSMENTS HAD LONG BECOME FINAL AND EXECUTORY FOR FAILURE OF THE PETITIONER TO INSTITUTE THE APPEAL FROM THE DEMAND LETTER OF THE CHIEF OF THE ACCOUNTS RECEIVABLE/BILLING DIVISION, BIR NATIONAL OFFICE, TO THE HONORABLE RESPONDENT CTA, WITHIN THIRTY (30) DAYS FROM RECEIPT THEREOF. Thus, the main issue is whether or not a demand letter for tax deficiency assessments issued and signed by a subordinate officer who was acting in behalf of the Commissioner of Internal Revenue, is deemed final and executory and subject to an appeal to the Court of Tax Appeals. We rule in the affirmative. A demand letter for payment of delinquent taxes may be considered a decision on a disputed or protested assessment. The determination on whether or not a demand letter is final is conditioned upon the language used or the tenor of the letter being sent to the taxpayer. We laid down the rule that the Commissioner of Internal Revenue should always indicate to the taxpayer in clear and unequivocal language what constitutes his final determination of the disputed assessment, thus: . . . we deem it appropriate to state that the Commissioner of Internal Revenue should always indicate to the taxpayer in clear and unequivocal language whenever his action on an assessment questioned by a taxpayer constitutes his final determination on the disputed assessment, as contemplated by Sections 7 and 11 of Republic Act No. 1125, as amended. On the basis of his statement indubitably showing that the Commissioner's communicated action is his final decision on the contested assessment, the aggrieved taxpayer would then be able to take recourse to the tax court at the opportune time. Without needless difficulty, the taxpayer would be able to determine when his right to appeal to the tax court accrues. The rule of conduct would also obviate all desire and opportunity on the part of the taxpayer to continually delay the finality of the assessment and, consequently, the collection of the amount demanded as taxes by repeated requests for recomputation and reconsideration. On the part of the Commissioner, this would encourage his office to conduct a careful and thorough study of every questioned assessment and render a correct and definite decision thereon in the first instance. This would also deter the Commissioner from unfairly making the taxpayer grope in the dark and speculate as to which action constitutes the decision appealable to the tax court. Of greater import, this rule of conduct would meet a pressing need for fair play, regularity, and orderliness in administrative action. [10] In this case, the letter of demand dated January 24, 1991, unquestionably constitutes the final action taken by the Bureau of Internal Revenue on petitioner's request for reconsideration when it reiterated the tax deficiency assessments due from petitioner, and requested its payment. Failure to do so would result in the "issuance of a warrant of distraint and levy to enforce its collection without further notice." [11] In addition, the letter contained a notation indicating that petitioner's request for reconsideration had been denied for lack of supporting documents. The above conclusion finds support in Commissioner of Internal Revenue v. Ayala Securities Corporation, [12] where we held: The letter of February 18, 1963 (Exh. G), in the view of the Court, is tantamount to a denial of the reconsideration or [respondent corporation's]...protest o[f] the assessment made by the petitioner, considering that the said letter [was] in itself a reiteration of the demand by the Bureau of Internal Revenue for the settlement of the assessment already made, and for the immediate payment of the sum of P758,687.04 in spite of the vehement protest of the respondent corporation on April 21, 1961. This certainly is a clear indication of the firm stand of petitioner against the reconsideration of the disputed assessment...This being so, the said letter amount[ed] to a decision on a disputed or protested assessment, and, there, the court a quo did not err in taking cognizance of this case. Similarly, in Surigao Electric Co., Inc v. Court of Tax Appeals, [13] and in CIR v. Union Shipping Corporation, [14] we held: ". . . In this letter, the commissioner not only in effect demanded that the petitioner pay the amount of P11,533.53 but also gave warning that in the event it failed to pay, the said commissioner would be constrained to enforce the collection thereof by means of the remedies provided by law. The tenor of the letter, specifically the statement regarding the resort to legal remedies, unmistakably indicate[d] the final nature of the determination made by the commissioner of the petitioner's deficiency franchise tax liability." The demand letter received by petitioner verily signified a character of finality. Therefore, it was tantamount to a rejection of the request for reconsideration. As correctly held by the Court of Tax Appeals, "while the denial of the protest was in the form of a demand letter, the notation in the said letter making reference to the protest filed by petitioner clearly shows the intention of the respondent to make it as [his] final decision." [15] This now brings us to the crux of the matter as to whether said demand letter indeed attained finality despite the fact that it was issued and signed by the Chief of the Accounts Receivable and Billing Division instead of the BIR Commissioner. The general rule is that the Commissioner of Internal Revenue may delegate any power vested upon him by law to Division Chiefs or to officials of higher rank. He cannot, however, delegate the four powers granted to him under the National Internal Revenue Code (NIRC) enumerated in Section 7. As amended by Republic Act No. 8424, Section 7 of the Code authorizes the BIR Commissioner to delegate the powers vested in him under the pertinent provisions of the Code to any subordinate official with the rank equivalent to a division chief or higher, except the following: (a) The power to recommend the promulgation of rules and regulations by the Secretary of Finance; (b) The power to issue rulings of first impression or to reverse, revoke or modify any existing ruling of the Bureau; (c) The power to compromise or abate under Section 204(A) and (B) of this Code, any tax deficiency: Provided, however, that assessments issued by the Regional Offices involving basic deficiency taxes of five hundred thousand pesos (P500,000) or less, and minor criminal violations as may be determined by rules and regulations to be promulgated by the Secretary of Finance, upon the recommendation of the Commissioner, discovered by regional and district officials, may be compromised by a regional evaluation board which shall be composed of the Regional Director as Chairman, the Assistant Regional Director, heads of the Legal, Assessment and Collection Divisions and the Revenue District Officer having jurisdiction over the taxpayer, as members; and (d) The power to assign or reassign internal revenue officers to establishments where articles subject to excise tax are produced or kept. It is clear from the above provision that the act of issuance of the demand letter by the Chief of the Accounts Receivable and Billing Division does not fall under any of the exceptions that have been mentioned as non-delegable. Section 6 of the Code further provides: "SEC. 6. Power of the Commissioner to Make Assessments and Prescribe Additional Requirements for Tax Administration and Enforcement. (A) Examination of Returns and Determination of Tax Due. - After a return has been filed as required under the provisions of this Code, the Commissioner or his duly authorized representative may authorize the examination of any taxpayer and the assessment of the correct amount of tax; Provided, however , That failure to file a return shall not prevent the Commissioner from authorizing the examination of any taxpayer. The tax or any deficiency tax so assessed shall be paid upon notice and demand from the Commissioner or from his duly authorized representative . . . ." (Emphasis supplied) Thus, the authority to make tax assessments may be delegated to subordinate officers. Said assessment has the same force and effect as that issued by the Commissioner himself, if not reviewed or revised by the latter such as in this case. [16] A request for reconsideration must be made within thirty (30) days from the taxpayer's receipt of the tax deficiency assessment, otherwise, the decision becomes final, unappealable and therefore, demandable. A tax assessment that has become final, executory and enforceable for failure of the taxpayer to assail the same as provided in Section 228 can no longer be contested, thus: "SEC. 228. Protesting of Assessment. When the Commissioner or his duly authorized representative finds that proper taxes should be assessed, he shall first notify the taxpayer of his findings...Such assessment may be protested administratively by filing a request for reconsideration or reinvestigation within thirty (30) days from receipt of the assessment in such form and manner as may be prescribed by implementing rules and regulations. Within sixty (60) days from filing of the protest, all relevant supporting documents shall have been submitted; otherwise, the assessment shall become final. If the protest is denied in whole or in part, or is not acted upon within one hundred (180) days from submission of documents, the taxpayer adversely affected by the decision or inaction may appeal to the Court of Tax Appeals within thirty (30) days from receipt of the said decision, or from the lapse of the one hundred eighty (180) - day period; otherwise, the decision shall become final, executory and demandable." Here, petitioner failed to avail of its right to bring the matter before the Court of Tax Appeals within the reglementary period upon the receipt of the demand letter reiterating the assessed delinquent taxes and denying its request for reconsideration which constituted the final determination by the Bureau of Internal Revenue on petitioner's protest. Being a final disposition by said agency, the same would have been a proper subject for appeal to the Court of Tax Appeals. The rule is that for the Court of Tax Appeals to acquire jurisdiction, an assessment must first be disputed by the taxpayer and ruled upon by the Commissioner of Internal Revenue to warrant a decision from which a petition for review may be taken to the Court of Tax Appeals. Where an adverse ruling has been rendered by the Commissioner of Internal Revenue with reference to a disputed assessment or a claim for refund or credit, the taxpayer may appeal the same within thirty (30) days after receipt thereof. [17] We agree with the factual findings of the Court of Tax Appeals that the demand letter may be presumed to have been duly directed, mailed and was received by petitioner in the regular course of the mail in the absence of evidence to the contrary. This is in accordance with Section 2(v), Rule 131 of the Rules of Court, and in this case, since the period to appeal has commenced to run from the time the letter of demand was presumably received by petitioner within a reasonable time after January 24, 1991, the period of thirty (30) days to appeal the adverse decision on the request for reconsideration had already lapsed when the petition was filed with the Court of Tax Appeals only on November 8, 1991. Hence, the Court of Tax Appeals properly dismissed the petition as the tax delinquency assessment had long become final and executory. WHEREFORE, premises considered, the Decision of the Court of Appeals dated October 31, 2000 and its Resolution dated May 3, 2001 in CA-G.R. SP No. 35581 are hereby AFFIRMED . The petition is accordingly DENIED for lack of merit. SO ORDERED. Davide, Jr., C.J., (Chairman), Quisumbing, Ynares-Santiago, and Carpio, JJ., concur. [1] Annex "C" of Petition, Rollo, p. 48. [2] Rollo, p. 7. [3] CA Rollo, pp. 38-39. [4] L-25289, June 28, 1974, 57 SCRA 524. [5] CA Rollo, pp. 40-41. [6] Id; Note: Section 224 is now Section 223. [7] Rollo, p. 9. [8] Id. at 10. [9] Id . at 22. [10] Surigao Electric Co., Inc. v. Court of Tax Appeals, L-25289, June 28, 1974, 57 SCRA 523. [11] Annex "C" of Petition, Rollo, p. 48. [12] No. L-24985, March 31, 1976, 70 SCRA 204, 209. [13] L-25289, June 28, 1974, 57 SCRA 523, 526. [14] G.R. No. 66160, May 21, 1990, 188 SCRA 547. [15] CA Rollo, p. 40. [16] Arches v. Bellosillo, 126 Phil. 426 (1967). [17] Section 11, Republic Act No. 1125. tags Facts Issues Ruling Principles Add to Casebook You are currently signed in as: User CONTINUE TO LAWYERLY APP
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What's New & FAQs QuickFacts Durham city, North Carolina; Greensboro city, North Carolina; Charlotte city, North Carolina; United States; North Carolina; Raleigh city, North Carolina QuickFacts provides statistics for all states and counties, and for cities and towns with a population of 5,000 or more . -- Select a fact -- Population Estimates, July 1, 2022, (V2022) Population estimates base, April 1, 2020, (V2022) Population, percent change - April 1, 2020 (estimates base) to July 1, 2022, (V2022) Population, Census, April 1, 2020 Population, Census, April 1, 2010 Persons under 5 years, percent Persons under 18 years, percent Persons 65 years and over, percent Female persons, percent White alone, percent Black or African American alone, percent (a) American Indian and Alaska Native alone, percent (a) Asian alone, percent (a) Native Hawaiian and Other Pacific Islander alone, percent (a) Two or More Races, percent Hispanic or Latino, percent (b) White alone, not Hispanic or Latino, percent Veterans, 2017-2021 Foreign born persons, percent, 2017-2021 Housing units, July 1, 2022, (V2022) Owner-occupied housing unit rate, 2017-2021 Median value of owner-occupied housing units, 2017-2021 Median selected monthly owner costs -with a mortgage, 2017-2021 Median selected monthly owner costs -without a mortgage, 2017-2021 Median gross rent, 2017-2021 Building permits, 2022 Households, 2017-2021 Persons per household, 2017-2021 Living in same house 1 year ago, percent of persons age 1 year+, 2017-2021 Language other than English spoken at home, percent of persons age 5 years+, 2017-2021 Households with a computer, percent, 2017-2021 Households with a broadband Internet subscription, percent, 2017-2021 High school graduate or higher, percent of persons age 25 years+, 2017-2021 Bachelor's degree or higher, percent of persons age 25 years+, 2017-2021 With a disability, under age 65 years, percent, 2017-2021 Persons without health insurance, under age 65 years, percent In civilian labor force, total, percent of population age 16 years+, 2017-2021 In civilian labor force, female, percent of population age 16 years+, 2017-2021 Total accommodation and food services sales, 2017 ($1,000) (c) Total health care and social assistance receipts/revenue, 2017 ($1,000) (c) Total transportation and warehousing receipts/revenue, 2017 ($1,000) (c) Total retail sales, 2017 ($1,000) (c) Total retail sales per capita, 2017 (c) Mean travel time to work (minutes), workers age 16 years+, 2017-2021 Median household income (in 2021 dollars), 2017-2021 Per capita income in past 12 months (in 2021 dollars), 2017-2021 Persons in poverty, percent Total employer establishments, 2021 Total employment, 2021 Total annual payroll, 2021 ($1,000) Total employment, percent change, 2020-2021 Total nonemployer establishments, 2019 All employer firms, Reference year 2017 Men-owned employer firms, Reference year 2017 Women-owned employer firms, Reference year 2017 Minority-owned employer firms, Reference year 2017 Nonminority-owned employer firms, Reference year 2017 Veteran-owned employer firms, Reference year 2017 Nonveteran-owned employer firms, Reference year 2017 Population per square mile, 2020 Population per square mile, 2010 Land area in square miles, 2020 Land area in square miles, 2010 Clear   6 Table Map   Durham city, North Carolina  Greensboro city, North Carolina  Charlotte city, North Carolina  United States  North Carolina  Raleigh city, North Carolina  More Print CSV Email Map TIGERweb Population Estimates, July 1, 2022, (V2022) - - - - - Populations below 5,000 are not in QuickFacts and therefore Not Selectable Selectable Not Selectable Value Notes   Estimates are not comparable to other geographic levels due to methodology differences that may exist between different data sources. 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Senate should say no to Kavanaugh | The Hill Confirming this nominee under this serious cloud of doubt puts at risk the integrity of the Supreme Court. Senate should say no to Kavanaugh Pool The United States Supreme Court plays a pivotal and indispensable role in the American system of government. The Framers envisioned the Supreme Court as the independent guardian of the Constitution and the symbol of the rule of law, dispensing equal justice under law without fear or favor. To ensure the court had the requisite independence from the political branches of government, Article III, section 1 of the Constitution provides that “Judges of the supreme and inferior courts shall hold their Office during Good Behavior” and shall receive a salary which “shall not be diminished during their continuance in Office.” The Framers wisely entrusted the responsibility of confirming a person nominated to serve on the Supreme Court to the United States Senate. In Federalist Paper No. 78,Hamilton wrote that the Senate was given the power to ‘advise and consent’ to presidential appointments to ensure that in the person nominated was united “the requisite integrity with the requisite knowledge.” An added safeguard of Senate concurrence to a president’s nominee is that “the necessity of its co-operation, in the business of appointments, will be a considerable and salutary restraint upon the conduct of [the President].” Federalist Paper No. 76. {mosads}In the view of the Framers, the Senate was the proper forum to repose the ‘advise and consent’ power because senators were older, presumably wiser, more mature and sophisticated, and with six-year terms not constrained by the prospect of an imminent election or beholden or dependent upon the executive. Finally, the Senate consisted of a smaller number of members, making it harder for any individual senator to avoid accountability and find anonymity. As stated earlier, the paramount objective of the Senate in exercising its ‘advise and consent’ prerogative is to determine whether a nominee possesses “the requisite integrity with the requisite knowledge.” In the case of Brett Kavanaugh, who has been nominated to succeed Associate Justice Anthony Kennedy, the answer is a resounding “no.” Nominees before the United States Senate bring with them two things: their records and themselves. And it should be noted that, as an initial matter, the burden of establishing fitness for appointment to the Court is on the nominee, not the Senate or the president. If there is to be a benefit of the doubt, as the late Sen. Robert Byrd (D-W.Va.) pointed out in 1991, it should be resolved in favor of the “Court and the country.” The Senate should refuse to consent to this nomination because Brett Kavanaugh has demonstrated by his conduct and testimony before the Senate Judiciary Committee that he manifestly lacks the temperament, the honesty, and impartiality reasonably expected of a traffic court judge, much less the highest court in the land and the court whose interpretations of the Constitution protect or abridge the rights of liberties of hundreds of millions of Americans. Brett Kavanaugh’s Sept. 27, 2018 testimony before the Senate Judiciary Committee was a case study in intemperate behavior. As an initial matter, his demeanor was inconsistent with that of a responsible judge. On many occasions, Kavanaugh evaded legitimate inquiries from senators with flippant remarks and rhetorical questions.  He repeatedly cut off questioning from senators, meandered when asked direct questions, and dissembled in the face of inquiries that went to the heart of the allegations lodged by the woman accusing him of sexual assault. Perhaps most troubling from his testimony-as-spectacle, was his brazen claim that the investigation of credible claims of sexual assault and excessive drinking were a function of “a calculated and orchestrated political hit” driven by “pent up anger at the 2016 election” and“revenge on behalf of the Clintons.”Kavanaugh then threatened senators and “left-wing” groups and organizations opposing his nomination, saying: “what goes around, comes around.” Such statements are wholly disqualifying for any jurist, let alone an individual seeking a seat on the highest court on the land. In the face of all this, the White House initiated nothing more than a farce to purportedly investigate the serious accusation against him. This effort is nothing more than cover to ram through this nomination. Critical witnesses who could corroborate aspects of Dr. Ford’s testimony were not interviewed; neither Dr. Ford nor Brett Kavanaugh were interviewed; and, individuals in a position to corroborate a second alleged victim of Kavanaugh were not interviewed. The FBI investigation which occurred into Kavanaugh’s alleged wrongdoing was inchoate with respect to certain, critical episodes of his life. Confirming this nominee under this serious cloud of doubt puts at risk the integrity of the Supreme Court. Because Brett Kavanaugh fails the character test, the Senate should reject his nomination to the U.S. Supreme Court, the final arbiter of equal justice under law. Congresswoman Jackson Lee is a Democrat from Texas’s 18th District. She is a senior member of the House Committees on Judiciary and Homeland Security and is ranking member of the Judiciary Subcommittee on Crime, Terrorism, Homeland Security, and Investigations. Tags
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Regression from stage 3 to stage 2 type 1 diabetes mellitus after discontinuing growth hormone therapy in: Endocrinology, Diabetes & Metabolism Case Reports Volume 2023 Issue 2 (2023) Summary Multiple research studies address the anti-insulinemic effect of growth hormone (GH). We report a case of a patient with anterior hypopituitarism on GH replacement who later developed type 1 diabetes mellitus (T1DM). Recombinant human growth hormone (rhGH) therapy was discontinued at the time of growth completion. Because of significantly improved glycemic control, this patient was weaned off subcutaneous insulin. He regressed from stage 3 to stage 2 T1DM and remained in this status for at least 2 years and until the writing of this paper. The diagnosis of T1DM was established based on relatively low C-peptide and insulin levels for the degree of hyperglycemia as well as seropositivity of zinc transporter antibody and islet antigen-2 antibody. Additional laboratory data obtained 2 months after discontinuing rhGH revealed improved endogenous insulin secretion. This case report calls attention to the diabetogenic effect of GH therapy in the setting of T1DM. It also demonstrates the possibility of regression from stage 3 T1DM requiring insulin therapy to stage 2 T1DM with asymptomatic dysglycemia after discontinuing rhGH. Learning points Given the diabetogenic effect of growth hormone, blood glucose levels should be monitored in patients with type 1 diabetes mellitus (T1DM) on insulin therapy and recombinant human growth hormone (rhGH) replacement. Clinicians should closely monitor for risk of hypoglycemia after discontinuing rhGH among T1DM patients who are on insulin treatment. The discontinuation of rhGH in the setting of T1DM may cause regression of symptomatic T1DM to asymptomatic dysglycemia requiring no insulin treatment. Regression from stage 3 to stage 2 type 1 diabetes mellitus after discontinuing growth hormone therapy in Endocrinology, Diabetes & Metabolism Case Reports Authors: Micah A Fischer Micah A Fischer Department of Pediatrics , University of Nebraska Medical Center, Children’s Hospital and Medical Center, Omaha, Nebraska, USA Search for other papers by Micah A Fischer in Current site Google Scholar PubMed Close https://orcid.org/0000-0002-9664-8826 , Ghada A Elmahmudi Ghada A Elmahmudi Department of Holland Regenerative Medicine Program , University of Nebraska Medical Center, Omaha, Nebraska, USA Search for other papers by Ghada A Elmahmudi in Current site Google Scholar PubMed Close , Bracha K Goldsweig Bracha K Goldsweig Division of Pediatric Endocrinology , University of Nebraska Medical Center, Children’s Hospital and Medical Center, Omaha, Nebraska, USA Search for other papers by Bracha K Goldsweig in Current site Google Scholar PubMed Close , and Salaheddin H Elrokhsi Salaheddin H Elrokhsi Division of Pediatric Endocrinology , University of Nebraska Medical Center, Children’s Hospital and Medical Center, Omaha, Nebraska, USA Search for other papers by Salaheddin H Elrokhsi in Current site Google Scholar PubMed Close Correspondence should be addressed to M A Fischer; Email: [email protected] DOI: https://doi.org/10.1530/EDM-22-0276 Volume/Issue: Volume 2023: Issue 2 Article Type: Research Article Online Publication Date: 16 May 2023 Summary Multiple research studies address the anti-insulinemic effect of growth hormone (GH). We report a case of a patient with anterior hypopituitarism on GH replacement who later developed type 1 diabetes mellitus (T1DM). Recombinant human growth hormone (rhGH) therapy was discontinued at the time of growth completion. Because of significantly improved glycemic control, this patient was weaned off subcutaneous insulin. He regressed from stage 3 to stage 2 T1DM and remained in this status for at least 2 years and until the writing of this paper. The diagnosis of T1DM was established based on relatively low C-peptide and insulin levels for the degree of hyperglycemia as well as seropositivity of zinc transporter antibody and islet antigen-2 antibody. Additional laboratory data obtained 2 months after discontinuing rhGH revealed improved endogenous insulin secretion. This case report calls attention to the diabetogenic effect of GH therapy in the setting of T1DM. It also demonstrates the possibility of regression from stage 3 T1DM requiring insulin therapy to stage 2 T1DM with asymptomatic dysglycemia after discontinuing rhGH. Learning points Given the diabetogenic effect of growth hormone, blood glucose levels should be monitored in patients with type 1 diabetes mellitus (T1DM) on insulin therapy and recombinant human growth hormone (rhGH) replacement. Clinicians should closely monitor for risk of hypoglycemia after discontinuing rhGH among T1DM patients who are on insulin treatment. The discontinuation of rhGH in the setting of T1DM may cause regression of symptomatic T1DM to asymptomatic dysglycemia requiring no insulin treatment. Abstract Summary Multiple research studies address the anti-insulinemic effect of growth hormone (GH). We report a case of a patient with anterior hypopituitarism on GH replacement who later developed type 1 diabetes mellitus (T1DM). Recombinant human growth hormone (rhGH) therapy was discontinued at the time of growth completion. Because of significantly improved glycemic control, this patient was weaned off subcutaneous insulin. He regressed from stage 3 to stage 2 T1DM and remained in this status for at least 2 years and until the writing of this paper. The diagnosis of T1DM was established based on relatively low C-peptide and insulin levels for the degree of hyperglycemia as well as seropositivity of zinc transporter antibody and islet antigen-2 antibody. Additional laboratory data obtained 2 months after discontinuing rhGH revealed improved endogenous insulin secretion. This case report calls attention to the diabetogenic effect of GH therapy in the setting of T1DM. It also demonstrates the possibility of regression from stage 3 T1DM requiring insulin therapy to stage 2 T1DM with asymptomatic dysglycemia after discontinuing rhGH. Learning points Given the diabetogenic effect of growth hormone, blood glucose levels should be monitored in patients with type 1 diabetes mellitus (T1DM) on insulin therapy and recombinant human growth hormone (rhGH) replacement. Clinicians should closely monitor for risk of hypoglycemia after discontinuing rhGH among T1DM patients who are on insulin treatment. The discontinuation of rhGH in the setting of T1DM may cause regression of symptomatic T1DM to asymptomatic dysglycemia requiring no insulin treatment. Keywords: Adult ; Male ; White ; United States ; Pancreas ; Growth factors ; Unique/unexpected symptoms or presentations of a disease ; May ; 2023 Background The development of type 1 diabetes mellitus (T1DM) has been classified into three stages. Stage 1 includes the presence of two or more islet autoantibodies with normoglycemia and no symptoms. Stage 2 presents with mild dysglycemia and no symptoms of T1DM. Stage 3 is defined as the onset of symptomatic T1DM according to criteria set by the American Diabetes Association (1). Young (1941) reported a diabetogenic effect of crude anterior pituitary gland extract injected subcutaneously into dogs (2). The effect of growth hormone (GH) on glucose homeostasis has been well described. GH influences glucose homeostasis by inducing hepatic gluconeogenesis and counteracting insulin action through a variety of biochemical pathways. The principal mechanism through which GH counteracts insulin action is by inhibiting the anabolic action of insulin on adipose tissue, leading to increased free fatty acids, which can give rise to insulin resistance (3). The reported incidence of T2DM was six times higher in children treated with rhGH than in untreated children. In contrast, there was no significant difference reported in the incidence and age at diagnosis of T1DM between rhGH-treated children and untreated individuals (4). Case presentation We report an 18-year-old Caucasian male with a history of anterior hypopituitarism secondary to craniopharyngioma that was diagnosed at 3 years of age. He was initially treated with neurosurgical excision of the craniopharyngioma followed by cranial radiation therapy. He was subsequently diagnosed with central hypothyroidism, central adrenal insufficiency, and then GH deficiency. He was started on recombinant human growth hormone (rhGH) at 4 years and 9 months of age. He demonstrated normal pubertal onset and progressed with normal pubertal gonadotropin and testosterone levels. When he reached 14 years, he presented with increased urination and increased thirst. Central diabetes insipidus was highly suspected given his hypopituitarism. However, his laboratory workup revealed new-onset T1DM. His body mass index (BMI) at the time of diagnosis with T1DM was 21.55 kg/m 2at 77.8 percentile. His hemoglobin A1c (HbA1c) was checked twice several years before the diagnosis of T1DM and reported normal. His family history was remarkable for one cousin diagnosed with T1DM, a paternal grandmother diagnosed with multiple sclerosis, and a maternal great-grandmother diagnosed with systemic lupus erythematosus. Investigation Fasting laboratory workup showed serum osmolality of 301 mOsm/kg (normal range (NR): 270–295 mOsm/kg), urine osmolality of 914 mOsm/kg (NR: 50–1400 mOsm/kg), serum blood glucose of 297 mg/dL, elevated A1c at 11.7%, corrected serum sodium for hyperglycemia of 144 mmol/L (NR: 135–148 mmol/L), potassium 4.4 mmol/L (NR: 3.5–5.5 mmol/L), CO 224 mmol/L (NR: 22–32 mmol/L), and beta-hydroxybutyrate of 1.23 mmol/L (NR: <0.30 mmol/L). His insulin-like growth factor-1 was within the therapeutic range at 558 ng/mL (NR: 220–574 ng/mL). Subsequent laboratory results revealed a C-peptide of 1.4 ng/mL (NR: 0.8–3.5 ng/mL) and an insulin level of 10 ulU/mL (NR: 3–19 uIU/mL) with serum glucose of 395 mg/dL. He tested positive for zinc transporter antibody with a titer of 137.6 U/mL (NR: 0.0–15.0 U/mL) and for islet antigen 2 (IA-2) antibody at 8.5 U/mL (NR: 0.0–0.8 U/mL). Glutamic acid decarboxylase (GAD) antibody as well as insulin antibody were negative. Treatment He was started on subcutaneous (s.c.) insulin with a total daily dose of 0.8 units/kg/day for glycemic control. Levothyroxine, rhGH, and hydrocortisone replacement therapies were all continued. Outcome and follow-up Shortly after the onset of T1DM, the patient demonstrated a 6- to 9-month honeymoon period when he only required 2–4 units of long-acting insulin per day and a weak carbohydrate ratio and rarely required any correction doses of short-acting insulin for hyperglycemia. When the honeymoon period was over, his insulin requirement increased back to approximately 0.8 units/kg/day. While the patient was on insulin treatment between 14 and 16 years of age, his BMI was fluctuating between 22.51 kg/m 2at 83.9 percentile and 25.28 kg/m 2at 89.25 percentile. After 2 years of treatment with s.c. insulin, linear growth was completed at 16 years of age, and rhGH was held. One month later, the patient underwent a repeat of the GH stimulation test. GH peak of 0.4 ng/mL confirmed the persistence of significant GH deficiency and indicated the need for adult GH replacement. Interestingly, the patient’s blood glucose decreased considerably after holding rhGH, and insulin requirements decreased dramatically until he was completely weaned off s.c. insulin about 1 month after holding rhGH. Through shared decision-making with the family, it was agreed upon to temporarily hold off on initiating adult GH replacement. Three months after discontinuing rhGH therapy, about 2 months after completely stopping the s.c. insulin, we obtained an oral glucose tolerance test and repeated HbA1c, C-peptide, and insulin levels, as well as antibody screening for T1DM for reevaluation. Laboratory reevaluation revealed ongoing positive IA-2 antibody and transporter antibody with higher IA-2 antibody titer (>120 U/mL (NR: 0.0–7.4 U/mL)) and lower zinc transporter antibody titer (53.8 U/mL (NR: 0.0–15.0 U/mL)). GAD antibody as well as insulin antibody remained negative. His fasting blood glucose was 93 mg/dL with fasting C-peptide of 1.0 ng/mL ng/mL (NR: 0.8–3.5 ng/mL) and fasting insulin level of 6 μlU/mL (NR: 3–19 μIU/mL). His 2-h blood glucose was 184 mg/dL with 2-h postprandial C-peptide of 3.8 ng/mL (NR: 0.8–3.5 ng/mL) and 2-h insulin level of 20 μlU/mL (3–19 μIU/mL) (Table 1). Furthermore, his serial HbA1c measurements in the follow-up visits have remained stable between 5.4% and 6.8% over 24 months and until the writing of this paper, while the patient has been completely off s.c. insulin and without dietary carbohydrate restrictions (Fig. 1). During this period of time, he did not report any polyuria, polydipsia, or fatigue. His BMI gradually dropped from 24.54 kg/m 2at 83.96 percentile to 21.88 kg/m 2at 46 percentile. Figure 1 HbA1c trend after the onset of T1DM as well as before and after holding rhGH. (A) Stage 3 T1DM; (B) honeymoon period; (C) increased insulin requirements; (D) regression to stage 2 T1DM. HbA1c, hemoglobin A1c; rhGH, recombinant human growth hormone; s.c., subcutaneous; T1DM, type 1 diabetes mellitus. Citation: Endocrinology, Diabetes & Metabolism Case Reports 2023, 2;10.1530/EDM-22-0276 Figure 1 HbA1c trend after the onset of T1DM as well as before and after holding rhGH. (A) Stage 3 T1DM; (B) honeymoon period; (C) increased insulin requirements; (D) regression to stage 2 T1DM. HbA1c, hemoglobin A1c; rhGH, recombinant human growth hormone; s.c., subcutaneous; T1DM, type 1 diabetes mellitus. Citation: Endocrinology, Diabetes & Metabolism Case Reports 2023, 2;10.1530/EDM-22-0276 Table 1 Comparison between laboratory values before and after holding rhGH. Normal range On rhGH 2 months off rhGH IGF-1 (ng/mL) 220–574* 558 IGF-1 z -score −2.0 to +2.0 +2.0 HbA1c (%) 11.7 5.7 IA-2 Ab (U/mL) 0–0.8, 0–7.4 8.5 >120.0 Insulin Ab (U/mL) 0–0.4 <0.4 <0.4 Zinc transporter Ab (U/mL) 0–15.0 137.6 53.8 GAD Ab (IU/mL) 0–5.0 <5.0 <5.0 Serum glucose (mg/dL) 70–100 397 Glucose tolerance test 0 min/fasting 93 60 min 207 120 min 184 C-peptide (ng/mL) 0.8–3.5 1.4 0 min/fasting 1.0 120 min 3.8 Insulin (µIU/mL) 3–19 10 0 min/fasting 6 120 min 20 *For his age and Tanner stage. Ab, antibody; GAD Ab, glutamic acid decarboxylase antibody; HbA1c, hemoglobin A1c; IA-2 Ab, islet antigen 2 antibody; IGF-1, insulin-like growth factor-1; rhGH, recombinant human growth hormone; Zn Ab, zinc transporter antibody. Discussion To the best of our knowledge, this is the first reported case of a patient with anterior hypopituitarism who developed T1DM and who 2 years later no longer needed exogenous insulin after discontinuing rhGH. Due to the counteracting effects of rhGH on insulin action (3), daily insulin requirement is reported to be higher in patients with T1DM who are treated with rhGH than diabetic patients who are not treated with rhGH (5). The patient we describe is likely to have a genetic predisposition to develop T1DM. It is possible that the rhGH replacement accelerated the progression to overt T1DM in our patient and likely countered the effects of his endogenous and exogenous insulin activity. Holding rhGH has drastically improved the glycemic control of this patient. He needed no more s.c. insulin, and his HbA1c remained between 5.4% and 6.8% without diabetes symptoms for at least 2 years and until the writing of this paper. Putting our patient back in the status of GH deficiency eliminated the diabetogenic effect from rhGH and likely improved the sensitivity of residual endogenous insulin. This change suggests that our patient is potentially still within the normal limits of T1DM progression and has reverted to stage 2 T1DM (1). Comparing the laboratory data between the onset of symptomatic T1DM and 2 months after holding rhGH showed an unexpected pattern. The patient’s C-peptide and insulin levels were considerably higher in relation to the serum glucose after the withdrawal of rhGH (Table 1). This suggested improvement in markers of beta-cell function in this patient. An in vitrostudy has described a direct long-term effect of GH on proliferation and insulin biosynthesis of pancreatic beta-cells in monolayer culture (6). However, there is no evidence that exogenous GH increases beta-cell number and function in humans. In the patient, we describe that the zinc transporter antibody titer dropped by about 60% after holding rhGH, whereas the IA-2 antibody titer increased significantly. We are not sure if these inverse antibody trends after discontinuing rhGH contributed to the regression from stage 3 to stage 2 T1DM. The development of T1DM in patients who are receiving rhGH is inconsistent with the findings of Villares et al.(2013). They stated that GH may prevent autoimmune diabetes in mice models via several immunoregulatory effects (7). Our patient is not the first case reported to develop T1DM while being treated with rhGH. Sadeghi-Nejad (2007) reported a 12-year-old boy who had GH deficiency and developed T1DM 11 months after initiation of rhGH (8). Additionally, Wang et al.(2015) reported an 8-year-old boy who developed T1DM 1 month after he was started on rhGH for slow growth (9). GH has been described to stimulate the proliferation of T and B cells and immunoglobulin production. GH also promotes the maturation of myeloid progenitor cells and can modulate cytokine response in vitroand in animal models (10). Nevertheless, to date, there is still no concrete evidence to support that rhGH has an immunomodulatory effect that plays a role in the development of autoimmune DM in humans. To conclude, glycemic control in patients with T1DM and GH deficiency can improve beyond expected when rhGH is discontinued. Additional research is warranted to explore the immunomodulatory effect of rhGH on autoimmune status and whether rhGH improves beta-cell function in the long-term. Declaration of interest The authors declare that there is no conflict of interest or financial disclosures that could be perceived as prejudicing the impartiality of the case reported. Funding This case presentation did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector. Patient consent Written informed consent for publication of their clinical details was obtained from the patient and parent of the patient. Author contribution statement MA Fischer and GA Elmahmudi drafted and revised the manuscript. BK Goldsweig and SHElrokhsi reviewed and edited the manuscript. SH Elrokhsi is the primary endocrinologist for the patient reported. References 1 ↑ Insel RA , Dunne JL , Atkinson MA , Chiang JL , Dabelea D , Gottlieb PA , Greenbaum CJ , Herold KC , Krischer JP , Lernmark Å ,et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association . Diabetes Care 2015 38 1964 – 1974 . (https://doi.org/10.2337/dc15-1419 ) PubMed Insel RA Dunne JL Atkinson MA Chiang JL Dabelea D Gottlieb PA Greenbaum CJ Herold KC Krischer JP Lernmark Å , Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association . Diabetes Care 2015 38 1964 – 1974 . ( https://doi.org/10.2337/dc15-1419 ) 26404926 )| false 2 ↑ Young FG . "Growth" and the diabetogenic action of anterior pituitary preparations . BMJ 1941 2 897 – 901 . (https://doi.org/10.1136/bmj.2.4225.897 ) Young FG . "Growth" and the diabetogenic action of anterior pituitary preparations . BMJ 1941 2 897 – 901 . ( https://doi.org/10.1136/bmj.2.4225.897 ) 20784024 3 ↑ Sharma R , Kopchick JJ , Puri V , & Sharma VM . Effect of growth hormone on insulin signaling . Molecular and Cellular Endocrinology 2020 518 111038 . (https://doi.org/10.1016/j.mce.2020.111038 ) PubMed Sharma R Kopchick JJ Puri V & Sharma VM . Effect of growth hormone on insulin signaling . Figures Figure 1 HbA1c trend after the onset of T1DM as well as before and after holding rhGH. (A) Stage 3 T1DM; (B) honeymoon period; (C) increased insulin requirements; (D) regression to stage 2 T1DM. HbA1c, hemoglobin A1c; rhGH, recombinant human growth hormone; s.c., subcutaneous; T1DM, type 1 diabetes mellitus. References 1 Insel RA , Dunne JL , Atkinson MA , Chiang JL , Dabelea D , Gottlieb PA , Greenbaum CJ , Herold KC , Krischer JP , Lernmark Å ,et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association . Diabetes Care 2015 38 1964 – 1974 . (https://doi.org/10.2337/dc15-1419 ) PubMed Insel RA Dunne JL Atkinson MA Chiang JL Dabelea D Gottlieb PA Greenbaum CJ Herold KC Krischer JP Lernmark Å , Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association . Diabetes Care 2015 38 1964 – 1974 . ( https://doi.org/10.2337/dc15-1419 ) 26404926 )| false Search Google Scholar Export Citation 2 Young FG . "Growth" and the diabetogenic action of anterior pituitary preparations . BMJ 1941 2 897 – 901 . (https://doi.org/10.1136/bmj.2.4225.897 ) PubMed Young FG . "Growth" and the diabetogenic action of anterior pituitary preparations . BMJ 1941 2 897 – 901 . ( https://doi.org/10.1136/bmj.2.4225.897 ) 20784024 )| false Search Google Scholar Export Citation 3 Sharma R , Kopchick JJ , Puri V , & Sharma VM . Effect of growth hormone on insulin signaling . Molecular and Cellular Endocrinology 2020 518 111038 . (https://doi.org/10.1016/j.mce.2020.111038 ) PubMed Sharma R Kopchick JJ Puri V & Sharma VM . Effect of growth hormone on insulin signaling . Molecular and Cellular Endocrinology 2020 518 111038 . ( https://doi.org/10.1016/j.mce.2020.111038 ) 32966863
https://edm.bioscientifica.com/view/journals/edm/2023/2/EDM22-0276.xml?result=10&rskey=ATEnv0
PART XIII PART XIII.  COMMERCIAL DRIVER LICENSING Law Journals and Reviews Intextication:  Txting Whl Drvng.  Does the Punishment Fit the Crime?  32 UH L. Rev. 359 (2010). §286-231  Definitions.As used in this part unless the context otherwise requires: "Commercial driver's license downgrade" means: (1)  Authorization to change a driver's self-certification pursuant to title 49 Code of Federal Regulations section 383.71, to interstate, but operating exclusively in transportation or operation excepted from the Federal Motor Carrier Safety Regulations as provided in title 49 Code of Federal Regulations sections 390.3(f), 391.2, 391.62, and 398.2(b); (2)  Authorization to change a driver's self-certification pursuant to title 49 Code of Federal Regulations section 383.71, to intrastate only if the driver qualifies under the State's physical qualification requirements for intrastate only; (3)  Authorization to change a driver's self-certification pursuant to title 49 Code of Federal Regulations section 383.71, to intrastate, but operating exclusively in transportation or operations excepted from all or part of the state driver qualification requirements; or (4)  Removing the commercial driver's license privilege from the driver's license. "Commercial driver's license information system driver record" means the electronic record of an individual commercial driver license driver's status and history stored by the state of record as part of the commercial driver's license information system established under title 49 United States Code section 31309. "Disqualification" means any of the following three actions: (1)  The suspension, revocation, or cancellation of a commercial driver's license by the state or jurisdiction of issuance; (2)  Any withdrawal of a person's privileges to drive a commercial motor vehicle by a state or other jurisdiction as the result of a violation of state or local law relating to motor vehicle traffic control (other than parking, vehicle weight, or vehicle defect violations); or (3)  A determination by the Federal Motor Carrier Safety Administration that a person is not qualified to operate a commercial motor vehicle under title 49, Code of Federal Regulations Part 391. "Driving a commercial motor vehicle while under the influence of an intoxicant" means committing any one or more of the following acts in a commercial motor vehicle: (1)  Driving a commercial motor vehicle while the person's alcohol concentration is 0.04 or more grams of alcohol per two hundred ten liters of breath or 0.04 or more grams of alcohol per one hundred milliliters or cubic centimeters of blood; (2)  Driving under the influence of an intoxicant pursuant to section 291E-61; or (3)  Refusing to undergo such testing as required by any state or jurisdiction in the enforcement of section 383.51(b) or 392.5(a)(2) of title 49 Code of Federal Regulations. "Employer" means any person, including the United States, a state or a political subdivision of a state, who owns or leases a commercial motor vehicle or assigns a person to drive a commercial motor vehicle. "Endorsement" means an authorization on an individual's commercial driver's license or commercial learner's permit required to permit the individual to operate certain types of commercial motor vehicles. "Fatality" means the death of a person as a result of a motor vehicle accident. "Imminent hazard" means the existence of a condition that presents a substantial likelihood that death, serious illness, severe personal injury, or a substantial endangerment to health, property, or the environment may occur before the reasonably foreseeable completion date of a formal proceeding begun to lessen the risk of such death, illness, injury, or endangerment. "Noncommercial motor vehicle" means a motor vehicle or combination of motor vehicles not defined by the term "commercial motor vehicle (CMV)" under section 286-2. "Non-domiciled commercial driver's license" means a commercial driver's license issued by a state under either of the following two conditions: (1)  To an individual domiciled in a foreign country meeting the requirements of title 49, Code of Federal Regulations section 383.23(b)(1); or (2)  To an individual domiciled in another state meeting the requirements of title 49, Code of Federal Regulations section 383.23(b)(2). "Non-domiciled commercial learner's permit" means a commercial learner's permit issued by a state under either of the following two conditions: (1)  To an individual domiciled in a foreign country meeting the requirements of title 49 Code of Federal Regulations section 383.23(b)(1); or (2)  To an individual domiciled in another state meeting the requirements of title 49 Code of Federal Regulations section 383.23(b)(2). "Out-of-service order" means a declaration by an authorized enforcement officer of a federal, state, Canadian, Mexican, or local jurisdiction that a driver, a commercial motor vehicle, or a motor carrier operation is out-of-service pursuant to Section 386.72, 392.5, 395.13, or 396.9 of title 49, Code of Federal Regulations, or compatible laws, or the North American Uniform Out-of-Service Criteria, which can be obtained from the Commercial Vehicle Safety Alliance. "School bus" means a commercial motor vehicle used to transport pre-primary, primary, or secondary school students from home to school, from school to home, or to and from school-sponsored events, but does not include a bus, as defined under section 286-2, used as a common carrier as defined under section 271-4. "Serious traffic violation" means conviction of any of the following offenses when operating a commercial motor vehicle, except for weight, defect, and parking violations: (1)  Excessive speeding involving any single offense for any speed of fifteen miles per hour or more above the posted speed limit; (2)  Reckless driving or driving a commercial motor vehicle in disregard of the safety of persons or property, including but not limited to offenses of driving a commercial motor vehicle in wilful or wanton disregard for the safety of persons or property; (3)  Improper or erratic traffic lane changes; (4)  Following a vehicle ahead too closely; (5)  A violation of any state or local law relating to motor vehicle traffic control, other than a parking violation, arising in connection with a fatal traffic accident; (6)  Driving a commercial motor vehicle without obtaining a commercial learner's permit or a commercial driver's license; (7)  Driving a commercial motor vehicle without a commercial learner's permit or a commercial driver's license in the driver's possession; provided that this paragraph shall not apply to a citation issued under, or an offense disposed of pursuant to section 286-116(a) or a substantially similar provision of law in another state; (8)  Driving a commercial motor vehicle without the proper class or endorsements of commercial driver's license or commercial learner's permit for the specific vehicle group being operated or for the passengers or type of cargo being transported; (9)  Texting while driving in violation of a state or county law or ordinance; or (10)  Using a mobile electronic device in violation of a state or a county law or ordinance. "Tank vehicle" means any commercial vehicle that is designed to transport any liquid or gaseous materials within a tank or tanks having an individual rated capacity of more than one hundred nineteen gallons and an aggregate rated capacity of one thousand gallons or more that is either permanently or temporarily attached to the vehicle or the chassis.  A commercial motor vehicle transporting an empty storage container tank, not designed for transportation with a rated capacity of one thousand gallons or more that is temporarily attached to a flatbed trailer is not considered a tank vehicle. "Texting" means manually entering alphanumeric text into, or reading text from, an electronic device, and includes short message service; e-mailing; instant messaging; a command or request to access a world wide web page; pressing more than a single button to initiate or terminate a voice communication using a mobile telephone; and engaging in any other form of electronic text retrieval or entry, for present or future communication. "Texting" does not include: (1)  Reading, selecting, or entering a telephone number, an extension number, or voicemail retrieval codes and commands into an electronic device for the purpose of initiating or receiving a phone call or using voice commands to initiate or receive a telephone call; (2)  Inputting, selecting, or reading information on a global positioning system or navigation system or pressing a single button to initiate or terminate a voice communication using a mobile telephone; or (3)  Using a device capable of performing multiple functions, including fleet management systems, dispatching devices, smart phones, citizens band radios, and music players, for a purpose that is not otherwise prohibited. [L 1989, c 320, pt of §2; am L 1990, c 342, §4; am L 1993, c 268, §2; am L 1996, c 135, §§1, 2; am L 2004, c 103, §§1, 3; am L 2011, c 67, §1 and c 121, §1; am L 2012, c 311, §2; am L 2013, c 114, §3] Note Definition of "nonresident commercial driver's license" changed to "non-domiciled commercial driver's license".  L 2013, c 114, §3(2). Previous Vol05_Ch0261-0319 Next
https://www.capitol.hawaii.gov/hrsarchive/hrs2016/Vol05_Ch0261-0319/HRS0286/HRS_0286-0231.htm
1 Thessalonians 5:20 (YLT) - Robertson's Book Notes (NT) prophesyings despise not; 1 Thessalonians 5:20  ( Young's Literal Translation ) A.F.VA.S.V.Amplified®DarbyI.S.V.K.J.V.N.A.S.B.NASB E-Prime Young'sCompare all Book Notes: Robertson's Book Notes (NT) I Thessalonians We cannot say that this is Paul's first letter to a church, for in II Thessalonians 2:2 he speaks of some as palming off letters as his and in II Thessalonians 3:17 he says that he appends his own signature to every letter after dictating it to an amanuensis (Romans 16:22). We know of one lost letter (I Corinthians 5:11) and perhaps another (II Corinthians 2:3). But this is the earliest one that has come down to us and it may even be the earliest New Testament book, unless the Epistle of James antedates it or even Mark's Gospel. We know, as already shown, that Paul was in Corinth and that Timothy and Silas had just arrived from Thessalonica (I Thessalonians 3:6;Acts 18:5). They had brought supplies from the Macedonian churches to supply Paul's need (II Corinthians 11:9), as the church in Philippi did once and again while Paul was in Thessalonica (Philippians 4:15f.). Before Timothy and Silas came to Corinth Paul had to work steadily at his trade as tent-maker with Aquila and Priscilla (Acts 18:3) and could only preach in the synagogue on sabbaths, but the rich stores from Macedonia released his hands and "Paul devoted himself to the word" ( suneixeto tw logw Paulov). He gave himself wholly to preaching now. But Timothy and Silas brought news of serious trouble in the church in Thessalonica. Some of the disciples there had misunderstood Paul's preaching about thesecond comingof Christ and had quit work and were making a decided disturbance on the subject. Undoubtedly Paul had touched upon eschatological matters while in Thessalonica. The Jewish leaders at Thessalonica charged it against Paul and Silas to the politarchs that they had preached another king,Jesus, in place of Caesar. Paul had preached Jesus as King of the spiritual kingdom which the Jews misrepresented to the politarchs as treason against Caesar as the Sanhedrin had done to Pilate about Jesus. Clearly Paul had said also that Jesus was going to come again according to his own promise before his ascension. Some asserted that Paul said Jesus was going to come right away and drew their own inferences for idleness and fanaticism as some do today. Strange as it may seem, there are scholars today who say that Paul did believe and say that Jesus was going to come back right away. They say this in spite of II Thessalonians 2:1 f. where Paul denies having ever said it. Undoubtedly Paul hoped for the early return of Jesus as most of the early Christians did, but that is a very different thing from setting a time for his coming. It is open to us all tohopefor the speedy return of Christ, but times and seasons are withGodand not with us. It is not open to us to excuse our negligence and idleness as Christians because of such a hope. That hope should serve as a spur to increased activity for Christ in order to hasten his coming. So Paul writes this group of Epistles to correct gross misapprehension and misrepresentation of his preaching about last things (eschatology). It is a rare preacher who has never been misunderstood or misrepresented.
https://www.bibletools.org/index.cfm/fuseaction/Bible.show/sVerseID/29642/eVerseID/29642/opt/BN/RTD/RBN/version/ylt
In search of Europe’s confidence lost | The Dahrendorf Forum Debating Europe (c) Dahrendorf Forum / Steffen Weigelt Europe China Mena Symposium 2016 North America Turkey Security In search of Europe’s confidence lost Europe’s existential struggles in recent years over everything from the euro to refugees Brexit has left little room in the public debate for discussion of the EU’s place in the world. The Union’s ambitions for deeper collaboration on foreign policy and security remain controversial in many member states. More broadly, basic questions about the EU’s relationship withChina, the U.S. andRussiareceive little attention. As the recentISILterror attacks, Russia’s annexation of Crimea and the refugee influx have illustrated, global crosswinds tend to thrust the EU into disarray. POLITICO Chief Europe CorrespondentMatthew Karnitschnigrecently sat down in Berlin with two of Europe’s pre-eminent thinkers on international affairs and Europe — Wolfgang Ischinger, a veteran German diplomat who now runs the Munich Security Conference, and Robert Cooper, a retired British diplomat and author who spent many years as a key adviser to Javier Solana, the EU’s former high representative for foreign and security affairs. On the sidelines of theDahrendorf Symposium, the Dahrendorf Senior Fellows discussed a range of issues surrounding Europe’s role in the world, in particular its evolving relations with the U.S., Russia and China. What follows is an edited transcript. POLITICO: When President Obama took office in 2009, there was a lot of worry in Europe that he would shift the U.S.’s focus away from its traditional Western allies to the Pacific. As he reaches the end of his presidency, what has that shift meant for Europe? ISCHINGER: It was supposed to mean quite a lot, but I think most Americans would rather that they hadn’t said it because it took only a little while after they first pronounced a pivot to Asia that they realized they needed to re-position to Europe. That speaks to the unpredictable nature of international affairs, but Obama did have a clear vision. Where do you see the U.S. headed now in terms of its foreign policy? ISCHINGER: The West, if the West is the United States, plus Europe plus a few others, seems to have a problem with knowing exactly what our vision is today. In the U.S., there is a lack of clarity about just what the future role of the United States should be. Should it be withdrawal like [Donald] Trump is proposing? In the European Union there is a total lack of clarity. We don’t even know if Britain will be part of the EU next year. We do not seem to be able to develop a vision about where we will go. Is the dearth of big ideas, which some believe is what is driving the populist resurgence, unique to the West? It seems other countries, if you look at Russia in the Crimea or China in the South China Sea, where it has created artificial islands for its military, have clear priorities. ISCHINGER: The non-West appears at least from my vantage point to know exactly where they want to go. Russia wants to go away from the West. China at least proclaims to know exactly where it wants to go, so at least we seem to have declared clarity among non-Western important countries. I think that makes our lack of clarity even more pronounced, more worrisome. COOPER: I don’t know whether I agree with Wolfgang that the Chinese and the Russians know what they’re going. You hear some things from Mr. Putin, but I don’t think it’s as simple as that. The retreat from the West doesn’t make much sense for Russia. Maybe it’s okay as a slogan, but whether it’s really policy? As for China, I don’t know if there’s anything like a sort of doctrine of the Chinese government. They are very cagey about what they’re doing with the islands. ISCHINGER: Putin’s strategy is to preserve the status quo. His message is we’ve now decided that we can’t modernize, but at least we want to preserve our security status and we need a buffer zone around us. The Chinese are building up diligently, slowly a global role from what was practically zero 20 years ago. In terms of global activity they are now proactively engaged all over the world, even in Latin America. And yet in Europe, China is almost solely seen in commercial terms, both as a market and as the world’s factory floor. ISCHINGER: It’s a specific German problem, I think. The Germans tend to look at a country of more than a billion people as a place that buys many BMWs etc. And that’s about it. Of course that’s not good enough. We need to become slightly more sophisticated. We are still unfortunately quite far removed from something that smells like and looks like and sounds like an EU strategy vis-à-vis China. COOPER: The EU states primarily see China in commercial terms and they compete with each other. I agree with Wolfgang that we should have two ways of thinking about China: one is in commercial terms, and one is in political and security terms. On the second, we should do the thinking together. We ought to try and keep the two distinct. Just how relevant is China’s growing power for Europe? Is it a threat? COOPER: I don’t think people on the whole feel threatened in Europe by China, but I think it’s quite different in the region…I think that the power shift hasn’t happened. It’s happening. I may not get the quote right, but the famous phrase fromThucydidesis that it was Sparta’s perception of the growing power of Athens that was the cause of the Peloponnesian wars. The perception of growing power is always something that has the potential for instability. When you see another power growing, the incentive is to say, ‘we better deal with it now before it gets too big for us.’ To what degree could China be a strategic partner for Europe? ISCHINGER: It’s important for us to try to make sure that China comes down on the right side and not on the wrong side of important issues. For example, we’re trying to inscribe into the annals of the United Nations that the annexation of the Crimea was illegal. Can we get China to sign up to that or to abstain? This is important. That is why our dialogue on political security issues with China is not only about China’s behavior in the South China Sea, which is very far from us, but is also about how China deals with Ukraine, Libya etc. The EU, to the degree it discusses the issues, doesn’t seem to agree on a strategy. ISCHINGER: It’s not working as well as it should. We do not agree at this point whether we should or should not recognize China as a market economy. It starts there and that’s not even the hardest question. ISCHINGER: I think that it’s actually healthy for Europe as a whole to learn that there will not forever be the protector from Washington who will handle all of our difficult issues. This experience of United States not jumping immediately in and running the show in Europe as they have done for decades now is actually forcing us to grow up little more … If European leaders were capable of speaking about our future the way Obama did, we would be in much less of a state of malaise. This is a historic change that many Europeans haven’t really digested yet, that the United States is now supporting a stronger more united European Union. Should taking more responsibility for European security mean we’ll see a European army, as some have called for for years? The U.K., which favors a strong NATO and bilateral cooperation with other countries, is against that idea. COOPER: I wish people wouldn’t rush to last stage of a European army because there are lots of things you can do before you get to European army which always causes trouble in my country. How do you see the U.S.’s role in the constellation. Will it be less of an ally? ISCHINGER: I think if we manage to have more European cooperation in the future, not a European army but more pooling and sharing, that does not automatically lead to a wider Atlantic. We will be even more meaningful, more relevant to the U.S. if we can show that we have something to offer. What needs to change in Europe’s overall mindset for it to play a more assertive role on the international stage? ISCHINGER: Russia today has in nominal terms a GNP that is less than Italy’s. In other words, the European Union alone is vastly bigger in economic terms than Russia, which is one reason why I believe that the one thing we need to learn in the European Union is that we don’t need to be too timid. We should have a little more self-confidence. That doesn’t mean we should be adventurous, but we are really important. We are half a billion people but we haven’t yet learned to behave like it. __ This interview was first published onPOLITICO Europe Edition.
https://www.dahrendorf-forum.eu/in-search-of-europes-confidence-lost/
George Steele Seymour, letter, 1927-04-09, to Hamlin Garland — Calisphere George Steele Seymour, letter, 1927-04-09, to Hamlin Garland — Calisphere Skip to main content Search over two million items Contributing Institutions Collections Exhibitions About University of Southern California Digital Library Hamlin Garland Correspondence, 1864-1941 George Steele Seymour, letter, 1927-04-09, to Hamlin Garland Text / George Steele… Read item on contributor's website. × Get Citation We recommend you include the following information in your citation. Look below the item for additional data you may want to include. Close × Contact Owning Institution All fields are required. University of Southern California Digital Library http://digitallibrary.usc.edu/cdm/contactus http://digitallibrary.usc.edu/ Name: Email: Verify Email: How would you best describe yourself? 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Title George Steele Seymour, letter, 1927-04-09, to Hamlin Garland Creator Seymour, George Steele, 1878-1945 Order of the Bookfellows Contributor Garland, Hamlin, 1860-1940, recipient Date Created and/or Issued 1927-04-09 Publication Information University of Southern California. Libraries Contributing Institution University of Southern California Digital Library Collection Hamlin Garland Correspondence, 1864-1941 Rights Information CC BY 4.0 (Attribution 4.0 International) https://creativecommons.org/licenses/by/4.0/ Doheny Memorial Library, Los Angeles, CA 90089-0189 Send requests to address or e-mail given. Phone (213) 821-2366; fax (213) 740-2343. USC Libraries Special Collections [email protected] Description George Steele Seymour (The Order of the Bookfellows), 1217 East 53rd Street, Chicago, Illinois, USA, letter, 1927 April 9, to Hamlin Garland. "I suspect the enclosed is an invitation to you from the Society of Midland Authors, though I haven't steamed it open to see." -- first line. Type text Format 1 letter (4 p.) application/pdf letters (correspondence) correspondence Identifier gar-200-33-45-17~01...~04 http://doi.org/10.25549/gar-c81-30492 http://thumbnails.digitallibrary.usc.edu/gar-200-33-45-17~01.jpg Language English Time Period 1927-04-09 Place 1217 East 53rd Street 41.799183,-87.595818 Chicago Cook Illinois USA Source Hamlin Garland checklist no. 3449 [Identifying number] University of Southern California [Contributing entity] Relation Correspondence Hamlin Garland Papers Online Archive of California: http://www.oac.cdlib.org/findaid/ark:/13030/tf4r29p0q5/ ; Research Guide: http://libguides.usc.edu/c.php?g=235147&p=1558896 ; Finding Aid: http://archives.usc.edu/repositories/3/resources/198 box 33 folder 45 Provenance Hamlin Garland bequest to the University of Southern California in 1939-1940. 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echovirus - OpenMD.com Journal Search Viewing results 1 - 10 of 1,973 Coxsackievirus B3 replication and pathogenesis. Future Microbiology 2015 Viruses such as coxsackievirus B3 (CVB3) are entirely host cell-dependent parasites. Indeed, they must cleverly exploit various compartments of host cells to complete... (Review) Review Authors:Farshid S Garmaroudi, David Marchant, Reid Hendry... Viruses such as coxsackievirus B3 (CVB3) are entirely host cell-dependent parasites. Indeed, they must cleverly exploit various compartments of host cells to complete their life cycle, and consequently launch disease. Evolution has equipped this pico-rna-virus, CVB3, to use different strategies, including CVB3-induced direct damage to host cells followed by a host inflammatory response to CVB3 infection, and cell death to super-additively promote target organ tissue injury, and dysfunction. In this update, the patho-stratagems of CVB3 are explored from molecular, and systems-level approaches. In summarizing recent developments in this field, we focus particularly on mechanisms by which CVB3 can harness different host cell processes including kinases, host cell-killing and cell-eating machineries, matrix metalloproteinases and miRNAs to promote disease. Topics:Enterovirus B, Human; Host-Pathogen Interactions; Humans; Virulence; Virus Replication Human Neonatal Fc Receptor Is the Cellular Uncoating Receptor for Enterovirus B. Cell May 2019 Enterovirus B (EV-B), a major proportion of the genus Enterovirus in the family Picornaviridae, is the causative agent of severe human infectious diseases. Although... Authors:Xin Zhao, Guigen Zhang, Sheng Liu... Enterovirus B (EV-B), a major proportion of the genus Enterovirus in the family Picornaviridae, is the causative agent of severe human infectious diseases. Although cellular receptors for coxsackievirus B in EV-B have been identified, receptors mediating virus entry, especially the uncoating process of echovirusand other EV-B remain obscure. Here, we found that human neonatal Fc receptor (FcRn) is the uncoating receptor for major EV-B. FcRn binds to the virus particles in the "canyon" through its FCGRT subunit. By obtaining multiple cryo-electron microscopy structures at different stages of virus entry at atomic or near-atomic resolution, we deciphered the underlying mechanisms of enterovirus attachment and uncoating. These structures revealed that different from the attachment receptor CD55, binding of FcRn to the virions induces efficient release of "pocket factor" under acidic conditions and initiates the conformational changes in viral particle, providing a structural basis for understanding the mechanisms of enterovirus entry. Topics:Capsid; Cryoelectron Microscopy; Enterovirus; Enterovirus B, Human; Enterovirus Infections; Histocompatibility Antigens Class I; Humans; Models, Molecular; Phylogeny; Receptors, Fc; Virion; Virus Internalization PubMed:31104841 DOI:10.1016/j.cell.2019.04.035 CVB3-Mediated Mitophagy Plays an Important Role in Viral Replication Abrogation of Interferon Pathways. Frontiers in Cellular and Infection... 2021 Coxsackievirus B3 (CVB3) is a common enterovirus that causes systemic inflammatory diseases, such as myocarditis, meningitis, and encephalitis. CVB3 has been... Authors:Soo-Jin Oh, Byung-Kwan Lim, Jeanho Yun... Coxsackievirus B3 (CVB3) is a common enterovirus that causes systemic inflammatory diseases, such as myocarditis, meningitis, and encephalitis. CVB3 has been demonstrated to subvert host cellular responses autophagy to support viral replication in neural stem cells. Mitophagy, a specialized form of autophagy, contributes to mitochondrial quality control degrading damaged mitochondria. Here, we show that CVB3 infection induces mitophagy in human neural progenitor cells, HeLa and H9C2 cardiomyocytes. In particular, CVB3 infection triggers mitochondrial fragmentation, loss of mitochondrial membrane potential, and Parkin/LC3 translocation to the mitochondria. Rapamycin or carbonyl cyanide m-chlorophenyl hydrazone (CCCP) treatment led to increased CVB3 RNA copy number in a dose-dependent manner, suggesting enhanced viral replication autophagy/mitophagy activation, whereas knockdown of PTEN-induced putative kinase protein 1(PINK1) led to impaired mitophagy and subsequent reduction in viral replication. Furthermore, CCCP treatment inhibits the interaction between mitochondrial antiviral signaling protein (MAVS) and TANK-binding kinase 1(TBK1), thus contributing to the abrogation of type I and III interferon (IFN) production, suggesting that mitophagy is essential for the inhibition of interferon signaling. Our findings suggest that CVB3-mediated mitophagy suppresses IFN pathways by promoting fragmentation and subsequent sequestration of mitochondria by autophagosomes. Cytolytic Properties and Genome Analysis of Rigvir Oncolytic Virotherapy Virus and Other Echovirus 7 Isolates. Viruses Mar 2022 Rigvir is a cell-adapted, oncolytic virotherapy enterovirus, which derives from an echovirus 7 (E7) isolate. While it is claimed that Rigvir causes cytolytic infection... Authors:Eero Hietanen, Marika K A Koivu, Petri Susi... Rigvir is a cell-adapted, oncolytic virotherapy enterovirus, which derives from an echovirus7 (E7) isolate. While it is claimed that Rigvir causes cytolytic infection in several cancer cell lines, there is little molecular evidence for its oncolytic and oncotropic potential. Previously, we genome-sequenced Rigvir and five echovirus7 isolates, and those sequences are further analyzed in this paper. A phylogenetic analysis of the full-length data suggested that Rigvir was most distant from the other E7 isolates used in this study, placing Rigvir in its own clade at the root of the phylogeny. Rigvir contained nine unique mutations in the viral capsid proteins VP1-VP4 across the whole data set, with a structural analysis showing six of the mutations concerning residues with surface exposure on the cytoplasmic side of the viral capsid. One of these mutations, E/Q/N162G, was located in the region that forms the contact interface between decay-accelerating factor (DAF) and E7. Rigvir and five other isolates were also subjected to cell infectivity assays performed on eight different cell lines. The used cell lines contained both cancer and non-cancer cell lines for observing Rigvir's claimed properties of being both oncolytic and oncotropic. Infectivity assays showed that Rigvir had no discernable difference in the viruses' oncolytic effect when compared to the Wallace prototype or the four other E7 isolates. Rigvir was also seen infecting non-cancer cell lines, bringing its claimed effect of being oncotropic into question. Thus, we conclude that Rigvir's claim of being an effective treatment against multiple different cancers is not warranted under the evidence presented here. Bioinformatic analyses do not reveal a clear mechanism that could elucidate Rigvir's function at a molecular level, and cell infectivity tests do not show a discernable difference in either the oncolytic or oncotropic effect between Rigvir and other clinical E7 isolates used in the study. Topics:DNA Viruses; Enterovirus B, Human; Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Phylogeny; Viruses, Unclassified First evidence of enterovirus A71 and echovirus 30 in Uruguay and genetic relationship with strains circulating in the South American region. PloS One 2021 Human enteroviruses (EVs) comprise more than 100 types of coxsackievirus, echovirus , poliovirus and numbered enteroviruses, which are mainly transmitted by the... Authors:Andrés Lizasoain, Daiana Mir, Matías Salvo... Human enteroviruses (EVs) comprise more than 100 types of coxsackievirus, echovirus, poliovirus and numbered enteroviruses, which are mainly transmitted by the faecal-oral route leading to diverse diseases such as aseptic meningitis, encephalitis, and acute flaccid paralysis, among others. Since enteroviruses are excreted in faeces, wastewater-based epidemiology approaches are useful to describe EV diversity in a community. In Uruguay, knowledge about enteroviruses is extremely limited. This study assessed the diversity of enteroviruses through Illumina next-generation sequencing of VP1-amplicons obtained by RT-PCR directly applied to viral concentrates of 84 wastewater samples collected in Uruguay during 2011-2012 and 2017-2018. Fifty out of the 84 samples were positive for enteroviruses. There were detected 27 different types belonging to Enterovirus A species (CVA2-A6, A10, A16, EV-A71, A90), Enterovirus B species (CVA9, B1-B5, E1, E6, E11, E14, E21, E30) and Enterovirus C species (CVA1, A13, A19, A22, A24, EV-C99). Enterovirus A71 (EV-A71) and echovirus30 (E30) strains were studied more in depth through phylogenetic analysis, together with some strains previously detected by us in Argentina. Results unveiled that EV-A71 sub-genogroup C2 circulates in both countries at least since 2011-2012, and that the C1-like emerging variant recently entered in Argentina. We also confirmed the circulation of echovirus30 genotypes E and F in Argentina, and reported the detection of genotype E in Uruguay. To the best of our knowledge this is the first report of the EV-A71 C1-like emerging variant in South-America, and the first report of EV-A71 and E30 in Uruguay. Topics:Capsid Proteins; Enterovirus A, Human; Enterovirus B, Human; Enterovirus C, Human; Genetic Linkage; Genotype; Humans; Phylogeny; RNA, Viral; Seasons; South America; Uruguay; Wastewater PubMed:34383835 DOI:10.1371/journal.pone.0255846 Par echovirus es. Journal of Virology Jul 1999 Review Authors:G Stanway, T Hyypiä Origin and evolution analysis and genetic characteristics of echovirus 9 in China. Virology Journal Jun 2022 Echovirus 9 (E9) is associated with a wide variety of diseases and medical conditions, and the clinical symptoms of sporadic cases caused by E9 often are severe. With a... Authors:Fenfen Si, Tianjiao Ji, Dongyan Wang... BACKGROUND Echovirus9 (E9) is associated with a wide variety of diseases and medical conditions, and the clinical symptoms of sporadic cases caused by E9 often are severe. With a high global prevalence, E9 has caused multiple outbreaks worldwide. However, little is known about the genetic and geographic population dynamics of E9. METHOD A total of 131 VP1 gene sequences, including15 generated in this study and 116 obtained from GenBank, were used to coestimate time-resolved phylogenies to infer viral evolution and transmission in worldwide. Overlapping fragments representing whole genomes were amplified by reverse transcription polymerase chain reaction (RT-PCR) using specific primers. Then, we reported the genetic characteristics of fifteen E9 strains in the Chinese Mainland. Similarity plots and bootscanning analysis were used to determine recombination patterns of E9. RESULTS The estimated mean evolutionary rate of global E9 VP1 gene was 4.278 × 10 substitutions per site per year (95% confidence interval [CI], 3.822 × 10/site/year to 4.710 × 10/site/year), and the common ancestor of E9 likely emerged around 1868 (95% CI, 1840 to 1892). The full-length genomic sequences of the fifteen E9 strains showed 76.9-79.6% nucleotide identity and 95.3-95.9% amino acid identity with E9 Barty strain. 11 of 15 E9 whole genome sequence present four recombination patterns, and E9 recombinants have extensive genetic exchanges in the 2C and P3 regions with other Enterovirus B (EV-B) circulated in China. Four of six E9 strains were temperature sensitive, and two were temperature resistant, and a comparative genomics analysis suggested that 411, 865 and 867 amino acid substitution in the P1 region was related to temperature sensitivity. CONCLUSION This study highlights a persistent transmission network of E9 in worldwide, provides valuable information regarding the molecular epidemiology of E9. Topics:China; Echovirus 9; Enterovirus B, Human; Evolution, Molecular; Genome, Viral; Phylogeny; Recombination, Genetic Echovirus induces autophagy to promote viral replication regulating mTOR/ULK1 signaling pathway. Frontiers in Immunology 2023 Among enteroviruses, echovirus can cause severe illnesses in neonates or infants, with high morbidity and mortality. Autophagy, a central component of host defense... Authors:Chunchen Wu, Luzhi Zeng, Wenfu Yi... Among enteroviruses, echoviruscan cause severe illnesses in neonates or infants, with high morbidity and mortality. Autophagy, a central component of host defense mechanisms, can function against diverse infections. In the present study, we investigated the interplay between echovirusand autophagy. We demonstrated that echovirusinfection increases LC3-II expression dose-dependently, accompanied by an increased intracellular LC3 puncta level. In addition, echovirusinfection induces the formation of autophagosome. These results suggest that echovirusinfection induces autophagy machinery. Furthermore, phosphorylated mTOR and ULK1 were both decreased upon echovirusinfection. In contrast, both levels of the vacuolar protein sorting 34 (VPS34) and Beclin-1, the downstream molecules which play essential roles in promoting the formation of autophagic vesicles, increased upon virus infection. These results imply that the signaling pathways involved in autophagosome formation were activated by echovirusinfection. Moreover, induction of autophagy promotes echovirusreplication and viral protein VP1 expression, while inhibition of autophagy impairs VP1 expression. Our findings suggest that autophagy can be induced by echovirusinfection regulating mTOR/ULK1 signaling pathway and exhibits a proviral function, revealing the potential role of autophagy in echovirusinfection. PubMed:37114059 DOI:10.3389/fimmu.2023.1162208 Human FcRn Is a Two-in-One Attachment-Uncoating Receptor for Echovirus 18. MBio Aug 2022 Virus-receptor interactions determine viral host range and tissue tropism. CD55 and human neonatal Fc receptor (FcRn) were found to be the binding and uncoating... Authors:Xiangpeng Chen, Xiao Qu, Congcong Liu... Virus-receptor interactions determine viral host range and tissue tropism. CD55 and human neonatal Fc receptor (FcRn) were found to be the binding and uncoating receptors for some of the echovirus-related enterovirus species B serotypes in our previous study. Echovirus18 (E18), as a member of enterovirus species B, is a significant causative agent of aseptic meningitis and viral encephalitis in children. However, it does not use CD55 as a critical host factor. We conducted CRISPR/Cas9 knockout screening to determine the receptors and entry mechanisms and identified FcRn working as a dual-function receptor for E18. Knockout of and , which encode the two subunits of FcRn, prevented infection by E18 and other echoviruses in the same physiological cluster. We then elucidated the underlying molecular mechanism of receptor recognition by E18 using cryogenic electron microscopy. The binding of the FCGRT subunit to the canyon region rotates the residues around the pocket, triggering the release of the pocket factor as observed for other enterovirus species B members. E18 is a member of enterovirus species B. As one of the most common enterovirus serotypes in nonpolio enterovirus detection, it easily infects children and causes various clinical symptoms. Aseptic meningitis and viral encephalitis are the most commonly reported syndromes associated with E18. No effective antiviral drugs or approved vaccines are available. Previous studies showed that CD55 and FcRn were the binding and uncoating receptors for some echoviruses. However, we found that CD55 is not the critical host factor for E18. Thus, we want to determine the receptors and elucidate the entry mechanism of E18. Our findings reveal that FcRn is a two-in-one attachment-uncoating receptor for E18. Topics:CD55 Antigens; Child; Encephalitis, Viral; Enterovirus; Enterovirus B, Human; Enterovirus Infections; Humans; Infant, Newborn; Meningitis, Aseptic PubMed:35862785 DOI:10.1128/mbio.01166-22 Human enteroviral infection in fibromyalgia: a case-control blinded study. Revista Da Associacao Medica Brasileira... Jul 2022 This study aimed to test the hypothesis that fibromyalgia is associated with a human enteroviral infection. Authors:Basant K Puri, Gary S Lee, Armin Schwarzbach... OBJECTIVE This study aimed to test the hypothesis that fibromyalgia is associated with a human enteroviral infection. METHODS Venous peripheral blood samples from 27 patients fulfilling the American College of Rheumatology revised diagnostic criteria for fibromyalgia and from 26 age- and sex-matched controls, who underwent immunofluorescence assays for coxsackievirus A7 IgG, coxsackievirus B1 IgG, coxsackievirus A7 IgA, coxsackievirus B1 IgA, echovirusIgG, and echovirusIgA. These immunological tests were performed blind to group status. RESULTS There were no significant differences between the patient and control groups in respect of positive results for coxsackievirus A7 IgG (p=0.467), coxsackievirus B1 IgG (p=0.491), coxsackievirus A7 IgA (p=0.586), coxsackievirus B1 IgA (p=0.467), echovirusIgG (p=0.236), and echovirusIgA (p=1). CONCLUSIONS The results of this systematic study do not support the hypothesis that fibromyalgia is associated with infection by a human enterovirus. PubMed:35830017 DOI:10.1590/1806-9282.20220139
https://openmd.com/journals?q=echovirus
REPUBLIC ACT NO. 10430 - AN ACT SEPARATING THE HALIAP NATIONAL HIGH SCHOOL — AMOWEG ANNEX IN BARANGAY CAMANDAG, MUNICIPALITY OF ASIPULO, PROVINCE OF IFUGAO FROM THE HALIAP NATIONAL HIGH SCHOOL, CONVERTING IT INTO AN INDEPENDENT NATIONAL HIGH SCHOOL TO BE KNOWN AS NATCAK NATIONAL HIGH SCHOOL AND APPROPRIATING FUNDS THEREFOR - Supreme Court E-Library SECOND DIVISION [ A.M. No. MTJ-10-1772. December 05, 2012 ] DR. JANOS B. VIZCAYNO, COMPLAINANT,VS. JUDGE JASPER JESSE G. DACANAY, IN HIS OFFICIAL CAPACITY AS THE PRESIDING JUDGE OF THE MUNICIPAL CIRCUIT TRIAL COURT OF LILOAN-COMPOSTELA, CEBU, RESPONDENT. D E C I S I O N CARPIO, ACTING C.J.: Dr. Janos B. Vizcayno (Dr. Vizcayno) filed the present administrative complaint against Judge Jasper Jesse G. Dacanay (Judge Dacanay), Presiding Judge of the 7 th Municipal Circuit Trial Court (MCTC), Liloan-Compostela, Cebu for Gross Ignorance of the Law, Abuse of Authority, Manifest Partiality and Delay relative to Civil Case No. 650-R entitled “ Deodito R. Pulido, et al. v. Janos B. Vizcayno .” The Office of the Court Administrator (OCA) recommended that Judge Dacanay be found guilty of committing conduct prejudicial to the best interest of the service and be imposed a fine of P25,000 with a stern warning that a repetition of the same offense shall be dealt with more severely. The OCA also recommended payment by Judge Dacanay of the fine of P11,000 imposed on him in Cabahug v. Dacanay, A.M. No. MTJ-03-1480, dated 10 September 2003, within 15 days from notice. The Facts The memorandum from the OCA narrated the facts as follows: In a VERIFIED ADMINISTRATIVE COMPLAINTdated September 25, 2009 (with enclosures), Dr. Janos B. Vizcayno (complainant) charges Judge Jasper Jesse G. Dacanay (respondent judge) of the Municipal Circuit Trial Court (MCTC), Liloan-Compostela, Cebu, with Gross Ignorance of the Law, Abuse of Authority, Manifest Partiality and Delay. Complainant is the defendant in a civil complaint for forcible entry and damages, docketed as Civil Case No. 650-R entitled, “ Deodito R. Pulido, et al. v. Janos B. Vizcayno,” filed before the MCTC, Liloan-Compostela, Cebu. On March 31, 2009, respondent judge (together with the plaintiff who allegedly fraternized with and entertained him), without notice to complainant, conducted an ex-parteocular inspection on the property subject of the civil action. Complainant only learned of the ocular inspection through neighbors Norma Tan, Herminia Domain, and Fernan Baguio. Feeling aggrieved, complainant filed a motion for inhibition of respondent judge to hear the civil action. The motion was set for hearing on April 24, 2009. However, respondent judge opted to proceed with the hearing of the case on May 29, 2009. In a heated argument, complainant and his counsel moved that the motion for inhibition be first resolved, but respondent judge ignored the same. Complainant argues that respondent judge committed a gross violation of the due process clause protected under the Constitution when the latter conducted an ex-parteocular inspection without notice to him. Also, respondent judge failed to live up to that norm of conduct that “judges should not only be impartial but should also appear impartial,” when he conducted the ocular inspection together with the plaintiffs. Such act, complainant claims, is highly improper and grossly inappropriate, and is a violation of Canon 2 of the New Code of Judicial Conduct for the Philippine Judiciary (New Code of Judicial Conduct) which provides that “a judge should avoid impropriety and the appearance of impropriety in all activities.” In his COMMENTdated November 24, 2009 (with enclosures), respondent judge, among others, explains that he went to the subject property with his utility personnel only to conduct his own personal investigation on the case to determine whether the disputed construction therein really exists, and to help him in suggesting to the parties to settle the case amicably. At the time of his personal inspection of the property, no one from either the plaintiffs or the defendant ever entertained him. What he did was to make a mere assessment of the property for his personal satisfaction, in all good faith and without fraud, dishonesty, or malicious intent. Respondent judge further stresses that it is still premature for complainant and his counsel to conclude that he is biased against them, as the case is still then in the preliminary stage wherein there is still a possibility of amicable settlement. Likewise, respondent judge maintains that complainant and his counsel should have waited for the finality of the denial of the motion for his inhibition. Citing the case of Roxas v. Eugenio, Jr., respondent judge argues that an administrative complaint against a judge cannot be pursued simultaneously with the judicial remedies accorded to parties aggrieved by an erroneous order or judgment, as administrative remedies are neither alternative nor cumulative to judicial review where such review is available to aggrieved parties and the same has not been resolved with finality. Respondent judge asserts that he cannot be accused of gross ignorance of the law, abuse of authority, manifest partiality, and delay, as he made the inspection in good faith and with noble intentions. Citing Lumbos v. Baliguat, he argues that to constitute gross ignorance of the law, it is not enough that the subject decision, order or actuation of the judge in the performance of his official duties is contrary to existing law and jurisprudence, but it must be moved by bad faith, fraud, dishonesty or corruption. He likewise denies incurring delay, averring that the records of the case easily reveal that it was complainant and his counsel who, for several instances, failed to appear during the scheduled hearings of the case. Respondent judge intimates that it was Atty. Gabriel Cañete (complainant’s counsel) who actually filed the instant administrative complaint against him. He states that complainant’s counsel got embarrassed before his client when, during the May 29, 2009 hearing, Atty. Carlos Allan Cardenas (opposing counsel for plaintiff) argued that the motion for inhibition was a mere scrap of paper for his failure to state thereat his Mandatory Continuing Legal Education (MCLE) number and the date of issue of the requisite certificate of compliance with respect thereto. Chagrined with what happened, complainant’s counsel threatened respondent judge that he was going to file several charges against him. Respondent judge states that the instant administrative case stemmed from two (2) events when he went to the area where the subject property is situated to without notifying the parties while the case is pending before his sala, and when he allegedly ignored the motion to inhibit himself from handling the case filed by the complainant, the defendant in Civil Case No. 650-R. When complainant’s counsel filed the Motion for Inhibition, he did not indicate his MCLE compliance. Thus, respondent judge did not inhibit from handling the case. Under Bar Matter No. 1922 (2009), the failure of a practicing lawyer to disclose the number and date of issue of his MCLE Certificate of Compliance or Certificate of Exemption in his pleadings in court “ would cause the dismissal of the case and the expunction of the pleadings from the records.” Complainant’s counsel might have felt that he was being forced out from the case, which might have made him angry. Nonetheless, respondent judge eventually inhibited from handling the case on March 10, 2010. From the time the civil case was filed in 2008 up to the time when he (respondent judge) inhibited himself on March 10, 2010, complainant cannot categorically say that he was placed at a disadvantage because no ruling was issued by the respondent judge. [1](Emphasis in the original) Dr. Vizcayno, through counsels, filed a Verified Reply [2] dated 14 December 2009. Dr. Vizcayno noted that Judge Dacanay’s Comment lacked verification as well as Mandatory Continuing Legal Education (MCLE) Compliance Number and asked for the expunction of the Comment from the case records. Dr. Vizcayno further stated that Judge Dacanay had shown undue preference to the opposing party, even making an off-the-record comment during the hearing: “ Dako man kayo na imong yuta, doctor! Kaning mga reklamante ba, pobre ni sila !” (“Your lot is very big, doctor! These complainants, they are poor!”) [3] The OCA’s Ruling On 10 March 2010, the OCA, under Court Administrator Jose Midas P. Marquez and Deputy Court Administrator Jesus Edwin A. Villasor, issued its Evaluation and Recommendation on the present complaint. The OCA held that Dr. Vizcayno and Judge Dacanay should be given the opportunity to adduce and establish their respective evidence on Judge Dacanay’s alleged impropriety and denial of due process. The OCA’s recommendation reads as follows: RECOMMENDATION: Respectfully submitted, for the consideration of the Honorable Court, is our recommendation that the instant administrative complaint against Judge Jasper Jesse G. Dacanayof the Municipal Circuit Trial Court, Liloan-Compostela, Cebu, be REDOCKETEDas a regular administrative case; and the same be REFERREDto the Executive Judge of the Regional Trial Court, Mandaue City, for investigation, report and recommendationwithin sixty (60) days from receipt of the records. [4](Emphasis in the original) This Court, in a Resolution [5] dated 17 November 2010, re-docketed administrative complaint OCA-IPI No. 09-2203-MTJ as regular administrative matter A.M. No. MTJ-10-1772 and referred the matter to the Executive Judge of the Regional Trial Court of Mandaue City for investigation, report, and recommendation. Executive Judge Marilyn Lagura-Yap (Judge Lagura-Yap), in her Partial Report [6] dated 5 July 2011, indicated that the investigation is already completed and ready for her resolution, findings, and recommendation. She asked for another 60 days to submit her complete report. In her Final Report [7] dated 22 September 2011, Judge Lagura-Yap stated that Judge Dacanay failed to show that his act of inspecting the property subject of Civil Case No. 650-R was proper. Although there was insufficient evidence to conclude that Judge Dacanay acted with bad faith, fraud, dishonesty, or corruption, there is still no doubt that the inspection of the property was done in the absence of Dr. Vizcayno and his counsels. Hence, Judge Dacanay’s lack of prudence merited liability for conduct prejudicial to the best interest of the service and not for gross ignorance of the law. Moreover, Judge Lagura-Yap found that Judge Dacanay did not incur delay in the resolution of the Motion for Inhibition dated 13 April 2009 because the motion did not comply with the requirements of Bar Matter No. 1922. [8] Judge Dacanay’s Order dated 30 September 2009 was issued within the required 90-day period for resolution because the 13 April 2009 Motion for Inhibition was submitted for resolution only on 19 August 2009. Judge Dacanay inhibited from Civil Case No. 650-R on 10 March 2010. Judge Lagura-Yap’s recommendation reads as follows: WHEREFORE, the undersigned Executive Judge respectfully submits the following recommendations to the Honorable Supreme Court, for consideration, to wit: a. To find the respondent judge, Judge Jasper Jesse G. Dacanay, liable for Conduct Prejudicial to the Best Interest of the Service; and b. To reprimand the respondent judge, Judge Japer [sic] Jesse G. Dacanay, with a warning that a repetition of the same or similar act in the future shall be dealt with severely. [9] In its Memorandum [10] dated 27 February 2012, the OCA found no reason to deviate from the findings of Judge Lagura-Yap but revised her recommendation as to the penalty. The OCA’s recommendation reads as follows: PREMISES CONSIDERED, for conducting an ocular inspection without informing the parties, we find respondent, Judge Jasper Jesse Dacanay, guilty of conduct prejudicial to the best interest of the servicein violation of Sec. 1, Canon 4 of The New Code of Judicial Conduct, which is considered a serious charge. x x x x Considering that respondent judge has been previously imposed a fine of eleven thousand pesos (P11,000) in A.M. No. MTJ-03-1480 dated September 10, 2003 which has not been paid yet, we respectfully recommend that Judge Jasper Jesse G. Dacanay be: 1. found GUILTYof committing conduct prejudicial to the best interest of the service in violation of Canon 4 of The New Code of Judicial Conduct for the Philippine Judiciary, and meted or imposed a FINEof twenty-five thousand pesos (P25,000.00) to be paid together with the FINEof eleven thousand pesos (P11,000.00) imposed in A.M. No. MTJ-03-1480, dated September 10, 2003, within fifteen (15) days from notice; and 2. STERNLY WARNEDthat a repetition of the same or similar offense shall be dealt with more severely. [11](Emphasis in the original) The Issues The issues which we consider for our resolution are: (1) whether Judge Dacanay should be held administratively liable for conduct prejudicial to the best interest of the service for conducting an ocular inspection without informing the parties, and (2) whether Judge Dacanay should be held administratively liable for the delay in the resolution of the Motion for Inhibition. The Court’s Ruling We affirm the recommendation of the OCA. Conduct prejudicialto the best interest of the service Section 1, Canon 4 of the New Code of Judicial Conduct [12] states that “[j]udges shall avoid impropriety and the appearance of impropriety in all of their activities.” From the OCA’s recommendation, we glean the following pertinent facts: (1) On 31 March 2009, Judge Dacanay went to Catarman, Liloan, Cebu to personally see Lot 1529-P, subject of the forcible entry and damages in Civil Case No. 650-R pending in his court; and (2) Judge Dacanay inspected the property in the presence of the plaintiffs and in the absence of Dr. Vizcayno and his counsels. Judge Dacanay’s actuations, although not necessarily attended with bad faith, fraud, dishonesty or corruption, were precipitate and imprudent. The pre-trial stage has not begun. There was failure to inform all parties about the ocular inspection. Judge Dacanay issued an Order dated 31 March 2009, the same day as the ocular inspection, resetting the preliminary conference on 29 May 2009, yet the order did not contain any notice to the parties of Judge Dacanay’s ocular inspection. We have previously ruled that an ocular inspection without notice to nor presence of the parties is highly improper. [13] Good and noble intentions notwithstanding, Judge Dacanay’s actuations gave an appearance of impropriety. His behavior diminished public confidence in the integrity and impartiality of the judiciary. We have repeatedly stressed that all those involved in the dispensation of justice, from the presiding judge to the lowliest clerk, must always be beyond reproach. Their conduct must, at all times, be circumscribed with the heavy burden of responsibility free from any suspicion that may taint the judiciary. As the administration of justice is a sacred task, this Court condemns and cannot countenance any act on the part of court personnel that would violate the norm of public accountability and diminish or even just tend to diminish the faith of the people in the judiciary. [14] Judges should be extra prudent in associating with litigants and counsel appearing before them to avoid even a mere perception of possible bias or partiality. Judges need not live in seclusion, nor avoid all social interrelations. When time and work commitments permit, judges may continue to relate to members of the bar in worthwhile endeavors in such fields of interest as are in keeping with the noble objectives of the legal profession. However, in pending or prospective litigations before them, judges should be scrupulously careful to avoid anything that may tend to awaken the suspicion that their personal, social or sundry relations could influence their objectivity. Not only must judges possess proficiency in law, they must also act and behave in such manner that would assure litigants and their counsel of the judges’ competence, integrity and independence. [15] Gross misconduct consisting of violations of the Code of Judicial Conduct is a serious charge. Section 11(A) of Rule 140, as amended, [16] provides: SEC. 11. Sanctions. – A. If the respondent is guilty of a serious charge, any of the following sanctions may be imposed: 1. Dismissal from the service, forfeiture of all or part of the benefits as the Court may determine, and disqualification from reinstatement or appointment to any public office, including government-owned or controlled corporations. Provided, however, that the forfeiture of benefits shall in no case include accrued leave credits; 2. Suspension from office without salary and other benefits for more than three (3) but not exceeding six (6) months; or 3. A fine of more than P20,000.00 but not exceeding P40,000.00. Delay in the resolutionof the motion for inhibition We see no reason to deviate from the OCA’s findings, which stated thus: x x x [R]espondent judge in his Order dated September 30, 2009, expunged from the records the said motion because the counsel of complainant failed to indicate the date of issue and number of his MCLE Compliance as required by Bar Matter No. 1922. Said Order may therefore be considered as a denial of the Motion for Inhibition, which was issued within the 90-day period to resolve a motion. The failure of respondent judge to resolve the Motion for Reconsideration of the Order dated September 30, 2009, which was filed on October 21, 2009, could not be attributable to him because on November 9, 2009, he received a directive from the Office of the Court Administrator to comment on the instant complaint. Since an order was issued on September 30, 2009 to expunge the Motion for Inhibition from the record of the case, and that on March 30, 2010, he eventually inhibited from the case, there was no unreasonable delay on the part of the respondent judge. [17] Judge Dacanay issued his Orders well within the three-month period imposed by Section 15, Article VIII of the Constitution. [18] Judge Dacanay’s ocular inspection without notice to the parties constitutes conduct prejudicial to the best interest of the service, in violation of Canon 4 of the New Code of Judicial Conduct for the Philippine Judiciary. However, in view of the still unpaid fine of P11,000 in the 10 September 2003 case of Cabahug v. Dacanay , A.M. No. MTJ-03-1480, for which Judge Dacanay was found guilty of undue delay in resolving a motion, it would seem that Judge Dacanay has a cavalier attitude in the performance of his judicial duties. For this reason, we increase the fine recommended by the OCA in the present case from P25,000 to P30,000. Judge Dacanay would well be reminded to behave at all times in a way that will promote public confidence in the integrity and impartiality of the judiciary. WHEREFORE , respondent Judge Jasper Jesse G. Dacanay is found guilty of committing conduct prejudicial to the best interest of the service in violation of Canon 4 of the New Code of Judicial Conduct for the Philippine Judiciary and is imposed a fine of ?30,000. Judge Dacanay is directed to pay, within 15 days from notice of this Decision, this fine together with the fine imposed in A.M. No. MTJ-03-1480. Judge Dacanay is sternly warned that a repetition of the same or similar offense shall be dealt with more severely. SO ORDERED. Brion, Del Castillo, Abad, ** and Perlas-Bernabe, JJ ., concur. * Per Special Order No. 1384 dated 4 December 2012. ** Designated additional member per Raffle dated 3 December 2012. [1] Rollo , pp. 293-295. [2] Id. at 122-130. [3] Id. at 164. [4] Id. at 165. [5] Id. at 169. [6] Id. at 196. [7] Id. at 204-214. [8] Bar Matter No. 1922 required “practicing members of the bar to indicate in all pleadings filed before the courts or quasi-judicial bodies, the number and date of issue of their MCLE Certificate of Compliance or Certificate of Exemption, as may be applicable, for the immediately preceding compliance period. Failure to disclose the required information would cause the dismissal of the case and the expunction of the pleadings from the records.” [9] Rollo , p. 214. [10] Id. at 293-300. [11] Id. at 299-300. [12] The New Code of Judicial Conduct for the Philippine Judiciary took effect on 1 June 2004, following its publication not later than 15 May 2004 in two newspapers of large circulation in the Philippines. [13] Adan v. Judge Abucejo-Luzano, 391 Phil. 853 (2000). See Justice Claudio Teehankee’s Separate Opinion in In re: Rafael C. Climaco, 154 Phil. 105, 124 (1974). [14] Chua v. Sorio , A.M. No. P-07-2409, 7 April 2010, 617 SCRA 474. [15] Atty. Molina v. Judge Paz , 462 Phil. 620, 630 (2003) citing Sibayan-Joaquin v. Judge Javellana, 420 Phil. 584 (2001). [16] The amendments to Rule 140, found in A.M. No. 01-8-10, took effect on 1 October 2001 following their publication in two newspapers of general circulation on or before 15 September 2001. [17] Rollo, pp. 298-299. [18] Sec. 15. (1) All cases or matters filed after the effectivity of this Constitution must be decided or resolved within x x x three months [from date of submission] for all other lower courts. (2) A case or matter shall be deemed submitted for decision or resolution upon the filing of the last pleading, brief or memorandum required by the Rules of Court or by the court itself.
https://elibrary.judiciary.gov.ph/thebookshelf/showdocs/21/55385
Full text of The Employment Situation : August 1994 | FRASER | St. Louis Fed Full text of The Employment Situation : August 1994 TEXT Table A-1. Employment status of the civilian population by sex and age Table A-2. Employment status of the civilian population by race, sex, age, and Hispanic origin Table A-3. Selected employment indicators Table A-4. Selected unemployment indicators, seasonally adjusted Table A-5. Duration of unemployment Table A-6. Reason for unemployment Table A-7. Unemployed persons by age and sex, seasonally adjusted Table A-8. Persons not in the labor force and multiple jobholders by sex, not seasonally adjusted Table A-9. Employment status of the civilian population for eleven large States Table B-1. Employees on nonfarm payrolls by industry Table B-1. Employees on nonfarm payrolls by industry Table B-2. Average weekly hours of production or nonsupervisory workers on private nonfarm payrolls by industry Table B-3. Average hourly and weekly earnings of production or nonsupervisory workers on private nonfarm Table B-4. Average hourly earnings of production or nonsupervisory workers on private nonfarm Table B-5. Indexes of aggregate weekly hours of production or nonsupervisory workers on private nonfarm payrolls Table B-6. Diffusion indexes of employment change, seasonally adjusted Technical Information: Household Data National State Establishment Data Media Contact: USDL 94-430 (202) 606-6378 606-6373 606-6392 606-6555 606-5902 THE EMPLOYMENT SITUATION: Transmission of material in this release is embargoed until 8:30 A.M. (EDT), Friday, September 2, 1994 AUGUST 1994 Employment continued to rise in August and the unemployment rate was unchanged, the Bureau of Labor Statistics of the U.S. Department of Labor reported today. Nonfarm payroll employment increased by 179,000, and the unemployment rate held at 6.1 percent. Unemployment (Household Survey Data) The number of unemployed persons, at 8.0 million in August, and the unemployment rate, 6.1 percent, were the same as in the prior month. Both measures had declined from January to May but have shown little change since then. (See table A-1.) There also was little movement in joblessness among the major labor force groups in August. The unemployment rates for adult men (5.4 percent), adult women (5.4 percent), teenagers (17.5 percent), whites (5.3 percent), blacks (11.5 percent), and Hispanics (10.2 percent) all were essentially unchanged over the month. (See tables A-1 and A-2.) The number of persons who were unemployed because they had lost their last jobs or completed temporary jobs, at 3.8 million in August, has decreased by 629,000 since January, accounting for most of the overall drop in unemployment. (See table A-6.) Total Employment and the Labor Force (Household Survey Data) Total employment showed an increase of 714,000 in August, seasonally adjusted, bringing the increase since January to 1.2 million. Nonfarm payroll employment has increased by 2.1 million over this same period. ---------------------------------------------------------------| Data from the household survey for 1994 are not directly | |comparable with data for 1993 and earlier years because of the | |implementation in January 1994 of a major redesign of the survey| |and the introduction of 1990 census-based population controls, | |adjusted for the estimated undercount. In addition, the 1994 | |data may be affected by the transition to the redesigned survey.| |For example, seasonal factors, of necessity, have been computed | |based on data collected in the survey prior to its revision, | |and these factors may not fully capture the pattern of | |seasonality in the current data. Hence, over-the-month | |comparisons of unemployment and other labor force estimates | |should be made with caution. For additional information on | |the redesign, see "Revisions in the Current Population Survey | |Effective January 1994" in the February 1994 issue of | |Employment and Earnings. | ---------------------------------------------------------------- - 2 Table A. Major indicators of labor market activity, seasonally adjusted (Numbers in thousands) ___________________________________________________________________________ | Quarterly | Monthly data | | averages | | |_________________|__________________________|JulyCategory | 1994 | 1994 |August |_________________|__________________________|change | I | II | June | July | August | ______________________|________|________|________|________|________|_______ HOUSEHOLD DATA | Labor force status |____________________________________________________ Civilian labor force..| 130,674| 130,589| 130,248| 130,457| 131,189| 732 Employment..........| 122,088| 122,547| 122,430| 122,452| 123,166| 714 Unemployment........| 8,586| 8,043| 7,817| 8,005| 8,023| 18 Not in labor force....| 65,411| 65,933| 66,445| 66,403| 65,854| -549 |________|________|________|________|________|_______ | Unemployment rates |____________________________________________________ All workers...........| 6.6| 6.2| 6.0| 6.1| 6.1| .0 Adult men...........| 5.9| 5.4| 5.3| 5.6| 5.4| -0.2 Adult women.........| 5.9| 5.4| 5.4| 5.3| 5.4| .1 Teenagers...........| 18.0| 18.4| 16.9| 17.7| 17.5| -.2 White...............| 5.7| 5.4| 5.3| 5.4| 5.3| -.1 Black...............| 12.8| 11.5| 11.2| 11.2| 11.5| .3 Hispanic origin.....| 10.2| 10.2| 10.3| 10.1| 10.2| .1 |________|________|________|________|________|_______ ESTABLISHMENT DATA | Employment |____________________________________________________ Nonfarm employment....| 111,976| 112,995| 113,334|p113,585|p113,764| p179 Goods-producing 1/..| 23,350| 23,534| 23,576| p23,595| p23,620| p25 Construction......| 4,765| 4,909| 4,927| p4,949| p4,943| p-6 Manufacturing.....| 17,973| 18,020| 18,044| p18,045| p18,077| p32 Service-producing 1/| 88,626| 89,461| 89,758| p89,990| p90,144| p154 Retail trade......| 19,972| 20,190| 20,279| p20,379| p20,379| p0 Services..........| 31,153| 31,620| 31,765| p31,897| p32,020| p123 Government........| 18,919| 19,004| 19,018| p19,009| p19,013| p4 |________|________|________|________|________|_______ | Hours of work 2/ |____________________________________________________ Total private.........| 34.6| 34.7| 34.6| p34.7| p34.5| p-0.2 Manufacturing.......| 41.7| 42.1| 42.0| p41.9| p42.0| p.1 Overtime..........| 4.6| 4.7| 4.7| p4.6| p4.8| p.2 |________|________|________|________|________|_______ | Earnings 2/ |____________________________________________________ Avg. hourly earnings, | | | | | | total private.......| $11.02| $11.07| $11.08| p$11.11| p$11.13| p$0.02 Avg. weekly earnings, | | | | | | total private.......| 381.04| 384.25| 383.37| p385.52| p383.99| p-1.53 ______________________|________|________|________|________|________|_______ 1/ Includes other industries, not shown separately. 2/ Data relate to private production or nonsupervisory workers. p = preliminary. NOTE: Household data for 1994 are not directly comparable with data for 1993 and earlier years. For additional information, see "Revisions in the Current Population Survey Effective January 1994" in the February 1994 issue of Employment and Earnings. - 3 The employment-to-population ratio increased by 0.3 percentage point in August to 62.5 percent, a return to the May level. (See table A-1.) The number of persons employed part time for economic reasons, at 4.3 million in August, has fallen by nearly 900,000 since January. Part-time employment for noneconomic (voluntary) reasons has risen over the period to 18.2 million. (See table A-3.) The number of workers holding two or more jobs in August totaled 7.1 million (not seasonally adjusted), or 5.7 percent of all employed persons (table A-8). The majority of these workers hold full-time jobs and moonlight in part-time jobs. The civilian labor force increased by 732,000 in August, after exhibiting no growth from January to July. With this increase, the proportion of the population in the labor force rose 0.3 percentage point over the month to 66.6 percent. (See table A-1.) Discouraged Workers (Household Survey Data) The number of discouraged workers--persons who want jobs but have given up searching because they do not think they could find work--was 489,000 in August (not seasonally adjusted). An additional 1.2 million former jobseekers reported that they would like to have a job and were available to work in August, but were not currently looking for reasons such as family obligations. (See table A-8.) Industry Payroll Employment (Establishment Survey Data) Total nonfarm payroll employment continued to rise in August, increasing by 179,000 to a level of 113.8 million, after seasonal adjustment. The number of payroll jobs has expanded by 2.1 million since January, an average gain of 293,000 a month. (See table B-1.) Manufacturing employment grew by 32,000 in August. Factory jobs have been on the rise since last September, with the gain totaling 143,000. Most of the jobs added over the month were in the durable goods sector. Motor vehicles employment rose by 10,000 and fabricated metals by 9,000 (mostly in auto stampings), reflecting strength in the auto industry and the reopening of plants that were closed for retooling. There also were sizable employment increases in electrical equipment and industrial machinery. Within the nondurable goods sector, gains continued in printing and publishing, and there were small increases in apparel and tobacco products. Construction employment held about steady in August, following 13 consecutive months of growth during which construction industry payrolls were augmented by more than 300,000 workers. A decline of 9,000 in heavy construction employment in August reversed an identical increase in the prior month. The services industry continued its pattern of solid job growth, adding 123,000 workers in August. The gains took place largely in business (53,000), health (38,000), and social services (22,000). The increase in business services included an unusually small gain in personnel supply-15,000--compared with a monthly average of 37,000 over the prior year. The large gain in health services payrolls included a rebound in hospital employment. In contrast, there were job losses in hotels and in amusement and recreation services. - 4 Retail trade employment was essentially flat in August, following 2 months of robust growth. Job gains in automobile dealerships and service stations, food stores, and furniture and home furnishings stores were offset by a 29,000 loss in eating and drinking places, which had added 133,000 jobs between May and July. Wholesale trade employment rose by 18,000 in August. Real estate added 6,000 jobs, continuing its 2-year uptrend. Within finance, jobs continued to decline in nondepository institutions (primarily in mortgage banking), while growth was sustained in security brokers and other types of investment companies. There was little change over the month in transportation and public utilities and in government. Federal government employment has held steady in the last 2 months, after declining by 124,000 since its April 1992 peak. Weekly Hours (Establishment Survey Data) The average workweek for production or nonsupervisory workers on private nonfarm payrolls declined by 0.2 hour in August to 34.5 hours, seasonally adjusted. The manufacturing workweek edged up 0.1 hour to 42.0 hours, after falling 0.1 hour in each of the prior 3 months. Factory overtime increased by 0.2 hour over the month to an alltime high of 4.8 hours (also reached in April), as auto manufacturers resumed their heavy production schedules. (See table B-2.) The index of aggregate weekly hours of private production or nonsupervisory workers on nonfarm payrolls declined 0.2 percent to 129.1 (1982=100) in August, resulting from the decline in the workweek. The manufacturing index rose 0.6 percent to 105.7, seasonally adjusted. (See table B-5.) Hourly and Weekly Earnings (Establishment Survey Data) Average hourly earnings of private production or nonsupervisory workers on nonfarm payrolls rose 0.2 percent in August to $11.13, after seasonal adjustment. Average weekly earnings declined by 0.4 percent to $383.99, because of the shorter workweek. Over the year, average hourly earnings and average weekly earnings increased by 2.5 and 2.2 percent, respectively. (See table B-3.) _________________________ The Employment Situation for September 1994 will be released on Friday, October 7, at 8:30 A.M. (EDT). HOUSEHOLD DATA Table A-1. Employment status of the civilian population by sex and age (Numbers in thousands) ___________________________________________________________________________________________________________________________________ | | | | 1/ Not seasonally adjusted Seasonally adjusted | | __________________________ _____________________________________________________ Employment status, sex, and age | | | | | | | | | | Aug. | Jul. | Aug. | Aug. | Apr. | May | June | July | Aug. | 1993 |19942/ | 1994 | 1993 |19942/ | 1994 | 1994 | 1994 | 1994 | | | | | | | | | ___________________________________________________________________________________________________________________________________ | | | | | | | | | | | | | | | | | | TOTAL | | | | | | | | | Civilian noninstitutional population..............| 193,793| 196,859| 197,043| 193,793| 196,363| 196,510| 196,693| 196,859| 197,043 Civilian labor force............................| 129,472| 132,783| 132,361| 128,334| 130,747| 130,774| 130,248| 130,457| 131,189 Participation rate........................| 66.8| 67.5| 67.2| 66.2| 66.6| 66.5| 66.2| 66.3| 66.6 Employed......................................| 121,002| 124,503| 124,493| 119,692| 122,338| 122,872| 122,430| 122,452| 123,166 Employment-population ratio...............| 62.4| 63.2| 63.2| 61.8| 62.3| 62.5| 62.2| 62.2| 62.5 Agriculture.................................| 3,295| 3,732| 3,780| 3,005| 3,459| 3,435| 3,235| 3,278| 3,444 Nonagricultural industries..................| 117,707| 120,770| 120,713| 116,687| 118,880| 119,437| 119,195| 119,173| 119,722 Unemployed....................................| 8,470| 8,281| 7,868| 8,642| 8,408| 7,902| 7,817| 8,005| 8,023 Unemployment rate.........................| 6.5| 6.2| 5.9| 6.7| 6.4| 6.0| 6.0| 6.1| 6.1 Not in labor force..............................| 64,321| 64,076| 64,682| 65,459| 65,616| 65,736| 66,445| 66,403| 65,854 | | | | | | | | | | | | | | | | | | Men, 16 years and over | | | | | | | | | Civilian noninstitutional population..............| 92,749| 94,377| 94,469| 92,749| 94,119| 94,196| 94,294| 94,377| 94,469 Civilian labor force............................| 70,725| 72,058| 71,748| 69,847| 70,621| 70,584| 70,328| 70,513| 70,833 Participation rate........................| 76.3| 76.4| 75.9| 75.3| 75.0| 74.9| 74.6| 74.7| 75.0 Employed......................................| 66,172| 67,649| 67,717| 64,904| 66,036| 66,301| 66,135| 66,036| 66,452 Employment-population ratio...............| 71.3| 71.7| 71.7| 70.0| 70.2| 70.4| 70.1| 70.0| 70.3 Unemployed....................................| 4,554| 4,409| 4,031| 4,943| 4,585| 4,283| 4,193| 4,478| 4,381 Unemployment rate.........................| 6.4| 6.1| 5.6| 7.1| 6.5| 6.1| 6.0| 6.3| 6.2 | | | | | | | | | | | | | | | | | | Men, 20 years and over | | | | | | | | | Civilian noninstitutional population..............| 86,002| 87,123| 87,248| 86,002| 86,946| 87,000| 87,095| 87,123| 87,248 Civilian labor force............................| 66,521| 67,138| 67,176| 66,221| 66,701| 66,692| 66,409| 66,596| 66,856 Participation rate........................| 77.3| 77.1| 77.0| 77.0| 76.7| 76.7| 76.2| 76.4| 76.6 Employed......................................| 62,650| 63,636| 63,841| 62,006| 62,958| 63,192| 62,916| 62,889| 63,216 Employment-population ratio...............| 72.8| 73.0| 73.2| 72.1| 72.4| 72.6| 72.2| 72.2| 72.5 Agriculture.................................| 2,324| 2,486| 2,534| 2,193| 2,376| 2,412| 2,307| 2,285| 2,395 Nonagricultural industries..................| 60,326| 61,150| 61,307| 59,813| 60,582| 60,780| 60,609| 60,605| 60,820 Unemployed....................................| 3,871| 3,503| 3,335| 4,215| 3,743| 3,500| 3,493| 3,706| 3,640 Unemployment rate.........................| 5.8| 5.2| 5.0| 6.4| 5.6| 5.2| 5.3| 5.6| 5.4 | | | | | | | | | | | | | | | | | | Women, 16 years and over | | | | | | | | | Civilian noninstitutional population..............| 101,044| 102,482| 102,575| 101,044| 102,244| 102,314| 102,399| 102,482| 102,575 Civilian labor force............................| 58,746| 60,725| 60,614| 58,487| 60,125| 60,190| 59,919| 59,943| 60,356 Participation rate........................| 58.1| 59.3| 59.1| 57.9| 58.8| 58.8| 58.5| 58.5| 58.8 Employed......................................| 54,830| 56,854| 56,776| 54,788| 56,302| 56,571| 56,295| 56,416| 56,714 Employment-population ratio...............| 54.3| 55.5| 55.4| 54.2| 55.1| 55.3| 55.0| 55.0| 55.3 Unemployed....................................| 3,916| 3,872| 3,838| 3,699| 3,823| 3,619| 3,625| 3,528| 3,642 Unemployment rate.........................| 6.7| 6.4| 6.3| 6.3| 6.4| 6.0| 6.0| 5.9| 6.0 | | | | | | | | | | | | | | | | | | Women, 20 years and over | | | | | | | | | Civilian noninstitutional population..............| 94,490| 95,469| 95,544| 94,490| 95,282| 95,329| 95,407| 95,469| 95,544 Civilian labor force............................| 55,075| 5 s account for approximately four-fifths of the total employees on private nonfarm payrolls. 2/ These series are not published seasonally adjusted since the seasonal component is small relative to the trend-cycle and/or irregular components and consequently cannot be separated with sufficient precision. p = preliminary. ESTABLISHMENT DATA ESTABLISHMENT DATA Table B-2. Average weekly hours of production or nonsupervisory workers 1/ on private nonfarm payrolls by industry ______________________________________________________________________________________________________________________________ | | | Not seasonally adjusted | Seasonally adjusted | | _______________________________ _______________________________________________ Industry | | | | | | | | | | | Aug. | June | July | Aug. | Aug. | Apr. | May | June | July | Aug. | 1993 | 1994 |1994p/ |1994p/ | 1993 | 1994 | 1994 | 1994 |1994p/ |1994p/ | | | | | | | | | | ______________________________________________________________________________________________________________________________ | | | | | | | | | | Total private...........................| 35.1 | 34.8 | 34.9 | 35.1 | 34.6 | 34.7 | 34.8 | 34.6 | 34.7 | 34.5 | | | | | | | | | | Mining........................................| 44.9 | 44.8 | 44.9 | 45.6 | 44.5 | 45.0 | 44.5 | 44.8 | 45.4 | 45.2 | | | | | | | | | | Construction..................................| 39.6 | 39.6 | 39.8 | 39.8 | (2) | (2) | (2) | (2) | (2) | (2) | | | | | | | | | | Manufacturing.................................| 41.5 | 42.2 | 41.5 | 42.1 | 41.5 | 42.2 | 42.1 | 42.0 | 41.9 | 42.0 Overtime hours...........................| 4.3 | 4.7 | 4.6 | 4.9 | 4.1 | 4.8 | 4.7 | 4.7 | 4.6 | 4.8 | | | | | | | | | | Durable goods...............................| 42.1 | 43.0 | 42.1 | 42.8 | 42.2 | 43.0 | 42.9 | 42.8 | 42.6 | 42.9 Overtime hours...........................| 4.4 | 5.1 | 4.7 | 5.3 | 4.3 | 5.2 | 5.0 | 5.0 | 4.9 | 5.2 | | | | | | | | | | Lumber and wood products...................| 41.2 | 41.6 | 41.0 | 41.8 | 40.8 | 41.4 | 41.4 | 41.3 | 41.1 | 41.4 Furniture and fixtures.....................| 40.7 | 40.7 | 40.1 | 40.6 | 40.4 | 40.3 | 40.3 | 40.8 | 40.4 | 40.3 Stone, clay, and glass products............| 43.4 | 44.2 | 43.9 | 44.2 | 42.8 | 43.4 | 43.7 | 43.6 | 43.6 | 43.6 Primary metal industries...................| 43.4 | 44.7 | 44.3 | 44.6 | 43.6 | 44.9 | 44.8 | 44.3 | 44.3 | 44.8 Blast furnaces and basic steel products..| 44.0 | 44.8 | 45.0 | 45.3 | 43.9 | 45.1 | 45.1 | 44.4 | 44.5 | 45.2 Fabricated metal products..................| 42.1 | 42.9 | 42.1 | 42.9 | 42.1 | 43.0 | 42.8 | 42.6 | 42.7 | 42.9 Industrial machinery and equipment.........| 42.6 | 43.8 | 43.1 | 43.1 | 43.0 | 43.9 | 43.8 | 43.8 | 43.6 | 43.4 Electronic and other electrical equipment..| 41.7 | 42.3 | 41.4 | 41.9 | 42.0 | 42.6 | 42.3 | 42.2 | 42.1 | 42.2 Transportation equipment...................| 42.8 | 44.4 | 42.4 | 44.2 | 43.2 | 44.6 | 44.3 | 44.0 | 43.2 | 44.6 Motor vehicles and equipment.............| 44.1 | 46.1 | 43.1 | 45.8 | 44.4 | 46.1 | 45.8 | 45.2 | 44.0 | 46.1 Instruments and related products...........| 40.7 | 41.7 | 41.4 | 41.9 | 41.0 | 41.6 | 41.9 | 41.6 | 42.1 | 42.2 Miscellaneous manufacturing................| 39.8 | 40.1 | 39.5 | 40.1 | 39.8 | 40.4 | 40.2 | 40.2 | 40.3 | 40.1 | | | | | | | | | | Nondurable goods............................| 40.7 | 41.1 | 40.8 | 41.1 | 40.5 | 41.1 | 41.0 | 41.0 | 41.1 | 40.9 Overtime hours...........................| 4.2 | 4.3 | 4.3 | 4.5 | 3.9 | 4.3 | 4.2 | 4.3 | 4.3 | 4.2 | | | | | | | | | | Food and kindred products..................| 41.2 | 41.1 | 41.6 | 41.9 | 40.7 | 41.2 | 41.1 | 41.3 | 41.7 | 41.4 Tobacco products...........................| 37.4 | 40.2 | 37.9 | 39.1 | (2) | (2) | (2) | (2) | (2) | (2) Textile mill products......................| 41.8 | 42.4 | 41.2 | 41.8 | 41.4 | 42.0 | 41.8 | 41.9 | 41.6 | 41.4 Apparel and other textile products.........| 37.4 | 38.0 | 37.3 | 37.8 | 37.2 | 38.0 | 37.8 | 37.8 | 37.5 | 37.6 Paper and allied products..................| 43.4 | 44.0 | 43.9 | 43.8 | 43.6 | 44.0 | 44.0 | 44.0 | 44.3 | 44.0 Printing and publishing....................| 38.4 | 38.4 | 38.4 | 38.8 | 38.2 | 38.8 | 38.8 | 38.8 | 38.7 | 38.6 Chemicals and allied products..............| 42.9 | 43.3 | 43.1 | 42.9 | 43.2 | 43.2 | 43.4 | 43.3 | 43.5 | 43.2 Petroleum and coal products................| 44.1 | 44.0 | 43.8 | 43.9 | (2) | (2) | (2) | (2) | (2) | (2) Rubber and misc. plastics products.........| 41.7 | 42.5 | 41.6 | 42.1 | 41.8 | 42.4 | 42.2 | 42.2 | 42.2 | 42.2 Leather and leather products...............| 38.4 | 38.9 | 37.8 | 38.1 | 38.4 | 39.0 | 38.4 | 38.3 | 37.8 | 38.1 | | | | | | | | | | Transportation and public utilities...........| 40.3 | 40.1 | 40.3 | 40.4 | 39.8 | 40.2 | 40.0 | 39.9 | 39.9 | 39.8 | | | | | | | | | | Wholesale trade...............................| 38.4 | 38.5 | 38.4 | 38.3 | 38.3 | 38.4 | 38.5 | 38.4 | 38.3 | 38.1 | | | | | | | | | | Retail trade..................................| 29.7 | 29.3 | 29.7 | 29.8 | 28.9 | 29.0 | 29.0 | 29.0 | 29.0 | 29.0 | | | | | | | | | | Finance, insurance, and real estate...........| 36.4 | 35.5 | 35.7 | 35.6 | (2) | (2) | (2) | (2) | (2) | (2) | | | | | | | | | | Services......................................| 33.1 | 32.5 | 32.8 | 32.8 | 32.6 | 32.5 | 32.8 | 32.4 | 32.5 | 32.3 | | | | | | | | | | ______________________________________________________________________________________________________________________________ 1/ Data relate to production workers in mining and manufacturing; construction workers in construction; and nonsupervisory workers in transportation and public utilities; wholesale and retail trade; finance,insurance, and real estate; and services. These groups account for approximately four-fifths of the total employees on private nonfarm payrolls. 2/ These series are not published seasonally adjusted since the seasonal component is small relative to the trend-cycle and/or irregular components and consequently cannot be separated with sufficient precision. p = preliminary. ESTABLISHMENT DATA ESTABLISHMENT DATA Table B-3. Average hourly and weekly earnings of production or nonsupervisory workers 1/ on private nonfarm payrolls by industry ______________________________________________________________________________________________________________ | | | Average hourly earnings | Average weekly earnings | | _______________________________ _______________________________ Industry | | | | | | | | | Aug. | June | July | Aug. | Aug. | June | July | Aug. | 1993 | 1994 |1994p/ |1994p/ | 1993 | 1994 |1994p/ |1994p/ | | | | | | | | ______________________________________________________________________________________________________________ | | | | | | | | Total private...........................|$10.78 |$11.03 |$11.04 |$11.04 |$378.38|$383.84|$385.30|$387.50 Seasonally adjusted....................| 10.86 | 11.08 | 11.11 | 11.13 | 375.76| 383.37| 385.52| 383.99 | | | | | | | | Mining........................................| 14.44 | 14.73 | 14.70 | 14.66 | 648.36| 659.90| 660.03| 668.50 | | | | | | | | Construction..................................| 14.45 | 14.57 | 14.72 | 14.77 | 572.22| 576.97| 585.86| 587.85 | | | | | | | | Manufacturing.................................| 11.70 | 12.03 | 12.05 | 12.03 | 485.55| 507.67| 500.08| 506.46 | | | | | | | | Durable goods...............................| 12.29 | 12.63 | 12.63 | 12.65 | 517.41| 543.09| 531.72| 541.42 Lumber and wood products...................| 9.67 | 9.83 | 9.87 | 9.88 | 398.40| 408.93| 404.67| 412.98 Furniture and fixtures.....................| 9.33 | 9.49 | 9.57 | 9.59 | 379.73| 386.24| 383.76| 389.35 Stone, clay, and glass products............| 11.89 | 12.13 | 12.16 | 12.18 | 516.03| 536.15| 533.82| 538.36 Primary metal industries...................| 14.00 | 14.29 | 14.39 | 14.33 | 607.60| 638.76| 637.48| 639.12 Blast furnaces and basic steel products..| 16.40 | 16.80 | 16.94 | 16.96 | 721.60| 752.64| 762.30| 768.29 Fabricated metal products..................| 11.67 | 11.90 | 11.88 | 11.94 | 491.31| 510.51| 500.15| 512.23 Industrial machinery and equipment.........| 12.74 | 12.94 | 12.95 | 12.93 | 542.72| 566.77| 558.15| 557.28 Electronic and other electrical equipment..| 11.26 | 11.54 | 11.58 | 11.59 | 469.54| 488.14| 479.41| 485.62 Transportation equipment...................| 15.67 | 16.43 | 16.42 | 16.48 | 670.68| 729.49| 696.21| 728.42 Motor vehicles and equipment.............| 15.89 | 16.91 | 16.92 | 16.97 | 700.75| 779.55| 729.25| 777.23 Instruments and related products...........| 12.24 | 12.42 | 12.46 | 12.42 | 498.17| 517.91| 515.84| 520.40 Miscellaneous manufacturing................| 9.32 | 9.59 | 9.58 | 9.60 | 370.94| 384.56| 378.41| 384.96 | | | | | | | | Nondurable goods............................| 10.96 | 11.22 | 11.29 | 11.21 | 446.07| 461.14| 460.63| 460.73 Food and kindred products..................| 10.43 | 10.66 | 10.70 | 10.61 | 429.72| 438.13| 445.12| 444.56 Tobacco products...........................| 17.22 | 20.48 | 20.38 | 18.57 | 644.03| 823.30| 772.40| 726.09 Textile mill products......................| 8.91 | 9.12 | 9.12 | 9.14 | 372.44| 386.69| 375.74| 382.05 Apparel and other textile products.........| 7.07 | 7.33 | 7.30 | 7.35 | 264.42| 278.54| 272.29| 277.83 Paper and allied products..................| 13.40 | 13.68 | 13.84 | 13.80 | 581.56| 601.92| 607.58| 604.44 Printing and publishing....................| 11.96 | 12.08 | 12.13 | 12.16 | 459.26| 463.87| 465.79| 471.81 Chemicals and allied products..............| 14.76 | 15.13 | 15.21 | 15.15 | 633.20| 655.13| 655.55| 649.94 Petroleum and coal products................| 18.36 | 18.92 | 18.94 | 18.89 | 809.68| 832.48| 829.57| 829.27 Rubber and misc. plastics products.........| 10.53 | 10.72 | 10.74 | 10.61 | 439.10| 455.60| 446.78| 446.68 Leather and leather products...............| 7.63 | 7.94 | 7.96 | 7.94 | 292.99| 308.87| 300.89| 302.51 | | | | | | | | Transportation and public utilities...........| 13.62 | 13.72 | 13.82 | 13.86 | 548.89| 550.17| 556.95| 559.94 | | | | | | | | Wholesale trade...............................| 11.75 | 11.94 | 11.99 | 11.96 | 451.20| 459.69| 460.42| 458.07 | | | | | | | | Retail trade..................................| 7.24 | 7.45 | 7.44 | 7.42 | 215.03| 218.29| 220.97| 221.12 | | | | | | | | Finance, insurance, and real estate...........| 11.39 | 11.67 | 11.71 | 11.74 | 414.60| 414.29| 418.05| 417.94 | | | | | | | | Services......................................| 10.66 | 10.92 | 10.92 | 10.92 | 352.85| 354.90| 358.18| 358.18 | | | | | | | | ______________________________________________________________________________________________________________ 1/ See footnote 1, table B-2. p = preliminary. ESTABLISHMENT DATA Table B-4. Average hourly earnings of production or nonsupervisory workers ESTABLISHMENT DATA 1/ on private nonfarm payrolls by industry, seasonally adjusted _________________________________________________________________________________________________ | | | | | | | | | | | | | | Percent | | | | | | | change Industry | Aug. | Apr. | May | June | July | Aug. | from: | 1993 | 1994 | 1994 | 1994 |1994p/ |1994p/ |July 1994| | | | | | | Aug. 1994 | | | | | | | _________________________________________________________________________________________________ | | | | | | | Total private: | | | | | | | Current dollars...................| $10.86| $11.05| $11.09| $11.08| $11.11| $11.13| 0.2 Constant (1982) dollars2/.........| 7.39| 7.40| 7.42| 7.39| 7.38| N.A. | (3) Mining.............................| 14.57| 14.87| 14.83| 14.73| 14.77| 14.79| .1 Construction.......................| 14.41| 14.52| 14.60| 14.67| 14.75| 14.73| -.1 Manufacturing......................| 11.77| 12.00| 12.00| 12.03| 12.06| 12.10| .3 Excluding overtime4/.............| 11.21| 11.33| 11.37| 11.40| 11.42| 11.44| .2 Transportation and public utilities| 13.63| 13.77| 13.80| 13.78| 13.82| 13.87| .4 Wholesale trade....................| 11.80| 11.95| 11.98| 11.99| 12.01| 12.01| .0 Retail trade.......................| 7.31| 7.45| 7.47| 7.47| 7.48| 7.49| .1 Finance, insurance, and real estate| 11.46| 11.77| 11.83| 11.74| 11.79| 11.81| .2 Services...........................| 10.81| 10.99| 11.04| 11.03| 11.06| 11.08| .2 | | | | | | | _________________________________________________________________________________________________ 1/ See footnote 1, table B-2. 2/ The Consumer Price Index for Urban Wage Earners and Clerical Workers (CPI-W) is used to deflate this series. 3/ Change was -.1 percent from June 1994 to July 1994, the latest month available. 4/ Derived by assuming that overtime hours are paid at the rate of time and onehalf. N.A. = not available. p/ = preliminary. ESTABLISHMENT DATA ESTABLISHMENT DATA Table B-5. Indexes of aggregate weekly hours of production or nonsupervisory workers 1/ on private nonfarm payrolls by industry (1982=100) __________________________________________________________________________________________________________________ | | | Not seasonally adjusted | Seasonally adjusted | | ___________________________ _______________________________________ Industry | | | | | | | | | | |Aug. |June | July | Aug. |Aug. |Apr. | May |June | July | Aug. |1993 |1994 |1994p/ |1994p/ |1993 |1994 |1994 |1994 |1994p/ |1994p/ | | | | | | | | | | __________________________________________________________________________________________________________________ | | | | | | | | | | Total private...........................|128.3|131.0| 131.6 | 132.6 |125.1|128.2|129.1|128.8| 129.3 | 129.1 | | | | | | | | | | Goods-producing industries....................|107.0|110.1| 108.9 | 111.3 |103.8|107.3|107.4|107.5| 107.7 | 107.9 | | | | | | | | | | Mining.......................................| 55.6| 55.5| 55.8 | 56.5 | 54.3| 54.9| 54.2| 55.1| 55.7 | 55.2 | | | | | | | | | | Construction.................................|140.4|144.3| 148.9 | 150.0 |125.9|132.7|134.8|134.0| 135.7 | 134.6 | | | | | | | | | | Manufacturing................................|103.3|106.3| 103.8 | 106.6 |102.4|105.4|105.1|105.3| 105.1 | 105.7 | | | | | | | | | | Durable goods...............................| 99.6|105.3| 101.8 | 104.6 | 99.8|104.0|103.8|104.0| 103.6 | 104.8 Lumber and wood products...................|129.1|135.1| 133.6 | 137.0 |124.5|131.3|131.6|131.7| 131.3 | 132.2 Furniture and fixtures.....................|122.1|126.3| 121.8 | 126.3 |121.3|123.5|124.2|126.0| 125.1 | 125.1 Stone, clay, and glass products............|107.0|112.0| 110.8 | 112.3 |102.7|107.3|107.8|107.8| 108.1 | 107.8 Primary metal industries...................| 84.7| 89.6| 87.7 | 89.2 | 84.9| 88.5| 88.5| 88.3| 88.7 | 89.7 Blast furnaces and basic steel products..| 71.7| 71.5| 72.0 | 71.9 | 71.1| 70.8| 70.8| 70.5| 71.1 | 71.4 Fabricated metal products..................|102.7|109.3| 105.6 | 109.9 |102.5|107.8|107.6|107.9| 108.4 | 109.7 Industrial machinery and equipment.........| 90.1| 97.9| 95.2 | 95.8 | 91.8| 96.9| 96.9| 97.5| 97.1 | 97.3 Electronic and other electrical equipment..| 99.5|105.1| 101.4 | 103.9 |100.4|104.6|103.8|104.3| 103.8 | 104.9 Transportation equipment...................|108.0|116.1| 108.4 | 114.3 |110.3|115.3|114.6|114.5| 111.7 | 116.3 Motor vehicles and equipment.............|133.7|152.3| 138.3 | 149.6 |136.0|149.5|147.9|147.7| 143.3 | 152.2 Instruments and related products...........| 75.4| 74.8| 73.4 | 74.4 | 75.9| 75.2| 75.4| 74.3| 75.1 | 74.9 Miscellaneous manufacturing................|100.6|101.2| 99.1 | 102.6 |100.0|101.9|101.0|101.4| 102.8 | 101.9 | | | | | | | | | | Nondurable goods............................|108.3|107.7| 106.6 | 109.4 |106.0|107.4|107.0|107.1| 107.2 | 106.9 Food and kindred products..................|121.4|112.8| 117.6 | 123.0 |112.5|113.6|113.2|113.5| 114.8 | 114.0 Tobacco products...........................| 58.0| 53.8| 49.8 | 60.9 | 57.0| 62.0| 60.3| 58.7| 55.7 | 59.6 Textile mill products......................| 99.7|101.3| 96.9 | 99.6 | 98.2| 99.8| 99.2| 99.4| 98.5 | 98.0 Apparel and other textile products.........| 90.5| 90.1| 85.5 | 89.1 | 89.6| 89.3| 88.9| 88.8| 87.7 | 88.3 Paper and allied products..................|110.6|112.3| 111.7 | 111.6 |110.3|111.1|111.1|111.1| 111.9 | 111.1 Printing and publishing....................|123.7|124.3| 124.0 | 126.0 |123.6|125.5|125.1|125.7| 125.5 | 125.6 Chemicals and allied products..............|101.0|102.2| 101.3 | 101.3 |100.8|101.3|101.6|101.6| 101.9 | 101.0 Petroleum and coal products................| 84.6| 82.2| 82.2 | 81.7 | 82.9| 82.1| 78.7| 80.1| 80.5 | 80.0 Rubber and misc. plastics products.........|132.7|140.9| 135.8 | 138.8 |132.7|138.3|138.4|138.6| 138.8 | 138.8 Leather and leather products...............| 56.1| 54.9| 50.4 | 53.3 | 55.5| 55.7| 53.7| 53.5| 51.7 | 52.7 | | | | | | | | | | Service-producing industries..................|137.8|140.4| 141.7 | 142.1 |134.7|137.6|138.8|138.4| 139.0 | 138.6 | | | | | | | | | | Transportation and public utilities..........|119.3|121.1| 120.6 | 120.9 |117.9|118.4|119.8|119.6| 119.5 | 119.3 | | | | | | | | | | Wholesale trade..............................|113.8|116.1| 116.0 | 115.8 |112.7|114.5|114.8|114.9| 114.6 | 114.4 | | | | | | | | | | Retail trade.................................|128.5|129.8| 132.0 | 132.8 |123.9|126.4|126.6|127.3| 127.9 | 127.8 | | | | | | | | | | Finance, insurance, and real estate..........|124.6|123.1| 124.0 | 123.7 |121.8|122.0|123.6|121.8| 122.4 | 120.9 | | | | | | | | | | Services.....................................|160.8|165.7| 167.5 | 168.0 |157.5|162.5|164.6|163.5| 164.5 | 164.1 | | | | | | | | | | __________________________________________________________________________________________________________________ 1/ See footnote 1, table B-2. p = preliminary. ESTABLISHMENT DATA Table B-6. ESTABLISHMENT DATA Diffusion indexes of employment change, seasonally adjusted (Percent) _______________________________________________________________________________________________________________________ | | | | | | | | | | | | TIME SPAN | Jan. | Feb. | Mar. | Apr. | May | June | July | Aug. | Sept. | Oct. | Nov. | Dec. | | | | | | | | | | | | _______________________________________________________________________________________________________________________ | | Private nonfarm payrolls, 356 industries1/ | _______________________________________________________________________________________________ | | | | | | | | | | | | Over 1-month span: | | | | | | | | | | | | 1990..............| 58.8 | 57.3 | 50.8 | 47.9 | 49.7 | 51.8 | 43.8 | 46.2 | 42.7 | 41.6 | 41.3 | 41.3 1991..............| 39.6 | 39.6 | 38.5 | 38.2 | 48.5 | 45.4 | 48.3 | 52.0 | 48.9 | 46.8 | 46.5 | 46.1 1992..............| 42.1 | 46.1 | 48.3 | 57.7 | 53.1 | 50.4 | 52.8 | 46.5 | 53.4 | 56.9 | 52.5 | 57.3 1993..............| 57.9 | 61.7 | 49.0 | 56.0 | 57.0 | 51.1 | 58.8 | 50.0 | 56.7 | 57.4 | 61.0 | 57.4 1994..............| 56.6 | 58.3 | 62.9 | 62.5 | 56.3 | 63.2 |p/58.8 |p/57.0 | | | | | | | | | | | | | | | | | | | | | | | | | | | | Over 3-month span: | | | | | | | | | | | | 1990..............| 59.0 | 59.1 | 52.5 | 48.9 | 49.0 | 47.3 | 45.9 | 40.6 | 38.3 | 36.2 | 35.7 | 35.4 1991..............| 34.3 | 32.0 | 31.6 | 38.2 | 39.3 | 44.2 | 49.4 | 50.7 | 50.8 | 44.9 | 43.7 | 40.9 1992..............| 39.7 | 42.3 | 51.0 | 56.2 | 57.6 | 54.1 | 50.4 | 49.9 | 51.7 | 56.2 | 58.6 | 59.8 1993..............| 64.0 | 61.4 | 59.7 | 55.8 | 54.9 | 57.7 | 54.6 | 55.9 | 55.8 | 62.4 | 61.5 | 60.8 1994..............| 62.1 | 64.5 | 65.2 | 65.0 | 65.4 |p/64.3 |p/64.9 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Over 6-month span: | | | | | | | | | | | | 1990..............| 57.2 | 54.9 | 55.8 | 50.4 | 46.8 | 44.0 | 41.3 | 38.9 | 35.8 | 33.6 | 32.0 | 30.2 1991..............| 30.2 | 32.4 | 31.2 | 33.7 | 39.2 | 44.7 | 46.5 | 45.6 | 47.8 | 44.5 | 41.4 | 39.9 1992..............| 43.5 | 46.3 | 47.2 | 52.0 | 54.2 | 56.6 | 52.8 | 53.1 | 55.8 | 56.3 | 64.2 | 62.2 1993..............| 61.4 | 60.8 | 59.0 | 59.8 | 54.4 | 54.5 | 57.9 | 58.8 | 59.7 | 60.8 | 62.8 | 63.6 1994..............| 67.0 | 65.9 | 68.8 |p/65.2 |p/66.4 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Over 12-month span: | | | | | | | | | | | | 1990..............| 55.5 | 52.7 | 51.7 | 48.5 | 45.4 | 42.6 | 39.3 | 36.1 | 35.8 | 33.0 | 33.0 | 30.6 1991..............| 31.0 | 31.0 | 31.7 | 31.9 | 31.7 | 33.8 | 35.8 | 37.5 | 40.0 | 45.2 | 45.6 | 45.4 1992..............| 47.2 | 42.3 | 42.7 | 44.1 | 48.0 | 52.5 | 55.8 | 60.7 | 59.7 | 60.4 | 60.1 | 60.7 1993..............| 60.0 | 61.1 | 60.7 | 62.2 | 63.2 | 62.1 | 62.4 | 60.8 | 63.5 | 62.8 | 63.1 | 63.5 1994..............|p/64.7 |p/65.9 | | | | | | | | | | | | | | | | | | | | | | _______________________________________________________________________________________________ | | Manufacturing payrolls, 139 industries1/ | _______________________________________________________________________________________________ | | | | | | | | | | | | Over 1-month span: | | | | | | | | | | | | 1990..............| 48.9 | 47.5 | 43.9 | 46.8 | 40.3 | 46.8 | 38.8 | 42.4 | 35.6 | 38.5 | 29.1 | 34.2 1991..............| 32.7 | 35.6 | 31.3 | 37.4 | 45.7 | 43.5 | 46.4 | 49.3 | 42.8 | 47.8 | 41.4 | 39.6 1992..............| 38.1 | 40.6 | 45.0 | 57.9 | 47.8 | 50.0 | 53.2 | 41.7 | 49.3 | 47.8 | 52.5 | 51.8 1993..............| 52.5 | 57.6 | 47.8 | 41.7 | 46.0 | 40.3 | 49.3 | 42.8 | 46.8 | 50.0 | 55.4 | 51.1 1994..............| 54.3 | 53.6 | 51.1 | 56.1 | 50.0 | 58.6 |p/52.5 |p/55.0 | | | | | | | | | | | | | | | | | | | | | | | | | | | | Over 3-month span: | | | | | | | | | | | | 1990..............| 44.6 | 45.3 | 45.0 | 38.8 | 41.7 | 38.8 | 38.1 | 28.8 | 30.9 | 23.0 | 23.0 | 21.6 1991..............| 24.5 | 21.9 | 20.5 | 32.7 | 36.3 | 39.6 | 47.1 | 46.0 | 48.2 | 39.9 | 36.7 | 33.5 1992..............| 30.9 | 36.3 | 45.3 | 50.7 | 55.4 | 53.6 | 47.1 | 47.1 | 42.4 | 50.0 | 51.1 | 55.0 1993..............| 60.1 | 58.3 | 51.4 | 40.6 | 37.1 | 43.5 | 40.3 | 41.0 | 43.2 | 52.9 | 54.7 | 56.1 1994..............| 56.1 | 57.6 | 56.5 | 53.2 | 57.2 |p/55.4 |p/59.7 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Over 6-month span: | | | | | | | | | | | | 1990..............| 43.5 | 39.9 | 42.8 | 41.0 | 36.3 | 34.2 | 29.1 | 25.2 | 22.3 | 21.2 | 18.0 | 16.9 1991..............| 15.8 | 20.9 | 21.2 | 26.3 | 34.9 | 39.2 | 42.1 | 40.3 | 40.3 | 37.1 | 32.4 | 32.7 1992..............| 34.2 | 37.1 | 41.0 | 48.6 | 52.2 | 54.7 | 46.4 | 49.3 | 50.4 | 48.9 | 57.9 | 56.8 1993..............| 54.0 | 51.8 | 48.6 | 47.1 | 37.1 | 34.2 | 39.6 | 45.7 | 47.8 | 50.4 | 54.3 | 55.8 1994..............| 58.3 | 56.1 | 59.4 |p/52.9 |p/57.2 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Over 12-month span: | | | | | | | | | | | | 1990..............| 37.8 | 35.3 | 33.5 | 33.1 | 28.1 | 26.3 | 23.7 | 20.5 | 19.4 | 16.5 | 16.2 | 15.8 1991..............| 16.5 | 16.2 | 17.3 | 18.0 | 20.9 | 24.1 | 26.3 | 30.6 | 32.7 | 38.1 | 38.8 | 37.4 1992..............| 42.4 | 36.7 | 36.3 | 36.0 | 39.6 | 45.7 | 50.0 | 55.8 | 57.9 | 55.4 | 52.9 | 52.9 1993..............| 50.0 | 52.5 | 48.6 | 49.3 | 50.7 | 48.9 | 50.0 | 48.9 | 50.0 | 50.7 | 51.4 | 51.4 1994..............|p/51.1 |p/54.7 | | | | | | | | | | | | | | | | | | | | | | _______________________________________________________________________________________________________________________ 1/ Based on seasonally adjusted data for 1-, 3-, and 6-month spans and unadjusted data for the 12-month span. Data are centered within the span. p = preliminary. NOTE: Figures are the percent of industries with employment increasing plus one-half of the industries with unchanged employment, where 50 percent indicates an equal balance between industries with increasing and decreasing employment.
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