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Particle-Shape Control and Formation Mechanisms of Hydrothermally Derived Lead Titanate | Request PDF
Request PDF | Particle-Shape Control and Formation Mechanisms of Hydrothermally Derived Lead Titanate | Phase-pure perovskite lead titanate with various morphologies has been synthesized by a hydrothermal method at 150 °C. Particle shapes include... | Find, read and cite all the research you need on ResearchGate
Article
Particle-Shape Control and Formation Mechanisms of Hydrothermally Derived Lead Titanate
March 1999
Journal of Materials Research 14(3):866-875
DOI: 10.1557/JMR.1999.0116
Authors:
Jooho Moon
Melanie L. Carasso
Henrik G. Krarup
Show all 5 authors Hide
Abstract
Phase-pure perovskite lead titanate with various morphologies has been synthesized by a hydrothermal method at 150 °C. Particle shapes include cubic, tabular, and aggregated platelike shapes. The feedstock concentration greatly influences particle morphology of the hydrothermally derived PbTiO3. At a concentration of 0.05 M, the tabular particles form while cubic particles are produced at 0.1 M. Aggregated plateletlike particles are synthesized at 0.125 M. It was observed that both tabular and cubic particles directly precipitate from the coprecipitated precursor gel. In contrast, the plateletlike shaped intermediate phase appears during the initial stage of reaction at 0.125 M and in situ transforms into perovskite PbTiO3 during further hydrothermal treatment. The intermediate phase preserves its particle shape during transformation and, acting as a template, gives rise to the final tabular PbTiO3 particles. It is demonstrated that only base reagents such KOH and NaOH, which provide a highly basic condition (i.e., pH > 14), promote transformation of the coprecipitated gel into the perovskite PbTiO3. A Hancock and Sharp kinetic analysis in conjunction with microstructural evidence suggests that the formation mechanism is dissolution and recrystallization in which the degree of supersaturation plays an important role in dictating the crystallographic particle phase and morphology of the particles. An experimentally constructed solubility diagram indicates that an excess lead condition is necessary to compensate for loss of lead species and to increase supersaturation to expedite precipitation of PbTiO3 at highly alkaline conditions.
No full-text available
... Photoluminescence (PL) study of the PbTiO 3 nanowires at room temperature for wavelength between 400 and 650 nm reveals a strong blue-green emission band peaking at ca. 471.4 nm (2.63 eV), which may be a promising candidate in future piezoelectric sensors, and optoelectric device. Moon J. et al.
[10]
synthesized PbTiO 3 particles with Here, we report a simple synthesis approach to build a novel PbTiO 3 donut-like structure under hydrothermal conditions using lead nitrate (Pb(NO 3 ) 2 ) and TiCl 4 as the starting materials and NaOH as a mineralizer. Furthermore, donut-like PbTiO 3 particles formation mechanism was investigated in conjunction with micro-structural evolution of the particles during reaction. ...
... The effect of initial concentration of [Ti 4+ ] and stoichiometric [Pb 2+ ]/ [Ti 4+ ] ratio on the phases and morphologies of the as-prepared particles was also investigated. The products obtained at the low initial concentration of [Ti 4+ ] (0.05 mol/L) and [Pb 2+ ]/[Ti 4+ ] = 1.5 were cubic PbTiO 3 particles, as shown in Fig. 3(a), which is same to the results of J. Moon
[10]
. And when the [Pb 2+ ]/[Ti 4+ ] ratio was adjusted to stoichiometric, the products was sphere-like PbTiO 3 aggregates, as shown in Fig. 3(b). ...
... The mechanism for the formation of the PbTiO 3 donut-like structures was proposed to involve different growth processes during the hydrothermal synthesis as schematically illustrated in Fig. 7: (i) initial ), and high solution pH value, the Pb 2 Ti 2 O 6 particles dissolve from its center of surface and recrystallize to form PbTiO 3 nanoparticles and adhere to its edges. The further growth of the donut-like PbTiO 3 particles continues at the effects of increasing temperature or prolonging reaction time to form platelet PbTiO 3 particles as shown in Fig. 8, which is differ to the growth mechanism of platelet PbTiO 3 particles introduced in the literature
[10]
and [12]. ...
Synthesis and growth mechanism of donut-like lead titanate particles by hydrothermal method
Article
Full-text available
Feb 2010
POWDER TECHNOL
Yun-fei Liu
Yi-Nong Lu
Dai Shenhua
Shu-zhe Shi
Tetragonal perovskite structure PbTiO3 donut-like particles have been synthesized by a hydrothermal method in strong alkaline environment using lead nitrate (Pb(NO3)2) as the lead source and TiCl4 as the titanium source. The as-prepared particles were characterized by X-ray powder diffraction (XRD) and scanning electron microscope (SEM), and it was indicated that the phase composition and particles shapes were influenced by the reaction temperature and reaction time. Based on the morphologies and phase evolutions as a function of reaction temperature or reaction time, a mechanism for the growth of the donut-like PbTiO3 particles was proposed to involve nucleation, agglomeration, phase in situ conversion, dissolution, and recrystallization. The spherical particles were formed by primary nucleation of PbTi0.8O2.6 followed by agglomeration into platelets. Then, the platelet PbTi0.8O2.6 particles in situ converted into Pb2Ti2O6 particles. Under the effects of temperature, pressure (autogenous pressure), and high solution pH value, the platelet Pb2Ti2O6 particles dissolved from its center of surface and recrystallized to form PbTiO3 nano-particles which adhered to its edges. Finally, the monocrystal donut-like PbTiO3 particles were formed as the dissolution of Pb2Ti2O6 particles completed.
... It was found that in hydrothermal synthesis phase composition and particle shape of PbTiO 3 were greatly influenced by reaction parameters and conditions, such as concentration, agitation and type of mineralizers. Moon et al.
[32]
reported mechanisms for shape control of PbTiO 3 in hydrothermal techniques, by using appropriate feedstock concentration and suitable reagent bases (to keep pH > 14). Kim and Matijevic [33] prepared amorphous spherical lead titanate particles with a narrow size distribution around 0.2 m by decomposing hydrogen peroxide species of Ti with Pb chelates in alkaline media and aging at 60 • C for 4 h. ...
... Among the chemical methods, sol-gel route has been very commonly applied for synthesizing high purity and homogeneous powders of micrometers and nanometers size [42,44]. Synthesis parameters i.e. reaction temperature, type and concentration of reaction media, ratio of Pb:Ti, type of template, calcination temperatures and duration of calcination, etc. control the composition and morphology of the powders [21,26,31,
32]
. Further, these synthesis parameters can be optimized in attempt to achieve phase pure, dense and crack free PbTiO 3 powders [25,40,46,51]. ...
Synthesis and Induced Multiferroicity of Perovskite PbTiO3; A review
Jan 2016
APPL SURF SCI
Humaira Bhatti
Syed Hussain
F. A Khan
Shahzad Hussain
... From the crystallization fraction as a function of time and a microscope study, a dissolution rate determining mechanism was suggested. Similarly Moon et al.
[72]
used this approach and confirmed a dissolution-precipitation mechanism. However, they suggested a chemical reaction at the interface of the growing particles is the rate-limiting step. ...
... Concentration can affect the particle size. For example, Moon et al.
[72]
found that the particle size decreased from 3 mm to 1.5 mm for PbTiO 3 with an increase in concentration from 0.05 M and 0.1 M feedstocks of Pb-acetate and Ti-acetyl acetone. The molar ratio of the precursors can affect the particle size. ...
9 Growth of Multicomponent Perovskite Oxide Crystals: Synthesis Conditions for the Hyrothermal Growth of Ferroelectric Powders
Full-text available
Jan 2003
Bonnie Gersten
In this chapter a general description of the hydrothermal process and ferroelectric materials will be presented. An overview of the approaches used for the synthesis will be outlined in table form. In addition, the specifics of the synthesis for con-trolled chemical and phase purity, kinetics and rate controlling mechanisms, con-trolled morphology, and controlled particle size will be discussed. Finally, conclu-sions about the synthesis of the hydrothermal growth of ferroelectric powders will be made. 9.2 General Overview 9.2.1 Description Hydrothermal synthesis is accomplished by the use of suspensions or homogene-ous solutions subjected to temperature and pressure to induce rapid phase trans-formation kinetics. This synthesis method falls under the category of wet chemical methods that includes sol-gel and coprecipitation. The wet chemical routes achieve purer and finer powders than the conventional solid-state calcination route. Unlike other wet chemical methods, the hydrothermal method can be used to prepare anhydrous phase-pure oxides in a single step synthesis route from inex-pensive precursors. During the process, no hazardous volatiles are produced. Fur-thermore, the water-based solvent can be recycled. All of these advantages make hydrothermal processing an environmentally friendly manufacturing process. The method has been used to prepare powders as reviewed in Dawson [1] and Riman [2]. Crystals have been discussed by Yanagisawa et al. [3–5], and films by Ben-dale et al. [6], Chien et al. [7–8], Kajiyoshi et al. [9], Pilleux et al. [10], Roeder et al. [11], and Yoshimura et al. [12].
... Furthermore, the introduction of alkali cations such as Na + and K + , which are introduced during hydrothermal processing, may affect the ferroelectric and the electrothermal properties of the final product. The negative effects of alkali ions on lead zirconium titanate (PZT) were reported [9,14,15,[19][20]
[21]
[22][23]. However, to the best of our knowledge, there is no scientific report on the synthesis of well-defined PT spherical particles without using TiO 2 seed grains of a specified shape. ...
Novel Sol-Gel Synthesis of Spherical Lead Titanate Submicrometer Powders
Article
Full-text available
Apr 2021
Radhouane Bel hadj tahar
Mohamed Abboud
Mohd. Shkir
Mhamed Benaissa
In this study, a novel and simple synthetic sol-gel procedure was established to directly prepare spherical lead titanate powders without prior synthesis/usage of spherical templates such as TiO2 particles. Isotropic submicron particles with a mean diameter of 1–4 μm were prepared in this way. This synthetic process takes advantage of acetone as a stabilizing ligand and autogenous pressure generated in the autoclave during the reaction. The influence of various experimental factors (nature of the ligand, thermal treatment mode, and post-calcining temperature) as well as the formation mechanism were studied. Scanning electron microscopy and transmission electron microscopy were used to explore the particle morphology. The crystalline phases were explored and identified by X-ray diffraction analysis.
... 106 For perovskite structures, different kinds of compositions are possible as alkali niobates, lead niobates, lead titanates, or bismuth sodium titanates. [106][107][108][109]
[110]
[111] These anisotropic perovskite materials are reported to contain piezoelectric properties. 112 Other interesting properties such as photoluminescence, ferroelectric and photocatalytic properties are also reported. ...
Effect pigments for textile coating: a review of the broad range of advantageous functionalization
Article
Nov 2016
Boris Mahltig
Jieyang Zhang
Linfei Wu
Hajo Haase
The presented review will introduce the use of effect pigments as a powerful tool for the functionalization of textiles. This review starts with a short introduction on the basics of effect pigments and their properties. Subsequently, some principles of effect pigment application onto textiles and the interaction of pigment to binder systems are reported. Different possible functionalizations realized on textiles are presented. Four main types of application are discussed: optical properties, electrical properties, barrier coatings, and antimicrobial applications. Also a view of some prospective anisotropic materials is given. Altogether it is shown that the application of effect pigments can be a powerful tool to realize functional textiles for a broad range of applications in different fields.
... Higher temperature treatments resulted in a better quenching of BaTiO 3 whereby crystalline defects were eleminated.
[37]
As a result, the meta-stable cubic phase at room temperature was transformed into the tetragonal phase at room temperature. Hence, BaTiO 3 with a high degree of tetragonality was obtained at higher reaction temperatures. ...
Molten-salt synthesis of tetragonal micron-sized barium titanate from a peroxo-hydroxide precursor
Article
Full-text available
Oct 2016
ADV POWDER TECHNOL
Murat Özen
Myrjam Mertens
Frans M.M Snijkers
Pegie Cool
Barium titanate (BaTiO3) was produced from an barium-titanate-peroxo-hydroxide precursor material in NaCl-KCl and Na2SO4-K2SO4 salt mixtures or fluxes at temperatures up to 1080 °C via the molten-salt synthesis (MSS) method. Beside the different salt mixtures several other parameters were studied to determine the effect on the particle morphology. A relatively fast heating rate and a relatively high salt to precursor ratio resulted in a highly faceted morphology. The effect of the salt flux was clearly seen in the morphology of BaTiO3 obtained by MSS at 1080 °C. Cube-shaped particles were observed for the chloride-flux-grown BaTiO3 while hexagonal-shaped flat particles were observed for the sulfate-flux-grown BaTiO3. BaTiO3 particles produced in the chloride-flux were either {1 0 1} or {0 0 1} faceted. The hexagonal surface of the sulfate-flux-grown BaTiO3 was {1 1 1} faceted.
View
Show abstract
... Parameters which affect super saturation conditions, hence particle morphology, are solution pH, temperature, precursor concentration, and agitation. [24,
25]
Little is known about the diamagnetic susceptibility axes of . The tetragonal crystal phase has a very low crystallographic anisotropy which can be derived from the low c:a ratio (~1.007). ...
Texturing of hydrothermally synthesized BaTiO3 in a strong magnetic field by slip casting
Article
Dec 2015
CERAM INT
Frans M.M Snijkers
Murat Özen
Myrjam Mertens
Pegie Cool
(Elsevier Share Link: http://authors.elsevier.com/a/1SPJW~2-EiuXc)
Barium titanate powder was processed by slip casting in a rotating strong magnetic field of 9.4. T. The orientation factor of the sintered compact was analyzed by the X-ray diffraction technique and the microstructure (grain-size) was analyzed by scanning electron microscope. The hydrothermally prepared barium titanate was used as matrix material and the molten-salt synthesized barium titanate, with a larger particle-size, was used as template for the templated grain-growth process. Addition of large template particles was observed to increase the orientation factor of the sintered cast (5. vol% loading). Template particles acted as starting grains for the abnormal grain-growth process and the average grain-size was increased after sintering. Increasing the solid loading (15. vol%) resulted in a similar orientation factor with a decrease of the average grain-size by more than half. However, addition of templates to the 15. vol% cast had a negative effect on the orientation factor. The impingement of growing particles was stated as the primary cause of particle misorientation resulting in a low orientation factor after sintering. Different heating conditions were tested and it was determined that a slow heating rate gave the highest orientation factor, the smallest average grain-size and the highest relative density.
... The materials' performances are closely related to the ways they are processed. Synthesis method played a significant role in determining the microstructure, electrical and optical properties of ferroelectric ceramics [16][17]
[18]
. Fully dense ferroelectric ceramics (> 95% of theoretical density) are required by most applications, because of several reasons. The dielectric constant of ferroelectric ceramics usually increases with increasing density and the presence of pores is generally a cause of high loss tangent. ...
Synthesis and Characterization of Nanocrystalline Barium–Samarium Titanate
Article
Full-text available
Jul 2015
HIGH TEMP MAT PR-ISR
Mahmoud Hessien
Nader El-Bagoury
Mohamed Hesham Hassan Mahmoud
Osama mohamed hemeda
Barium-samarium titanate nanopowder (Ba0.85Sm0.1TiO3) was synthesized through tartrate precursor route. The effect of annealing temperature on the formation, crystalline size, morphology and magnetic properties was systematically studied. The annealing temperature was varied from 600 degrees C to 1,100 degrees C. Thermal analysis measurement (TG-DSC, thermogravimetry-differential scanning calorimetry) was carried out on the precursor to characterize the thermal decomposition behavior. The results showed that the precursor of Ba-Sm-Ti mixture decomposed thermally in multistep weight loss up to about 480 degrees C and perovskite Ba0.85Sm0.1TiO3 started to form at similar to 520 degrees C. X-ray diffraction and Fourier transform infrared (FTIR) spectroscopic measurements showed that the synthesized Ba0.85Sm0.1TiO3 has a tetragonal dominant structure with the presence of intermediate SmTi2O3 at lower annealing temperature. The ratio of SmTi2O3 was decreased and completely disappeared at higher annealing temperatures. The tetragonality, the theoretical density and the crystalline size were increased by increasing annealing temperature. The crystalline size is still in nano-range of 12.4-19.9 nm even after annealing at 1,100 degrees C. The morphology of the produced sample transferred from nano-cubes to nano-whisker to nano-mace (nano-aggregates) with the increase of annealing temperature.
... Particle morphology, phase composition and surface chemical properties are some advantages of this technique. Hydrothermal processes are under great interest for the production of ceramic powders with varying morphologies and sizes [5,[7][8][9]
[10]
. One of the main issues in the synthesis of BaTiO 3 is the problem of carbonate formation during the synthesis and/or due to process conditions. ...
Hydrothermal synthesis of carbonate-free submicron-sized barium titanate from an amorphous precursor: Synthesis and characterization
Article
Jan 2012
CERAM INT
Murat Özen
Myrjam Mertens
Jan Luyten
Pegie Cool
In this paper, the amorphous barium titanate precursor was prepared by the peroxo-hydroxide method and post-treated by various drying procedures, such as: room temperature drying, room temperature vacuum drying and vacuum drying at 50°C. The objective in the latter two treatments was to increase the Ti–O–Ba bonds of the precursor. The post-treated precursors were compared with the untreated (i.e., ‘wet’) precursor. Also, a barium titanate precursor was prepared by an alkoxide route. Afterwards, the precursors were hydrothermally treated at 200°C in a 10M NaOH solution. Vacuum drying of the precursor seemingly promoted the formation of Ti–O–Ti bonds in the hydrothermal end-product. The low Ba:Ti ratio (0.66) of the alkoxide-route prepared precursor lead to a multi-phase hydrothermal product with BaTiO3 as the main phase. In contrast, phase pure BaTiO3, i.e. without BaCO3 contamination, was obtained for the precursor which was dried at room temperature. Cube-shaped and highly crystalline BaTiO3 particles were observed by electron microscopy for the hydrothermally treated peroxo-hydroxide-route prepared precursor.
... However, the electrical properties of BST materials are closely linked to their microstructural feature and fabrication process. [5][6]
[7]
[8] Their manufacturing technology is known to have a strong effect on the structural and properties of ceramics and thin films: the size and shape of grains, the domain size and the atomic structure of grain boundaries. ...
Barium strontium titanate nanocrystalline thin films prepared by soft chemical method
Article
Dec 2007
J EUR CERAM SOC
T. Mazon
Maria Aparecida Zaghete
Jose A. Varela
Elson Longo
Barium strontium titanate (Ba0.65Sr0.35TiO3) nanocrystalline thin films, which were produced by the soft chemical method, were crystallized at low temperature using a domestic microwave oven. A SiC susceptor were used to absorb the microwave energy and rapidly transfer the heat to the film. Low microwave power and short time have been used. The films obtained are crack-free, well-adhered, and fully crystallized. The microstructure displayed a polycrystalline nature with nanograin size. The metal-BST-metal structure of the thin films treated at 700 °C show good electric properties. The ferroelectric nature of the BST35 thin film was indicated by butterfly-shaped C–V curves. The capacitance–frequency curves reveal that the dielectric constant may reach a value up to 800 at 100 kHz. The dissipation factor was 0.01 at 100 kHz. The charge storage density as function of applied voltage graph showed that the charge storage densities are suitable for use in trench type 64 Mb (1–5 μC/cm2) and 265 Mb (2–11 μC/cm2) DRAMs.
... At first, the concentration of elemental sulfur increase slowly(stage I). In this stage no appreciable nucleation occurs even if the concentration level exceed the solubility level which is called as critical concentration (
Moon et al., 1998;
Finney & Finke, 2008; Keshmiri & Kesler, 2006; Tovstun & Razumov, 2010). When the concentration reaches to a critical level (critical supersaturation level) the nucleation process can be started (stage II). ...
Nucleation and Growth of TiO2 Nanoparticles
Chapter
Full-text available
Dec 2011
H. Mehranpour
Masoud Askari
Morteza Sasani Ghamsari
... The electrical properties of BST materials are closely linked to their microstructural feature and fabrication process4950
51
52.Their manufacturing technology is known to have a strong effect on the structural and properties of ceramics and thin films: the size and shape of grains, the domain size and the atomic structure of grain boundaries. A factor which has critical influence on the structure and property of the materials is the temperature of heat treatment [20]. ...
Synthesis and characterization of barium strontium titanate (BST) micro/nanostructures prepared by improved methods, A review
Article
Full-text available
Jan 2011
Morteza Enhessari
Azam Parviz
Keyvan Ozaee
Hossein habibi abyaneh
http://ijnd.ir/index.php?option=com_content&view=article&id=119&Itemid=81
... The platelet growth may thus be a pure ionby-ion growth. As described by Moon et al
[34]
and Peterson and Slamovich [35], PbTiO 3 platelets can form during hydrothermal synthesis because of slower crystal growth on (001) than on {100} planes. This corresponds to the growth in the 100 directions of the substrate (figures 2(c), (f) and (i)). ...
PbTiO 3 nanorod arrays grown by self-assembly of nanocrystals
Article
Jun 2008
Asmund Almli
A. T. J. van Helvoort
Per Martin Rørvik
Mari-Ann Einarsrud
Arrays of ferroelectric lead titanate (PbTiO(3)) nanorods have been grown on a substrate by a novel template-free method. Hydrothermal treatment of an amorphous PbTiO(3) precursor in the presence of a surfactant and PbTiO(3) or SrTiO(3) substrates resulted in the growth of PbTiO(3) nanorod arrays aligned perpendicular to the substrate surface. Two steps in the growth mechanism were demonstrated: first an epitaxial layer was formed on the substrate; this was followed by self-assembly of nanocrystals forming a mesocrystal layer which matured into arrays of PbTiO(3) nanorods.
Kohlenstoffgruppe: Elemente der vierten Hauptgruppe
Chapter
Feb 2023
Hermann Sicius
Die Elemente der Kohlenstoffgruppe, also die der vierten Hauptgruppe, haben stark voneinander abweichende Eigenschaften. Die Atome dieser Elemente nehmen entweder vier Elektronen auf oder geben meist zwei oder vier ab, um eine stabile Elektronenkonfiguration zu erreichen. Kohle und damit Grafit ist seit vorgeschichtlicher Zeit bekannt, und Diamant als zweite wichtige Modifikation des Kohlenstoffs ist bereits in chinesischen Quellen aus dem 3. Jahrtausend vor Christus erwähnt. Seit der Bronzezeit kennen die Menschen Blei, und Zinn auch schon seit 6000 Jahren. Dass Sand Silicium zugrunde liegt, wissen wir aber erst seit etwa 200 Jahren, und Germanium wurde ebenfalls erst 1886 beschrieben. Atome des Fleroviums konnten 1999, also noch im letzten Jahrtausend, dargestellt werden. Wir haben also eine lange bekannte Familie von Elementen vor uns. Das Nichtmetall Kohlenstoff ist in seiner Modifikation Grafit ein hochschmelzender Feststoff, ebenso die Halbmetalle Silicium und -mit Abstrichen- Germanium. Zinn und Blei, die metallischen Vertreter dieser Gruppe, weisen dagegen tiefe Schmelzpunkte auf. Flerovium ist möglicherweise sogar ein leicht flüchtiges Halbedelmetall.
Kohlenstoffgruppe: Elemente der vierten Hauptgruppe
Chapter
Jul 2021
Hermann Sicius
Die Elemente der Kohlenstoffgruppe, also die der vierten Hauptgruppe, haben stark voneinander abweichende Eigenschaften. Die Atome dieser Elemente nehmen entweder vier Elektronen auf oder geben meist zwei oder vier ab, um eine stabile Elektronenkonfiguration zu erreichen.
Kohlenstoffgruppe: Elemente der vierten Hauptgruppe
Chapter
Jan 2020
Hermann Sicius
Hydrothermal growth of PX-PbTiO3 nanowires with K2Ti6O13 as precursors
Article
Jul 2020
J CRYST GROWTH
Shutong Yuan
Bo Li
Jin Wang
Morphology control is a challenging subject in preparing monocrystalline 1D perovskite structures due to high symmetry of their crystal structure. Herein, we employed K2Ti6O13 as the precursor and demonstrated its effectiveness in synthesizing the PX-PbTiO3 nanowires, which could be transformed into monocrystalline perovskite-type PbTiO3 nanowires by facile heat treatment in air. We studied the impact of hydrothermal reaction parameters such as temperature, reaction duration and surfactant concentration on the phase and morphology of the products. It was shown that the employment of a proper concentration of PVA was necessary to the formation of high-quality PX-PT nanowires. Based on the results of control experiments, a possible mechanism for the formation of PX-PT nanowires was proposed.
Structure and shape control of hydrothermally synthesized PbTiO3 - Effects of pH and complexing agents
Article
Jan 2003
CHEM RES CHINESE U
LH Xiao
DR Chen
X.-L. Xu
SW Liu
Tabular PE-PbTiO3, spherical PY-PbTiO3,, and acicular PX-PbTiO3 powders were hydrothermally synthesized from triethanolamine(TEA)-complexed precursor; clubbed PE-PbTiO3 powders were obtained from diethanolamine(DEA)-complexed precursor. The effects of pH of the hydrolyzation as well as complexing agents including TEA, DEA, and MEA(monoethanolamine) on the structure and the morphology of PbTiO3 powders are discussed. The optimal conditions for hydrothermal syntheses of acicular and clubbed PbTiO3 powders have been established. The products were characterized by means of XRD, TEM and other techniques.
Synthesis and Characterization of Tungsten Oxide Nanostructures
Article
Dec 2010
CHINESE J INORG CHEM
Y.-X. Qin
Z.-Y. Bao
M. Hu
P. Sun
One- and two-dimensional tungsten oxide nanostructures were synthesized by solvothermal method using tungsten hexachloride (WCl 6) as the precursor. The effects of the solvent and the concentration of WCl 6 on the phase and the morphology of the as-synthesized tungsten oxide nanostructures were investigated and the NO 2-sensing properties were evaluated. X-ray diffraction, field emission scanning electron microscope, transmission electron microscope, X-ray photoelectron spectroscopy were employed to characterize the as-synthesized products and the results indicate that the W 18O 49 nanorod, W 18O 49 nanowire and WO 3 nanosheet with monoclinic structure can be formed by adjusting the solvent and WCl 6 concentration. The NO 2-sensing properties measurements show that the synthesized tungsten oxides have reversible response to NO 2 at different concentrations. In comparison with WO 3 nanosheet or W 18O 49 nanorod, the W 18O 49nanowire exhibits much higher response to NO 2 gas.
Influence of Space Charge Layers on the Dielectric Properties of Ba0.6 Sr0.4TiO3 Nanostructured Thin Films
Article
Jan 2015
INTEGR FERROELECTR
Hidangmayum Basantakumar Sharma
Bobby Singh Soram
Barium strontium titanate (Ba0.6Sr0.4TiO3) nanostructured thin films have been deposited on platinized silicon substrates by the sol-gel method. The as-fired films were found to be amorphous, which crystallize to cubic phase after annealing at 550°C in air for one hour. The low-frequency dielectric responses of the BST films were measured as functions of frequency range from 1 kHz to 1MHz. The thickness dependence dielectric constant of the BST thin films were measured in the temperature range from −150°C to 150°C at 100 kHz and discussed in the light of an interfacial dead layer. All the samples showed a diffuse type phase transitions. Both the dielectric constant and loss tangent showed anomaly peaks at about 10°C, which corresponds to a tetragonal ferroelectric-to-cubic paraelectric phase transition.
Vanadium pentoxide hierarchical structure networks for high performance ethanol gas sensor with dual working temperature characteristic
Article
Jan 2014
SENSOR ACTUAT B-CHEM
Guangtao Fan
Kaixuan Liu
Yuxiang Qin
Ming Hu
Gas sensors based on V2O5 hierarchical structure networks were formed through a direct seed-induced hydrothermal growth of nanostructured V2O5 on the substrate attached a pair of patterned Pt electrodes. Porous flower-or honeycomb-like V2O5 hierarchical structures could be controlledly synthesized under different precursor (NH4VO3) concentrations. The as-prepared hierarchical structures of V2O5, especially the flower-like network with radially oriented ultrathin nanoneedles and nanoribbons and the over-laped nanowires as constituents, show favorable microstructure features for gas-sensing application. The ethanol gas sensing properties of V2O5 network-structured sensors were investigated at room temperature (20 degrees C) up to 300 degrees C over ethanol concentration ranging from 5 to 1000 ppm. The sensor based on V2O5 hierarchical structure network showed temperature-dependent p-to n-type response characteristic reversal, resulting in dual working temperature characteristic with the dual response extremes reached at room temperature (20 degrees C) and 250 degrees C respectively. The flower-like V2O5 network sensor exhibits perfect reversibility, high response value and fast response-recovery characteristic to ethanol gas at the dual working temperatures, due to the good interface performance and gas adsorption-desorption properties of the directly assembled porous network. At 250 degrees C, the flower-like V2O5 network sensor is much sensitive to both ethanol gas and NH3, while at room temperature, the sensor presents very good selectivity to ethanol gas.
Synthesis and NO<SUB>2</SUB>-Sensing Properties of One-Dimensional Tungsten Oxide Nanowire Bundles
Article
Dec 2011
J NANOSCI NANOTECHNO
Zhiying Bao
Yuxiang Qin
Ming Hu
Jie Zhang
Tungsten oxide nanowires were synthesized by solvothermal method with tungsten hexachloride (WCl6) as precursor. X-ray diffraction, field emission scanning electron microscope and transmission electron microscope characterizations indicated that the as-synthesized nanowires
are single phase monoclinic W18O49. With WCl6 concentration increasing, the bundled nanowire became shorter and thicker. The gas-sensing properties of W18O49 nanowire towards NO2 gas were evaluated and the results showed that
the optimal gas sensitivity is achieved at 150 °C and the thinner nanowire exhibits the higher sensitivity. The results indicate that tungsten oxide nanowire is a promising gassensing material for high performance and low power cost NO2 gas sensor.
Physicochemical Aspects, Current Opinion in Colloid & Interface Science, 5(2), 70-172 (2000)
Full-text available
Jan 2000
John Texter
www.elsevier.nl/locate/cocis Editorial overview Physicochemical aspects of colloid and interface science 1. Physicochemical . . . The physicochemical aspects theme of this issue is very broad. The term of art, physicochemical, sub-sumes most topics that combine physical properties with some chemical step or some type of chemistry. Such aspects are further restricted in the present context, as they apply to colloid and interface science. Most physical measurement techniques that have been applied to bulk phases are directly applicable to col-loidal solutions and suspensions, and further have been refined and modified in applications to inter-faces. Techniques developed for intefaces, such as second harmonic generation methods for non-centrosymmetric systems (ideally articulated by inter-faces), have been modified and applied successfully to colloidal suspensions [ 1°,200]. Various aspects of elec-trochemistry and dielectric spectroscopy [3] have been instituted as raster-scanning microscopies, augment-ing AFM-related techniques. The contributions to this issue span a wide range of technology and instru-mentation. The interfaces examined in these con-tributions are finite (particles, micelles, vesicles) through infinite (liquid-gas interfaces, electrode in-terfaces). 2. Planar interfaces 2.1. Spectroscopy A tour de force for non-linear optical techniques has been the extension of vibrational and electronic spectroscopy to planar interfaces using second har-monic generation (SHG) techniques. A key result is that these SHG methods probe vibrational, vibronic, and electronic structure, as conventionally probed in the bulk by infrared, Raman, and UV/Vis spectro-scopy, but rely on fluorescence emission processes that yield high interfacial sensitivity. Allen et al. (this issue) extend the seminal contribu-tions of Richmond's group in the analysis of surfactant aggregation at liquid-liquid interfaces [4"] by vibrational sum frequency spectroscopy (VSFS) to the more detailed analysis of water at aqueous inter-faces. Water, a non-normal liquid, is key to many interfacial chemistries, and the results reviewed here show how orientation of important solutes and inter-facial structure may be directly probed by VSFS.
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Synthesis of High Aspect Ratio PbBi4Ti4O15 and Topochemical Conversion to PbTiO3-Based Microplatelets
Aug 2011
J AM CERAM SOC
Stephen F. Poterala
Meyer Richard J.
Gary L. Messing
Perovskite microplatelets of the composition 0.4(Na1/2Bi1/2) TiO3–0.6PbTiO3 (0.4NBT–0.6PT) were synthesized by topochemical conversion of the Aurivillius phase PbBi4Ti4O15 in a NaCl/Bi2O3/PbO flux system. To facilitate morphologic control, we investigate the effects of TiO2 particle size on molten salt growth of the PbBi4Ti4O15 phase. We find that the initial nucleation density and [100] thickness of this phase are controlled by the TiO2 dissolution rate, while the platelet diameter is determined by Ostwald ripening. PbBi4Ti4O15 microplatelets produced using these methods can be converted entirely to a tetragonal perovskite phase (c/a=1.051) while retaining the dimensions of the precursor PbBi4Ti4O15 phase. We propose that the resulting 0.4NBT–0.6PT composition is favored thermodynamically due to the lower free energy of this composition relative to pure PbTiO3. In addition, partial (Na1/2Bi1/2)TiO3 substitution is kinetically favored as it reduces A-site diffusion during the topochemical conversion process.
Structure and properties of BT and BST thin films
Jan 2013
FERROELECTRICS
Hidangmayum Basantakumar Sharma
Barium titanate [BT] and barium strontium titanate [BST] solid solution films have been fabricated by a modified sol-gel processing technique from barium acetate {Ba(CH3COOH)2}, strontium acetate [Sr(CH3COOH)2] and titanium (IV) Isopropoxide [Ti[(CH3)2CHO]4] precursors. The as-fired films were found to be amorphous that crystallized to perovskite phase after annealing the films at 550°C in air for one hour. The dielectric constant () and loss tangent (tanδ) of the BaTiO3 film at 1 kHz was found to be 360 and 0.01 respectively. The dielectric constant showed a broad anomaly peak at 130°C that confirms ferroelectric-paraelectric transition. The room temperature dielectric constant and loss factor of this film were found to be 450 and 0.005 respectively. The dielectric anomaly peak of the BST film was found to shift towards lower temperature with Sr content. Both BT and BST showed butterfly capacitance-voltage (C-V) and conductance-voltage (G-V) loops, confirming the existence of ferroelectricity in these films.
Synthesis and characterization of novel nanorod superstructures and twin octahedral morphologies of WO3 by hydrothermal treatment
Sep 2012
MATER CHEM PHYS
Amokrane Sonia
Yahia Djaoued
Balaji Subramanian
Benrejdal Achour
Controlled WO3 morphologies, such as nanorods and octahedral structures, were synthesized by the hydrothermal technique using sulfate salts based structure directing agents (SDAs). The role of the sulfate salts’ cation in controlling the shape, size and phase of WO3 nanomaterials was investigated by choosing sulfate salts whose cations are from d-bloc elements (FeSO4, (NH4)2Fe(SO4)2, CoSO4, CuSO4, ZnSO4), an alkaline earth metal (MgSO4) and a non-metal ((NH4)2SO4). In addition chloride (MnCl2) and acetate (Zn(CH3CO2)2) anion based SDAs were also used in order to clarify the role of sulfate ions in the growth of WO3 nanostructures. We controlled the pH of the reaction medium with oxalic acid. The obtained WO3 samples were investigated by SEM, micro-Raman, and XRD. At pH = 1, the WO3 samples exhibit novel superstructures consisting of aligned hexagonal nanorods, whereas at pH = 5.25, novel twin octahedral morphology with a cubic structure is obtained. The results demonstrate that the phase and morphology change is influenced by the pH and both the anion and the cation of the SDA. A growth mechanism for the obtained novel WO3 morphologies is presented.
Temperature Dependent Dielectric Properties of Ba0.8Sr0.2TiO3 Nanocrystalline Thin Films
Article
Oct 2010
Bobby Singh Soram
Hidangmayum Basantakumar Sharma
Barium strontium titanate (Ba0.8Sr0.2TiO3) nanocrystalline thin film fabricated by a modified sol-gel process was crystallized at low temperature 550 °C. The microstructure displayed a polycrystalline nature with average nanograin size of 11 nm. The BST thin film annealed at 550 °C show good dielectric properties. The BST thin films show a diffuse type phase transition. The room temperature dielectric constant and dissipation factors are 310 and 0.03 at 100 kHz, respectively. The capacitance-frequency curves reveal that the film shows typical frequency dispersion at low frequency. The ferroelectric nature of the BST thin film was indicated by butterfly-shaped C-V curves. The effect of temperature on C-V characteristic of the BST thin films has been investigated. The sample shows paraelectric nature well above the transition temperature as indicated by the absence of butterfly-shaped C-V curves.
Synthesis of Well-Crystallized Manganese Oxide from Precipitation: Effect of Introducing Carbonate Anions
Article
Jan 2005
Ting Fang
Jenq Gong Duh
Powdery hausmannite (Mn3O4) is of interest in many industrial and technological applications. It is widely used as reactive catalysts, raw material of humidity sensors, and the cathode oxides of Li-ion secondary batteries. In this study, sub-micron and nano-meter sized Mn 3O4 powders are prepared by an efficient method at room temperature. Mn(OH)2 nanocrystals are commonly precipitated at first and then oxidized in the alkaline solution containing excess OH- anions. However, conventionally prepared Mn3O4 powders by the above process are ill-crystallized. To enhance the crystallinity of fabricated powders, CO32- anions are introduced into the process. The modified autoxidation method is practical to fabricate low-cost and high grade powders of Mn3O4 Advantages of the modified method are confirmed by both the electron micrographs and XRD patterns of synthesized powders. It is revealed that particle size of the products is in the sub-micron meter range, and the particle morphology can be adjusted by altering the precipitation sequence.
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Hydrothermal Synthesis of Tabular Perovskite Particles
Article
Jan 2002
Ender Suvaci
Julie M. Anderson
Gary L. Messing
James Adair
Phase pure perovskite lead titanate and lead zirconate titanate powders were produced by hydrothermal synthesis. Reaction temperature and time are critical processing parameters for formation of phase-pure perovskite particles. In addition, solution pH should be greater than 14 to produce well-crystallized lead-based perovskite particles. Particle size and morphology of the particles can be tailored by mineralizer concentration and/or stirring rate.
Role of colloidal chemistry in synthesis and processing of alpha-alumina
Article
Jan 2005
Rajneesh Kumar
The role of colloidal chemistry in solution synthesis and processing of alpha-alumina (alpha-Al2O3, corundum) was investigated. Experiments were designed to investigate the role of water, produced by degradation of 1,4-butanediol, on equilibrium morphology of alpha-Al2O 3 particles synthesized under glycothermal conditions. Development of platelet like morphology was promoted by low water concentrations in the solvent, and development of polyhedron morphology was promoted by high water concentrations in the solvent. A theoretical model predicting morphology for particles produced under solution conditions is proposed, with the possibility of extension of the model to any particle produced under solution conditions. A comparison was made between theoretically predicted and experimentally observed morphologies of alpha-Al2O3. Glycothermal synthesis process for preparing sub 100 nm phase pure alpha-Al2O3 nanoparticles with platelet morphology has been developed. The role of treatment temperature, seed concentration, stirring speed and solvent water content was investigated in controlling particle size and shape. Phase pure alpha-Al2O 3 nanoparticles were synthesized with specific surface area (SSA) as high as 40 m2/gm and temperatures as low as 235°C. An attempt has been made towards understanding the aggregation mechanism in alumina nanoparticles. The modeling of hydration and aggregation of alumina clusters was done using PM5 semi-empirical parameters as implemented in CAChe Worksystem. Prolonged aging of hydrated nanoparticles, even under ambient conditions, can cause bridging among the particles that can lead to neck formation resulting in aggregation of nanoparticles. Nanophase alumina powder was de-aggregated and successfully dispersed from 11 mum agglomerate/aggregate sizes down to 20 nm in 1 hr by using a chemically aided milling (CAAM) technique. Design of Experiments (DOE) was used to determine the important experimental factors to efficiently mill alumina by the CAAM process. The size of grinding media had the most significant effect in achieving average agglomeration number (AAN) less than 10, indicating well dispersed suspensions. Shaft rpm emerged as the most significant factor in controlling impurity through media wear.
Synthesis and colloidal properties of anisotropic hydrothermal barium titanate
Article
Jan 2005
Timothy Yosenick
Nanoparticles of high dielectric constant materials, especially BaTiO3,
are required to achieve decreased layer thickness in multilayer ceramic
capacitors (MLCCs). Tabular metal nanoparticles can produce thin metal
layers with low surface roughness via electrophoretic deposition (EPD).
To achieve similar results with dielectric layers requires the synthesis
and dispersion of tabular BaTiO3 nanoparticles. The goal of this study
was to investigate the deposition of thin BaTiO3 layers using a
colloidal process. The synthesis, interfacial chemistry and colloidal
properties of hydrothermal BaTiO3 a model particle system, was
investigated. After characterization of the material system particulates
were deposited to form thin layers using EPD. In the current study, the
synthesis of BaTiO3 has been investigated using a hydrothermal route.
TEM and AFM analyses show that the synthesized particles are single
crystal with a majority of the particle having a <111> zone axis
and {111} large face. The particles have a median thickness of 5.8 +/-
3.1 nm and face diameter of 27.1 +/- 12.3 nm. Particle growth was likely
controlled by the formation of {111} twins and the synthesis pH which
stabilizes the {111} face during growth. With limited growth in the
<111> direction, the particles developed a plate-like morphology.
Physical property characterization shows the powder was suitable for
further processing with high purity, low hydrothermal defect
concentration, and controlled stoichiometry. TEM observations of
thermally treated powders indicate that the particles begin to loose the
plate-like morphology by 900 °C. The aqueous passivation,
dispersion, and doping of nanoscale BaTiO 3 powders was investigated.
Passivation BaTiO3 was achieved through the addition of oxalic acid. The
oxalic acid selectively adsorbs onto the particle surface and forms a
chemically stable 2-3 nm layer of barium oxalate. The negative surface
charge of the oxalate effectively passivated the BaTiO3 providing a
surface suitable for the use of a cationic dispersant, polyethylenimine
(PEI). Rheological properties indicate the presence of an oxalate-PEI
interaction which can be detrimental to dispersion. With a better
understanding of the aqueous surface chemistry of BaTiO3 the surface
chemistry was manipulated to control the adsorption of aqueous soluble
complexes of Co, Nb, and Bi, three common dopants in the processing of
BaTiO3 Surface charge, TEM, and EDS analysis showed that while in
suspension the dopants selectively absorbed onto the particle surface
forming an engineered coating. (Abstract shortened by UMI.)
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Templated Grain Growth of Textured Piezoelectric Ceramics
Article
Full-text available
Apr 2004
CRIT REV SOLID STATE
Gary L. Messing
S. Trolier-McKinstry
Edward Sabolsky
Kyung-Sik Oh
Templated grain growth (TGG) which enables the fabrication of textured ceramics with single crystal-like properties was discussed. In TGG, nucleation and growth of the desired crystal on aligned single crystal template particles results in an increased fraction of oriented material with heating. To facilitate alignment during forming, template particles must be anisometric in shape. Means to further improve the quality of texture and thus properties of textured piezoelectric ceramics by TGG were presented.
Dielectric Properties of Nanocrystalline Ba0.6Sr0.4TiO3 Thin Films Prepared by a Modified Sol-Gel Process
Article
Nov 2010
INTEGR FERROELECTR
Hidangmayum Basantakumar Sharma
Bobby Singh Soram
Barium strontium titanate (Ba0.6Sr0.4TiO3) nanocrystalline thin film fabricated by a modified sol-gel process was crystallized at low temperature 550°C. The microstructure displayed a polycrystalline nanostructure. The BST thin film annealed at 550°C show good dielectric properties. The room temperature dielectric constant and dielectric loss were, respectively 335 and 0.0447 with no bias, while 263 and 0.0379 with dc bias of 10 V at 100 kHz. The film shows typical frequency dispersion at low frequency. The paraelectric nature of the BST thin film was indicated by non-linear field dependence capacitance-voltage curve with the absence of butterfly-shaped C-V curve. The tunability and figure of merit of the BST thin film are calculated to be 21.44% and 5.66 respectively, at an applied voltage of 10 V.
Hydrothermal synthesis of lead titanate and lead zirconate titanate electroceramic particles
Article
May 2003
CHEM ENG COMMUN
Aydin Doğan
Julie M. Anderson
Ender Suvaci
James Adair
Hydrothermal synthesis of two lead-based perovskite powder systems, lead titanate and lead zirconate titanate, was investigated. Phase-pure perovskite lead titanate and lead zirconate titanate with various morphologies have been synthesized by hydrothermal methods at 150° and 175°C, respectively. Solution pH should be greater than 14 to obtain the phase-pure perovskite phases in a reasonable time. In addition, the KOH concentration and the stirring rate significantly influence particle morphology of the hydrothermally derived PT and PZT. Therefore, these parameters can be used to tailor particle size and morphology.
Synthesis of Nanotabular Barium Titanate Via a Hydrothermal Route
Article
Apr 2005
J MATER RES
Timothy Yosenick
David V. Miller
Rajneesh Kumar
James Adair
As layer thickness of multilayer ceramic capacitors decreases, nanoparticles of high dielectric materials, especially BaTiO3, are needed. Tabular metal nanoparticles produce thin metal layers with low surface roughness via electrophoretic deposition. To achieve similar results in dielectric layers requires the synthesis and dispersion of tabular BaTiO3 nanoparticles. In the current study, the synthesis of BaTiO3 was investigated using a hydrothermal route. Transmission electron microscopy and atomic force microscpy analyses show that the synthesized particles are single crystal with a 〈111〉 zone axis and a median thickness of 5.8 nm and face diameter of 27.1 nm. Particle growth is likely controlled by the formation of {111} twins and the synthesis pH, which stabilizes the {111} face during growth. With limited growth in the 〈111〉 direction, the particles develop a platelike morphology. Physical property characterization shows the powder is of high purity with low hydrothermal defect concentrations and controlled stoichiometry.
Self-Assembled Growth of PbTiO3 Nanoparticles into Microspheres and Bur-Like Structures
Article
Mar 2007
ChemInform
Randi Holmestad
Per Martin Rørvik
A. T. J. van Helvoort
Mari-Ann Einarsrud
Novel bur-like hierarchical nanostructures of PbTiO3 were prepared by hydrothermal synthesis. Surfactants containing phenyl-sulfonic groups resulted in self-assembly of nanocrystals. In absence of the surfactant, monodisperse PbTiO3 microspheres were formed. The microspheres were 1−5 μm in diameter, and consisted of 20 nm tetragonal PbTiO3 crystals. The microspheres were formed by primary nucleation of PbTiO3 nanocrystals followed by aggregation into microspheres. The hierarchical bur-like nanostructures exhibit a unique geometry consisting of a microsphere core with an outer shell of nanorods. The nanorods, which grow along the [001] direction, were 50−100 nm in diameter and from several hundreds of nanometers up to 2 μm in length. A mechanism for the growth of the bur-like nanostructures was proposed. First, agglomeration of PbTiO3 nanocrystals into microspheres occurs. PbTiO3 mesocrystals are formed at the surface of the microspheres by self-assembly of cube-shaped or facetted PbTiO3 nanocrystals, and the mesocrystals ripen and grow further into nanorods.
Decomposition and Crystallization of a Sol–Gel-Derived PbTiO3 Precursor
Article
Aug 2007
Sverre M. Selbach
Tor Grande
Guozhong Wang
Mari-Ann Einarsrud
A lead titanate (PbTiO 3) precursor, prepared by the Pechini method, has been heat treated to study the transformation from amorphous to crystalline PbTiO 3 . Nucleation of PbTiO 3 in the temperature interval 4001–4751C occurred before completion of the thermal decomposition of the polymeric precursor, resulting in nanocrystalline PbTiO 3 with an unexpectedly high tetragon-ality (c/a ratio). Annealing and crystallite growth at 6001C resulted in an increasing c/a ratio with annealing time in line with the expected finite size effect of PbTiO 3 . The unusually high c/a ratios observed in PbTiO 3 nucleated at 4001–4751C are discussed in relation to partial reduction and point defects in PbTiO 3 .
Nucleation and growth of self-assembled nanofibre-structured rutile (TiO2) particles via controlled forced hydrolysis of titanium tetrachloride solution
Article
Dec 2009
J CRYST GROWTH
Cecile Charbonneau
Raynald Gauvin
George P. Demopoulos
In this study the production of rutile (TiO2) nanostructured powders by forced hydrolysis of aqueous Ti(IV) chloride solutions was investigated in terms of precipitation kinetics and nucleation and growth mechanism over the temperature range 70–90 °C and Ti(IV) concentration 0.5–1.5 M. The precipitation kinetics was found to follow the Avrami model exhibiting a slow induction–nucleation stage and accelerating growth stage. The type and speed of agitation was found to have a pronounced effect on the nucleation kinetics that required the adoption of a mechanically agitated (1000 rpm) reactor for the obtainment of reproducible results. An increase in Ti(IV) chloride concentration was found to have a negative effect on kinetics pointing to differences in a precursor complex formation and polymerization behaviour. The obtained nanostructured rutile powder had a spheroidal particle morphology with the interior of the particles characterized by a nucleation core and self-assembled elongated fibres. The nucleation core consisted of primary aggregates of elementary nanocrystallites of ∼10–20 nm size. The nanofibres were found to form via preferential growth of the (1 1 0) atomic planes. The nanostructured rutile powder exhibited high specific surface area in the order of 80 m2/g.
Hydrothermal Synthesis and Formation Mechanism of Lanthanum Tin Pyrochlore Oxide
Article
Dec 2004
J AM CERAM SOC
Jooho Moon
Masanobu Awano
Kunihiro Maeda
Well-defined La2Sn2O7 with a phase-pure pyrochlore structure was produced by hydrothermal synthesis at temperatures as low as 200°C. Production of phase-pure La2Sn2O7 requires a pH above 10, and higher pH accelerates the crystallization process. The synthesis produced spherical particles of average particle size ∼0.59 μm (±0.12) and surface area ∼14.1 m2/g. SEM and TEM observation for morphologic evolution and kinetic analysis during crystallization indicated that La2Sn2O7 formation probably proceeds via a two-step reaction. First a transient dissolution–precipitation occurs. Then the primary crystallites aggregate because of their colloidal instability, and heterocoagulation with the lanthanum hydrous oxide precursor particles also occurs. The sluggish reaction rate at the later stage of reaction is characterized by an insitu transformation, where the soluble tin species is diffused through the porous La2Sn2O7 aggregates to react with entrapped lanthanum precursors.
Solvothermal Synthesis of Tungsten Oxide Nanorod/Nanowire/Nanosheet
Article
Jun 2005
J AM CERAM SOC
Hong Goo Choi
Young Hwa Jung
Do Kyung Kim
A simple process enables to synthesize tungsten oxide with various nanomorphologies, i.e. nanorods, nanowires, and nanosheets. The tungsten hexachloride (WCl6) was used as a raw material and the tungsten oxide nanoparticles were obtained by solvothermal treatment with solvents, i.e., ethanol, mixed solvent (ethanol+water), and water, at 200°C for 10 h. The various crystalline phases of tungsten oxide, such as monoclinic W18O49 nanorods, hexagonal WO3 platelets, and monoclinic WO3 nanosheets, were synthesized by simply changing the composition of the solvent. The oxygen, which was contained in water, played an important role in the final tungsten oxide phase. Especially, W18O49 nanorods grew to nanowires as the concentration of WCl6 was decreased. Using this simple process, it will be possible to control the crystalline phase and morphologies of nanostructured tungsten oxide system.
Hydrothermal Synthesis of Nanomaterials
Chapter
Jan 2004
O. Schäf
H. Ghobarkar
Philippe Knauth
Morphological Control of Particles
Article
Mar 2000
CURR OPIN COLLOID IN
James Adair
Ender Suvaci
The objective of this review is to highlight the theoretical and practical aspects of particle morphological control. Materials with directional properties are opening new horizons in material science. Structural, optical, and electrical properties can be greatly augmented by the fabrication of composite materials with anisotropic microstructures or with anisotropic particles uniformly dispersed in an isotropic matrix. Examples include structural composites, magnetic and optical recording media, photographic film, and certain metal and ceramic alloys. The new applications and the need for model particles in scientific investigations are rapidly outdistancing the ability to synthesize anisotropic particles with specific chemistries and narrowly distributed physical characteristics (e.g. size distribution, shape, and aspect ratio). Anisotropic particles of many compositions have been produced but only a few (γ-Fe2O3 and AgI) are produced with any degree of chemical and physical control. These two examples are the result of literally decades of study. Unfortunately, the science and technology (mainly the technology) that have evolved are maintained as proprietary information. Thus, while we generally know what systems yield single crystal, anisotropic-shaped particles, we do not know how to make powders of these crystals with the desired control of shape uniformity, aspect ratio and phase composition. Particle shape control is a complex process requiring a fundamental understanding of the interactions between solid state chemistry, interfacial reactions and kinetics, and solution (or vapor) chemistry. During synthesis of other than a large single crystal the parameters controlling crystal growth must be balanced with the requirements for anisotropic powder nucleation and growth. Although there has been considerable progress in large single crystal growth and the synthesis of powders composed of monodispersed, spherical particles, these efforts have not often been transferred to the synthesis of anisotropic particles.
Microstructure characterization and NO2-sensing properties of tungsten oxide nanostructures
Article
Sep 2010
SENSOR ACTUAT B-CHEM
Yuxiang Qin
Ming Hu
Jie Zhang
Nanowires and nanosheets of tungsten oxide were synthesized by solvothermal method with different tungsten hexachloride (WCl6) concentrations in 1-propanol solvent. The morphology and crystal structure of the tungsten oxide nanostructures were investigated by means of field emission scanning electron microscope, X-ray diffraction and transmission electron microscope. The specific surface area and pore size distribution were characterized by Brunauer–Emmett–Teller gas-sorption measurements. One-dimensional W18O49 nanowire bundles were synthesized at the WCl6 concentration of 0.01 M. With the concentration increasing to 0.02 M, the structure of the pure two-dimensional WO3 nanosheets was formed. The NO2 gas sensing properties of W18O49 nanowires and WO3 nanosheets were investigated at 100 °C up to 250 °C over NO2 concentration ranging from 1 to 20 ppm. Both nanowires and nanosheets exhibit reversible response to NO2 gas at different concentrations. In comparison to WO3 nanosheets, W18O49 nanowire bundles showed a much higher response value and faster response–recovery characteristics to NO2 gas, especially a much quicker response characteristic with response time of 19 s at the concentration of 5 ppm.
Synthesis of bundled tungsten oxide nanowires with controllable morphology
Article
May 2009
MATER CHARACT
Shibin Sun
Zengda Zou
Guanghui Min
Bundled tungsten oxide nanowires with controllable morphology were synthesized by a simple solvothermal method with tungsten hexachloride (WCl6) as precursor and cyclohexanol as solvent. The as-synthesized products were systematically characterized by using scanning electron microscopy, X-ray diffraction and transition electron microscopy. Brunauer–Emmett–Teller gas-sorption measurements were also employed. Accompanied by an apparent drop of specific surface area from 151 m2 g− 1 for the longer nanowires synthesized using a lower concentration of WCl6 to 106 m2 g− 1 for the shorter nanowires synthesized using a higher concentration of WCl6, a dramatically morphological evolution was also observed. With increasing concentration of tungsten hexachloride (WCl6) in cyclohexanol, the nanostructured bundles became larger, shorter and straighter, and finally a block-shape product occurred.
Hierarchical Nanostructures of PbTiO3 Through Mesocrystal Formation
Article
Full-text available
Aug 2007
J NANOSCI NANOTECHNO
Guozhong Wang
Ragnhild Sæterli
Per Martin Rørvik
Mari-Ann Einarsrud
Novel hierarchical self-assembled structures; bur-like PbTiO3 nanostructures were made by self-assembly of PbTiO3 nanocrystals under hydrothermal conditions using sodium dodecylbenzene sulfonate surfactant. The bur-like nanostructures exhibit a unique geometrical shape with cores of agglomerated nanocrystals and outershells of nanorods. The nanorods were between 30 nm and 100 nm in diameter and from several hundred nm up to 2 microm in length. We demonstrate that these nanostructures are formed in a two step process where agglomeration of PbTiO3 nanoparticles into microspheres occurs in a first step, followed by assembly of cube-shaped nanoparticle building blocks into PbTiO3 mesocrystals in a second step. The mesocrystals continuously grow into nanorods from the surface of the microspheres acting as a substrate.
Particle-shape control of molten salt synthesized lead titanate
Conference Paper
Feb 2000
Y. Ito
B. Jadidian
Mehdi Allahverdi
Ahmad Safari
Lead titanate PbTiO<sub>3</sub> (PT) powders with different
morphologies were synthesized using a molten salt method. Amorphous PT
powder was prepared from an aqueous nitrate solution, mixed with a
eutectic of NaCl-KCl, and then heated at 850°C for 1 h. The effect
of additives such as LiF, NaF and LiCl on the particle morphology and
size of the derived PT was studied. Adding small amount of LiF (<1
wt.%) to the salt, cubic-shaped particles were obtained. The Li ions
played an important role on the formation of cubic PT particles. In
addition, LiF was more effective on the growth of cubic particle than
LiCl. Furthermore, new useful molten salt systems composed of KCl and
LiF were developed to make cubic and rectangular-shaped PT particles
Aqueous chemistry and geochemistry of oxides, oxyhydroxides, and related materials
Conference Paper
Full-text available
Aug 1997
J. A. Voigt
T.E. Wood
B.C. Bunker
Laura J. Crossey
| https://www.researchgate.net/publication/237652068_Particle-Shape_Control_and_Formation_Mechanisms_of_Hydrothermally_Derived_Lead_Titanate |
UNPO: Catalonia: ECJ Rules that Jailed Catalan Leader 'Should Have Had Immunity'
Catalonia: ECJ Rules that Jailed Catalan Leader 'Should Have Had Immunity'
Below is an article published by BBC
The European Court of Justice (ECJ) said that Oriol Junqueras had become an MEP the moment he was elected in May, despite being on trial for sedition.
Junqueras was later convicted and jailed for his role in an illegal 2017 Catalan independence referendum.
The separatist leader said on Thursday that "justice has come from Europe".
"Our rights and those of two million citizens who voted for us have been violated," he tweeted, adding: "Annulment of the sentence and freedom for all!"
However, the ruling does not address Junqueras's prison term.
Two other top Catalan separatists were elected as MEPs in May and the ruling may affect them too. Former Catalan President Carles Puigdemont and Toni Comin fled to Belgium before Spain could detain them.
However, they could not take up their seats in European Parliament as, like Junqueras, they had not sworn the Spanish oath.
Spanish law requires new MEPs to swear an oath on the constitution in Spain. Junqueras, the former Catalan vice-president who has been in custody since November 2017, was not allowed to do this while on trial and in provisional detention.
On Thursday, the ECJ ruled that Junqueras should have "enjoyed the immunities guaranteed" by EU law after the election results were confirmed.
It added that if Spanish courts had wanted to maintain his detention to prevent him from travelling to the European Parliament for his inauguration, they should have requested that Parliament waive his immunity.
"The purpose of that immunity is to allow such persons to... travel to and take part in the inaugural session of the newly-elected European Parliament," the ruling stated.
Responding to Thursday's ruling, Mr Puigdemont tweeted: "Immediate freedom for @junqueras."
The immunity rules protect an MEPfrom any investigation or prosecution based on their opinions or votes as an MEP. But an MEP found to have committed an offence cannot claim immunity.
Junqueras was sentenced to 13 years in jail for sedition and misuse of public funds by the Supreme Court in October. Eight other Catalan separatists also received jail sentences.
After Thursday's ruling, his defence team immediately filed an appeal to Spain's Supreme Court over the legitimacy of his trial and conviction.
Massive street protests have periodically erupted in Catalonia since the separatist leaders were jailed, with hundreds of people injured in rioting.
During Barcelona's march against Real Madrid at the Nou Camp on Wednesday night,protesters demanding Catalan independence clashed with policeoutside the ground while thousands of fans held up banners inside the stadium.
Catalan nationalists have long complained that their region, which has a distinct history dating back almost 1,000 years, sends too much money to poorer parts of Spain, as taxes are controlled by Madrid.
In 2017, police and protesters clashed in the streets when Catalonia's pro-independence leaders went ahead with a referendum, which had been ruled illegal by Spain's constitutional court.
The Catalan regional parliament subsequently voted to declare independence from Spain. Angered by that, Madrid imposed direct rule by invoking Article 155 of the constitution - a first for Spain.
The Spanish government sacked the Catalan leaders, dissolved parliament and called a snap regional election on 21 December 2017, which nationalist parties won.
At their trial Junqueras and other separatists said they were victims of an injustice and "false" charges.
In a separate development on Thursday, a court in Barcelona banned Quim Torra, the pro-independence leader of Catalonia's regional government and a close ally of Mr Puigdemont, from holding public office for 18 months.
The ruling, which relates to Mr Torra's refusal to order the removal of separatist symbols from buildings during an election campaign, will only come into effect if it is approved by Spain's Supreme Court.
Photo: Getty images
| https://unpo.org/article/21721 |
Debate: Budget Resolutions - 30th Oct 2018 - Drew Hendry extracts
Tue 30th Oct 2018 - Commons - Budget Resolutions debate Drew Hendry contributions to the 30th October 2018 Budget Resolutions debate
Drew Hendry Excerpts Business Rates Reform
Tuesday 30th October 2018
(4 years, 8 months ago)
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Do you know what? The reality is that we have argued for a very long time—I have argued for my entire adult life—against the current democratic system, because it does not work for the people of Scotland. We do not get the Governments we vote for and we do not get the result that we voted for in the EU referendum. If the democratic system meant that Scotland’s votes were reflected in reality, we would be in a very different situation today.
On a serious note, every week in our communities and at our surgeries MPs from both sides of the House are faced with the consequences of Westminster’s poor decisions. We see working mothers forced to go to food banks. We see and hear about the Home Office-enforced separation of families. We meet young men struggling with mental health problems who have been sanctioned yet again because they are unable to jump through the unreasonable hoops put in their way by the Department for Work and Pensions. I do not know how anybody,
even in this Westminster Government, can believe that their policies are having a positive benefit. The tears and desperation with which we are all faced on a regular basis give the lie to that notion.
The Chancellor has failed adequately to fund our public services in this Budget. He has failed to undo the devastating social security cuts, he has failed to legislate for a real living wage and he has failed to provide adequate support for businesses facing the impending cliff edge of Brexit.
The Budget should have included decisions to help support all those who have been hit by a decade of austerity, and all those who will be hit by the forthcoming Brexit. The roll-out of universal credit should have been halted. A third of working-age households will be entitled to some universal credit. Of those, around a third will be at least £1,000 a year worse off than under the legacy system.
Drew Hendry (Inverness, Nairn, Badenoch and Strathspey) (SNP)
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Does my hon. Friend agree that the Government missed an opportunity in the Budget yesterday not only to correct the injustices of universal credit but to compensate councils such as Highland Council that are having to foot a £2.5 million bill out of council tax funds simply for administering this failed and shambolic universal credit roll-out?
Kirsty Blackman
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Absolutely. The Highland Council area has been particularly badly hit as one of the first areas in which universal credit was rolled out. It is currently rolling out in Aberdeen, and I am hugely concerned about the impact it will have on my constituents. The roll-out needs to be halted, because the issues that happened in the highlands and elsewhere have not been fixed, and they need to be fixed before any further roll-out can occur.
The benefits freeze should have been lifted, the sanctions regime should be scrapped, support for lone parents under the age of 25 must be reintroduced and the WASPI issue must be sorted, with those women being given the money they are owed. I am pleased that the Government have made a commitment to the pensions dashboard, but they now need to legislate to compel companies to comply so that people can access information about the pensions they are owed, and so that they can then get those pensions. That is important, and lots of people have been calling for it.
Workers’ rights are another reserved issue, and the Chancellor should have committed to increasing the minimum wage to the living wage—an amount people can actually live on—by the end of this Parliament. The Office for National Statistics said this week:
“Among the countries of the UK, long-term pay growth has been highest in Scotland… Median pay for full-time workers was 87% higher in Scotland than it was in 1997.”
The Scottish Government are doing all they can, particularly for staff employed in public sector roles, but we need the powers to do more. In Scotland, our Government have focused on uplifting the pay packets of the lowest paid, which is a progressive choice that makes the most positive difference. The UK Government have not chosen to do that.
We have fought long and hard for a single, real living wage rate. The UK Government need to recognise that it does not cost a 24-year-old less to live than it costs a
25-year-old. If the Chancellor will not make the required commitment to a real living wage for all, he should devolve it so that we can.
Statutory paternity leave should be doubled from two to four weeks, giving fathers even more opportunity to bond with their babies. A complete review of parental leave should be undertaken, including consideration of the start date of maternity leave, especially when a baby is born prematurely.
We propose that the Government set up a labour participation committee to consider groups that are currently under-represented or over-represented in certain sectors, and to examine barriers to work for women, disabled people, parents and other marginalised groups.
The Institute of Directors has called for a pot to be set aside so that small and medium-sized enterprises can bid for advice on how to cope with Brexit. The UK Government’s advice thus far has been wholly inadequate, and we have only five months to go until the UK crashes out of the EU.
Businesses need to be able to access finance in order to grow. To do that, they need to have trust in financial institutions and, crucially, financial institutions need to earn that trust. The Chancellor should have committed to setting up a tribunal service so that those affected by business banking fraud—through the Royal Bank of Scotland’s global restructuring group, Lloyds Bank, Halifax Bank of Scotland or others—can seek affordable redress, rather than having to go through a court process that is too expensive to access.
The UK Government must also ensure that current EU funding will continue until the end of the current multi-annual financial framework. Scotland must not be any worse off in respect of the funding allocations that replace those provided from the EU, and any arrangements must fully respect devolution and must be put in place with the consultation and agreement of the Scottish Parliament.
The Chancellor had an opportunity to make a commitment to the oil and gas sector deal, and he failed to do so. Our industry needs the deal to be signed off now, particularly with the impending lack of access to labour and investment following Brexit. I am pleased that he has heeded calls to make a clear statement on the future fiscal regime, because we cannot have unforeseen, sudden tax hikes like those made by previous Chancellors.
The other part of the jigsaw that is missing is a commitment to reducing the harmful climate change effects of the use of fossil fuels. In 2015, the UK Government cancelled their £1 billion carbon capture and storage competition, just six months before it was due to be awarded, after spending £100 million on it. That left Peterhead—a key candidate for support—behind. After three years of research and development, we have missed out on this vital industry of the future. The UK Government need to make an unequivocal commitment to supporting the development of CCS.
Drew Hendry
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My hon. Friend makes a powerful point about carbon capture, and about the betrayal of the £1 billion project at Peterhead. Does she agree that, if the UK Government are serious about meeting the climate change targets under the Paris agreement, spending
£100 million now, when we are behind the pace after abandoning a three-year £1 billion project, is just not good enough?
Kirsty Blackman
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Absolutely. The potential benefits of CCS are unquestionable and, as my hon. Friend says, we need to get ahead of the curve again. We need the UK Government to commit to putting the money in now. That is especially important because their pulling the plug means there is now a lack of trust among the companies that are developing CCS. The UK Government need to make a clear and unequivocal commitment.
On evolving technologies, Scotland is a global leader in tidal, and the UK Government must work with the Scottish Government on the contract for difference process to support the technology journey from development to commercialisation, which is particularly important for tidal.
On solar power, we have been contacted by so many individuals who are concerned about what is happening to export tariffs for homes, small businesses and community energy projects from next April. The tariff is a vital support that encourages people to invest in solar power, and it must continue.
Lastly, in order to reduce climate change and to increase the use of healthier methods of transport, this Budget was an opportunity to reduce VAT on bikes. Just as we would like to see VAT removed from digital books, reducing VAT on bikes would make them cheaper for all and would be a real statement of intent from the Government on reducing climate change.
Return to start of debate
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A Swedish Stonehenge?
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Possible history of Dairy
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More Neanderthal remains found in Kurdistan’s Shanidar cave
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The Nuragic civilization.
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Underground 'superhenge' discovered in Wiltshire
6500 Year Old Necropolis Found in Bulgaria
Mummification in Bronze Age Britain
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Question about the relation of Tarim Mummies and Tocharians.
Rewriting the Central European Early Bronze Age Chronology
Steppe Populations Carried the Plague into Europe?
Pushing back the timeline for Stonehedge
First Farmers in the Levant Grew Legumes Not Grain
200,000-year-old lanterns and 100 other artifacts found in Duhok in Iraqi Kurdistan
Hunting for Doggerland
Bronze Age Settlement Found in Orkney,Scotland
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Found near Berlin an exceptional mesolithic burial...
3400 year old Caananite figurine of a woman discovered in Israel.
Mesolithic pendant found in Britain
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9000 years old neolithic bones discovered in Kurdistan, Zagros Mountains!
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Were Megalithic Tombs Also Telescopes?
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11,000 year old PPN Neolithic Village in Cyprus
Excavation of Must farm, UK's best bronze age site
Bronze Age Wall in Poland
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The Cimbri
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Otzi's clothing analyzed
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Cereals not part of the early Neolithic package in all places
Hemorrhagic fever in Iron Age Germany
upside-down pyramids?
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More Evidence of plague in LN/BA steppe populations
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Tensions between incoming Corded Ware herders/farmers and local Neolithic farmers
How did "cavemen" clean their teeth?
Is possibly metallurgy born with hunter-gatherers ?
6000 year old mask found in Neolithic setting in Germany
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Difference between revisions of "Extending Reflective Dialogue Support (Katz & Connelly)" - LearnLab
Difference between revisions of "Extending Reflective Dialogue Support (Katz & Connelly)"
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Research on student understanding and problem-solving ability in first-year college physics courses shows that instructors deal with a double-edged sword. Some students become adept at solving quantitative problems but do poorly on tests of conceptual knowledge and qualitative problem-solving ability. Other students display the reverse problem: they show at least a glimmer of understanding of basic physics concepts and principles, but are unable to use this knowledge to solve quantitative problems. Still other students master neither qualitative nor quantitative understanding of physics; very few master both. Thus, the instructional challenge motivating this project is to find effective pedagogical strategies to ''integrate'' quantitative and qualitative knowledge. Our scientific goal is to determine whether explicit and implicit learning can be effectively combined via post-practice dialogues that guide students in reflecting on the concepts and principles associated with a just-solved physics problem. The main hypothesis tested is that, in the context of tutored problem solving, ''integrative reflective dialogues'' that explicitly tie qualitative knowledge to quantitative knowledge can improve quantitative problem-solving ability and retention of qualitative knowledge better than problem-solving practice (implicit learning) alone.
Research on student understanding and problem-solving ability in first-year college physics courses shows that instructors deal with a double-edged sword. Some students become adept at solving quantitative problems but do poorly on tests of conceptual knowledge and qualitative problem-solving ability. Other students display the reverse problem: they show at least a glimmer of understanding of basic physics concepts and principles, but are unable to use this knowledge to solve quantitative problems. Still other students master neither qualitative nor quantitative understanding of physics; very few master both. Thus, the instructional challenge motivating this project is to find effective pedagogical strategies to ''integrate'' quantitative and qualitative knowledge. Our scientific goal is to determine whether explicit and implicit learning can be effectively combined via post-practice dialogues that guide students in reflecting on the concepts and principles associated with a just-solved physics problem. The main hypothesis tested is that, in the context of tutored problem solving, ''integrative reflective dialogues'' that explicitly tie qualitative knowledge to quantitative knowledge can improve quantitative problem-solving ability and retention of qualitative knowledge better than problem-solving practice (implicit learning) alone.
To test this hypothesis, we conducted an experiment in the PSLC Physics LearnLab at the US Naval Academy in sections that use the [[Andes]] physics tutoring system (VanLehn et al., 2005a, 2005b). We compared students who were randomly assigned to one of three conditions on measures of qualitative and quantitative problem-solving performance. The two treatment conditions engaged in automated reflective dialogues after solving quantitative physics problems, while the control condition solved the same set of problems (plus a few additional problems to balance time on task) without any reflective dialogues, using the standard version of Andes. In one treatment condition, the reflective dialogues individually targeted the three main types of knowledge that experts employ during problem solving, according to Leonard, Dufesne, & Mestre (1996): knowledge about ''what'' principle(s) to apply to a given problem, ''how'' to apply these principles (e.g., what equations to use), and ''why'' to apply them—that is, what the applicability conditions are (Leonard, Dufresne, & Mestre, 1996). In a prior LearnLab study [[Reflective Dialogues (Katz)|(Katz, Connelly & Treacy)]], this intervention significantly improved students’ qualitative understanding of basic mechanics, as measured by pre-test to post-test gain scores. However, students did not outperform standard Andes users on more [[robust learning]] measures of [[transfer]] (e.g., performance on quantitative course exams) and on a measure of retention of qualitative problem-solving ability (Katz, Connelly, & Wilson, 2007). The
alternative
dialogue condition we
evaluated
differs from the other dialogue condition in three main ways: (1) reflective dialogues contained more problem variations (''what if'' scenarios), designed to support both qualitative and quantitative knowledge (most of our previous ''what if'' scenarios were qualitative only); (2) these “what if” scenarios were tied to the corresponding Andes problem-solving context '''and''' to new contexts, to help support near and far [[transfer]]; and (3) students were prompted to state the rules ([[knowledge components]]) applied to solving the problem variations, in order to promote a principle-based approach to learning, and they were given feedback that makes these rules explicit. Our goal is to determine whether reflective dialogues that make the links between qualitative and quantitative physics knowledge explicit are more effective than both our previous dialogues and an implicit learning condition that is based on problem-solving practice alone.
To test this hypothesis, we conducted an experiment in the PSLC Physics LearnLab at the US Naval Academy in sections that use the [[Andes]] physics tutoring system (VanLehn et al., 2005a, 2005b). We compared students who were randomly assigned to one of three conditions on measures of qualitative and quantitative problem-solving performance. The two treatment conditions engaged in automated reflective dialogues after solving quantitative physics problems, while the control condition solved the same set of problems (plus a few additional problems to balance time on task) without any reflective dialogues, using the standard version of Andes. In one treatment condition, the reflective dialogues individually targeted the three main types of knowledge that experts employ during problem solving, according to Leonard, Dufesne, & Mestre (1996): knowledge about ''what'' principle(s) to apply to a given problem, ''how'' to apply these principles (e.g., what equations to use), and ''why'' to apply them—that is, what the applicability conditions are (Leonard, Dufresne, & Mestre, 1996). In a prior LearnLab study [[Reflective Dialogues (Katz)|(Katz, Connelly & Treacy)]], this intervention significantly improved students’ qualitative understanding of basic mechanics, as measured by pre-test to post-test gain scores. However, students did not outperform standard Andes users on more [[robust learning]] measures of [[transfer]] (e.g., performance on quantitative course exams) and on a measure of retention of qualitative problem-solving ability (Katz, Connelly, & Wilson, 2007). The
extended
dialogue condition we
implemented
differs from the other dialogue condition in three main ways: (1) reflective dialogues contained more problem variations (''what if'' scenarios), designed to support both qualitative and quantitative knowledge (most of our previous ''what if'' scenarios were qualitative only); (2) these “what if” scenarios were tied to the corresponding Andes problem-solving context '''and''' to new contexts, to help support near and far [[transfer]]; and (3) students were prompted to state the rules ([[knowledge components]]) applied to solving the problem variations, in order to promote a principle-based approach to learning, and they were given feedback that makes these rules explicit. Our goal is to determine whether reflective dialogues that make the links between qualitative and quantitative physics knowledge explicit are more effective than both our previous dialogues and an implicit learning condition that is based on problem-solving practice alone.
Contents
1 Extending Automated Dialogue Support for Robust Learning of Physics
1.1 Summary Table
1.2 Abstract
1.3 Glossary
Extending Automated Dialogue Support for Robust Learning of Physics
Sandra Katz
Summary Table
PIs Sandra Katz & John Connelly Study Start Date 10/1/07 Study End Date 9/30/08 LearnLab Site USNA LearnLab Course General Physics I Number of Students N = 75 Total Participant Hours approx. 125 hrs DataShop Yes
Abstract
integrate
quantitative and qualitative knowledge. Our scientific goal is to determine whether explicit and implicit learning can be effectively combined via post-practice dialogues that guide students in reflecting on the concepts and principles associated with a just-solved physics problem. The main hypothesis tested is that, in the context of tutored problem solving,
integrative reflective dialogues
that explicitly tie qualitative knowledge to quantitative knowledge can improve quantitative problem-solving ability and retention of qualitative knowledge better than problem-solving practice (implicit learning) alone.
To test this hypothesis, we conducted an experiment in the PSLC Physics LearnLab at the US Naval Academy in sections that use the
Andes
what
principle(s) to apply to a given problem,
how
to apply these principles (e.g., what equations to use), and
why
to apply them—that is, what the applicability conditions are (Leonard, Dufresne, & Mestre, 1996). In a prior LearnLab study
(Katz, Connelly & Treacy)
, this intervention significantly improved students’ qualitative understanding of basic mechanics, as measured by pre-test to post-test gain scores. However, students did not outperform standard Andes users on more
robust learning
measures of
transfer
(e.g., performance on quantitative course exams) and on a measure of retention of qualitative problem-solving ability (Katz, Connelly, & Wilson, 2007). The extended dialogue condition we implemented differs from the other dialogue condition in three main ways: (1) reflective dialogues contained more problem variations (
what if
scenarios), designed to support both qualitative and quantitative knowledge (most of our previous
what if
scenarios were qualitative only); (2) these “what if” scenarios were tied to the corresponding Andes problem-solving context
and
to new contexts, to help support near and far
transfer
; and (3) students were prompted to state the rules (
knowledge components
) applied to solving the problem variations, in order to promote a principle-based approach to learning, and they were given feedback that makes these rules explicit. Our goal is to determine whether reflective dialogues that make the links between qualitative and quantitative physics knowledge explicit are more effective than both our previous dialogues and an implicit learning condition that is based on problem-solving practice alone.
| https://learnlab.org/research/wiki/?diff=prev&oldid=7772&title=Extending_Reflective_Dialogue_Support_%28Katz_ |
A Foolish War - Part Two: Time For a New Covenant, by Keith Shugarts
The Libertarian Enterprise electronic magazine, Issue 146, for November 5, 2001 -- A Foolish War - Part Two: Time For a New Covenant, by Keith Shugarts
A Foolish War - Part Two: Time For a New Covenant
Special to TLE
"If this be treason then make the most of it," Patrick Henry
With due respect to L. Neil Smith and the others who support the Bill
of Rights and the Constitution, I must put forth the argument that
inherent in both the Bill of Rights and the Constitution are the very
tools for the destruction of freedom and liberty that we are bearing
witness to these very dark days. It is the ability to interpret both
the Bill of Rights and Constitution that threatens liberty and
freedom. The evidence I put forth to support this argument arises
from the prophetic words of the Anti-Federalists as they fought
against implementation of the Constitution some 220 years ago, arises
from the works of Trenchard and Gordon from their Cato's Letters, and
from the fevered ferment of my own mind.
Attorney General John Ashcroft, the zealotic, pedantic, and strident
little prick, stands before the microphone appearing more and more
like a later day incarnation on Maximilien Robespierre speaking of
the newly enacted terrorism legislation states that there is no
reason to worry, that the Constitutional rights guaranteed all
Americans were preserved. King-General George the Shrub cheering on
the passing of the USA Patriot Act of 2001 says that rights have been
preserved and that the "Constitutional rights of American's have been
preserved." Both Attorney General Ashcroft and King-General George
the Shrub believe themselves to be staunch defenders of their
versions of liberty and freedom as put forth in their interpretation
of the Bill of Rights and the Constitution. They have used both the
Bill of Rights and the Constitution to subvert American's freedom and
liberty as Aristocrotis wrote in Anti-Federalist #51 when he wanted
to show the American public what would come to pass if the
Constitution were approved when he writes. "Happy thy servants! Happy
thy vassals! And happy thy slaves, which fit under the shade of thy
omnipotent authority and behold the majesty! For such a state who
would not part with the idea blessings of liberty? Who would not
cheerfully resign the nominal advantages of freedom?"
The problem that I see with L. Neil Smith's and others ideas to more
vigorously enforce the Bill of Rights and the Constitution is that it
is already being done. However, it is being done by those who would
interpret them differently - Bush and Ashcroft, Clinton and Reno,
Alexander Hamilton, Abraham Lincoln, Woodrow Wilson, Franklin Delano
Roosevelt, and Lyndon Baines Johnson to name but a few. The problem
is within the documents themselves.
The Anti-Federalists realized that the interpretability of the
Constitution would cause problems for the preservation of freedom and
liberty. Again I will quote Aristocrotis writing in Anti-Federalist
#51 when he writes, "for the convention has so happily worded
themselves that every part of this constitution either bears double
meaning, or no means at all; and if any concessions are made to the
people in one place, it is eventually cancelled in another - so that
in fact his constitution is much better and gives more scope to the
rulers than they durst safely take if there was no constitution at
all."
Speaking on the intrusion of the State through the ability to lay and
collect taxes, imposts, duties, and excises under the Constitution
even before the imposition of an income tax, Brutus writes in
Anti-Federalist #6," this power, exercised without limitations will
introduce itself into every corner of the city, and the country - It
will wait upon the ladies at the toilett, and will not leave them in
any of their domestic concerns." Has this not also come to pass under
those perceived protections of both the Constitution and Bill of
Rights?
Brutus, still writing in Anti-Federalist #6, like Aristocrotis, warns
of the broad interpretability of the Constitution siting the clause
establishing justice, providing for the common defense when he
writes, "Are these terms definite, and will they be understood in the
same manner of opinion, what tends to be general welfare; and the
Congress will be the only judges in the matter." Later in that same
essay, Brutus gives more insight into ways the State would use the
clauses to increase its power and sway over freedom and liberty
stating, "the government would always say, their measures were
designed and calculated to promote the public good, and there being
no judge between them and the people, the rulers themselves must, and
would always judge for themselves." The State uses the
interpretability of the Constitution and the Bill of Rights not to
expand upon the freedoms offered within but to restrict them and
ultimately deny them.
How can these problems be solved merely with stricter enforcement of
the Bill of Rights and the Constitution when it is by those very
mechanisms that freedom and liberty are threatened? Will a Bill of
Rights Party be able to stem the tide of government and stop the
interpretations of both the Bill of Rights and Constitution? And if
it is initially successful, what then of further generations that may
not hold to such a strict interpretation of those hallowed documents?
Where is the preservation of liberty and freedom when those who
founded the party begin to die? The Libertarian Party, around only
since 1971 has seen many fractures and dissolution of its ideals.
Would not the same fate befall the Bill of Rights party?
I therefor humbly propose this solution. The solution would be to
work towards the implementation and unanimous consent to accept the
New Covenant, also known as the Covenant of Unanimous Consent. This
document was written by L. Neil Smith himself and contained within
his work
The Gallatin Divergence.
This solution I propose would
have the effect of "laying its foundation on such principles and
organizing its powers in such form, as to them shall seem most likely
to effect their Safety and Happiness." Fatal flaws lay entwined
around the very heart of the Constitution and Bill of Rights, fatal
flaws that would be the death of liberty and freedom. It is time to
work towards the enactment of a new covenant and allow the old one to
die.
A Quick word to King George the Shrub, the King-General of the United
States on declaring the terrorists evil-doers that I have taken from
Trenchard and Gordon's Cato's Letters as they spoke on tyranny, "Nor
can there be a more provoking, impudent, shocking, and blasphemous
position, than to assert all this group of horrors, or the author of
them, to be of God's appointment."
The Antifederalist Papers
; another
Antifederalist Papers
site
| https://ncc-1776.org/tle2001/libe146-20011105-04.html |
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Echard, William Echeverría, María del Puy Pe Ecke, Andreas Eckes, Jutta Eckhardt, M Eckhardt, Mária Ecsedi, Zsuzsa Ed.), Ossa-Martínez; Marco Anto Edel Germany GmbH Edexcel (Organization) Edgar, Kate. Edgar, William Edgar-Hunt, Robert Edinburgh University Library. Edith Cowan University. EDITION GORZ Edjabe, Ntone Edling, Anders. Edling, Cecilia Wahlströ Edling, Anders Edlund, Bengt Edström, Olle Edwards, Janet. Edwards, Christine Edwards, Scott Lee Egan, Sean Egea, Susana Egeland, Ånon Egey, Emese Eggenschwiler, Byron Eglinton, Mark Ehmann, Julia Ehrlich, David Ehrlich, Robert Eigeldinger, Jean-Jacques. Eigeldinger, Jean-Jacques Eilish, Billie Eisel, John C. Eisendle, Reinhard Ejeby, Bo Eken, Cecilie Ekenberg, Anders Ekho Verlag Eklund, Christer. Eklund, Karl Johan Elek, Koloh Elgar, Edward Elgar, Alice Elias, Berner Elie, Paul Elixir Piping and Drumming (Firm), Elkins, Elizabeth Elliott, Paul Elliott, David J. 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Englund, Axel Englund, Axel Engström, Andreas Enikő, Gyenge Eno, Brian Enstice, Wayne Eősze, L Eötvös, P Epstein, Dan Epstein, Marcia Jenneth Epting, Chris Érdi, T Erdmann, Hans Erickson, Kris Ericson-Roos, Catarina Erika, Nyerges Erika, Simon Erika, Fernbach Eriksen, Dorthe Eriksen, Jan Eriksson, Gunnar Eriksson, Karin L. Eriksson, Jeanette Eriksson, Karin. Eriksson, Maria Eriksson, Josef Eriksson, Magnus Eriksson, Åke Eriksson, Torbjörn Eriksson, Maria Erlmann, Veit Ernő, Kiss Erricker, Jane Erwin, Max Escuer-Salcedo, Sara Eshbach, Robert Whitehouse Espada, Martín Espeland, Magne I. Espiña-Campos, Yolanda Espínola, Francisco Espinosa, Santiago Esse, Melina Essex, David Esteve-Faubel, José María Esteve-Roldán, Eva Esteve-Roldán, Eva Estévez-Sola, Juan A. Eszter, Gombocz Ethniko kai kapodistriako panepisti̲mio Etter, Brian K. Etxebeste-Espina, Elixabete Etxeverria-Jaime, Jesús European Cantors Association, Éva, Fehér Éva, Kelemen Éva, Bieliczkyné Buzás Éva, Fehérné Sulyok Éva, Kondicsné Kovács Evans, Mark Evans, Timothy Evans, Julie Evans, Bob Evans, Steve Evans, Elfed Evans, David Evans, Mike Evans, David T. Evans, Tristian Everett, Walter Everett, William A. Everett, Andrew Everist, Mark. Everist, Mark Everley, Dave Evertsson, Maria Ewens, Hannah Eybl, Martin. Eybl, Martin Eydmann, Stuart Ezaki, Kimiko Ezquerro-Esteban, Antonio Fabényi, J Faber, Phillip Faber, Phillip. Fábián, Éva Fabian, Dorottya Facci, Serena. Fadipe, Israel A. 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Faulkner, Simon Faulkner, Robert Faure, Michel Fauré, Gabriel Fauser, Annegret Fay, Brendan Fazakas, I Fazekas, G Fazekas, Gergely Fazekas, G Fearnley, James Featherstone, Sally Federico, Gabriel Fedoszov, J Fedrová, Stanislava Fein, Michael Fejérvári, Boldizsár Fejérvári, B Fejős, J Fekete, A Fekete, Károly Feldman, Zev. Feldman, Morton. Feldman, Morton Feldman, Heidi Carolyn Feldman, Evan Feldman-Barrett, Christine Jacqueline Feldstein, Ruth Fell, Mark Fell, Alex Fellani, Matin Felton, Dickie. Feneyrou, Laurent Fenlon, Ian Fenlon, Iain Fenton, Kathryn Fényes, G Ferenc, Verseghy Ferenc, Szénási Ferenc, Liszt Ferenc, Rátkai Ferenc, Apró Ferenczi, I Ferge, Béla Ferguson, Paul Ferić, Mihael Fernandes, Cristina Fernández, Gabriel Fernández-de-Latorre, R. Fernández-Manzano, Reynaldo Ferrada-Noli, Nicholas Ringskog Ferraguto, Mark Ferraiuolo, Augusto Ferrari, Brunhild Ferrari, Giordano. Ferreira, Manuel Pedro Ferreiro-Carballo, David Ferrer-Cayón, Jesús Ferrero, Lena Kagg Ferrett, D Ferri-Durà, Jaime. Ferris, William R. Fertel, Rien Ferzacca, Steve Festival de Música Antigua de Úbeda y Baeza Feurzeig, Lisa Feustle, Maristella Fèis Rois. Fhuartháin, Méabh Ní Fiala, Michele Fiddes, Luke Fiegel, Eddi. Field, Kim Fields, Kenneth Fifer, Julian Fifield, Christopher Fifield, Christopher Figueiredo, Marcio Figueroa, Michael A. Filippi, Daniele V. Fillerup, Jessie Fillion, Éric Fink, Jesse Finnerty, Adrian Finney, John Finscher, Ludwig Finzi, Gerald Fiore, Ivana Fiorentino, Giuseppe Fischer, Rebecca Fischer, Paul Fischlin, Daniel. Fischlin, Daniel Fišer, Ernest Fisher, Elizabeth Fisher, Mark Fiskvik, Anne Margrete Fitch, Fabrice FitzGerald, Martin Fitzgerald, Mark Fitzner, Frauke Fitzpatrick, Rob. 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Freiburghaus, Gabriela French, Stewart French, Mark Frenkel, A Frenz, Barbara Freund, Julia Friberg, Anders Frid, Emma Friddle, David Friedberg, Jeffrey Frieden, Ken Friedl, Erika Friedler, M Friedman, Allan Jay Friedmann, Jonathan L. Friedrich, Á Friehs, Julia Teresa Frierson-Campbell, Carol Friesen, Orin Frigyesi, Judit Frith, Simon Fritsch, Melanie Froehlich, Hildegard C. Frolova-Walker, Marina Frölich, Emilia. Frühauf, Tina Fry, Robert W. Fu, Hong = 傅鈜 Fuchs, Emily Fuchs, Dieter Fuente-Charfolé, José-Luis Fügedi, J Fugelso, Karl Fuhrich, Edda Fuhrmann, Wolfgang Fukuoka, Madoka. Fukuoka, Shōta. Fukushima, Kazuo Fukushima, Mutsumi Fuller, Nicholas Lester Fuller, Sophie Fundación Juan March, Fung, Victor. Furia, Philip G, Németh Gaar, Gillian G. GABARRÓN-TORRECILLAS, Antonio-Francisco Gabbard, Krin Gábor, Vásárhelyi Gábor, Barna Gábor, Eredics Gábor, Turi Gábor, Winkler Gábor, Simon Géza Gábor, Sarbak Gábor, Presser Gábriel, Szoliva Gabriēl, Angelos Gabriella, Gilányi Gaddy, K. R. 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Symposium (6 ; 2018 ; Sinj) International Music Education Research Centre. International Musicological Society International Society for Music Education. Internationale Richard-Strauss-Gesellschaft Internationale Stiftung Mozarteum Salzburg. Iommi, Tony. Iott, Sheryl Iovene, Paola Ippolito, J. M. Irby, Samantha Ireland, Brian Irons, Yoon Irvine, Thomas Irwin, William Irwin, Colin. Irwin, Colin Isacoff, Stuart Isacsson, Jonas Isakoff, Katia Ishida, Yutaka Isnard, Vincent. Isserlis, S Isserlis, Steven István, Pávai István, Bátori László István, Németh István, Kilián István, Gróf István, Korody-Paku István, Elmer István, Kereszty István, Mustos István, Balázs István, Bogárdi Szabó István, Berczelly István, Gáti Istvandity, Lauren Isusi-Fagoaga, Rosa Ittzés, M Ittzés, Mihály Ittzés, M Ittzésné, K Iturrioz-Petralanda, Nekane Iván, Cs Ivarson, Karin Iverson, Jennifer Ivković, Želimir Ž. Izabella, Bartalis Jaccard, JL Jacke, Christoph Jacks, Will H. Jacks, David Jackson, Amy S. 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Jauset-Berrocal, Jordi-Àngel Jávorszky, B Jávorszky, BS Jávorszky, Béla Szilárd Jay, Norman JayZ, JayZ Jazzforeningen Jazzinstitut Darmstadt Jäger, Markus Jeanneret, Christine Jedrzejewski, Franck Jefferies, Graeme Jena, Stefan Jena, Stefan. Jenkins, Delyth Jenkins, Willard Jenkins, Mark Jenkins, Jeff Jenkins, Katrina E. Jenkins, Jim Jenkins, Steve Jenkins, Paul Jennex, Craig. Jennings, Sarah Jennings, Ros Jensen, Oskar Cox Jensen, Kurt Balle Jensen, Erik Jensen, Anne Ørbæk Jensen, Jacob Wendt Jensenius, Alexander Refsum Jepson, Louisa Jerković, Berislav Jerold, Beverly Jersild, Margareta Jethro Tull (Musical group), Jewell, Alan. Jian, Miaoju Jiang, Ying = 蒋英 Jimenez, Javier Jiménez, José Luis Jin, Tielin = 金铁霖 JLS (Musical group), Jnr., HOwie Morrison Johann, Lurf Johansen, Geir Johansen, Guro Gravem Johansson, Karin Johansson, Anna Johansson, Ola Johansson, Carina Johler, J John, Elton John, Elton John, Corner John, Graham St. John, Emma John Ireland Charitable Trust. 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Waldingbrett, Ingrid Waligórska, Magdalena Walker, STan Walker, Norman Walker, Stan Walker, Alan Walker, Lucy Walker, Jason P. Walker, Ian Walker, Michael Walker, David Walker, James Walker, A Walkling, Andrew R. Wallace, John Wallace, Robin Wallén, Göran Wallis, John Wallmark, Zachary Wallrup, Erik. Wallrup, Erik Wallrup, Erik Walls, Peter. Walsh, Stephen Walsh, Michael J. K. Walter, Meinrad Walter, Meinrad Walter de Gruyter GmbH & Co. KG Walthaus, Asing Walton, Chris Walton, Andrew Walton, Benjamin Walton, Chris Wan, Shuangwu Wang, Li Wang, Jing Wang, Jing Wang, Klavier J. Wang, Guiping Wang, Helen Wang, Ka Wang, Chenwei Wang, Oliver Wang, Hui = 王辉 Wang, Jin = 王进 Wang, Liping = 王黎平 Wang, Lixin = 王丽新 Wang, Min = 王敏 Wang, Peiyu = 王培瑜 Wang, Yaohua = 王耀华 Wang, Yarui = 王娅蕊 Wang, Yimeng = 王艺萌 Wang, Zonglin = 王纵林 Wannamaker, Rob Ward, Philip. Ward, Miranda. Ward, Christopher Wardhaugh, Benjamin Ware, Evan Warner, Daniel Warner, Andrea Warner, Alan Warren, Andrew Warren, Jeff R. Warwick, Dionne. Warwick, Jacqueline C. Wash, Martha Washabaugh, William Washida, Kiyokazu Watanabe, Yawara. Watanabe, Tamotsu Waterman, Bryan Waterman, Christopher Alan Waters, Keith Waters, Robert Watkins, Huw Watkins, Jane Watkinson, David Watson, Jada E. Watson, Laura Watson, Jada Watson, Allan Watson, Philip Watt, Paul Way, Lyndon C. S. Webb, Michael D. Webb, Jimmy Webb, Sioned Webb, Martin Weber, Zdenka Weber, William Webster, Patrick Webster, Emma Webster, Peter Richard Weel, Liva Wehn, Jan Weid, Jean-Noël von der. Weidinger, Hans Ernst. Weinel, Jonathan Weinstein, Anna Weiss, Jernej Weissglas, Birgitta Östlund Weissman, Dick Weitzman, Simon Welander-Berggren, Elsebeth Welch, Graham Welin, Cissi Weliver, Phyllis Wellings, Ben Wellington, Tony Wellmann, N Wellmer, Albrecht Wells, Christi Jay Welsh, Louise Welsh Association of Male Choirs. Welsh Folk-Song Society. Weltman, Sandy Wendler, Merete Wennberg, S Wenner-Gren Foundation for Anthropological Research. Wente, Allison Rebecca Werger, Carola Werley, Matthew Michael Werner, Goebl Wernlid, Eva Wertheimer, Alfred Wertheimer, Melissa E. West, Christopher West, Chad Wester, Bertil Westerlund, Heidi Western, Tom Westhoff, Ben Westminster Media Forum, Westrup, Laurel Westvall, Maria Wetterqvist, Anna Wheaton, R. J. Whedon, Joss Wheeldon, Marianne Whidden, Lynn Whineup, Tony Whitall, Susan. White, Danny White, Harry. White, Danny White, Vernon White, Michael White, Bryan White, Paul. White, Paul White, Matthew White, Timothy White, Harry White, John Whitehead, Gillian Whiteley, Sheila Whiteley, Jon Whiteoak, John Whitfield, Sarah Whitfield, Sarah Whiting Society of Ringers, Whitmer, Mariana Whitney, Karl Whittaker, Jason Whittaker, Sheila Whittall, Arnold Whyton, Tony Wicke, Peter Wickström, David-Emil Widdess, Richard Wide, Steve Widmer, Gerhard Wieczorek, Sławomir Wiegand, Gottfried Wienbibliothek im Rathaus, Wiener Institut für Strauss-Forschung, Wiener Volksliedwerk Wiens, Kathleen Wiersema, Robert J. Wierzbicki, James Eugene Wiesenfeldt, Christiane Wiffen, Charles. Wiggins, Jackie. Wiggins, Phil Wikström, Per Wikström, Patrik Wilbourne, Emily Wilcher, Phillip Wilcox, Beverly Wild, Andrew Wild, David Anthony. Wilder, Alec Wilding, Philip Wildmann, Daniel Wilentz, Sean Wilfing, Alexander. Wilfing-Albrecht, Meike. Wilheim, A Wilkie, Katie Wilkins, Frances Wilky, Pete Will, Richard James Willard, Timothy D. Wille, Irmgard Willemetz, Jacqueline. Willert, Søren Williams, Alastair Williams, James Williams, David A. Williams, Grace Williams, Katherine Williams, Stuart Williams, Liz Williams, Joseph Williams, John Williams, Alex Williams, Georgina Williams, James Gordon Williams, David A. Williams, Hermine Weigel Williams, Jonathan. Williams, Quentin Williams, Jane Q. Williams, William Lewis Williams, Sarah F. Williams, Sean Williams, David Anson Williamson, Brian Williamson, Victoria Williamson, John Williamson, Nigel Willin, Melvyn J. Willingham, Lee Willis, Peter Willis, Victoria Willson, Rachel Beckles. Willsteed, John Wilsmore, Robert Wilson, Blake McDowell Wilson, Mary Wilson, Joe Wilson, Brian Wilson, Christopher R. Wilson, Scott Wilson, Jason Wilson, Brett Wilson, Charles Wilson, Jen Wilson, Nick Winans, BeBe Windhager, Ákos Windhager, K Winehouse, Mitch. Winfried, Pauleit Winkler, Heinz-Jürgen Winkler, Amanda Eubanks Winnett, Susan Winslow, Luke Winter, Tomáš Winters, Ben Winterson, Julia Wintle, Christopher. Wintle, Christopher Wipplinger, Jonathan O. Wise, Stuart Wiseman, Bob Wiseman-Trowse, Nathan Wistreich, Richard. Wistreich, Richard Withers, Deborah M. Wittkowski, Désirée Witulski, Christopher Witvliet, John D. Wladika, Michael Wode Psalter Project Team. Woitas, Monika Wolf, Richard K. Wolf, Norbert Christian Wolf, Stacy Ellen Wolfe, Paula Wolff, Christoph Wolff, Loup. Wolff, Christian Wolin, Ada Wolke Verlagsgesellschaft mbH Wolkowicz, Vera Woller, Megan Wollman, Elizabeth L. Wolman, Baron. Womack, Kenneth Wong, Samuel Shengmiao Wong, Casey Philip Wood, Alistair Wood, David. Wood, Jo Wood, Caroline Woodcock, Rob. Woodford, Paul Woodhead, Leslie Woodhouse, Susi Woods, Clyde Adrian Woods, Paul A. Woodward, Ian Woodward, Keren Woody, Robert H. Woolaver, Lance Wooldike, Mogens Wooley, David Freeman. Woolf, Ray Woolford, Julian Woollacott, Ron Woolley, Robin E. H. Woolley, Andrew Wottle, Martin Woznicki, Lisa M. Wöllner, Clemens. Wrangsjö, Björn Wright, Jon Wright, James K. Wright, Lesley Alison Wright, Michael Wright, David C. H. Wright, Ruth Wright, Ruth. Wright, Samuel Wright, Dan Wright, Adrian Wright, Owen Wright, Julie Lobalzo Wright, Joshua K. Wright, Mark Peter Wu, Jiayue Cecilia Wu, Dequn = 吴德群 Wu, Ye = 吴叶 Wurnell, Mats Wyatt, Robert Wylde, Zakk Wyndham-Jones, Guy. Wynne, Ben X, King of Castile Xepapadakou, Avra Xiang, Hengfang = 项衡方 Xiang, Xiaogang = 项筱刚 Xiang, Yang = 项阳 Xiao, Dongfa = 肖东发 Xiao, Mei = 萧梅 Xiao, Wenli = 肖文礼 Xie, Jiaxing = 谢嘉幸 Xie, Yongxiong = 谢永雄 Xin, Xuefeng = 辛雪峰 Xiong, Qi = 熊琦 Xiong, Xiaoyu = 熊小玉 Xu, Chengbei Xu, Delei = 徐德雷 Xu, Ximao = 徐希茅 Xue, Ming = 薛明 Yakupov, Alexander N. Yamada, Kōsaku. Yamada, Chieko Yamada, Takafumi Yamaguchi, Mutsumi Yamakawa, Shizuo Yamamoto, Hiroko Yamamoto, Hiroyuki Yamashita, Hiroaki Yang, Zoua Sylvia Yang, Dingwang = 杨丁旺 Yang, Heping = 杨和平 Yang, Sai = 杨赛 Yang, Xifan = 杨曦帆 Yao, Zhihui = 姚志辉 Yard, Ryan Yawson, Jude Yeaman, G. E. Yearsley, David Gaynor Yearsley, David Gaynor Yeo, Douglas Yewdall, Julian Leonard Yi, Yŏng-mi Yi, Shucheng = 易述程 Yip, Joyce Yoon, Sunmin Yoon, Jean Yordanova, Iskrena Yordanova, Iskrena. York St John University. Yorkshire Association of Change Ringers. Yorkston, James. Yoshida, Tamao Yoshida, Yukako. Yoshida, Minosuke Yoshihara, Mari Yoshikami, Miyuki Yoshizaki, Masaki. You, Jingbo = 尤静波 Young, John Bell Young, Miriama Young, La Monte Young, Rob Young, Toby Young Classical Artists Trust. Young Musician Hebrides (Organization) Ystad, Sølvi Yu, Jun Yu, Danhong = 余丹红 Yuan, Quanyou Yudkin, Jeremy Yue, Kaifeng = 乐开丰 Yun, Isang Yusta, Miguel Ángel Yuste-Martínez, Luis Yusuke, Nakahara Zackrisson, Lasse Zadig, Sverker. Zaeri, Mehrdad Zagorski-Thomas, Simon Zakić, Mirjana Zamora-Caro, Katerine Žanić, Ivo Zapke, Susana Zarate, Rebecca Zatkalik, Miloš Zauner, Michelle Zazulia, Emily Zdanowicz, Gina Zebec, Tvrtko Zeck, Melanie Zeller, Regine. Zembylas, Tasos Zepf, Markus Zeppetelli, John Zerbe, Michael J. Zervos, Giōrgos Zhang, Deyu = 章德瑜 Zhang, Wei = 张巍 Zhang, Xiaoxia = 张笑侠 Zhang, Xin = 张欣 Zhang, Yingfen = 张迎芬 Zhang, Yishan = 张翼善 Zhang, Zhongqiao = 张仲樵 Zhang, Zonghong = 张宗红 Zhao, Sitong = 赵思童 Zhao, Talimu = 赵塔里木 Zhao, Zhi'an = 赵志安 Zheng, Yan = 郑艳 Zhong, Enfu = 钟恩富 Zhou, Danny Zhou, Ji = 周吉 Zhou, Liang = 周亮 Zhu, Hengfu = 朱恒夫 Zhu, Jian'er = 朱践耳 Zhu, Lixing = 朱理惺 Zhu, Yujiang = 朱玉江 Zhuo, Sun Zi, Yin = 紫茵 Zicari, Massimo Ziegler, Robert Ziegler, Lulu Ziemer, Hansjakob Ziemska, Joanna Zilli, Anna Zimmerman, Lee Zimmermann, Walter Zohn, Steven David Zöldi, Gergely Zoltán, Császár Zoltán, Bicskei Zoltán, Molnár Zoltán, Szabó Zoltán, Göllesz Zoltán, Tumpek Zoltán, Gergely Zoltán, Kodály Zoltán, Csermák Zolten, Jerome Zombie, Rob. Zomparelli, Elena Zon, Bennett. Zon, Bennett Zondi, Nompumelelo Bernadette Zornica Hagyományőrző Egyesület Zouhar, Vít Zoumpoulakēs, Petros Zsófia, Borz Zsombor, Németh Zsuzsa, Kővágó Zsuzsa, Czagány Zsuzsa, Czagány Zsuzsanna, Erdélyi Zsuzsanna, Pintér Márta Zsuzsanna, Domokos Zsuzsanna, Réfi Zsuzsanna, Glavina Zsuzsanna, Szepesi Zsuzsanna, Bálint Zubillaga, Igor Contreras Zuckermann, Moshe. Zunigo, Xavier. Zurmühl, Sabine Žuvela, Sanja Kiš Zürcher Hochschule der Künste Østergaard, Per Јанковић-Бегуш, Јелена Маринковић, Соња 국남., 배 음악사연구회 川﨑, 瑞穂 Type any Book Miscellaneous Conference Proceedings Journal Website Web Article Audiovisual Thesis Conference Paper Report Journal Article Presentation Term any Year any 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2009 2001 Keyword any 7 (CaQQLa)201-0000282 (CaQQLa)201-0001542 (CaQQLa)201-0004568 (CaQQLa)201-0005777 (CaQQLa)201-0009248 (CaQQLa)201-0010484 (CaQQLa)201-0013983 (CaQQLa)201-0013986 (CaQQLa)201-0017854 (CaQQLa)201-0022164 (CaQQLa)201-0032589 (CaQQLa)201-0038053 (CaQQLa)201-0038355 (CaQQLa)201-0041435 (CaQQLa)201-0046052 (CaQQLa)201-0046054 (CaQQLa)201-0046163 (CaQQLa)201-0053875 (CaQQLa)201-0066316 (CaQQLa)201-0070033 (CaQQLa)201-0081252 (CaQQLa)201-0093787 (CaQQLa)201-0117737 (CaQQLa)201-0164320 (CaQQLa)201-0164324 (CaQQLa)201-0278656 (CaQQLa)201-0343563 (CaQQLa)201-0356887 (CaQQLa)201-0387198 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(OCoLC)fst02021107 (OCoLC)fst02021978 (OCoLC)fst02022009 (OCoLC)fst02023092 (OCoLC)fst02023366 (OCoLC)fst02024003 (OCoLC)fst02027038 (OCoLC)fst02029199 (OCoLC)fst02031393 (OCoLC)fst02032989 (OCoLC)fst02033725 (OCoLC)fst02033891 (OCoLC)fst02033893 (OCoLC)fst02033910 (OCoLC)fst02040679 (RERO)A021003248 (RERO)A021096923 (RERO)A022509224 (RERO)A024797456 (uri) http://id.loc.gov/authorities/subjects/sh2008108258 (uri) http://id.loc.gov/authorities/subjects/sh85088762 (uri) http://id.worldcat.org/fast/fst01033799 13th century 15e siècle 15e siècle. 15th century 15th century. 16. century 16e siècle 16e siècle. 16th century 16th century. 17e siècle 17e siècle-18e siècle 17e siècle. 17th century 17th century. 17the century 18. století. 18.-20. století. 18.century 1814-1918 18e siècle 18e siècle. 18th century 18th century. 18th-20th centuries. 19. century 19.-20. století. 1900-1945. 1901-1910 1911-1920 1914 May 16- Auckland Boys' Choir -- History. 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Avant-garde (Aesthetics) Avant-garde (Music) Avante-garde (Music) New Zealand Awards Ästhetik Background music; Sociology of music Badalić Bagpipe Bagpipe music Bagpipe music, Arranged. Bagpipe music. Bagpipe. Bagpipers Bagpipers. Balkan Peninsula Balkan Peninsula. Ballader Ballades Ballads Ballads, English Ballads, English. Ballads, Japanese. Ballads, Scots Ballads. Ballet Ballet dancers Ballet dancers in art Ballet dancing. Ballet. Ballets Ballets. Ballroom dancing Ballroom dancing. Ballrooms Baloković Band music Bandes dessinées. Bands (Music) Bands (Music) Ireland Banjo Banjo. Bankers Barbados Barbados. Barcelona Bards and bardism. Baritō. Barnes, Jimmy. Baroque Baroque music Baroque music (c 1600 to c 1750). Barroco Barroque Bars (Drinking establishments) Bartók Bartol Đurđević/Jurjević Bass guitar Bass guitarists Batterie (Instrument de musique) Batteurs (Instrumentistes) Battle of Szigetvár Bawdy songs beat music Beatles. Bedeutung. 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Diversity in the workforce Diversity in the workplace Divine office Divine office (Music) Do-it-yourself work Documentary films Dohnányi Domenico Scarlatti Domkyrkor Domnérus, Arne, 1924-2008 Don Juan (Legendary character) Don Quijote Doo-wop (Music) Double bass Double bassists Double bassists. Double Happys (musical group) Double-bassists Douglas Lilburn Dōwa. Dōyō-Nihon. Drama Drama. Dramatic music Dramatic music. Dramatisk och scenisk musik Dramatists, American Dramatists, English Dramatists, German Dramaturgie. Dramaturgy Dramaturgy. Droit d'auteur Droit d'auteur. Drottningar Musik – historia S{\aa}ngerskor – historia Kulturliv – historia Drug addicts Drug addicts. Drugs and popular music. Druids and druidism. Drum Drum and bugle corps. Drum circles Drum circles. drum language. Drum machine Drum machine. Drum set Drum set. Drum. Drummers Drummers (Musicians) dřevěné dechové nástroje. 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Electronica (Music) Elegiac poetry, English Elegiac poetry, English. Elektroakustisk musik Elektronisk musik Elektronmusikstudion Elementary school teaching. Elever Elgitarr – historia Gitarr – historia Ellington, Duke, 1899-1974-- influenser Elvis Presley Elvis Presley impersonators Elvis Presley impersonators. Embellishment (Vocal music) embne Emeralds Emeralds. Emigration and immigration Emigration and immigration. Emotions Emotions in art. Emotions in children. Emotions in music Emotions in music. Emotions in the performing arts Emotions in the performing arts. Empathy. Employees Empowerment Encyclopedias Encyclopedias. Encyclopédies. End of the world. Engeki-Nihon. Engeki-Roshia. Engelskspråkiga författare-- historia Engineering instruments Engineering instruments. England England, North East England, North East. England, Northern England. English English language English literature English literature. English New Zealand. 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Écosse. Écoute (Philosophie) Écrits de musiciens rock. Écrivaines noires américaines. Écrivains autrichiens Éditeurs audionumériques. Éditeurs de musique Édition Éducation holistique. Éducation humaniste. Éducation. Église catholique Église luthérienne Église luthérienne. Églises protestantes. Électronica (Musique) Électrophones États arabes États-Unis États-Unis (Sud) États-Unis. Éthiopie. Éthiopiens Étude et enseignement Étude et enseignement. Études de cas. Facsimiles. Facteurs d'orgues Facteurs liés à l'âge. Facture Facture. Faculty of Music in Belgrade Fair use (Copyright) Fairy tales Faith. Fame Families Families. Family relationships Fan magazines Fan magazines. Fandangos Fanfares (Orchestres) Fängelser Musik och samhälle Fans (Persons) Fantasy fiction Fantasy fiction. Fantasy films Fantasy games. Fanzines Farm life Farmers Fascism and culture Fascism and culture. Fascism and music Fascism and music. Fascisme et musique Fashion Fashion designers Fashion in art. fast Fathers and daughters Fathers and daughters. Fathers and sons Fathers and sons. Faust (Legendary character) Fågelsång. Feasts for the Blessed Virgin Mary. Federico García Lorca Feliks Petančić Femininity in music. Femininity in popular culture Femininity in popular culture. Feminism Feminism & Feminist Theory. Feminism and literature Feminism and literature. Feminism and music Feminism and music. Femmes dans l'industrie musicale. Femmes dans la musique. Femmes mécènes de la musique Femmes sauvages dans la littérature. Femmes violonistes Fender guitar Fender guitar. Fernsehproduzent. Festivals Festivals de musique Festivals. Féminisme et musique. Fiddle tunes Fiddle tunes. Fiddlers Fiddlers. Fiddling Field recordings Fife and drum corps Fife and drum corps music Fife and drum corps music. Fife and drum corps. Fifre et tambour, Musique de Filipino American youth Filipino Americans Film Film adaptations. Film catalogs. Film composers Film composers. Film music Film soundtracks Film soundtracks. Film theory & criticism,Film: styles & genres,Opera. Film, Musique de Filmmusik Filmmusik Animerad film Publiker Filmmusik, USA. Filmmusik. Filmska umjetnost filosofi Musik – sociala aspekter Finance, Personal. Fingering Fingering. Finland Finlandssvenskar Finn, Liam Finn, Neil Flageolet Flamenco Flamenco dancers; Biographies Flamenco dancers; Homosexuality; Gender studies Flamenco music Flamenco singers Flamenco; Ethnomusicology; Work songs Flight in art. Flöjt Musikframträdanden Florida Floride Flute Flute music Flute music. Flute players Flute players. Flûte à bec Flying Nun Records - History 20th century Flying Nun Records - History; Sound recording industry - New Zealand - History; Rock musicians - New Zealand; Music trade - New Zealand - history Flying Nun Records history Folk art Folk art. folk custom Folk dance folk dance in Hungary Folk dance music Folk dance music. folk dance research Folk dancing Folk dancing, Irish Folk dancing, Irish. Folk dancing, Scottish. Folk dancing. folk epics folk instrument Folk music folk music collection Folk music festivals Folk music festivals. folk music history Folk music Hungarian folk music research Folk music Southern Slavs in Hungary Folk music symphosyum Folk music, Irish. Folk music. folk musical instruments Folk musicians Folk musicians. folk musicof South Slavs in Hungary Folk poetry, Arabic Folk poetry, Bakhtiari. Folk poetry, Greek (Modern) Folk poetry, Italian Folk poetry, Italian. Folk singers Folk singers. Folk songs Folk songs, Aboriginal Australian Folk songs, Arabic Folk songs, Bakhtiari. Folk songs, Chinese Folk songs, Czech Folk songs, Czech. Folk songs, English Folk songs, English. Folk songs, Indonesian Folk songs, Indonesian. Folk songs, Japanese Folk songs, Japanese. Folk songs, Kannada. Folk songs, Korean Folk songs, Ladino Folk songs, Ladino. Folk songs, Manx. Folk songs, Nenets Folk songs, Old French Folk songs, Scots Folk songs, Scots. Folk songs, Scottish Gaelic Folk songs, Welsh. Folk songs. Folk-rock music Folk-rock music. folkdance Folkliga koraler Folklore Folklore. Folklorists Folkmusik Folkmusik Spelmän Folkmusik-- historia Folkmusik-- sociala aspekter folksongs folktradition Folkvisor-- forskning Fonds d'archives. Food in music Food in music. Football (Soccer Association Football) Forecasting. Foreign influences. FOREIGN LANGUAGE STUDY / Multi-Language Phrasebooks. Förenta staterna Forests and forestry. formal analysis Formation. Former Yugoslav republics Former Yugoslav republics. Foster children Fourrures Fragmente. fragments. France France, Southern France, Southern. France. Francoism Francoist dictatorship Franjo Ksaver Kuhač = Franz Ksaver Koch Frankrike Franz Joseph (František) Gläser Franz Xaver Kleinheinz Französisch Frederick May Free jazz Free jazz. French influences. French language French poetry French poetry. French. Friendship Friendship. From Scratch(Musical Group) Fue. Functor theory. Fundamentalism Fundamentalism. Funds Preservation Funeral consultants Funeral music Funeral music. Funeral service Funk (Music) Funk musicians Fur trade Fur trade. Fur traders Futurism (Literary movement) Futurism (Music) Fuzzy logic. Gagaku Gagaku. gaita Gakufu-Rekishi. ganga Gangsta rap (Music) Gangsters Gangsters. Garamut García family Gardberg, Tom, 1941- Gasshō. Gay culture Gay culture. Gay men Gay men. Gay musicians Gay musicians. Gay musicologists Gehörslära Geijutsu-Indoneshia. Geishas. Geistliche Musik. Gender Gender identity in music Gender identity in music. Gender nonconformity Gender nonconformity. Gender studies Gender studies, gender groups. Gender studies: women. Gender studies; Pedagogy Gender-nonconforming people Gender-nonconforming people. General & world history. General certificate of education examination (Great Britain) General. Generation Y. Generation Z Genetic algorithms. Genres & Styles genusaspekter. George Frideric Handel Georgia Gerald Dawe German influences. German language German literature German literature. German poetry German speaking countries German. Germany Germany (East) Germany (West) Germany. Gesang Geschlechterrolle Gestes dans la musique. Gestion numérique des droits Gestion. Gesture in music. Géorgie (État) Gēmu sofuto. Ghana Ghana. Ghāna Ghāna. Gidayūbushi. gipsy musicians Girei. Girl groups (Musical groups) Gitarrer-- historia Giuseppe Verdi Glam metal (Music) Glam rock (Music) - New Zealand - History and criticism Glam rock music Glam rock music - History and criticism - New Zealand Glam rock music. Glam rock musicians Glasgow glazbeni nakladnici - Hrvatska - 20/21. st. Glee clubs Glee clubs. Globalisierung Globalization Globalization. Gluck-Piccinni controversy. gnd God (Christianity) Godfrey Gong Gospel Gospel music Gospel music. Gospel musicians Gospel musicians. Gospel singers Gospel singers. Govori Grading and marking (Students) Grainger, Percy, 1882-1961 Grammar. Grande-Bretagne Grande-Bretagne. Graphic novels. Greager, Richard, Great Britain Great Britain. Greece Greece. Greek Americans Greek influences. Greek literature Greek music Greek poetry, Modern Greek poetry, Modern. Greeks gregorian Gregorian chants Gregorian chants. Group identity Group identity in the performing arts Group identity. Groupes rock Groupes vocaux Groupies Growth Growth. Grunge (Musique) Grunge music Grunge music. gtt Guadeloupe Guadeloupe. Guerre mondiale, 1939-1945 Guidebooks. Guides touristiques (Personnes) Guinbri Guinea. Guitar Guitar makers Guitar makers. Guitar music Guitar music (Blues) Guitar music (Rock) Guitar music. Guitar teachers Guitar. Guitare Guitare, Musique de. Guitaristes Guitarists Guitarists. Gullahs Gunnar, Eriksson, 1936- Guralnick, Peter Gymnasieskolan Gypsy musicians Hagström Hainichi mondai. Haiyū. Håkanson, Knut, 1887-1929 Hallucinations and illusions. Handbooks, manuals, etc. Hardcore (Music) Hardcore (Musique) Hardcore musicians Harmonica Harmonica music. Harmonica players Harmonica players. Harmonicistes Harmonie (musique) Harmonie. Harmony Harmony of the spheres. Harmony. Harp Harp music Harpistes Harpists Harpists. Harpsichord Harpsichord. Harpsichordists Hassaniyya dialect Hate groups. Hawaii. Hayes, Roland, 1887-1977. hälsoaspekter. HEALTH & FITNESS / Healthy Living HEALTH & FITNESS / Work-Related Health Health and hygiene. Health aspects Health aspects. Health facilities Hearing Hearing Aids Hearing aids. Hearing impaired. Hearing. Heavy Metal Heavy metal (Music) Heavy metal (Musique) Heian period, 794-1185 Heike monogatari. Heritage tourism Heroines in opera. Higashinihon daishinsai. higher education. Hindu goddesses Hindu goddesses. Hindu music Hindu music. Hinduism Hindustani music Hindustani music. hip-hop Hip-hop dance Hip-hop in art. Hip-hop. Hiphop (musik) Samhällskritik Feminism Antirasism Musiksociologi Musik – sociala aspekter Hispanic Americans Histoire Histoire et critique Histoire et critique. Histoire. Histoires, intrigues, etc. Historia historia. Historically informed performance (Music) Historiographie Historiography historiography Croatia Historiography. History History & Criticism. HISTORY / Africa / South / Republic of South Africa. HISTORY / African American HISTORY / Asia / General HISTORY / Australia & New Zealand. HISTORY / Europe / France. HISTORY / Europe / Great Britain / General. HISTORY / Europe / Spain & Portugal HISTORY / Europe / Western HISTORY / General. HISTORY / Jewish HISTORY / Latin America / South America. HISTORY / Modern / General HISTORY / Oceania. HISTORY / Social History HISTORY / Social History. HISTORY / United States / 19th Century. HISTORY / United States / 20th Century. HISTORY / United States / General HISTORY / United States / State & Local / South (AL, AR, FL, GA, KY, LA, MS, NC, SC, TN, VA, WV) History and criticism History and criticism. History and criticsm. History and critisicm. History in literature. History in opera. History in popular culture History in popular culture. History of music history of opera History. Högstadiet Holistic education. Holistic Health Holocaust survivors Holocaust, Jewish (1939-1945) Homages Homeland in music. Homes and haunts. Homes. homoit Homosexualité et musique. Homosexuality Homosexuality and music. Homosexuality and popular music Homosexuality and popular music. Homosexuality. Hongrie Hongrie. Honnête homme Horn (Musical instrument) Horror films Horror films. Horses Hospital care. Hospital patients Hospitalers Hospitalers. Hospitals Hospitals. House music House music. Hōgaku-Rekishi. Hōgaku. hrvatska poezija - 20/21. st. - antologije http://id.loc.gov/authorities/subjects/sh2008106048 http://id.loc.gov/authorities/subjects/sh85069833 http://id.worldcat.org/fast/871620 http://id.worldcat.org/fast/871649 http://id.worldcat.org/fast/982165 http://id.worldcat.org/fast/982175 http://id.worldcat.org/fast/982185 https://id.kb.se/term/sao/Kultur https://id.kb.se/term/sao/Kulturhistoria https://id.kb.se/term/sao/Musik https://id.kb.se/term/sao/Musikhistoria https://id.kb.se/term/sao/Nazism%20och%20musik https://id.kb.se/term/sao/Orgel https://id.kb.se/term/sao/Propaganda--historia https://id.kb.se/term/sao/Reggae https://scigraph.springernature.com/ontologies/product-market-codes/I13022 https://scigraph.springernature.com/ontologies/product-market-codes/I14002 https://scigraph.springernature.com/ontologies/product-market-codes/I18067 https://scigraph.springernature.com/ontologies/product-market-codes/I21000 https://scigraph.springernature.com/ontologies/product-market-codes/I22005 https://scigraph.springernature.com/ontologies/product-market-codes/I24032 Huang zhong (Musical instrument) hudba hudebniny hudební kritici hudební kritika hudební sbírky hudební skladatelé hudební skladatelky hudební vzdělávání hudební život hudebníci Hugo Badalić Human body Human body in music. Human body. Human evolution. Human geography. Human rights Human rights workers Human rights workers. Human rights. Human sacrifice in opera. Human-animal relationships Human-computer interaction. Humaniora och konst. Humanism Humanism in music Humanism in music. Humanism. Humanisme dans la musique. Humanists Humanities and the Arts. Humor in music. Humor. Hungarian hungarian composers Hungarian folk music Hungarian Folk songs Hungarian folksongs Hungarian music life hungarian musiciians hungarian musicology hungarian pop music Hungarian song Hungary Hungary. Hurdy-gurdy. Husband and wife. Hydroponics Hymnes Hymnes. Hymns Hymns, English Hymns, English. Hymns, Pitjantjatjara. Hymns, Welsh. Hymns. IAML Ian McGillis Iberian Peninsula Iceland Iconography Identification Identification (Religion) Identification. Identité sexuelle dans la musique. Identity (Psychology) in adolescence Identity (Psychology) in adolescence. Identity politics. Identity. Ideology Igor Illinois Illumination of books and manuscripts. Illustrators Imagery (Psychology) Imagination. Imitation (Littérature) Imitation in literature. Immigrants Immigrants. Impresarios Impression Impression. Imprésarios Improvisation (Music) Improvisation (Musique) Improvisation in art Ina Boyle Incas Incas. Inclusive education Inde Inde (Sud) Inde. Indexes. India India, South. India. Indian influences. Indian women activists Indian women singers Indians of North America Indie culture. Indie pop music Indigenous musicians Indigenous peoples Individual Composer & Musician. Individual composers & musicians, specific bands & groups. Indonesia Indonesia. Industrial music Industrial music. Industrie Industrie de la musique et du son. Industrie. Influence (Literary, artistic, etc.) Influence africaine. Influence américaine. Influence. Information literacy Information resources Informatique. Ingénieurs du son Inlärning Inscriptions. Installations sonores (Art) Institute of Registered Music Teachers of New Zealand Institute of Registered Music Teachers of New Zealand history Institutional care institutional history Instruction & Study Instruction and study Instruction and study. Instrumental music Instrumental music. instrumental works Instrumentation and orchestration Instrumentation and orchestration. Instrumentation et orchestration Instruments à clavier Instruments à cordes Instruments de musique Instruments de musique électroniques Intangible property Intelectual property Intellectual life Intellectual life. Intellectual property Intelligence artificielle. Intercultural communication Intercultural communication. Interfaith worship. Interior decoration Interior decoration. Intermediality. International relations. International trade. Internationalism Internationalism. Interpersonal conflict Interpersonal conflict. Interpretation Interpretation (Phrasing, dynamics, etc.) Interpretation and construction Interpretation and construction. Interracial adoption Intertextuality. Interviews Interviews. Inuit Invective in music. Iolo Morganwg iPad (Computer) iPhone (Smartphone) iPod (Digital music player) Iran Iraq Ireland Ireland. Irish Irish American soldiers Irish American soldiers. Irish American. Irish Americans Irlandais Irlandais. Irlande Irlande. Irony in music. Irving, Dorothy, 1927- Islam Islam Semiotik Hiphop Islam. Islamic arts Islamic countries Islamic countries. Islamic influences. Islamic music Islamic music. Islands. Isle of Man Isle of Man. Israel Israel. Israël. Italian language Italian Opera Italian poetry Italian poetry. Italie Italie. Italy Italy. Itálie Ivan Kukuljević Sakcinski Ivan pl. Zajc Ivan Zajc Jacinto Guerrero Jacinto Valledor Jack Jam bands Jam bands. Jamaica Jamaica. Jamaicans Jamaïque Jamaïque. James Goodman James Wilson Japan Japan. Japanese drama Japanese drama. Japanese influences. Japanese literature Japanese poetry Japon. Japonism Järnbruk-- historia Jay-Z. Jazz Jazz au cinéma. Jazz clubs Jazz dance. Jazz dans la littérature. Jazz festivals jazz history in Hungary Jazz history in Spain Jazz in Croatia Jazz in literature. Jazz in motion pictures. Jazz musicians Jazz Musicians - New Zealand jazz musicians - New Zealand - anecdotes; Clark Jazz musicians. Jazz New Zealand jazz record history Jazz singers Jazz singers. jazz theory Jazz vocals Jazz-- historia Jazz. Jazzklubbar Jazzmusiker Jazzmusiker Basister Tonsättare Jefferies, Graeme Jelena Zrinska=Ilona Zrínyi Jenny Jeux vidéo, Musique de Jew's harp Jewelry Jewelry theft Jewelry theft. Jewelry. Jewish composers Jewish composers. Jewish jazz musicians Jewish music Jewish musicians Jewish musicians. Jewish studies. Jewish theater Jews Jews in the performing arts Jews, German Jews, German. Jews. jlabsh/4 Joan Denise Moriarty Job stress. Joe Dolan John Barry John Beckett John Buckley John Egan Jojk Folkmusikuppteckningar Josep Mestres-Quadreny Journalism (Film & Media) Journalism. Journalists Jōruri Jōruri-Rekishi. Jōruri. Judaism Judaïsme. Judenverfolgung Jugaku. Jugoton Juifs Jukebox musicals Jukebox musicals. Jungian psychology. Jusqu'à 1500 Jusqu'à 1901 Jusqu'à 1931 Justice sociale Justice sociale. Juvenile Juvenile literature. K-pop Kabuki Kabuki music Kabuki music. Kabuki plays Kabuki plays. Kabuki-Rekishi. Kabuki. Kageki. Kagura Kagura. Kaitito waiata reo Korero taumata Kaiwaiata. Kamengeki. Kansas Karl Goldmark Kashu. Kayō. Keiongaku. Kentucky Kenya Kenya Nairobi Kenya. Kerry Kevin (trumpeter) - anecdotes - Keyboard instrument music Keyboard instrument music. Keyboard instruments Keyboard instruments. Keyboard music Keyboard players Keyboards (Music) Keybord music Kildare Kinematografija Kirchenmusik Kirtana (Hinduism) Klangfärg Improvisation (musik) Preparerat piano Klangkunst. Klapa singing Klarinettister Klassische Musik Klassische Musik. Klassisk musik Konserter (framträdanden) Pianister Scenframträdanden Nervsystemet Prestations{\aa}ngest Klassisk musik-- historia Klassisk musik-- mottagande Klezmer music Klezmer music. Knowableness. Knowledge, Theory of (Religion) Knowledge, Theory of. Kokusai bunka kōryū. Komponist Komponistin Komposition (musik) Komposition Musikframträdanden Kompositörer Konserter (framträdanden) Rock Könsmaktsordning Könsroller Konst Konst. Konstfilosofi Konstmusik Konstnärlig forskning Konstnärligt skapande Konzert Kördirigering Korea Korea (South) Korea. Korean Americans Korean language materials. Körer-- historia Körledning Körsång-- forskning Körsångng Körs{\aa}ng – sociala aspekter Körs{\aa}ng – psykologiska aspekter Kōrero taumata. Kŏmunʼgo music Kŏmunʼgo music. Kranjčević Vladimir Kropp och själ Kultur. Kulturell identitet Migration Musik – sociala aspekter Kulturförderung Kulturhistoria. kulturni kapital ; vrijednosti ; mladi ; kulturna potrošnja ; glazbeni ukus ; televizijske preferencije ; Jadranska Hrvatska (cultural capital ; values ; youth ; cultural consumption ; taste in music ; television preferences ; Adriatic Croatia) Kulturpolitik Kulturpolitik Offentliga sektorn Musikliv Kurt Weil Kuyō. Künste Kvarner Kvinnliga musiker Kvinnliga tonsättare Kvinnliga tonsättare Tonsättare Kvinnoförtryck Musik – historia – genusaspekter Kvinnor i musiken – historia Kvinnlighet – historia Kärlekss{\aa}nger – historia – genusaspekter Kwansei Gakuin Glee Club Kyōdo geinō. kyōdogeinō Kyōgen Kyōgen plays Kyōgen plays. Kyōgen-Rekishi. Kyōgen. Kyrkomusik Kyrkomusik – historia Kyrkomusiker. Kyrkos{\aa}ng Kyrkomusik Labor productivity Labour law Laienspiel Landscape architecture. Landscapes in music. Language Language acquisition. Language and languages Language and languages. LANGUAGE ARTS & DISCIPLINES LANGUAGE ARTS & DISCIPLINES / Alphabets & Writing Systems. LANGUAGE ARTS & DISCIPLINES / Composition & Creative Writing LANGUAGE ARTS & DISCIPLINES / Grammar & Punctuation. LANGUAGE ARTS & DISCIPLINES / Linguistics / General. LANGUAGE ARTS & DISCIPLINES / Linguistics / Syntax. LANGUAGE ARTS & DISCIPLINES / Publishing LANGUAGE ARTS & DISCIPLINES / Readers. LANGUAGE ARTS & DISCIPLINES / Spelling. Language. Large type books. Larsson Gothe, Mats, 1965- Last years of a person's life. Latin America Latin America. Latin drama (Comedy) Law LAW / Jurisprudence Law and legislation Law and legislation. Lawyers lcgft Leadership. Learning Learning disabled children Legacies Legal status, laws, etc. Leisure Lent Lenten music Leonard Cohen Lesbian musicians Lesbian musicians. Letters Letters. Lésions et blessures. LGBT LGBT Studies. LGBT. LGBTQ+ musicians. Liberalism Libraries and minorities Libraries and minorities. Libraries. Librarinaship Library Library fund raising Library fund raising. Library outreach programs libreto Librettists Libretto Libretto Librettologi Libretto. Librettos Librettos. Licenses lidové hudební nástroje Lied Lieu (Philosophie) Life cycle, Human Lifestyle, sport and leisure / Sports and outdoor recreation / Active outdoor pursuits / Walking, hiking, trekking likovi kao alegorija nacije Lindblad, Adolf Fredrik, 1801-1878 Lindh, Björn J:son, 1944-2013 Lisa; Pearl (musical group Listening Listening (Philosophy) Listening. Literacy LITERARY COLLECTIONS / Essays. Literary collections. LITERARY CRITICISM LITERARY CRITICISM / American / Asian American & Pacific Islander. LITERARY CRITICISM / American / General LITERARY CRITICISM / American / General. LITERARY CRITICISM / European / English, Irish, Scottish, Welsh LITERARY CRITICISM / European / English, Irish, Scottish, Welsh. LITERARY CRITICISM / Feminist. LITERARY CRITICISM / General. LITERARY CRITICISM / Modern / General. LITERARY CRITICISM / Poetry Literary sources Literary themes, motives. Literatur Literature Literature on music. Literature, Modern Literature, Modern. Littérature Liturgical drama; Religious festivities; Oral tradition liturgical songs Liturgics. Liturgie. Liturgies liturgy. Livres d'heures Livret (Musique) Ljudeffekter Ljudevit Gaj Ljudkonst Loggers Logging. Logiciels. Logistik Streamad media Programvara Musikbranschen – tekniska aspekter Loisir loneliness Longitudinal studies. Lorde Loss (Psychology) Louisiana Louisiane Love poetry, Scottish. Love songs Ludwig van Luis de Pablo Lullabies. Lumber trade. Lur (Iranian people) Lute Lutheran Church Lutheran Church. Luthiers Lyric writing (Popular music) Lyricists Lyricists. Lyrics. Maček Ivo Machine learning. Madrid Madrigal. Madrigaler. Madrigalkomödie. Madrigals Madrigals. Maintenance and repair Maintenance and repair. Makerspaces Maksimilijan Vrhovac Malawi Malawi. Malaysia Male actors. Male musicians Male singers Male singers. Malec Ivo Malerei Malta Malta. Män Man-woman relationships. Management. Mandolin Mandolinists Mandolinists. Manners and customs Manners and customs. Manuel de Falla manufacture of musical instruments. Manuscripts Manuscripts, German Manuscripts, German. Manuscripts, Latin (Medieval and modern) Manuscripts. Manuscrits latins médiévaux et modernes Maori (New Zealand people) Maori (New Zealand people), Maori in the performing arts Maori; Maori (New Zealand people) - music; wood instruments - New Zealand; Birds - New Zealand - songs and music Marcus, Greil Markedness (Linguistics) Marketing Marketing. Marque (Linguistique) Marriage. Marshall Islands Marshall Islands. Marshallais Marshallese Martin P. anecdotes Martin, Hans, 1934- Masculinité dans la musique. Masculinity Masculinity in music. Maskanda Maskanda. Mass Mass (Music) Mass media Mass media and music Mass media and music. Mass media; Broadcasting Massachusetts Masses Mastering (Sound recordings) Materialität. materiality. Materials and instruments Materials and instruments. Materials. Mathematics MATHEMATICS / Applied MATHEMATICS / General Mathematics. Mathematik Mathématiques Mathématiques. Matsuri-Miyagiken. Matsuri-Nihon. Matsuri-Tōhoku chihō. Matsuri-Tōkyōto chiyodaku. McIntyre, Donald, 1934 McPherson, Suzanne Meaning (Philosophy) Means of communication. Mechanical aids. Mechanical musical instruments Media Studies. mediaeval music. MEDICAL MEDICAL / Alternative Medicine medicine Medicine and art. Medicine. Medieval influences. Medieval music Medieval. Medievalism in opera. Medievalism. Mediterranean Region. Melancholy in music. Melbourne Melbourne (Vic.) Melodi Svenska skillingtryck – historia Svenska skillingtryck – sociala aspekter – historia Svenska skillingtryck – politiska aspekter – historia Melodic analysis. Melodrama. memoir. memoires Memorials Memorials. Memory Memory in motion pictures. Memory in old age. Memory. Men's choirs Mennonite Church Canada. Mensch Mensural notation. Mental disorders Mentoring. Messe (Musique) Messes Messiah Mesure et rythme Mesure et rythme. Metaphor in musical criticism. Metaphysics. Metaphysique. Methodology Methodology. Methods Methods (Blues) Methods (Rock) Methods. Metronome. Mexican American cooking. Mexican Americans Mexican-American Border Region Mexican-American Border Region. Mexicans Mexico Mexico. Mexique Mezzo-sopranos Mécénat Médias et musique. Médias numériques Mémoire Mémoire collective Méthodes statistiques. Méthodologie Michael W. Balfe Michigan Microphone Microphone. Microtones. Middle Age Middle age. Middle Age; Carmina Burana Middle Ages Middle Ages, 600-1500 Middle Ages, 600-1500. Middle Ages. Middle East Middle East. Middle West Middle West. MIDI (Standard) MIDI controllers. migrations Miguel de Cervantes Miguel Fisac Miklós Zrinyi Mil neuf cent soixante-huit. Militärmusiker Military music Military occupation Military occupation. Military participation Military spouses Mills and mill-work Mind and body. Mindfulness (Psychology) Minimal music Minimal music. Minorités dans les arts du spectacle. Minorities Minorities in the performing arts. Minstrel music Minstrel show Minwa. Minzoku ongaku. Miscellanea. Miscellanées. Misogyny in music. Mississippi Mississippi River Valley mixed choir Mixed reality. Mod culture (Subculture) Modality (Linguistics) Modan dansu-Rekishi. Models (Persons) Modern Age - Spain Modern dance Modern dance music Modern dance music. Modern dance. Modern history to 20th century: c 1700 to c 1900. Modernism (Art) Modernism (Literature) Modernism (Music) Modulation (Music) Modulation (Musique) Moguchai͡a kuchka (Group of composers) Monarchy Monastic and religious life Monasticism and religious orders Mongolia Mongolia. Mongolie Mongolie. Mongols Monism. Monisme. monography Monologues with music (Chorus with orchestra) Monsters. Moog synthesizer. Moral and ethical aspects. Morale pratique. Mormons Mörne, Arvid, 1876-1946. Sjömansvisa Morocco Morocco. Morrison, Howard Motets Motets. Motette Motherhood and the arts. Mothers Mothers. Motion detectors Motion picture actors and actresses Motion picture actors and actresses. Motion picture music Motion picture music. Motion picture plays Motion picture plays. Motion picture producers and directors Motion picture theater managers Motion pictures Motion pictures and music Motion pictures and music. Motion pictures and opera. Motion pictures and the war. Motion pictures and transnationalism. Motion pictures in psychotherapy. Motion pictures, Hindi Motion pictures. Motiv Motocyclisme Motorcycling Mouvements des droits de l'homme Movement education. Movement, Aesthetics of. Mozambique Mozambique. Mozarabic chants Mozarabic rite (Catholic Church) Mozart Mridanga MUISC / Genres & Styles / Rock. Multi-sided platform businesses Multiagent systems. Multicultural education. Multiculturalism Multiculturalism. Munich Biennale For New Music Theatre. Munster Murai Jurica MUS020000. Museology & heritage studies. Museu de la Música de Barcelona museum history Museum Studies. Museum techniques. Museums Museums of Instruments Music Music & Sound Studies. Music - Church music - Hymns, Choruses and Carols. music - private collctions- New Zealand Music - private collections - Australia Music -- New Zealand -- Dunedin -- History and criticism. MUSIC / Business Aspects MUSIC / Discography & Buyer's Guides. MUSIC / Essays. MUSIC / Ethnic MUSIC / Ethnomusicology MUSIC / Ethnomusicology. MUSIC / General MUSIC / General. MUSIC / Genres & Styles / Ballet MUSIC / Genres & Styles / Blues MUSIC / Genres & Styles / Classical MUSIC / Genres & Styles / Classical. MUSIC / Genres & Styles / Dance. MUSIC / Genres & Styles / Folk & Traditional MUSIC / Genres & Styles / Folk & Traditional. MUSIC / Genres & Styles / General MUSIC / Genres & Styles / Heavy Metal. MUSIC / Genres & Styles / Jazz MUSIC / Genres & Styles / Jazz. MUSIC / Genres & Styles / Latin. MUSIC / Genres & Styles / Opera MUSIC / Genres & Styles / Opera. MUSIC / Genres & Styles / Pop Vocal MUSIC / Genres & Styles / Pop Vocal. MUSIC / Genres & Styles / Punk MUSIC / Genres & Styles / Punk. MUSIC / Genres & Styles / Rap & Hip Hop MUSIC / Genres & Styles / Rap & Hip Hop. MUSIC / Genres & Styles / Reggae MUSIC / Genres & Styles / Rock MUSIC / Genres & Styles / Rock. MUSIC / Genres & Styles / Soul & R 'n B. MUSIC / History & Criticism MUSIC / History & Criticism. MUSIC / History & Criticism. MUSIC / History ; Criticism. MUSIC / Individual Composer & Musician MUSIC / Individual Composer & Musician. MUSIC / Instruction & Study / Appreciation MUSIC / Instruction & Study / Composition MUSIC / Instruction & Study / General MUSIC / Instruction & Study / General. MUSIC / Instruction & Study / Songwriting MUSIC / Instruction & Study / Songwriting. MUSIC / Instruction & Study / Theory MUSIC / Instruction & Study / Theory. MUSIC / Instruction & Study / Voice MUSIC / Instruction & Study / Voice. Music / Italy / 16th century / History. MUSIC / Lyrics MUSIC / Lyrics. MUSIC / Musical Instruments / Guitar. MUSIC / Musical Instruments / Piano & Keyboard MUSIC / Musical Instruments / Piano & Keyboard. MUSIC / Musical Instruments / Strings MUSIC / Musical Instruments / Strings. MUSIC / Philosophy & Social Aspects. MUSIC / Printed Music / Percussion MUSIC / Printed Music / Percussion. MUSIC / Printed Music / Vocal MUSIC / Printed Music / Vocal. MUSIC / Recording & Reproduction MUSIC / Recording & Reproduction. MUSIC / Reference MUSIC / Reference. MUSIC / Religious / Christian MUSIC / Religious / General MUSIC / Religious / Jewish music academy music aesthetics music amateurism Music and anthropology. Music and antisemitism Music and antisemitism. Music and architecture. Music and aristocracy Music and children Music and children. Music and crime. Music and Culture (Music) Music and dance Music and dance. Music and diplomacy Music and diplomacy. Music and geography Music and geography. Music and globalization Music and globalization. Music and history Music and history. Music and identity politics. Music and intergenerational communication. Music and language Music and language. Music and literature Music and literature. Music and magic Music and magic. Music and Media (Music) Music and medicine Music and mythology Music and older people. music and painting Music and philosophy Music and philosophy. Music and politics music and potry Music and race Music and race. Music and rhetoric. Music and science Music and science. Music and sports. Music and state Music and state. Music and technology Music and technology. Music and text Music and the conflict. Music and the Internet Music and the Internet. Music and the war. Music and tourism Music and tourism. Music and transnationalism Music and transnationalism. Music and war Music and war. Music and youth Music and youth. Music appreciation Music appreciation. Music archaeology Music archaeology. music archive Music as recreation. music association Music Association of Ireland Music audiences. Music avantgarde Music Biographies (Music) Music by African American composers Music by African American composers. Music by black composers Music by women composers Music by women composers. Music chapells Music collections Music criticism Music critics Music critics New Zealand biography Music critics. music dictionary Music Documentation Music Drama Music Education Music education; Pedagogy music esthetic Music fans Music fans. Music festivals Music festivals. Music for people with mental disabilities. Music for people with visual disabilities. Music for the developmentally disabled. Music for the hearing impaired. Music history Music history and criticism music history in Hungary Music History; Occult sciences; Secret societies Music in advertising Music in advertising. Music in art Music in art. Music in Christian education Music in churches Music in churches. Music in Dubrovnik Music in education Music in education. Music in historic house museums. Music in intercultural communication Music in intercultural communication. Music in literature. Music in prisons Music in prisons. Music in synagogues Music in the Bible Music in the Bible. Music in the home Music in the home. Music in the theater Music in the theater. Music in universities and colleges Music in universities and colleges. Music instruction and study Music Instruments Music journalists Music journalists. Music libraires Music librarians Music librarians. Music librarianship Music librarianship. Music libraries Music libraries. music life Music life history music life in Hungary Music Linguistics Music Management. Music manuscripts Music memorizing. music migrations Music museums Music museums. Music New Zealand Auckland history and criticism music New Zealand Invercargill history and criticism Music patronage Music patronage. music pedagogy Music performance Music printing Music printing. Music publicity Music publicity. Music publishers Music publishers. Music publishing Music publishing. Music recording & reproduction. Music reviews & criticism. Music rooms and equipment music school Music stores Music students Music study and teaching New Zealand Christchurch history Music teachers Music teachers New Zealand biography Music teachers. Music teaching Music television Music thanatology. Music theater Music theater. Music Theatre New Zealand Auckland History Music theorists Music theory Music theory. Music therapists Music therapy Music therapy for children Music therapy for children. Music therapy for families Music therapy for older people. Music therapy for teenagers. Music therapy New Zealand Case studies; Music therapy; New Zealand poetry 21st century Music therapy. Music trade Music trade New Zealand Music Trade New Zealand 20th Century Music trade. Music videos Music videos. Music › Genres & Styles › Pop Vocal Music, Greek and Roman Music, Greek and Roman. Music, Influence of Music, Influence of. Music, Slovenian Music--20th century--Analysis Music--21st century--Analysis music--instruction and study--New Zealand; Educational change--New Zealand; Education Music--Latin America Music-halls Music-halls (Variety theaters, cabarets, etc.) Music-halls (Variety-theaters, cabarets, etc.) music-halls New Zealand 20th Century Music-halls. Music. Music: Genres & Styles / Classical. Music: History & Criticism. Music: Individual Composer & Musician. Music: styles & genres. Musica ficta. Musical ability in children Musical ability. Musical accompaniment Musical accompaniment. Musical aesthetics Musical analysis Musical analysis. Musical applications Musical applications. Musical bow Musical canon Musical canon. Musical chapells Musical creation Musical criticism Musical criticism. Musical dictation. Musical education Musical Encoding Musical films Musical films. Musical form Musical genres Musical groups Musical groups. Musical heritage management Musical heritage; Oral tradition; Ethnousicology musical instrument Musical instrument collections Musical instrument makers Musical instruments Musical instruments & instrumental ensembles. Musical instruments collections Musical instruments, Ancient Musical instruments. Musical instruments; Archeological sources; Islamic art; Al-Andalus Musical intervals and scales Musical intervals and scales. Musical inventions and patents. Musical landmarks Musical landmarks. Musical Libraries musical life Musical manuscripts Musical memory Musical meter and rhythm Musical meter and rhythm. musical migrations Musical New Zealand Auckland history Musical notation Musical notation. musical papers Musical perception Musical perception. musical performance Musical pitch Musical practice Musical scores, lyrics & libretti Musical settings Musical settings. Musical sources Musical structure musical tales Musical teaching Musical temperament Musical temperament. Musical theater Musical theater producers and directors Musical theater. Musical theatre New Zealand Auckland history Musical thought Musicalproduktion Musicals Musicals New Zealand Auckland History Musicals. Musician angels Musicians Musicians -- New Zealand -- Biography. Musicians -- New Zealand -- Portraits. Musicians -- New Zealand -- Tauranga -- History. Musicians as artists. Musicians as authors. Musicians Career Musicians Musicians in art Musicians in art. 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Musicothérapie. musictheory Musictherapy; Medicine Musik Musik i massmedia Musikinspelningar – historia Musik och samhälle – historia Musik Musikhistoria Musik och dans Musik och samhälle Invandrare Musiksociologi Folkmusik – sociala aspekter Musik och samhälle Musikframträdanden Koreografi Genus (socialt kön) Gester – sociala aspekter Gester – genusaspekter Musik och samhälle-- historia Musik-- historia Musik-- idéhistoriska aspekter Musik-- sociala aspekter Musik-- teori, filosofi Musik. Musik/Mittelalter. Musikalische Analyse Musikalische Semiotik. Musikalität Musikalitet Musikalitet Sinnen och förnimmelser Musikanschauung Musikdruck Musiker Musiker Ungdomar Datorspel Digitalisering Musikundervisning Musiker-- genusaspekter Musiker-- historia Musikethnologie Musiketnologi Musikfestivaler Musikfilosofi Instrumentalmusik Musikforskare Museimän Folkhögskolelärare Musikgeschichte. 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Sublime, The Sublime, The, in literature. Sublime, The, in music. Sublime, The. Substitute teaching Suburban life in popular culture Suburban life in popular culture. Subversive activities in mass media. Sufi music Sufi music. Sufism Suites (Harpsichord) Šulek Stjepan Suomi Surgical instruments and apparatus Surrealism and music Surrealism and music. sustainable development Svenska författare Svenska operas{\aa}ngerskor Operas{\aa}ngare Sverige Sverige-- Medelpad -- Timrå Sverige-- Småland -- Växjö Sverige-- Småland -- Visingsborg Sverige-- Stockholm Sverige-- Uppland Sverige-- Uppland -- Lövstabruk swd Sweden Sweden. Swing (Music) Switzerland Symbolism in music. Symbolism in opera. Symmetry Symphonic music Symphonic poem. Symphonies Symphonies (Chamber orchestra), Arranged Symphonies (Chamber orchestra), Arranged. Symphonism; Repertory Symphonism; Repertory; 20th Century; 21th Century Symphonism; Repertory; Ludwig van Beethoven Symphony Symphony orchestras Symphony orchestras. 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Women drummers (Musicians) Women entertainers Women executives Women folk musicians Women in Dance Women in music Women in music. Women in opera. Women in television broadcasting Women in the music trade Women in the music trade. Women jazz musicians Women jazz musicians. Women jazz singers Women jazz singers. Women lyricists Women lyricists. Women music patrons Women music patrons. Women music teachers Women music teachers. Women musicians Women musicians. Women painters Women performance artists Women philanthropists Women pianists Women pianists. Women poets Women poets. Women popular music fans. Women punk rock musicians Women punk rock musicians. women rap musicians Women rock musicians Women rock musicians. Women singers Women singers. Women social reformers Women sound engineers Women sound engineers. Women sound recording executives and producers Women sound recording executives and producers. Women television personalities Women violinists Women violinists. Women's music Women, Black Women, Celtic Women. Wood. woodwind instruments. Work catalogues Working class World history. World music World music. World War World War 1914-1918 World War, 1914-1918 World War, 1939-1945 World War, 1939-1945. World. Worship. Wounds and injuries. Wörterbuch Writers Writers; Generation of '27 Writing Writing and publishing Writing and publishing. Writing. Written communication Yaozoku. Yew Yiddish Yoruba (African people) Young adults Youth Youth development. Yugoslavia breakdown Zagreb Zajc Zajc Ivan Zarzuela Zarzuela. Zarzuela; Sound recordings; Mechanical instruments Zealandia Performances Zeichentrickfilm. Zheng Zheng music Zingen Zither Zora Zrinjski Zulu (African people) Zulu music Zydeco music ] Đàn tranh Đorđević 고전 음악[古典音乐] 교수 학습 방법[敎授学习方法] 교육 프로그램[敎育 러시아 문학 문학 평론文学评论 문화 예술 교육[文化艺术敎育] 서양 음악[西洋音乐] 심리학[心理学] 유아 음악 교육[幼儿音乐敎育] 음악 교육[音乐敎育] 음악(교과과목)[音乐] 음악(예술)[音乐] 음악사[音乐史] 작곡가[作曲家] 전기(인물)[传记] 클래식[classic] レコード音楽. 医学. 埼玉県 文学 流行歌. 演剧. 神楽 舞踊. 音楽.
Found 205 results Author Title Type
[ Year
]
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2020
Thornton, Richard
. If I Can't Open..i'm Not Closing!
. United Kingdom : London : Balboa Press UK, 2020.
Strasfogel, Ian
. Ignace Strasfogel : Die Wiederentdeckung Eines Musikalischen Wunderkinds /
. Vol. Band 257. 1. Auflage.st ed. Germany: Berlin ; Leipzig : Hentrich & Hentrich ; [Berlin] : Akademie der Künste,, 2020.
Horne, Craig
. I'll Be Gone Mike Rudd, Spectrum And How One Song Captured A Generation.
. La Vergne, Australia: Melbourne Books, 2020.
http://public.eblib.com/choice/PublicFullRecord.aspx?p=6387127
.
Ochs, Phil , and David Cohen
. I'm Gonna Say It Now : The Writings Of Phil Ochs /
. United States: Guilford, Connecticut :Backbeat Books , 2020.
Padgett, Ray
. I'm Your Fan : The Songs Of Leonard Cohen /
. Vol. 147. United States: New York, NY : Bloomsbury Academic, Bloomsbury Publishing Inc, 2020.
Panagl, Oswald
. Im Zeichen Der Moderne Musiktheater Zwischen Fin De Siècle Und Avantgarde.
. Wien, Austria: Hollitzer Wissenschaftsverlag, 2020.
http://search.ebscohost.com/login.aspx?direct=true&scope=site&db=nlebk&db=nlabk&AN=2708957
.
Walker, STan , and Margie Thomson
. Impossible : My Story
. Auckland, New Zealand: HarperCollins, 2020.
Walker, Stan , and Margie Thomson
. Impossible : My Story /
. Auckland, New Zealand Sydney, Australia: HarperCollins Publishers, 2020.
Harris, Paul
. Improve Your Sight-Reading! : A Piece A Week.
. United Kingdom : London : Faber Music, 2020.
Galán-Bueno, Carlos
. Improvisación En El Flamenco. Tratado Teórico-Práctico
. Spain: Madrid: Enclave Creativa Ediciones, 2020.
Doky, Niels Lan , and Heidi Vesterberg
.
Improvisation : I Musikken, På Arbejdet Og I Livet
. 1. særudgave st ed. Kbh., Denmark : Gyldendal Business , 2020.
Cook, James
. In Her Room : How Music Helped Me Connect With My Autistic Daughter /
. United Kingdom : London : Lagom, 2020.
Dawidoff, Nicholas
. In The Country Of Country
. United Kingdom : London : Faber & Faber, 2020.
Pacciolla, Paolo
. The Indian Drum Of The King-God And The Pakhawaj Of Nathdwara
. United Kingdom : London : Routledge, 2020.
Craske, Oliver
. Indian Sun : The Life And Music Of Ravi Shankar /
. Main. United Kingdom : London : Faber & Faber, 2020.
Oleksiuk, Olga
. Individual Spirituality In Post-Nonclassical Arts Education
. United Kingdom : Newcastle upon Tyne : Cambridge Scholars Publishing, 2020.
Piusz, Balogh Péter , and Réger Ádám
. Insigni Die Sollemnitatis : Írások Ullmann Péter Ágoston O. Praem. 80. Születésnapjára
. Gödöllő: Gödöllői Premontrei Apátság, 2020.
Feldman, Evan , and Ari Contzius
. Instrumental Music Education : Teaching With The Musical And Practical In Harmony /
. Third edition. United Kingdom : London : Routledge, 2020.
W. Sutcliffe, Dean
. Instrumental Music In An Age Of Sociability : Haydn, Mozart And Friends /
. United Kingdom : Cambridge : Cambridge University Press, 2020.
Boyle, Kerry
. The Instrumental Music Teacher : Autonomy, Identity And The Portfolio Career In Music /
. United Kingdom : London : Routledge, 2020.
Mahlert, Ulrich
. Instrumentalpädagogik In Studium Und Beruf Eine Persönliche Bestandsaufnahme
. Germany: Mainz : Schott, 2020.
Instrumente Und Aufführungspraxis Der Barockmusik
. Germany: Laaber : Laaber-Verlag, 2020.
Navarro-Coba, María Dolores
. “ Instrumentos Musicales Encontrados En Excavaciones Arqueológicas Pertenecientes A Los Siglos Iv-Xv En El Territorio Andaluz ”
. Granada: Universidad de Granada, 2020.
http://hdl.handle.net/10481/62888
.
De Man, Brecht , Ryan Stables , and Joshua D Reiss
.
Intelligent Music Production
. United States ; United Kingdom: New York : London ; Routledge, 2020.
https://www.taylorfrancis.com/books/9781315166100
.
International Who's Who In Classical Music 2020
. United Kingdom : London : Routledge, 2020.
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Submarine robots learn teamwork | Engineering News
New technology developed by researchers will allow autonomous underwater vehicles to work together as a team. It increases the scope of submarine applications for autonomous vehicles. Even better, the technology can be retrofitted.
Submarine robots learn teamwork
Engineers Edge - One could reasonably argue that the ocean floor is composed primarily of surprise. Surprise is the most common finding when scientists investigate some unexplored portion of the sea bed. And the ocean is 90 percent unexplored.
We know more about the surface of the moon than we do of the watery depths. The most advanced alien life form so far encountered by humanity – a species using chemosynthesis, an entirely new metabolic process to create energy, cells and life - was found by Professor Colleen Cavanaugh at a hydrothermal vent in the ocean deep just 30 years ago.
Studying the deep ocean floor like this is cumbersome, expensive and dangerous. The majority of exploration efforts have to employ an autonomous unmanned vehicle (AUV), which works without control cables.
But many AUVs are specialized, they cannot travel far alone and they can only provide a narrow range of data. Moreover, there are few AUVs and the unexplored kilometers of ocean are many.
Underwater robots: The work of one European project, however, has the potential to dramatically increase the range and functionality of the world's AUV fleet. The GREX project sought to develop appropriate networking technologies and software to have coordinated missions with heterogeneous AUVs acting as a team.
There are many advantages. For a start, multiple AUVs can map a larger area in one sweep, performing a sort of synchronized swimming thanks to some very clever software developed by GREX.
What is more, the formation benefits from the sum of its sensing equipment, making the AUVs potentially much more versatile and capable of getting both a greater variety of data at a higher granularity in one pass.
GREX's results have the potential to extend the range of underwater exploration. Coordinated AUVs can daisy-chain the control signal from one to the other, so they can stretch out, bouncing the control signal from the mother ship to the networked submarines, over many kilometers.
"Underwater communication between vehicles is a very difficult area," explains Michael Jarowinsky of MC Marketing Consulting, a partner of the GREX project. "You have no link, so these vehicles are totally autonomous."
Until now, there have been only solo AUVs out there.
Tough technical challenges: Coordinating multiple AUVs requires sophisticated software. Seawater is a difficult medium for linking up submarine robots and bandwidth is very limited, which affects the quality and range of the signal – measured in the hundreds of meters.
"So we did not work with individual vehicles, we sought to create a ‘GREX' box that incorporates communications… tied into the vehicle controls. This can be simply added to existing vehicles, dramatically increasing their functionality," notes Jarowinsky.
There is high demand for this kind of functionality and the number of potential applications is enormous, from studying hydrothermal vents and their rich, alien ecosystems to making new discoveries in biology, geology, magnetism and any number of other studies.
"We focused on scientific applications in the GREX project. We were interested in fish data for fisheries research, a very important area. We aimed at marine mapping and also the study of hydrothermal vents," Jarowinsky reveals.
"Scientific applications are an important area for submarine exploration and it requires adaptable software that can be applied to many different tasks. It was useful to prove the technology."
The sophistication of the GREX technology is amply demonstrated by the hydrothermal vent application. Methane escaping from the vent creates a plume that degrades slowly, and a formation of submarines can ‘track' concentrations to follow the plume to its source.
This requires the AUVs to move almost as a single, distributed vehicle, honing in on the highest concentrations of methane. It is analogous to the slow and graceful yaw of a space shuttle as it docks with the International Space Station.
However, Jarowinsky points out that there are many other potential commercial applications that were not studied by the GREX project.
In the meantime, GREX has created a platform for the coordination of AUVs. This platform has been successfully tested in a serious of sea trails. The research results will be disseminated and exploited in three phases. The first, short-term, phase is publishing the research results and informing the submarine exploration community.
In the second phase, SeeByte, one of the project's partners, plans to market the control software and graphical user interface for managing AUV schools. And in three or four years the project coordinator, ATLAS Elektronik, aims to start offering a complete system, including the GREX box, software and installation and training.
"The marine exploration community is very conservative, and they have to know that a system works, that it is reliable. It takes time to completely prove a technology like this," stresses Joerg Kalwa from ATLAS Elektronik.
GREX was a research project, but the partners will develop a further proposal for a commercial project to take the results from GREX and apply them to commercial problems, perhaps also looking at fundamental technical constraints of the marine environment, like modem technology.
The GREX project received funding from the ICT strand of the Sixth Framework Program for research.Modified from materials provided by ICT/CORDIS.
| https://www.engineersedge.com/engineering/Engineers_Edge/submarine_robots_learn_teamwork_5488.htm |
EHRI - Wiener Holocaust Library - Items 781 to 800 of 1,825
The European Holocaust Research Infrastructure Online Portal
Wiener Holocaust Library
Displaying items 781 to 800 of 1,825
Hadjeret el Meguil, Algeria: Various documents
Wiener Holocaust Library
WL537
English
1950-1970
c76 frames
Readers need to reserve a reading room terminal to access a digital version of this archive.This microfilm collection of documents concerning life in Hadjeret el Meguil and other internment camps in Vichy North Africa was, according to a covering note at the beginning of the collection, donated to the Wiener Library, by way of gratitude for the assistance that was given to the depositor with respect to his restitution claims.Material re camps in North Africa including the following:Type-written copy of a novel, "Levinstein", by Peter Andreas, based on his experiences in forced labour units ...
Hahlo family collection
Wiener Holocaust Library
WL2199
English
4 folders
The collection contains vital records, identity papers and other personal papers of members of the Hahlo family, principally Peter Hahlo. In addition there are interviews with Peter and Fay Hahlo conducted by their son, Gerry, as well as the memoirs Georg Hahlo wrote for his children and family photographs.
Joyce Rozendaal Haldinstein: letters
Wiener Holocaust Library
WL1576
English
1940-1946
1 folder
The correspondence includes letters from Joyce in Holland and Switzerland and letters from friends in Great Britain and USA. Also included is the issue of the Dutch journal Sliepsteen, Spring 1998, No. 55, whose main feature is an article on Joyce Rozendaal Haldinstein.
Hamburg-Amerika Linie: Copy notice re illegal emigration to Palestine
Wiener Holocaust Library
WL1077
English
1939
1 folder
Copy of a notice from the Hamburg Amerika Linie, travel company, Breslau office, re sailings and prices for illegal emigration to PalestineGerman
Hammerschlag and Stein families: personal papers
Wiener Holocaust Library
WL1753
English
1911-1992
3 boxes
This collection contains the family papers of Istvan and Eva Stein, Hungarian Jews from Budapest who emigrated to Cairo in 1938 whilst some members of their family stayed behind and perished in the Holocaust.
Hampstead Garden Suburb Care Committee for Refugee Children: index
Wiener Holocaust Library
WL965
English
1939
1 file
These index cards are evidence of the activities of the Hampstead Garden Suburb Care Committee for Refugee Children in connection with the Movement for the Care of Children from Germany (British Inter-Aid Committee). The index cards of the children contain personal data and passport photographs. It seems that the cards were produced following a British Government initiative to simplify admittance procedures for children up to the age of 17 years.There are essentially 3 types of index card. One gives the particulars of the child, including the fate of the parents, and often has passport phot...
Hana's suitcase : a documentary
Wiener Holocaust Library
65702
English
2002
Hanau and Wallach family papers
Wiener Holocaust Library
WL1592
English
1829-1939
1 folder
This collection contains papers relating to the Hanau family of Friedberg, Hesse and other related Jewish families including the Wallach family of Alsfeld, Hesse and the Rosenberg family of Kassel, Hesse.The material consists of family trees, memoirs, copy official documents and correspondence.
Hanna and Peter Singer collection
Wiener Holocaust Library
WL2196
English
1 folder
Hannah Callman collection
Wiener Holocaust Library
WL2081
English
1 folder
Hannele Kuhn: family papers
Wiener Holocaust Library
WL1574
English
1893-1945
1 folder
Readers need to book a reading room terminal to access this digital contentThis collection of family papers consists primarily of letters from the Jewish parents, Franz and Hertha Kuhn, in Berlin, to their daughter, Hannele or Hannah, who had managed to find refuge in Great Britain, having come out on one of the Kindertransporte in 1939. The letters give a very moving account of the trials and tribulations of a very close-knit, loving family split asunder by the Nazis and ultimately condemned to death. The correspondence includes Red Cross telegrams between Hannele and her parents and...
Hannelore Jacob collection
Wiener Holocaust Library
WL2098
English
1 folder
Hans Globke: deposition concerning Jewish name changes in the Third Reich
Wiener Holocaust Library
WL959
English
1947
1 file
This is an original signed statement by Hans Globke, formerly chief adviser to Konrad Adenauer and earlier, official commentator on the Nuremberg Racial Laws. The statement deals with the provision of names denoting the Jewish origins of German citizens. The document is typescript with corrections apparently initialled, signed and dated by Globke.
Hans Hartmut Weil collection
Wiener Holocaust Library
WL2126
English
1 folder
Harry Edward Anderson Collection
Wiener Holocaust Library
WL1735
English
1938-1970
1 folder
This collection contains some personal papers and photographs of Harry Edward Anderson (formerly Hans Israel Abraham) who emigrated to England as a Jewish refugee upon release from Buchenwald concentration camp in Germany.
Hans Kroker: papers re law suit
Wiener Holocaust Library
WL1522
English
1979
1 folder
This collection contains papers concerning a threatened law suit which arose out of an assertion made in the famous TV programme Holocaust, which was broadcast in Germany in 1979. In particular, Hans Kroker, a former SS member, refutes the assertion made by one of the programme's participants that the family of this person was murdered in gas chambers, claiming that, without proof, it amounted to a vicious slur on the SS. The papers include a news magazine cutting with details of the story; a copy letter from Hans Kroker's lawyer, Eberhard Engelhardt, to the person who uttered the alleged s...
Hans Litten: Correspondence
Wiener Holocaust Library
WL572
English
1933-1938
c356 frames
This microfilm collection of correspondence of Irmgard Litten contains copy letters to her son whilst in concentration camps Lichtenburg and Dachau; copy correspondence to various authorities including Hitler, Hess and Göring asking for clemency; and some original letters from Hans Litten and various authorities. Most of it is typescript.
Hans Peter Frank collection
Wiener Holocaust Library
WL2083
English
1936-1938
1 folder
Hans Schäffer: catalogue to diaries and other papers - no date
Wiener Holocaust Library
WL951
English
1 box
This collection consists of the copy archival catalogue to the diaries and other papers of Hans Schäffer, formerly ministerial official and finance expert during the Weimar era. The original diaries are owned by the Wiener Library and are on permanent loan at the archive of the Institut für Zeitgeschichte, München which produced the catalogue. In addition to the catalogue and related papers there are two additional items, the provenance of which is not known. These are a partial copy of an analysis of the economic crisis of the early 1930s (951/3) and unidentified material relating to Germa...
Hans Schmoller: Family papers
Wiener Holocaust Library
WL1690
English
1907-1975
3 boxes
This collection contains the personal correspondence and papers of Hans Schmoller.Papers containing correspondence from Hans Peter Schmoller to his parents, Hans Israel and Marie Schmoller (1690/1) and other family members and friends, ranging from the time of his studies in London in the early 1930s to his emigration to Morija, Basutoland (now Lesotho) in 1938 and subsequent internment in Ganspan camp in 1939; detailed accounts by his parents of the persecutions and worsening conditions for Jews in Nazi Germany particularly after the November pogroms; and his parents' incarceration at Ther...
| https://portal.ehri-project.eu/institutions/gb-003348/search?country=gb&page=40&sort=name_sort.asc |
$680,000 in 2005 → 2022 | Inflation Calculator
The 2.41% inflation rate means $680,000 in 2005 is equivalent to $1,018,975.76 in 2022. This inflation calculator uses the official US consumer price index.
$680,000in 2005 is worth $1,018,975.76in 2022
Amount
$ 680000
Start year
End year
Value of $680,000 from 2005 to 2022
$680,000 in 2005 is equivalent in purchasing power to about $1,018,975.76in 2022, an increase of $338,975.76 over 17 years. The dollar had an average inflation rate of 2.41% per yearbetween 2005 and 2022, producing a cumulative price increase of 49.85%.
This means that prices in 2022 are 1.50 times as high as average prices since 2005, according to the Bureau of Labor Statistics consumer price index.
The inflation rate in 2005 was 3.39%. The inflation rate in 2022 was 8.00%. The 2022 inflation rate is higher compared to the average inflation rate of 3.92% per year between 2022 and 2023.
Contents
Overview
Buying Power of $680,000
Inflation by City / Country
Inflation by Spending Category
Formulas & How to Calculate
Alternate Measurements
Comparison to S&P 500 Index
Data Source
<table> Inflation from 2005 to 2022<tbody><tr><td> Cumulative price change</td><td> 49.85%</td></tr><tr><td> Average inflation rate</td><td> 2.41%</td></tr><tr><td> Converted amount
$680,000 base</td><td> $1,018,975.76</td></tr><tr><td> Price difference
$680,000 base</td><td> $338,975.76</td></tr><tr><td> CPI in 2005</td><td> 195.300</td></tr><tr><td> CPI in 2022</td><td> 292.656</td></tr><tr><td> Inflation in 2005</td><td> 3.39%</td></tr><tr><td> Inflation in 2022</td><td> 8.00%</td></tr><tr><td> $680,000 in 2005</td><td> $1,018,975.76 in 2022</td></tr></tbody></table>
USD inflation since 2005
Annual Rate, the Bureau of Labor Statistics CPI
Buying power of $680,000 in 2005
This chart shows a calculation of buying power equivalence for $680,000 in 2005 (price index tracking began in 1635).
For example, if you started with $680,000, you would need to end with $1,018,975.76 in order to "adjust" for inflation (sometimes refered to as "beating inflation").
When $680,000 is equivalent to $1,018,975.76 over time, that means that the "real value" of a single U.S. dollar decreases over time. In other words, a dollar will pay for fewer items at the store.
This effect explains how inflation erodes the value of a dollar over time. By calculating the value in 2005 dollars, the chart below shows how $680,000 is worth less over 17 years.
According to the Bureau of Labor Statistics, each of these USD amounts below is equal in terms of what it could buy at the time:
<table> Dollar inflation: 2005-2022<tr><th> Year</th><th> Dollar Value</th><th> Inflation Rate</th></tr><tbody><tr><td> 2005</td><td> $680,000.00</td><td> 3.39%</td></tr><tr><td> 2006</td><td> $701,935.48</td><td> 3.23%</td></tr><tr><td> 2007</td><td> $721,928.11</td><td> 2.85%</td></tr><tr><td> 2008</td><td> $749,646.90</td><td> 3.84%</td></tr><tr><td> 2009</td><td> $746,979.83</td><td> -0.36%</td></tr><tr><td> 2010</td><td> $759,232.36</td><td> 1.64%</td></tr><tr><td> 2011</td><td> $783,197.75</td><td> 3.16%</td></tr><tr><td> 2012</td><td> $799,405.63</td><td> 2.07%</td></tr><tr><td> 2013</td><td> $811,115.00</td><td> 1.46%</td></tr><tr><td> 2014</td><td> $824,272.81</td><td> 1.62%</td></tr><tr><td> 2015</td><td> $825,251.20</td><td> 0.12%</td></tr><tr><td> 2016</td><td> $835,661.85</td><td> 1.26%</td></tr><tr><td> 2017</td><td> $853,464.41</td><td> 2.13%</td></tr><tr><td> 2018</td><td> $874,738.35</td><td> 2.49%</td></tr><tr><td> 2019</td><td> $890,154.12</td><td> 1.76%</td></tr><tr><td> 2020</td><td> $901,136.37</td><td> 1.23%</td></tr><tr><td> 2021</td><td> $943,470.11</td><td> 4.70%</td></tr><tr><td> 2022</td><td> $1,018,975.76</td><td> 8.00%</td></tr><tr><td> 2023</td><td> $1,058,916.33</td><td> 3.92%*</td></tr></tbody></table>
* Compared to previous annual rate. Not final. See
inflation summary
for latest 12-month trailing value.
This conversion table shows various other 2005 amounts in 2022 dollars, based on the 49.85% change in prices:
<table> Conversion: 2005 dollars in 2022<tr><th> Initial value</th><th> Equivalent value</th></tr><tbody><tr><td> $1 dollar in 2005</td><td> $1.50 dollars in 2022</td></tr><tr><td> $5 dollars in 2005</td><td> $7.49 dollars in 2022</td></tr><tr><td> $10 dollars in 2005</td><td> $14.98 dollars in 2022</td></tr><tr><td> $50 dollars in 2005</td><td> $74.92 dollars in 2022</td></tr><tr><td> $100 dollars in 2005</td><td> $149.85 dollars in 2022</td></tr><tr><td> $500 dollars in 2005</td><td> $749.25 dollars in 2022</td></tr><tr><td> $1,000 dollars in 2005</td><td> $1,498.49 dollars in 2022</td></tr><tr><td> $5,000 dollars in 2005</td><td> $7,492.47 dollars in 2022</td></tr><tr><td> $10,000 dollars in 2005</td><td> $14,984.94 dollars in 2022</td></tr><tr><td> $50,000 dollars in 2005</td><td> $74,924.69 dollars in 2022</td></tr><tr><td> $100,000 dollars in 2005</td><td> $149,849.38 dollars in 2022</td></tr><tr><td> $500,000 dollars in 2005</td><td> $749,246.89 dollars in 2022</td></tr><tr><td> $1,000,000 dollars in 2005</td><td> $1,498,493.77 dollars in 2022</td></tr></tbody></table>
Inflation by City
Inflation can vary widely by city, even within the United States. Here's how some cities fared in 2005 to 2022 (figures shown are purchasing power equivalents of $680,000):
San Diego, California: 3.26%average rate, $680,000 → $1,172,702.81, cumulative change of 72.46%
Tampa, Florida: 2.89%average rate, $680,000 → $1,104,130.33, cumulative change of 62.37%
San Francisco, California: 2.85%average rate, $680,000 → $1,096,761.80, cumulative change of 61.29%
Seattle, Washington: 2.83%average rate, $680,000 → $1,092,568.00, cumulative change of 60.67%
Miami-Fort Lauderdale, Florida: 2.80%average rate, $680,000 → $1,087,355.53, cumulative change of 59.91%
Denver, Colorado: 2.78%average rate, $680,000 → $1,084,380.93, cumulative change of 59.47%
Phoenix, Arizona: 2.71%average rate, $680,000 → $1,071,499.17, cumulative change of 57.57%
Atlanta, Georgia: 2.54%average rate, $680,000 → $1,041,033.31, cumulative change of 53.09%
Dallas-Fort Worth, Texas: 2.34%average rate, $680,000 → $1,008,097.23, cumulative change of 48.25%
Minneapolis-St Paul, Minnesota: 2.32%average rate, $680,000 → $1,003,653.24, cumulative change of 47.60%
Houston, Texas: 2.30%average rate, $680,000 → $1,001,580.02, cumulative change of 47.29%
New York: 2.24%average rate, $680,000 → $991,480.23, cumulative change of 45.81%
Boston, Massachusetts: 2.22%average rate, $680,000 → $988,448.21, cumulative change of 45.36%
Philadelphia, Pennsylvania: 2.09%average rate, $680,000 → $966,577.50, cumulative change of 42.14%
St Louis, Missouri: 2.03%average rate, $680,000 → $956,790.36, cumulative change of 40.70%
Chicago, Illinois: 2.03%average rate, $680,000 → $956,470.84, cumulative change of 40.66%
Detroit, Michigan: 2.02%average rate, $680,000 → $955,452.19, cumulative change of 40.51%
San Diego, California experienced the highest rate of inflation during the 17 years between 2005 and 2022 (3.26%).
Detroit, Michigan experienced the lowest rate of inflation during the 17 years between 2005 and 2022 (2.02%).
Note that some locations showing 0% inflation may have not yet reported latest data.
Inflation by Country
Inflation can also vary widely by country. For comparison, in the UK £680,000.00 in 2005 would be equivalent to £1,173,511.32 in 2022, an absolute change of £493,511.32 and a cumulative change of 72.58%.
In Canada, CA$680,000.00 in 2005 would be equivalent to CA$964,962.01 in 2022, an absolute change of CA$284,962.01 and a cumulative change of 41.91%.
Compare these numbers to the US's overall absolute change of $338,975.76 and total percent change of 49.85%.
Inflation by Spending Category
CPI is the weighted combination of many categories of spending that are tracked by the government. Breaking down these categories helps explain the main drivers behind price changes.
Between 2005 and 2022:
Gas pricesincreased from $1.82 per gallon to $3.41
Bread pricesincreased from $1.00 per loaf to $1.56
Egg pricesincreased from $1.21 per carton to $1.93
Chicken pricesincreased from $1.03 per per 1 lb of whole chicken to $1.62
Electricity pricesincreased from $0.09 per KwH to $0.15
This chart shows the average rate of inflation for select CPI categories between 2005 and 2022.
Compare these values to the overall average of 2.41% per year:
<table><tr><th> Category</th><th> Avg Inflation (%)</th><th> Total Inflation (%)</th><th> $680,000 in 2005 → 2022</th></tr><tbody><tr><td> Food and beverages</td><td> 2.75</td><td> 58.67</td><td> 1,078,922.94</td></tr><tr><td> Housing</td><td> 2.56</td><td> 53.69</td><td> 1,045,079.61</td></tr><tr><td> Apparel</td><td> 0.36</td><td> 6.31</td><td> 722,904.76</td></tr><tr><td> Transportation</td><td> 2.54</td><td> 53.14</td><td> 1,041,381.74</td></tr><tr><td> Medical care</td><td> 3.14</td><td> 69.09</td><td> 1,149,844.90</td></tr><tr><td> Recreation</td><td> 1.06</td><td> 19.65</td><td> 813,645.16</td></tr><tr><td> Education and communication</td><td> 1.39</td><td> 26.49</td><td> 860,137.65</td></tr><tr><td> Other goods and services</td><td> 2.86</td><td> 61.61</td><td> 1,098,917.46</td></tr></tbody></table>
The graph below compares inflation in categories of goods over time. Click on a category such as "Food" to toggle it on or off:
For all these visualizations, it's important to note that not all categories may have been tracked since 2005. This table and charts use the earliest available data for each category.
Inflation rates of specific categories
Medical Care
·
Housing
·
Rent
·
Food
·
More
Inflation-adjusted measures
S&P 500 price
·
S&P 500 earnings
·
Shiller P/E
How to calculate inflation rate for $680,000, 2005 to 2022
Our calculations use the following inflation rate formula to calculate the change in value between 2005 and 2022:
CPI in 2022 CPI in 2005
×
2005 USD value
=
2022 USD value
Then plug inhistorical CPI values. The U.S. CPI was 195.3 in the year 2005 and 292.65583333333 in 2022:
292.65583333333 195.3
×
$680,000
=
$1,018,975.76
$680,000 in 2005 has the same "purchasing power" or "buying power" as $1,018,975.76 in 2022.
To get the total inflation rate for the 17 years between 2005 and 2022, we use the following formula:
CPI in 2022 - CPI in 2005 CPI in 2005
×
100
=
Cumulative inflation rate (17 years)
Plugging in the values to this equation, we get:
292.65583333333 - 195.3 195.3
×
100
=
50%
Alternate Measurements of Inflation
There are multiple ways to measure inflation. Published rates of inflation will vary depending on methodology. The Consumer Price Index, used above, is the most common standard used globally.
Alternative measurements are sometimes used based on context and economic/political circumstances. Below are a few examples of alternative measurements.
Personal Consumption Expenditures (PCE) Inflation
The PCE Price Index is the U.S. Federal Reserve's preferred measure of inflation, compiled by the Bureau of Economic Analysis. It measures the change in prices of goods and services purchased by consumers.
The PCE Price Index changed by 2.06% per year on average between 2005 and 2022. The total PCE inflation between these dates was 41.42%. In 2005, PCE inflation was 2.88%.
This means that the PCE Index equates $680,000 in 2005 with $961,662.76in 2022, a difference of $281,662.76. Compare this to the standard CPI measurement, which equates $680,000 with $1,018,975.76. The PCE measured -8.43% inflation compared to standard CPI.
For more information on the difference between PCE and CPI, seethis analysisprovided by the Bureau of Labor Statistics.
Core Inflation
Also of note is theCore CPI, which uses the standard CPI but omits the more volatile categories of food and energy.
Core inflation averaged 2.27% per year between 2005 and 2022 (vs all-CPI inflation of 2.41%), for an inflation total of 46.50%. In 2005, core inflation was 2.17%.
When using the core inflation measurement, $680,000 in 2005 is equivalent in buying power to $996,199.74in 2022, a difference of $316,199.74. Recall that the converted amount is $1,018,975.76 when all items including food and energy are measured.
Chained Inflation
Chained CPIis an alternative measurement that takes into account how consumers adjust spending for similar items. Chained inflation averaged 2.17% per year between 2005 and 2022, a total inflation amount of 44.13%.
According to the Chained CPI measurement, $680,000 in 2005 is equal in buying power to $980,072.20in 2022, a difference of $300,072.20 (versus a converted amount of $1,018,975.76/change of $338,975.76 for All Items).
In 2005, chained inflation was 2.92%.
Comparison to S&P 500 Index
The average inflation rate of 2.41% has a compounding effect between 2005 and 2022. As noted above, this yearly inflation rate compounds to produce an overall price difference of 49.85% over 17 years.
To help put this inflation into perspective, if we had invested $680,000 in the S&P 500 index in 2005, our investment would be nominallyworth approximately $3,232,501.81in 2022. This is a return on investment of 375.37%, with an absolute return of $2,552,501.81 on top of the original $680,000.
These numbers are not inflation adjusted, so they are considered nominal. In order to evaluate the realreturn on our investment, we must calculate the return with inflation taken into account.
The compounding effect of inflation would account for 33.27% of returns ($1,075,334.48) during this period. This means the inflation-adjusted realreturn of our $680,000 investment is $1,477,167.34. You may also want to account for capital gains tax, which would take your real return down to around $1,255,592 for most people.
<table> Investment in S&P 500 Index, 2005-2022<tr><th></th><th> Original Amount</th><th> Final Amount</th><th> Change</th></tr><tbody><tr><td> Nominal</td><td> $680,000</td><td> $3,232,501.81</td><td> 375.37%</td></tr><tr><td> Real
Inflation Adjusted</td><td> $680,000</td><td> $2,157,167.34</td><td> 217.23%</td></tr></tbody></table>
Information displayed above may differ slightly from other S&P 500 calculators. Minor discrepancies can occur because we use the latest CPI data for inflation, annualized inflation numbers for previous years, and we compute S&P price and dividends from January of 2005 to latest available data for 2022 using average monthly close price.
Data source & citation
Raw data for these calculations comes from the Bureau of Labor Statistics'Consumer Price Index (CPI), established in 1913. Price index data from 1774 to 1912 is sourced from ahistorical studyconducted by political science professor Robert Sahr at Oregon State University and from the American Antiquarian Society. Price index data from 1634 to 1773 is from the American Antiquarian Society, using British pound equivalents.
You may use the following MLA citation for this page: “$680,000 in 2005 → 2022 | Inflation Calculator.” Official Inflation Data, Alioth Finance, 2 Jul. 2023, https://www.officialdata.org/2005-dollars-in-2022?amount=680000.
| https://www.in2013dollars.com/2005-dollars-in-2022?amount=680000 |
Dynamic and Steady-State Behavior of Continuous Sedimentation | SIAM Journal on Applied Mathematics
Continuous sedimentation of solid particles in a liquid takes place in a clarifier-thickener unit, which has one feed inlet and two outlets. The process can be modeled by a nonlinear scalar conserv...
Author : Stefan Diehl Authors Info & Affiliations
https://doi.org/10.1137/S0036139995290101
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Abstract
Continuous sedimentation of solid particles in a liquid takes place in a clarifier-thickener unit, which has one feed inlet and two outlets. The process can be modeled by a nonlinear scalar conservation law with point source and discontinuous flux function. This paper presents existence and uniqueness results in the case of varying cross-sectional area and a complete classification of the steady-state solutions when the cross-sectional area decreases with depth. The classification is utilized to formulate a static control strategy for the large discontinuity called the sludge blanket that appears in steady-state operation. A numerical algorithm and a few simulations are also presented.
MSC codes
35L65 35Q80 35R05
Keywords
conservation laws discontinuous flux
point source continuous sedimentation
clarifier-thickener settler
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Information & Authors Information Authors Information Published In SIAM Journal on Applied Mathematics Volume 57 • Issue 4 • August 1997 Pages
: 991 - 1018 DOI
: 10.1137/S0036139995290101 ISSN (online)
: 1095-712X Copyright
Copyright © 1997 Society for Industrial and Applied Mathematics. History Published online
: 26 July 2006 MSC codes 35L65 35Q80 35R05 Keywords conservation laws discontinuous flux point source continuous sedimentation clarifier-thickener settler Authors Affiliations Expand All Stefan Diehl View all articles by this author Metrics & Citations Metrics Citations Metrics Metrics Downloads Citations No data available. 0 1 2 3 4 Jan 2014 Jan 2016 Jan 2018 Jan 2020 Jan 2022 67 48 Total 6 Months 12 Months
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Nguyen SIAM Journal on Control and Optimization, Vol. 59, No. 6 | 15 November 2021 Abstract PDF (661 KB) Disengagement of dispersed cerium oxalate from nitric-oxalic acid medium in a batch settler: Measurements and CFD simulations Annals of Nuclear Energy, Vol. 144 | 1 Sep 2020 Cross Ref A simulation model for settling tanks with varying cross-sectional area Chemical Engineering Communications, Vol. 204, No. 11 | 2 August 2017 Cross Ref Entropy Solutions of a Scalar Conservation Law Modeling Sedimentation in Vessels With Varying Cross-Sectional Area Raimund Bürger , Julio Careaga , and Stefan Diehl SIAM Journal on Applied Mathematics, Vol. 77, No. 2 | 27 April 2017 Abstract PDF (1344 KB) BV regularity near the interface for nonuniform convex discontinuous flux Networks and Heterogeneous Media, Vol. 11, No. 2 | 1 Mar 2016 Cross Ref Modelling, simulation and validation of continuous sedimentation process 2016 Indian Control Conference (ICC) | 1 Jan 2016 Cross Ref Quasi Steady-State Analysis of Continuous Sedimentation with Applications to Stability Analysis and Design Journal of Chemical Engineering of Japan, Vol. 49, No. 4 | 1 Jan 2016 Cross Ref Construction of analytical solutions and numerical methods comparison of the ideal continuous settling model Computers & Chemical Engineering, Vol. 80 | 1 Sep 2015 Cross Ref Optimal results on TV bounds for scalar conservation laws with discontinuous flux Journal of Differential Equations, Vol. 258, No. 3 | 1 Feb 2015 Cross Ref Thickening Solid-Liquid Separation in the Mining Industry | 20 December 2013 Cross Ref Convexity-preserving flux identification for scalar conservation laws modelling sedimentation Inverse Problems, Vol. 29, No. 4 | 28 March 2013 Cross Ref Control of an ideal activated sludge process in wastewater treatment via an ODE–PDE model Journal of Process Control, Vol. 23, No. 3 | 1 Mar 2013 Cross Ref A Stabilized Finite Volume Element Formulation for Sedimentation-Consolidation Processes Raimund Bürger , Ricardo Ruiz-Baier , and Héctor Torres SIAM Journal on Scientific Computing, Vol. 34, No. 3 | 29 May 2012 Abstract PDF (2706 KB) Shock-Wave Behaviour of Sedimentation in Wastewater Treatment: A Rich Problem Analysis for Science, Engineering and Beyond | 18 May 2011 Cross Ref Existence and nonexistence of TV bounds for scalar conservation laws with discontinuous flux Communications on Pure and Applied Mathematics, Vol. 64, No. 1 | 17 September 2010 Cross Ref Second-order schemes for conservation laws with discontinuous flux modelling clarifier–thickener units Numerische Mathematik, Vol. 116, No. 4 | 7 July 2010 Cross Ref Application Analysis of One-Dimensional Sedimentation Model 2010 4th International Conference on Bioinformatics and Biomedical Engineering | 1 Jun 2010 Cross Ref Conceptual Analysis of the Effect of Kinetics on the Stability and Multiplicity of a Coupled Bioreactor−Separator System Using a Cybernetic Modeling Approach Industrial & Engineering Chemistry Research, Vol. 48, No. 24 | 16 October 2009 Cross Ref Unscented Kalman filter approach to tracking a moving interfacial boundary in sedimentation processes using three-dimensional electrical impedance tomography Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, Vol. 367, No. 1900 | 13 August 2009 Cross Ref A regulator for continuous sedimentation in ideal clarifier–thickener units Journal of Engineering Mathematics, Vol. 60, No. 3-4 | 18 July 2007 Cross Ref Operating charts for continuous sedimentation IV: limitations for control of dynamic behaviour Journal of Engineering Mathematics, Vol. 60, No. 3-4 | 25 July 2007 Cross Ref Steady-state, control, and capacity calculations for flocculated suspensions in clarifier–thickeners International Journal of Mineral Processing, Vol. 84, No. 1-4 | 1 Oct 2007 Cross Ref A three-dimensional shape estimation approach for tracking of phase interfaces in sedimentation processes using electrical impedance tomography Measurement Science and Technology, Vol. 18, No. 5 | 20 March 2007 Cross Ref Tracking of moving interfaces in sedimentation processes using electrical impedance tomography Chemical Engineering Science, Vol. 61, No. 23 | 1 Dec 2006 Cross Ref Numerical simulation of clarifier-thickener units treating ideal suspensions with a flux density function having two inflection points Mathematical and Computer Modelling, Vol. 44, No. 3-4 | 1 Aug 2006 Cross Ref Effect of the Minimum Flux Condition in the Settler on the Nonlinear Behavior of the Activated Sludge Process Industrial & Engineering Chemistry Research, Vol. 45, No. 17 | 7 July 2006 Cross Ref Mathematical modelling of distributed feed in continuous sedimentation Simulation Modelling Practice and Theory, Vol. 14, No. 5 | 1 Jul 2006 Cross Ref A relaxation scheme forcontinuous sedimentation in ideal clarifier-thickener units Computers & Mathematics with Applications, Vol. 50, No. 7 | 1 Oct 2005 Cross Ref Mathematical model and numerical simulation of the dynamics of flocculated suspensions in clarifier–thickeners Chemical Engineering Journal, Vol. 111, No. 2-3 | 1 Aug 2005 Cross Ref A Model of Continuous Sedimentation of Flocculated Suspensions in Clarifier-Thickener Units Raimund Bürger , Kenneth H. 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Towers SIAM Journal on Applied Mathematics, Vol. 65, No. 3 | 31 July 2006 Abstract PDF (5403 KB) Dynamic and steady-state sedimentation of polydisperse suspension and prediction of outlets particle-size distribution Chemical Engineering Science, Vol. 59, No. 13 | 1 Jul 2004 Cross Ref Monotone difference approximations for the simulation of clarifier-thickener units Computing and Visualization in Science, Vol. 6, No. 2-3 | 1 March 2004 Cross Ref Central schemes and systems of conservation laws with discontinuous coefficients modeling gravity separation of polydisperse suspensions Journal of Computational and Applied Mathematics, Vol. 164-165 | 1 Mar 2004 Cross Ref A mathematical model for batch and continuous thickening of flocculated suspensions in vessels with varying cross-section International Journal of Mineral Processing, Vol. 73, No. 2-4 | 1 Feb 2004 Cross Ref Numerical methods for the simulation of continuous sedimentation in ideal clarifier-thickener units International Journal of Mineral Processing, Vol. 73, No. 2-4 | 1 Feb 2004 Cross Ref Molecular dynamics modified transfer function for phosphate thickener control International Journal of Mineral Processing, Vol. 73, No. 1 | 1 Jan 2004 Cross Ref BioSys: software for wastewater treatment simulation Advances in Engineering Software, Vol. 34, No. 9 | 1 Sep 2003 Cross Ref A front tracking approach to a model of continuous sedimentation in ideal clarifier–thickener units Nonlinear Analysis: Real World Applications, Vol. 4, No. 3 | 1 Sep 2003 Cross Ref Thickening in the 20th century: a historical perspective Mining, Metallurgy & Exploration, Vol. 20, No. 2 | 1 May 2003 Cross Ref On a Model for Continuous Sedimentation in Vessels with Discontinuous Cross-sectional Area Hyperbolic Problems: Theory, Numerics, Applications | 1 Jan 2003 Cross Ref Numerical methods for the simulation of the settling of flocculated suspensions Chemical Engineering Journal, Vol. 80, No. 1-3 | 1 Dec 2000 Cross Ref On boundary conditions and solutions for ideal clarifier–thickener units Chemical Engineering Journal, Vol. 80, No. 1-3 | 1 Dec 2000 Cross Ref Phenomenological foundation and mathematical theory of sedimentation–consolidation processes Chemical Engineering Journal, Vol. 80, No. 1-3 | 1 Dec 2000 Cross Ref Numerical simulation of the settling of polydisperse suspensions of spheres Powder Technology, Vol. 113, No. 1-2 | 1 Nov 2000 Cross Ref A model of the settler coupled to the biological reactor Water Research, Vol. 32, No. 2 | 1 Feb 1998 Cross Ref Continuous sedimentation of multi-component particles Mathematical Methods in the Applied Sciences, Vol. 20, No. 15 | 1 Oct 1997 Cross Ref Media Figures Other Figures Other Tables Share Share Copy the content Link https://epubs.siam.org/doi/10.1137/S0036139995290101 Copy Link Copied! 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Recommended Content
On Scalar Conservation Laws with Point Source and Discontinuous Flux Function
Stefan Diehl
Abstract
The conservation law studied is $\frac{{\partial u(x,t)}} {{\partial t}} + \frac{\partial } {{\partial t}}(F(u(x,t),x)) = s(t)\delta (x)$, where u
is a concentration, s
is a source, $\delta $ is the Dirac measure, and \[ F(u,x) = \left\{ \begin{gathered} f(u),\quad x > 0, \hfill \\ g(u),\quad x < 0 \hfill \\ \end{gathered} \right.\] is the flux function. The special feature of this problem is the discontinuity that appears along the t
-axis and the curves of discontinuity that go into and emanate from it. Necessary conditions for the existence of a piecewise smooth solution are given. Under some regularity assumptions sufficient conditions are given enabling construction of piecewise smooth solutions by the method of characteristics. The selection of a unique solution is made by a coupling condition at $x = 0$, which is a generalization of the classical entropy condition and is justified by studying a discretized version of the problem by Godunov’s method.
The motivation for studying this problem is the fact that it arises in the modelling of continuous sedimentation of solid particles in a liquid.
A conservation Law with Point Source and Discontinuous Flux Function Modelling Continuous Sedimentation
Stefan Diehl
Abstract
Continuous sedimentation of solid particles in a liquid takes place in a clarifier-thickener unit, which has one feed inlet and two outlets. The aim of the paper is to formulate and analyse a dynamic model for this process under idealized physical conditions. The conservation of mass yields the scalar conservation law $\frac{\partial u( {x,t} )}{\partial t} + \frac{\partial }{\partial x}( {F( {u( {x,t} ),x} )} ) = s( t )\delta ( x )$, where $\delta $ is the Dirac measure, s
is a source, and F
is a flux function, which is discontinuous at three points in the one-dimensional space coordinate x
. Under certain regularity assumptions a procedure for constructing a solution, locally in time, is presented. The nonlinear phenomena are complicated, and so is the general construction of a solution. The problem of nonuniqueness due to the discontinuities of $F( {u, \cdot } )$ is handled by a generalized entropy condition. An advantage of this approach is that the a priori boundary conditions (at the discontinuities of $ F( {u, \cdot } ) $ that have been used earlier can be omitted. The steady-state solutions are also presented.
A Model of Continuous Sedimentation of Flocculated Suspensions in Clarifier-Thickener Units
Raimund Bürger , Kenneth H. Karlsen ,
John D. Towers
Abstract
The chief purpose of this paper is to formulate and partly analyze a new mathematical model for continuous sedimentation-consolidation processes of flocculated suspensions in clarifier-thickener units. This model appears in two variants for cylindrical and variable cross-sectional area units, respectively (Models 1 and 2). In both cases, the governing equation is a scalar, strongly degenerate parabolic equation in which both the convective and diffusion fluxes depend on parameters that are discontinuous functions of the depth variable. The initial value problem for this equation is analyzed for Model 1. We introduce a simple finite difference scheme and prove its convergence to a weak solution that satisfies an entropy condition. A limited analysis of steady states as desired stationary modes of operation is performed. Numerical examples illustrate that the model realistically describes the dynamics of flocculated suspensions in clarifier-thickeners.
Convergence of a Difference Scheme for Conservation Laws with a Discontinuous Flux
John D. Towers
Abstract
Convergence is established for a scalar finite difference scheme, based on the Godunov or Engquist--Osher (EO) flux, for scalar conservation laws having a flux that is spatially dependent through a possibly discontinuous coefficient. Other works in this direction have established convergence for methods employing the solution of 2 × 2 Riemann problems. The algorithm discussed here uses only scalar Riemann solvers. Satisfaction of a set of Kruzkov-type entropy inequalities is established for the limit solution, from which geometric entropy conditions follow. Assuming a piecewise constant coefficient, it is shown that these conditions imply L 1
-contractiveness for piecewise C 1
solutions, thus extending a well-known theorem.
Large-Time Behavior of a Branching Diffusion on a Hyperbolic Space
M. Kelbert , Y. Suhov
Abstract
In this paper we consider a general hyperbolic branching diffusion on a Lobachevsky space ${\bf H}^d$. The question is to evaluate the Hausdorff dimension of the limiting set on the boundary (i.e., absolute) $\partial{\bf H}^d$. In the case of a homogeneous branching diffusion, an elegant formula for the Hausdorff dimension was obtained by Lalley and Sellke [ Probab. Theory Related Fields
, 108 (1997), pp. 171–192] for $d=2$ and by Karpelevich, Pechersky, and Suhov [ Commun. Math. Phys.
, 195 (1998), pp. 627–642] for a general d
. Later on, Kelbert and Suhov [ Probab. Theory Appl.
, 51 (2007), pp. 155–167] extended the formula to the case where the branching diffusion was in a sense asymptotically homogeneous (i.e., its main relevant parameter, the fission potential, approached a constant limiting value near the absolute). In this paper we show that the Hausdorff dimension of the limiting set can be bounded from above and below in terms of the maximum and minimum points of the fission potential. As in [M. Kelbert and Y. M. Suhov, Probab. Theory Appl.
, 51 (2007), pp. 155–167], the method is based on properties of the minimal solution to a Sturm–Liouville problem with general potential and elements of the harmonic analysis on ${\bf H}^d$. We also relate the Hausdorff dimension with properties of recurrence and transience of a branching diffusion, as was defined by Grigoryan and Kelbert [ Ann. Probab.
, 31 (2003), pp. 244–284] on a general-type manifold.
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Ocular surface disorders are frequently encountered in patients in Intensive Care Units (ICUs). Because of significant impairment of major organs, treatment is focused on the management of organ failures. Therefore, ophthalmological complications are frequently overlooked in this setting. To identify the types and frequencies of ocular surface disorders reported in patients in ICUs, a literature review... article
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The traditional model of dry eye disease based on tear deficiency has presented us with many unanswered questions. Recent studies support the notion that dry eye-like symptoms represent non-specific corneal pain and provide new insights into the mechanisms that sustain the integrity of the optical tear layer. Thus, this enigmatic disease can be viewed with a new perspective, which involves the dysfunctional... article
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The clinical tests used to assess tear film and diagnose dry eye are invasive and produce results that are different from natural tear characteristics. There is a need to objectively and noninvasively assess tear parameters under controlled environmental circumstances to refine dry eye diagnosis and therapy. We have developed multimodal tear imaging systems integrated in a chamber in which individual... article
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Case series on osteo-odonto keratoprosthesis (OOKP) published in English from 1950-June 2010 were identified in Medline/PubMed. Indications for surgery, visual acuity, anatomical survival, complication and repeat surgery rates were compared among the different studies. Our own case series is a retrospective review of all OOKP surgeries performed in our center from February 2004-July 2011. Eight case... article
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To determine the ratio of IGFBP3:IGF-1 in normal and diabetic human tears, and in telomerase-immortalized human corneal epithelial cells (hTCEpi) cultured under elevated glucose conditions and to correlate these changes with total and phosphorylated levels of IGF-1R. Tear samples were collected noninvasively from diabetic subjects and non-diabetic controls; corneal sensitivity was assessed using a... article
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Corneal avascularity is necessary for the preservation of optimal vision. The cornea maintains a dynamic balance between pro- and antiangiogenic factors that allows it to remain avascular under normal homeostatic conditions; however, corneal avascularity can be compromised by pathologic conditions that negate the cornea’s ”angiogenic privilege.” The clinical relevance of corneal neovascularization... article
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In September 2010, a Symposium in Florence, Italy, was held to address the unmet need for global treatments for dry eye disease (DED). It was sponsored by The Tear Film & Ocular Surface Society (TFOS; www.TearFilm.org) and co-sponsored by the Association for Research in Vision & Ophthalmology (www.arvo.org). The Symposium objectives were two-fold: first, to discuss accepted and emerging clinical... article
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Clinical signs in dry eye (DE) often underestimate the severity of the condition, correlating poorly with symptoms and the impact on patients’ health-related quality of life (HRQL). Patient-reported outcome (PRO) questionnaires are therefore essential to accurately evaluate the health status of DE patients and the severity of their condition. A comprehensive evaluation of HRQL in addition to clinical... article
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FAU receives $2.1 million to study effectiveness of schizophrenia medication | EurekAlert! Science News
In patients with severe illnesses such as schizophrenia, the risk for relapse and re-hospitalization is substantially increased following hospitalizations. There is great interest from clinicians, policy-makers, and health care administrators on the effect of new medications in containing health care costs. This multi-center, longitudinal study will investigate an injectable long-acting antipsychotic medication and its impact on hospital readmission rates in the high-cost population of patients with schizophrenia who use hospital services.
Study to examine treatment adherence and impact on 30-day hospital readmission rates
Florida Atlantic University
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John W. Newcomer, M.D., principal investigator of the study, executive vice dean of FAU's Charles E. Schmidt College of Medicine, and a physician-scientist who has been studying schizophrenia for more... view more
Credit: Florida Atlantic University
Florida Atlantic University's Charles E. Schmidt College of Medicine was recently awarded a $2.1 million, two-year contract by Otsuka America Pharmaceutical Inc. to conduct a study to examine the effectiveness of an injectable long-acting antipsychotic medication for schizophrenia and its impact on 30-day hospital readmission rates.
In patients with severe illnesses such as schizophrenia, the risk for relapse and re-hospitalization is substantially increased following hospitalizations. Efforts to promote the use of evidence-based treatments that reduce relapse, improve clinical outcomes and contain health care costs, especially in chronic illnesses, have been a major focus of health quality improvement initiatives in the United States.
"This research is important because the availability of second-generation long-acting antipsychotic medications offers an important tool to assist patients with medication adherence, which in turn may help lower health care costs and improve quality of life," said John W. Newcomer, M.D., principal investigator of the study, executive vice dean of FAU's Charles E. Schmidt College of Medicine, and a physician-scientist who has been studying schizophrenia for more than 25 years.
According to the Agency for Healthcare Research and Quality (Healthcare Cost and Utilization Project), schizophrenia and other psychotic disorders are listed as No. 2 in the top 10, 30-day readmissions for Medicaid patients (aged 18-64 years). They accounted for 35,800 readmissions (24.9 per 100 admissions) with $302 million in readmissions costs in 2011.
FAU is the coordinating site for this multi-center, longitudinal clinical trial and will work with faculty collaborators at Washington University in St. Louis School of Medicine as well as other sites. The team will evaluate hospitalization rates and metabolic measurements during treatment with long-acting injectable aripiprazole compared with daily oral antipsychotic treatment in the six months following an inpatient hospital stay related to schizophrenia.
This study is a collaboratively designed, investigator-initiated study that will be conducted across five other centers in the U.S. in addition to FAU: Washington University School of Medicine, University of Missouri-Kansas City, University of Missouri-Columbia, Missouri Institute of Mental Health and Burrell Behavioral Health.
"There is great interest from clinicians, policy-makers, and health care administrators on the effect of new medications in containing health care costs," said Newcomer. "We will be investigating an injectable long-acting antipsychotic medication and its impact on hospital readmission rates in the high-cost population of patients with schizophrenia who use hospital services."
The Centers for Medicare and Medicaid Services (CMS) has focused interest on 30-day hospital readmission rates as an indicator of cost-effective health care delivery. The American College of Emergency Physicians and American Hospital Association reported a 13 percent increase in behavioral health-related hospital emergency department visits between 2005 and 2012.
Schizophrenia is a serious mental illness that interferes with a person's ability to relate to others, think clearly, make decisions and manage emotions. Symptoms of the illness can include hallucinations, cognitive issues, confusion, psychosis and withdrawn behavior. There is currently no cure for schizophrenia, however it can be treated and managed in several ways such as antipsychotic medications and psychotherapy. In the U.S., approximately 2.2 million adults age 18 and older in a given year have schizophrenia.
###
Florida Atlantic University
Florida Atlantic University, established in 1961, officially opened its doors in 1964 as the fifth public university in Florida. Today, the University, with an annual economic impact of $6.3 billion, serves more than 30,000 undergraduate and graduate students at sites throughout its six-county service region in southeast Florida. FAU's world-class teaching and research faculty serves students through 10 colleges: the Dorothy F. Schmidt College of Arts and Letters, the College of Business, the College for Design and Social Inquiry, the College of Education, the College of Engineering and Computer Science, the Graduate College, the Harriet L. Wilkes Honors College, the Charles E. Schmidt College of Medicine, the Christine E. Lynn College of Nursing and the Charles E. Schmidt College of Science. FAU is ranked as a High Research Activity institution by the Carnegie Foundation for the Advancement of Teaching. The University is placing special focus on the rapid development of critical areas that form the basis of its strategic plan: Healthy aging, biotech, coastal and marine issues, neuroscience, regenerative medicine, informatics, lifespan and the environment. These areas provide opportunities for faculty and students to build upon FAU's existing strengths in research and scholarship. For more information, visit
http://www. fau. edu
.
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FAU receives $2.1 million to study effectiveness of schizophrenia medication
Florida Atlantic University
Funder
Otsuka America Pharmaceutical Inc.
Keywords
CLINICAL TRIALS HEALTH CARE INSURANCE
MEDICINE/HEALTH MENTAL HEALTH
PUBLIC HEALTH
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John W. Newcomer, M.D., Florida Atlantic University
(IMAGE)
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[Qemu-devel] [PATCH 25/26] qidl: qidl.h, definitions for qidl annotation
[Qemu-devel] [PATCH 25/26] qidl: qidl.h, definitions for qidl annotation
From : Michael Roth Subject : [Qemu-devel] [PATCH 25/26] qidl: qidl.h, definitions for qidl annotations Date : Thu, 18 Oct 2012 21:42:19 -0500
Signed-off-by: Michael Roth <address@hidden>
---
qidl.h | 149 ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
1 file changed, 149 insertions(+)
create mode 100644 qidl.h
diff --git a/qidl.h b/qidl.h
new file mode 100644
index 0000000..27f04ac
--- /dev/null
+++ b/qidl.h
@@ -0,0 +1,149 @@
+/*
+ * QEMU IDL Macros/stubs
+ *
+ * See docs/qidl.txt for usage information.
+ *
+ * Copyright IBM, Corp. 2012
+ *
+ * Authors:
+ * Michael Roth <address@hidden>
+ *
+ * This work is licensed under the terms of the GNU GPLv2 or later.
+ * See the COPYING file in the top-level directory.
+ *
+ */
+
+#ifndef QIDL_H
+#define QIDL_H
+
+#include <glib.h>
+#include "qapi/qapi-visit-core.h"
+#include "qemu/object.h"
+#include "hw/qdev-properties.h"
+
+/* must be "called" in any C files that make use of QIDL-generated code */
+#define QIDL_ENABLE()
+
+#define QIDL_DATA_DECLARE(name) \
+ typedef struct QIDLData##name { \
+ void (*visitor)(Visitor *, struct name **, const char *, Error **); \
+ const char *schema_json_text; \
+ Object *schema_obj; \
+ Property *properties; \
+ } QIDLData##name;
+
+/* we pass the code through the preprocessor with QIDL_GEN defined to parse
+ * structures as they'd appear after preprocessing, and use the following
+ * definitions mostly to re-insert the initial macros/annotations so they
+ * stick around for the parser to process
+ */
+#ifdef QIDL_GEN
+
+#define QIDL(...) QIDL(__VA_ARGS__)
+#define QIDL_START(name, ...) QIDL_START(name, ##__VA_ARGS__)
+
+#else
+
+#define QIDL(...)
+#ifdef QIDL_ENABLED
+#define QIDL_START(name, ...) \
+ QIDL_DATA_DECLARE(name) \
+ static QIDLData##name qidl_data_##name; \
+ static void visit_type_##name(Visitor *, struct name **, const char *,
Error **);
+#define QIDL_START_PUBLIC(name, ...) \
+ QIDL_DATA_DECLARE(name) \
+ extern QIDLData##name qidl_data_##name; \
+ void visit_type_##name(Visitor *, struct name **, const char *, Error **);
+#define QIDL_START_IMPLEMENTATION(name, ...) \
+ QIDLData##name qidl_data_##name;
+#else
+#define QIDL_START(name, ...)
+#define QIDL_START_PUBLIC(name, ...)
+#define QIDL_START_IMPLEMENTATION(name, ...)
+#endif /* QIDL_ENABLED */
+
+#endif /* QIDL_GEN */
+
+/* QIDL serialization annotations/markers
+ *
+ * q_standard: default/standard serialization handling for this type. this
marker
+ * does not need to be specified explicitly, and should in fact be left out
if
+ * the default handling is sufficient. in general, the default is to
serialize
+ * the field, except in case where we determine it does not need to be
serialized
+ * (such as by analyzing any serialization annotations provided as part of
the
+ * field's type declaration to determine if there is any guest-volatile
state)
+ *
+ * q_immutable: state is fully restorable via device
+ * [re-]initialization/realization
+ *
+ * q_derived: state can be fully reconstructed from other fields (and will be,
+ * via [re-]initialization of the device or a separate hook)
+ *
+ * q_broken: state should (or possibly should) be saved, but isn't. mostly an
aid
+ * for device developers having issues with serialization of a particular
+ * field, committed code should contain these except in special circumstances
+ *
+ * q_optional: <field> should only be serialized if the field by the name of
+ * has_<field> is true
+ *
+ * q_elsewhere: state should be serialized, but is done so elsewhere (for
+ * instance, by another device with a pointer to the same data)
+ *
+ * q_size(field): for static/dynamically-allocated arrays. specifies the field
+ * in the structure containing the number of elements that should be
+ * serialized. if argument is wrapped in parenthesis it is instead
interpreted
+ * as an expression that should be invaluated to determine the size.
+ */
+#define q_standard QIDL(serialize, standard)
+#define q_immutable QIDL(serialize, immutable)
+#define q_derived QIDL(serialize, derived)
+#define q_broken QIDL(serialize, broken)
+#define q_optional QIDL(serialize, optional)
+#define q_elsewhere QIDL(serialize, elsewhere)
+#define q_size(...) QIDL(serialize, size_is, ##__VA_ARGS__)
+
+/* QIDL property annotations/markers
+ *
+ * q_property(<property name> [, <default value>]): specifies that field is a
+ * qdev-style property. all properties of the struct are then accessible via
+ * QIDL_PROPERTIES(<device name>) macro.
+ */
+#define q_property(name, ...) QIDL(property, name, ##__VA_ARGS__)
+
+/* declare a QIDL-annotated structure, private to source file.
+ * generated code will be injected into the source file's compiled
+ * code
+ */
+#define QIDL_DECLARE(name, ...) \
+ QIDL_START(name, ##__VA_ARGS__) \
+ struct name
+
+/* declare a QIDL-annotated structure, publically accessible.
+ * source files that use/include this must be linked against the object
+ * containing the corresponding QIDL_IMPLEMENT_PUBLIC(name, ...) for the
+ * structure in question to have access to the generated code
+ */
+#define QIDL_DECLARE_PUBLIC(name, ...) \
+ QIDL_START_PUBLIC(name, ##__VA_ARGS__) \
+ struct name
+
+/* implement the QIDL structure that QIDL_DECLARE_PUBLIC(name) will
+ * reference. this should be done in a source file that
+ * QIDL_DECLARE_PUBLIC(name) users will link against.
+ */
+#define QIDL_IMPLEMENT_PUBLIC(name, ...) \
+ QIDL_START_IMPLEMENTATION(name, ##__VA_ARGS__)
+
+#define QIDL_VISIT_TYPE(name, v, s, f, e) \
+ g_assert(qidl_data_##name.visitor); \
+ qidl_data_##name.visitor(v, s, NULL, e)
+
+#define QIDL_SCHEMA_ADD_LINK(name, obj, path, errp) \
+ g_assert(qidl_data_##name.schema_obj); \
+ object_property_add_link(obj, path, "container", \
+ &qidl_data_##name.schema_obj, errp)
+
+#define QIDL_PROPERTIES(name) \
+ qidl_data_##name.properties
+
+#endif
--
1.7.9.5
[Qemu-devel] [PATCH 14/26] qapi: qapi.py, make json parser more robust
,
(continued)
[Qemu-devel] [PATCH 14/26] qapi: qapi.py, make json parser more robust , Michael Roth , 2012/10/18
[Qemu-devel] [PATCH 17/26] qom-fuse: force single-threaded mode to avoid QMP races , Michael Roth , 2012/10/18
[Qemu-devel] [PATCH 19/26] module additions for schema registration , Michael Roth , 2012/10/18
[Qemu-devel] [PATCH 18/26] qom-fuse: workaround for truncated properties > 4096 , Michael Roth , 2012/10/18
[Qemu-devel] [PATCH 16/26] qapi: Improve existing docs and document annotated QAPI types , Michael Roth , 2012/10/18
[Qemu-devel] [PATCH 21/26] qidl: add documentation , Michael Roth , 2012/10/18
[Qemu-devel] [PATCH 23/26] qidl: add C parser (based on QC parser) , Michael Roth , 2012/10/18
[Qemu-devel] [PATCH 22/26] qidl: add lexer library (based on QC parser) , Michael Roth , 2012/10/18
[Qemu-devel] [PATCH 20/26] qdev: move Property-related declarations to qdev-properties.h , Michael Roth , 2012/10/18
[Qemu-devel] [PATCH 24/26] qidl: add QAPI-based code generator , Michael Roth , 2012/10/18
[Qemu-devel] [PATCH 25/26] qidl: qidl.h, definitions for qidl annotations , Michael Roth
[Qemu-devel] [PATCH 26/26] qidl: unit tests and build infrastructure
Re: [Qemu-devel] [PATCH 26/26] qidl: unit tests and build infrastructure
Re: [Qemu-devel] [PATCH 26/26] qidl: unit tests and build infrastructure , Michael Roth , 2012/10/25
Index(es):
Date
Thread
| https://lists.gnu.org/archive/html/qemu-devel/2012-10/msg03365.html |
Irby v. Panama Ice Co., Inc., 33763 - Louisiana - Case Law - VLEX 898348946
0: [object Object]. 1: [object Object]. 2: [object Object]. 3: [object Object]. 4: [object Object]. 5: [object Object]
Louisiana
Irby v. Panama Ice Co., Inc., 33763
Court Supreme Court of Louisiana Writing for the Court ROGERS, Justice. Citation 184 La. 1082,168 So. 306 Parties IRBY et al. v. PANAMA ICE CO., Inc Docket Number 33763 Decision Date 30 March 1936
168 So.306
184 La. 1082
IRBY et al.v. PANAMA ICE CO., Inc
No. 33763
Supreme Court of Louisiana
March 30, 1936
Appeal from Civil District Court, Parish of Orleans; William H. Byrnes, Jr., Judge.
Suit by Jane W. Irby and others against the Panama Ice Company, Incorporated. From refusal of the trial judge to grant a preliminary injunction, plaintiffs appeal.
Affirmed.
Miller, Bloch & Martin, of New Orleans, for appellants.
Sanders, Baldwin, Haspel & Molony, of New Orleans, for appellee.
ROGERS, Justice. O'NIELL, C. J., absent.
OPINION[168 So. 307]
[184 La. 1083] ROGERS, Justice.
This is an appeal from the refusal of the trial judge to grant a preliminary injunction to abate an alleged nuisance.
The defendant company is the owner and operator of an ice manufacturing plant situated at the corner of Chartres and Toulouse streets, in the square bounded by Royal and St. Louis streets, in the city of New Orleans. The plaintiffs, thirteen in number, reside on Royal street, in the vicinity of defendant's plant.
Plaintiffs allege, in substance, that during the month of June, 1935, the defendant changed its power plant from steam, generated quietly in a brick building fronting Toulouse street, to high-speed internal combustion gas engines set up in a shed in the rear portion of its property, and installed other and larger noisy equipment, and [184 La. 1084] permitted ammonia and gas fumes to escape into plaintiffs' premises. That the noises and vibrations "are unusual, excessive, disturbing and burdensome to such an extent as to interfere with and substantially prevent the rest and sleep of each and all of your petitioners, the said noise and vibrations being particularly disturbing and offensive during the hours of the night; that the aforesaid noises and vibrations interfere with and prevent the rest and sleep of each and all of your petitioners to such an extent as to threaten the impairment of their health, unless the same be abated." The petition charges that the enlargement and expansion of defendant's plant was violative of the municipality's Comprehensive Zoning Ordinance, which was made a part of the petition. Miss Irby further complained that the alleged nuisance impaired the value of her property in excess of $ 5,000.
The defendant company, after its exception of no cause of action was overruled, answered the petition, denying all the allegations, except as specially admitted. Defendant averred that the ice plant had been established at its present location since the year 1907. That the capacity of its plant when first installed and at the time of the passage of the zoning ordinance was 100 tons per day, and that since the installation of the new machinery referred to in the petition the capacity of the plant has been reduced to 50 tons per day. Defendant specially denied that the internal combustion gas engines were set up in a rear shed and averred that they were set up in the main building of its plant.
[184 La. 1085] The issues involve only questions of fact, which the trial judge, after hearing a number of witnesses produced by the parties, resolved in favor of the defendant. After a close reading of the testimony, we are not prepared to hold that the trial judge erred in his findings.
This appeal is by twelve of the thirteen original plaintiffs. Among the appellants are five married couples, the other appellants being Miss Irby and Mrs. L. W. Hutchinson, one of her tenants. Three of the married couples -- Mr. and Mrs. Allen, Mr. and Mrs. Hutchinson, and Mr. and Mrs. Sherry -- live on the lake side of Royal street, facing in the direction of defendant's factory. The Allens and the Hutchinsons live in the block opposite the block in which the factory is situated, and the Sherrys live in the adjoining block towards Canal street. Mr. and Mrs. R. I. McClure, Miss Irby, her mother, Mrs. George D. Lilly, her stepfather, Dr. George D. Lilly, and her tenant, Mrs. L. W. Hutchinson, live in the same block with the factory, so that the rears of the McClure property and the Irby property are in close proximity to it. The record indicates that the Lillys and Miss Irby are the principal complainants against defendant's plant, and that they are the real prosecutors of this suit.
The evidence shows that the defendant purchased the ice plant in 1912 and has continuously operated it since July 15, 1913. From time to time, defendant has made needed changes in the machinery and equipment. For the purpose of more economical operation to meet sharp competition of its business rivals, defendant found it necessary [184 La. 1086] to install two internal combustion engines in its plant. The engines which are of a semi-Deisel type, were placed in position in the early summer of 1933.They [168 So. 308] are mounted on large concrete foundations which, in turn, rest on a concrete slab three feet thick. When installed, the engines were equipped with standard size Maxim silencers. Shortly after their installation, Dr. Lilly complained about the noise, and the officers of the defendant company, not, as they contend, because their plant was making more noise than any other ice factory, but in an earnest endeavor to please the adjacent...
| https://case-law.vlex.com/vid/irby-v-panama-ice-898348946 |
Difference between revisions of "Public relations" - New World Encyclopedia
Difference between revisions of "Public relations" - New World Encyclopedia
Revision as of 17:15, 24 February 2007 ( view source ) Hidemasa Kato ( talk | contribs ) ( →References ) ← Previous diff Latest revision as of 18:08, 14 April 2023 ( view source ) Rosie Tanabe ( talk | contribs ) (16 intermediate revisions by 7 users not shown) Line 1: Line 1: [[Category:Politics and social sciences]] [[Category:Politics and social sciences]] [[Category:Communication]] [[Category:Communication]] − {{ Claimed }}{{ Contracted }} + {{ Copyedited }}{{ Paid}}{{Approved}}{{Images OK}}{{Submitted }} + [[Image:Kvinde-emancipation.gif|thumb|right|260px|In the 1890s, when gender role reversals could be caricaturized, the idea of an aggressive woman who also smoked was considered laughable. In 1929, Edward Bernays proved otherwise when he convinced women to smoke in public during an Easter parade in Manhattan as a show of defiance against male domination. The demonstrators were not aware that a tobacco company was behind the publicity stunt, a form of '''public relations'''.]] + '''Public relations''' ('''PR''') is the art of managing [[communication]] between an organization and its key publics to build, manage, and sustain a positive image. Public relations involves evaluation of public [[attitude]]s and [[public opinion]]s; formulation and implementation of an organization's procedures and policy regarding communication with its publics; coordination of communications programs; developing rapport and good-will through a two way communication process; and fostering a positive relationship between an organization and its public constituents. Public relations often involves news management—optimizing good news and forestalling bad news. Equally, good public relations managers conduct "damage control" when a disaster occurs, gathering the facts and assessing the situation to prepare appropriate information to be offered to the [[mass media]]. While public relations may be criticized as [[propaganda]] on occasion, the role of managing communication between the organization and the public is a necessary one in society. As [[technology|technologies]] have developed, it has become both more difficult to hide information and equally easier to distort it. The quality of PR material produced, and how much it reflects the truth of the situation, depend on the character and motivations of all involved. + {{toc}} + ==History== + Precursors to '''public relations''' are found in publicists who specialized in promoting [[circus]]es, [[theater|theatrical]] performances, and other public spectacles. In the [[United States]], where public relations has its origins, many early public relations practices were developed in support of the expansive power of the [[railroad]]s. In fact, the first documented use of the term "public relations" appeared in the ''1897 Year Book of Railway Literature''. + Later, public relations practitioners were—and are still often—recruited from the ranks of [[journalism]]. Some journalists, concerned with [[ethics]], have criticized former colleagues for using their inside understanding of news media to help clients receive favorable [[mass media]] coverage.<ref>Clarke Caywood, ''The Handbook of Strategic Public Relations & Integrated Communications'' (New York: McGraw Hill, 1997, ISBN 0786311312).</ref> − '''Public relations''' ('''PR''') is the art of managing [[ communication ]] between an organization and its key publics to build, manage, and sustain a positive image . Public relations involves evaluation of public [[ attitude ]] s and [[ public opinion ]] s ; formulation and implementation of an organization 's procedures and policy regarding communication with its publics; coordination of communications programs; developing rapport and good-will through a two way communication process; and fostering a positive relationship between an organization and its public constituents . + The [[ World War I|First World War ]] also helped stimulate the development of public relations as a profession . Many of the first public relations professionals—including [[ Edward L. Bernays ]] and [[ Carl Byoir ]] &mdash ; got their start with the Committee on Public Information (also known as the “Creel Commission”), which organized publicity on behalf of U.S. objectives during World War I. Some historians regard [[Ivy Lee]] as the first real practitioner of public relations, but Bernays is generally regarded today as the profession 's founder. In describing the origin of the term “public relations,” Bernays commented, "When I came back to the United States, I decided that if you could use [[propaganda]] for [[war]], you could certainly use it for peace. And propaganda got to be a bad word because of the Germans using it. So what I did was to try to find some other words, so we found the words Council on Public Relations . " − ==History== + Lee, who has been credited with developing the modern "news release" (or "press release") , espoused a philosophy consistent with what has sometimes been called the "two-way street" approach to public relations, in which public relations consists of helping clients listen as well as communicate messages to their publics . In the words of the Public Relations Society of America, " Public relations helps an organization and its publics adapt mutually to each other. " − Precursors to public relations are found in publicists who specialized in promoting [[circus]]es , [[theater|theatrical]] performances, and other public spectacles. In the [[United States]], where public relations has its origins , many early PR practices were developed in support of the expansive power of the [[railroad]]s . In fact, many scholars believe that the first appearance of the term " public relations" appeared in the ''1897 Year Book of Railway Literature''. − Later , PR practitioners were, and are still often, recruited from the ranks of [[ journalism ]]. Some journalists , concerned with [[ ethics ]], criticize former colleagues for using their inside understanding of news media to help clients receive favorable media coverage.<ref>Clarke Caywood. 1997. ''The Handbook of Strategic Public Relations & Integrated Communications'' . New York, NY:McGraw Hill. p . 23</ref> + Bernays was the profession's first theorist. A nephew of [[Sigmund Freud]] , Bernays drew many of his ideas from Freud's theories about the irrational, [[unconscious]] motives that shape human behavior. One of Bernays' early clients was the [[ tobacco ]] industry . In 1929 , he orchestrated a legendary publicity stunt aimed at persuading women to take up [[ cigarette ]] smoking , which was then considered unfeminine and inappropriate for women with any social standing . Bernays arranged for [[ New York City]] débutantes to march in that year's Easter Day Parade , defiantly smoking cigarettes as a statement of rebellion against the norms of a male-dominated society . − The [[World War I|First World War]] also helped stimulate the development of public relations as a profession. Many of the first PR professionals , including [[Ivy Lee]] , [[Edward L. Bernays]] , and [[Carl Byoir]], got their start with the Committee on Public Information ( also known as the Creel Commission ), which organized publicity on behalf of U.S. objectives during World War I. Some historians regard Ivy Lee as the first real practitioner of public relations , but Edward Bernays is generally regarded today as the profession's founder. In describing the origin of the term Public Relations, Bernays commented, " When I came back to the United States , I decided that if you could use [[ propaganda ]] for war , you could certainly use it for peace. And propaganda got to be a bad word because of the Germans using it. So what I did was to try to find some other words, so we found the words Council on Public Relations " . + Bernays authored several books , including ''Crystallizing Public Opinion'' (1923) , ''Propaganda'' (1928) , and ''The Engineering of Consent'' ( 1947 ), regarding public relations as an "applied social science " that uses insights from [[psychology]] , [[ sociology ]], and other disciplines to scientifically manage and manipulate the thinking and behavior of an irrational and "herdlike " public: − Ivy Lee, who has been credited with developing the modern "news release" (or "press release"), espoused a philosophy consistent with what has sometimes been called the "two-way street" approach to public relations, in which PR consists of helping clients listen as well as communicate messages to their publics . In the words of the Public Relations Society of America ( PRSA ) , "Public relations helps an organization and its publics adapt mutually to each other . " + <blockquote>The conscious and intelligent manipulation of the organized habits and opinions of the masses is an important element in democratic society . Those who manipulate this unseen mechanism of society constitute an invisible government which is the true ruling power of our country.<ref>Edward Bernays, ''Propaganda'' ( 1928; Brooklyn, NY: Ig Publishing, 2004, ISBN 0970312598 ). </ref></blockquote> − Bernays was the profession's first theorist. A nephew of [[Sigmund Freud]], Bernays drew many of his ideas from Freud's theories about the irrational, unconscious motives that shape human behavior. He authored several books, including ''Crystallizing Public Opinion'' (1923), ''Propaganda'' (1928), and ''The Engineering of Consent'' (1947) , regarding public relations as an " applied social science" that uses insights from [[psychology]], [[sociology]], and other disciplines to scientifically manage and manipulate the thinking and behavior of an irrational and "herdlike" public: + In 1950, PRSA enacted the first "Professional Standards for the Practice of Public Relations ," a forerunner to the current Code of Ethics, revised in 2000 to include six core values and six code provisions. < ref > [http://www.prsa.org/aboutUs/ethics/preamble_en . html Public Relations Society of America Member Code of Ethics 2000 ,] Public Relations Society of America . Retrieved September 10, 2007 .</ref> These six core values are "Advocacy, Honesty, Expertise, Independence, Loyalty, and Fairness." The six code provisions are "Free Flow of Information, Competition, Disclosure of Information, Safeguarding Confidences, Conflicts of Interest, and Enhancing the Profession." − < blockquote > The conscious and intelligent manipulation of the organized habits and opinions of the masses is an important element in democratic society . Those who manipulate this unseen mechanism of society constitute an invisible government which is the true ruling power of our country.<ref>Bernays , Edward. [1928 ] 2004 . ''Propaganda''. Ig Publishing . ISBN 0970312598 </ref> </blockquote> − In 1950, PRSA enacted the first "Professional Standards for the Practice of Public Relations , " a forerunner to the current Code of Ethics , revised in 2000 to include six core values and six code provisions .<ref>[http://www. prsa . org / aboutUs / ethics/preamble_en . html Code of Ethics 2000] Retrieved from PRSA website. February 20 , 2007.</ref> These six core values are "Advocacy, Honesty, Expertise, Independence, Loyalty, and Fairness." The six code provisions are "Free Flow of Information, Competition, Disclosure of Information, Safeguarding Confidences, Conflicts of Interest, and Enhancing the Profession." + ==The industry today== + According to the U.S. Bureau of Labor Statistics, there were approximately 122 , 000 public relations specialists in the [[United States]] in 1998, while there were approximately 485,000 [[advertising]], [[marketing]] , and public relations managers working in all industries .<ref>[http://www. bls . gov / oco / ocos086.htm Public Relations Specialists,] U.S . Department of Labor, 2006. Retrieved September 10 , 2007.</ref> − == The industry today== + The practice is also growing across the world . As other countries are entering into the [[ globalization|globalized ]] free market economy, they find they would like to promote their best face to the public. Countries in the former [[ Soviet Union ]] are finding the opportunity for the first time since the fall of the [[ Berlin Wall ]] . Over one hundred public relations firms have emerged in the formerly Soviet [[Ukraine]] .<ref> Ihor Eros, “PR firms cashing in on reputation and image building , ” ''Kyiv Post'' .</ref> Similar numbers are developing all over [[Europe]], [[Africa]], and [[South America]]. − According to the U . S. Bureau of Labor Statistics, there were approximately 122,000 public relations specialists in the [[ United States ]] in 1998, while there were approximately 485,000 [[ advertising ]] , [[ marketing ]] , and public relations managers working in all industries .<ref> U.S. Department of Labor. 2006. [http://www.bls.gov/oco/ocos086.htm Public Relations Specialists] Occupational Outlook Handbook. Retrieved January 4 , 2007 .</ref> − The practice is also growing across the world. As other countries are entering into the [[globalization|globalized]] free market economy, they find they would like to promote their best face to the public . Countries in the former [[Soviet Union]] are finding the opportunity for the first time since the fall of the [[ Berlin Wall]]. Over 100 public relations firms have emerged in the formerly Soviet [[Ukraine ]] .<ref>Eros , Ihor. [http://www.kyivpost.com/business/industglance/25999/ PR firms cashing in on reputation and image building] Kyiv Post. Retrieved February 6 , 2007.</ref> Similar numbers are developing all over [[ Europe ]], [[ Africa ]], and [[South America]] . + Modern public relations uses a variety of techniques including opinion polling and focus groups to evaluate [[public opinion ]], combined with a variety of high-tech techniques for distributing information on behalf of their clients , including [[ satellite ]] feeds , the [[ Internet ]] , broadcast faxes , and database-driven phone banks to recruit supporters for a client's cause . − Modern public relations uses a variety of techniques including opinion polling and focus groups to evaluate public opinion , combined with a variety of high-tech techniques for distributing information on behalf of their clients, including [[satellite]] feeds, the [[Internet]] , broadcast faxes , and database - driven phone banks to recruit supporters for a client's cause . + Although public relations professionals are stereotypically seen as corporate servants , the reality is that almost any organization that has a stake in how it is portrayed in the public arena employs at least one public relations professional. Large organizations may even have dedicated communications departments. Government agencies , trade associations , and other non - profit organizations commonly carry out public relations activities . − Although public relations professionals are stereotypically seen as corporate servants, the reality is that almost any organization that has a stake in how it is portrayed in the public arena employs at least one PR manager. Large organizations may even have dedicated communications departments. Government agencies, trade associations, and other non-profit organizations commonly carry out PR activities. + ==Public Relations Process== − Public relations should be seen as a management function in any organization. An effective communication, or public relations , plan for an organization is developed to communicate to an audience (whether internal or external publics) in such a way the message coincides with organizational goals and seeks to benefit mutual interests whenever possible . + An effective public relations plan for an organization is designed to communicate to an audience (whether internal or external publics) in such a way that the message coincides with organizational goals and seeks to benefit mutual interests . The process of developing such a plan consists of a number of steps . − ==Public Relations Process== + One common model has four steps . <ref>Scott M. Cutlip, Allen H. Center, & Glen M. Broom , ''Effective Public Relations'' ( Englewood Cliffs , NJ: Prentice Hall, 2005, ISBN 0130082007 ). </ref> The first step is " defining public relations problems ," usually in terms of a "situational analysis," or what public relations professionals call a "SWOT analysis" (strengths, weaknesses, opportunities, threats). This should answer the question, "What's happening now?" The next step in the public relations process is " planning and programming ," where the main focus is "strategy." This step should answer the question " what should we do and say, and why?" The third step in the public relations process is " taking action and communicating ," also known as " implementation" ; This step should answer the question , "How and when do we do and say it?" The final step is " evaluating the program ," making a final "assessment," which should answer the question " how did we do?" This is where public relations professionals make a final analysis of the success of their campaign or communication. − The public relations process may be described as consisting of a number of steps. One common model has four steps<ref>Scott M. Cutlip , Scott M. , Allen H. Center, and Glen M. Broom . 2005. ''Effective Public Relations'' Englewood Cliff , NJ: Prentice - Hall, Inc. Figure 10-1 ISBN 0130082007</ref> . The first step is " Defining Public Relations Problems ," usually in terms of a "situational analysis," or what public relations professionals call a "SWOT analysis" (strengths, weaknesses, opportunities, threats). This should answer the question, "What's happening now?" The next step in the public relations process is " Planning and Programming ," where the main focus is "strategy." This step should answer the question " What should we do and say, and why?" The third step in the public relations process is " Taking action and Communicating ," also known as " Implementation ; " This step should answer the question "How and when do we do and say it?" The final step is " Evaluating The Program ," making a final "assessment," which should answer the question " How did we do?" This is where public relations professionals make a final analysis of the success of their campaign or communication. − Another model defines the process of public relations through four steps: "Fact-finding and data gathering; Planning and programming; Action and communication; Evaluation."<ref> Center, Allen H. and Jackson, Patrick. 2002. ''Public Relations Practices'' . Upper Saddle River, NJ: Prentice Hall . ISBN 0136138039</ref> + Another model defines the process of public relations through four steps: "Fact-finding and data gathering; Planning and programming; Action and communication; Evaluation."<ref>Allen H. Center and Patrick Jackson, ''Public Relations Practices'' ( Upper Saddle River, NJ: Prentice Hall , 2002, ISBN 0136138039 ). </ref> − A different process model uses the acronym "ROSIE" to define a five-step process of "Research , Objectives , Strategies , Implementation and Evaluation .<ref> Crifasi, Sheila C. 2000. "Everything's Coming Up Rosie," from ''Public Relations Tactics , '' September, 2000, Vol. 7 , Issue 9 , Public Relations Society of America, New York .</ref> + A different process model uses the acronym "ROSIE" to define a five-step process of research , objectives , strategies , implementation and evaluation .<ref>Sheila C. Crifasi, "Everything's Coming Up Rosie," ''Public Relations Tactics'' 7 ( 9 ) (2000) .</ref> − People who are professionals in public relations use different methods for analyzing the results of their work such as focus groups, surveys, and one-on-one interviews . These same methods are used in defining what medium of communication will be used in the process of strategy and what tools will be used in relaying the message, such as press releases, brochures, Web sites , media packs, video news releases, news conferences and in-house publications. + People who are professionals in public relations use different methods for analyzing the results of their work such as focus groups, surveys, and one-on-one [[interview]]s . These same methods are used in defining what medium of [[ communication ]] will be used in the process of strategy and what tools will be used in relaying the message, such as press releases, brochures, websites , media packs, video news releases, news conferences , and in-house publications. ==Methods, tools and tactics== ==Methods, tools and tactics== − Public relations and publicity are not synonyms. Publicity is the spreading of information simply to gain public awareness of a product, service, candidate, and so forth. Publicity and public relations may use similar techniques, such as [[Public relations#Press conferences|press conferences]] and [[Public relations# | Press releases|press releases]]. + Public relations and publicity are not synonyms. Publicity is the spreading of information simply to gain public awareness of a product, service, candidate, and so forth. Publicity and public relations may use similar techniques, such as [[Public relations#Press conferences|press conferences]] and [[Public relations#Press releases|press releases]]. ===Audience targeting=== ===Audience targeting=== A fundamental technique used in public relations is to identify the target audience, and to tailor every message to appeal to that audience. The audience can be local, nationwide, or worldwide, but it is more often a segment of a population. [[Marketing|Marketers]] often refer to economy-driven "[[demographics]]," such as "white males 18-49," but in public relations an audience is more fluid, being whoever someone wants to reach. For example, political audiences may include "soccer moms" and "NASCAR dads." A fundamental technique used in public relations is to identify the target audience, and to tailor every message to appeal to that audience. The audience can be local, nationwide, or worldwide, but it is more often a segment of a population. [[Marketing|Marketers]] often refer to economy-driven "[[demographics]]," such as "white males 18-49," but in public relations an audience is more fluid, being whoever someone wants to reach. For example, political audiences may include "soccer moms" and "NASCAR dads." − In addition to audiences, there are usually stakeholders, literally people who have a "stake" in a given issue. All audiences are stakeholders (or presumptive stakeholders), but not all stakeholders are audiences. For example, a [[charitable organization |charity ]] may commission a PR agency to create an [[advertising]] campaign to raise money to find a cure for a [[disease]]. The charity and the people with the disease are stakeholders, but the audience is anyone who is likely to donate money. + In addition to audiences, there are usually stakeholders, literally people who have a "stake" in a given issue. All audiences are stakeholders (or presumptive stakeholders), but not all stakeholders are audiences. For example, a [[charitable organization]] may commission a public relations agency to create an [[advertising]] campaign to raise money to find a cure for a [[disease]]. The charity and the people with the disease are stakeholders, but the audience is anyone who is likely to donate money. − Sometimes the interests of differing audiences and stakeholders common to a PR effort necessitate the creation of several distinct but still complementary messages. This is not always easy to do, and sometimes & ndash ; especially in [[politics]] & ndash ; a spokesperson or client says something to one audience that angers another audience or group of stakeholders. + Sometimes the interests of differing audiences and stakeholders common to a public relations effort necessitate the creation of several distinct but still complementary messages. This is not always easy to do, and sometimes& mdash ;especially in [[politics]]& mdash ;a spokesperson or client says something to one audience that angers another audience or group of stakeholders. ===Press conferences=== ===Press conferences=== − A press conference consists of someone speaking to the news media at a predetermined time and place . Press conferences usually take place in a public or quasi-public place. Press conferences provide an opportunity for speakers to control information and who gets it; depending on the circumstances, speakers may hand-pick the journalists they invite to the conference instead of making themselves available to any journalist who wishes to attend. For example, the Communist government in [[China]] has used regular press conferences to share the Party 's latest policy decisions or to afford reporters access to officials.<ref>[http://www.fmprc.gov.cn/eng/xwfw/s2510/t293308.htm Foreign Ministry Spokeswoman Jiang Yu's Regular Press Conference on 30 January, 2007] Ministry of Foreign Affairs. Retrieved February 6 , 2007.</ref> + A press conference consists of a presentation to the news media at a predetermined time and place , usually public or quasi-public place. Press conferences provide an opportunity for speakers to control information and who has access to it; depending on the circumstances, speakers may hand-pick the journalists they invite to the conference instead of making themselves available to any journalist who wishes to attend. For example, the communist government in [[China]] has used regular press conferences to share the party 's latest policy decisions or to afford reporters access to officials.<ref>[http://www.fmprc.gov.cn/eng/xwfw/s2510/t293308.htm “Foreign Ministry Spokeswoman Jiang Yu's Regular Press Conference on 30 January, 2007 ,” ] Ministry of Foreign Affairs. Retrieved September 10 , 2007.</ref> − It is also assumed that the speaker will answer journalists' questions at a press conference, although they are not obliged to. However, someone who holds several press conferences on a topic (especially a scandal) will be asked questions by the press, regardless of whether they indicate they will entertain them, and the more conferences the person holds, the more aggressive the questioning may become. Therefore, it is in a speaker's interest to answer journalists' questions at a press conference to avoid appearing as if they have something to hide. + It is also assumed that the speaker will answer journalists' questions at a press conference, although they are not obliged to. However, someone who holds several press conferences on a topic (especially a [[ scandal ]] ) will be asked questions by the press, regardless of whether they indicate they will entertain them, and the more conferences the person holds, the more aggressive the questioning may become. Therefore, it is in a speaker's interest to answer journalists' questions at a press conference to avoid appearing as if they have something to hide. − However, questions from reporters & ndash ; especially hostile reporters & ndash ; detracts from the control a speaker has over the information they give out. For more control, but less interactivity, a person may choose to issue a press release. + However, questions from reporters& mdash ;especially hostile reporters& mdash ;detracts from the control a speaker has over the information they give out. For more control, but less interactivity, a person may choose to issue a press release. ===Press releases=== ===Press releases=== Line 72: Line 75: }} }} − A press release is a written statement distributed to the media. It is a fundamental tool of public relations. Press releases are usually communicated by a newswire service to various news media and journalists may use them as they see fit. Very often the information in a press release finds its way verbatim, or minimally altered , to print and broadcast reports. + A press release is a written statement distributed to the media. It is a fundamental tool of public relations. Press releases are usually communicated by a newswire service to various news media and journalists may use them as they see fit. Very often the information in a press release finds its way minimally altered or verbatim to print and broadcast reports. − The text of a release is usually (but not always) written in the style of a news story, with an eye-catching headline and text written standard [[journalism|journalistic]] "inverted pyramid" style. This style of news writing makes it easier for reporters to quickly grasp the message. Journalists are free to use the information verbatim, or alter it as they see fit. PR practitioners research and write releases that encourage to lift the information directly as possible. + The text of a release is usually (but not always) written in the style of a news story, with an eye-catching headline and text written standard [[journalism|journalistic]] "inverted pyramid" style. This style of news writing makes it easier for reporters to quickly grasp the message. Journalists are free to use the information verbatim, or alter it as they see fit. Public relations practitioners research and write releases that encourage journalists to lift the information as directly as possible. Since press releases reflect their issuer's preferred interpretation or positive packaging of a story, journalists are often skeptical of their contents. Newsrooms receive so many press releases that, unless it is a story that the media are already paying attention to, a press release alone often is not enough to catch a journalist's attention. Since press releases reflect their issuer's preferred interpretation or positive packaging of a story, journalists are often skeptical of their contents. Newsrooms receive so many press releases that, unless it is a story that the media are already paying attention to, a press release alone often is not enough to catch a journalist's attention. − With the advent of electronic media and new technology, press releases now have equivalents in these media & ndash ; video news releases and audio news releases. + With the advent of electronic media and new [[ technology ]] , press releases now have equivalents in these media& mdash ;video news releases and audio news releases. + The advent of the [[Internet]] has ushered in another kind of press release known as an "optimized press release." Unlike conventional press releases of yore, written for journalists' eyes only, in hopes the editor or reporter would find the content compelling enough to turn it into print or electronic news coverage, the optimized press release is posted on an online news portal. Here the writer carefully selects keywords or keyword phrases relevant to the press release contents. If written skillfully, the press release can rank highly in searches for the chosen keyword phrases by anyone searching the news portal. The advent of the [[Internet]] has ushered in another kind of press release known as an "optimized press release." Unlike conventional press releases of yore, written for journalists' eyes only, in hopes the editor or reporter would find the content compelling enough to turn it into print or electronic news coverage, the optimized press release is posted on an online news portal. Here the writer carefully selects keywords or keyword phrases relevant to the press release contents. If written skillfully, the press release can rank highly in searches for the chosen keyword phrases by anyone searching the news portal. ===Lobby groups=== ===Lobby groups=== − [[Lobbying|Lobby]] groups are established to influence government policy, corporate policy, or public opinion. These groups purport to represent a particular interest. A lobby group that hides its true purpose and support base is known as a "front group." Lobbying can take the form of private conversations with people in power, or large scale public demonstrations on behalf of a client. Lobbyists also direct people wanting to donate money to campaigns to politicians they believe would best serve those donors. These same lobbyists will also often set up meetings between influential citizens with politicians. Lobbyists are often accused of having a corrupting influence over legislators. As a result of this suspected influence, many states and countries require lobbyists to register with a central commission. Some groups that spend a lot of money on lobbying are representatives of the finance, energy, labor, transportation, and legal sectors.<ref> {{cite web|url=http://www.opensecrets .org /lobbyists/overview . asp?txtindextype=c|publisher=OpenSecrets.org|title=Lobbying Spending Database}} </ref> + [[Lobbying|Lobby]] groups are established to influence government policy, corporate policy, or public opinion. These groups purport to represent a particular interest. A lobby group that hides its true purpose and support base is known as a "front group." Lobbying can take the form of private conversations with people in power, or large scale public demonstrations on behalf of a client. Lobbyists also direct people wanting to donate money to campaigns to politicians they believe would best serve those donors. These same lobbyists will also often set up meetings between influential citizens with politicians. Lobbyists are often accused of having a corrupting influence over legislators. As a result of this suspected influence, many states and countries require lobbyists to register with a central commission. Some groups that spend a lot of money on lobbying are representatives of the finance, energy, labor, transportation, and legal sectors.<ref> Lobbying Spending Database, OpenSecrets .org. </ref> ===Astroturfing=== ===Astroturfing=== − Another PR practice is that of "astroturfing." This is the creation of artificial "grassroots" movements in order to sway public opinion over an issue. A typical example would be the writing of letters to multiple [[newspaper]] editors under different names to express an opinion on an issue, creating the impression of widespread public feeling but being controlled by one central entity. Another example would be if people are hired to put on a protest under the auspices of being genuinely concerned citizens. + Another public relations practice is that of "astroturfing." This is the creation of artificial "grassroots" movements in order to sway public opinion over an issue. A typical example would be the writing of letters to multiple [[newspaper]] editors under different names to express an opinion on an issue, creating the impression of widespread public feeling but being controlled by one central entity. Another example would be if people are hired to put on a protest under the auspices of being genuinely concerned citizens. ===Spin=== ===Spin=== − In public relations, "spin" is a , sometimes pejorative , term signifying a heavily biased portrayal in one's own favor of an event or situation. While traditional public relations may also rely on creative presentation of the facts, "spin" often , though not always , implies disingenuous, deceptive and/or highly manipulative tactics. Politicians are often accused of spin by commentators and political opponents, when they produce a counter argument or position. + In public relations, "spin" is a sometimes pejorative term signifying a heavily biased portrayal in one's own favor of an event or situation. While traditional public relations may also rely on creative presentation of the facts, "spin" often — though not always — implies disingenuous, deceptive and/or highly manipulative tactics. Politicians are often accused of spin by commentators and political opponents, when they produce a counter argument or position. The term is borrowed from ball sports such as [[cricket]], where a spin bowler may impart spin on the ball during a delivery so that it will curve through the air or bounce in an advantageous manner. The term is borrowed from ball sports such as [[cricket]], where a spin bowler may impart spin on the ball during a delivery so that it will curve through the air or bounce in an advantageous manner. Line 100: Line 104: Skilled practitioners of spin are sometimes called "spin doctors." Alastair Campbell, who was involved with [[Great Britain|British]] Prime Minister [[Tony Blair]]'s public relations between 1994 and 2003, and also played a controversial role as press relations officer to the British and Irish Lions [[rugby]] team during their 2005 tour of [[New Zealand]], has often been referred to as a "spin doctor." Skilled practitioners of spin are sometimes called "spin doctors." Alastair Campbell, who was involved with [[Great Britain|British]] Prime Minister [[Tony Blair]]'s public relations between 1994 and 2003, and also played a controversial role as press relations officer to the British and Irish Lions [[rugby]] team during their 2005 tour of [[New Zealand]], has often been referred to as a "spin doctor." − State-run media in many countries also engage in spin by selectively allowing news stories that are favorable to the government while censoring anything that could be considered critical. They may also use [[propaganda]] to indoctrinate or actively influence citizens' opinions. The [[Russia]]n state-owned [[natural gas]] firm Gazprom has relyed on favorable coverage in newspapers loyal to the government to give it an image boost.<ref>Yasmann, Victor. [http://www.rferl.org/featuresarticle/2007/02/01743CD3-2F57-49D6-91D0-15D2E62CC15F.html Russia : Rebranding The Nation] Radio Free Europe. Retrieved February 6 , 2007.</ref> + State-run media in many countries also engage in spin by selectively allowing news stories that are favorable to the government while censoring anything that could be considered critical. They may also use [[propaganda]] to indoctrinate or actively influence citizens' opinions. The [[Russia]]n state-owned [[natural gas]] firm Gazprom has relied on favorable coverage in newspapers loyal to the government to give it an image boost.<ref> Victor Yasmann, [http://www.rferl.org/featuresarticle/2007/02/01743CD3-2F57-49D6-91D0-15D2E62CC15F.html “Russia : Rebranding The Nation ,” ] Radio Free Europe. Retrieved September 10 , 2007.</ref> ===Other=== ===Other=== * Publicity events or publicity stunts * Publicity events or publicity stunts − * Talk shows – a PR spokesperson (or his/her client) "does the circuit" by being interviewed on television and radio talk shows with audiences that the client wishes to reach . + * Talk shows – a public relations spokesperson (or his/her client) "does the circuit" by being interviewed on [[ television ]] and [[ radio ]] talk shows with audiences that the client wishes to reach * Books and other writings * Books and other writings − * Direct communication (carrying messages directly to constituents, rather than through the mass media) for example through newsletters both in print and over the internet . + * Direct communication (carrying messages directly to constituents, rather than through the [[ mass media ]] ) for example through newsletters both in print and over the [[ internet ]] − * Collateral literature, traditionally in print and now predominantly as web sites. + * Collateral literature, traditionally in print and now predominantly as websites − * Speeches to constituent groups and professional organizations; receptions; seminars, and other events; personal appearances . + * Speeches to constituent groups and professional organizations; receptions; seminars, and other events; personal appearances ==Politics and civil society== ==Politics and civil society== Line 114: Line 118: A tactic used in [[politics|political]] campaigns is known as "defining one's opponent." Opponents can be candidates, organizations, or other groups of people. A tactic used in [[politics|political]] campaigns is known as "defining one's opponent." Opponents can be candidates, organizations, or other groups of people. − In the 2004 [[United States| US ]] presidential campaign, [[George W. Bush]] defined opponent John Kerry as a "flip-flopper," among other characterizations, which were widely reported and repeated by the media, particularly the conservative media.<ref>Harris, John. 2004. [http://www.washingtonpost.com/wp-dyn/articles/A43093-2004Sep22.html spite Bush Flip-Flops, Kerry Gets Label] ''The Washington Post''. Retrieved January 4, 2007.</ref> Similarly, [[George H.W. Bush]] characterized Michael Dukakis as weak on [[crime]] and as hopelessly liberal ("a card-carrying member of the [[ACLU]]").<ref>Saunders, Debra. 2002. [http://www.sfgate.com/cgi-bin/article.cgi? file =/ chronicle / archive /2002/12/12/ED194565.DTL Willie Horton's legacy] ''San Francisco Chronicle''. Retrieved January 4 , 2007.</ref> In 1996, President [[Bill Clinton]] seized upon opponent Bob Dole's promise to take America back to a simpler time, promising in contrast to "build a bridge to the twenty-first century," thus painting Dole as a person who was somehow opposed to progress.<ref>[http://www-cgi.cnn.com/ALLPOLITICS/1996/news/9608/30/clinton.speech/ Clinton Proposes Bridge To 21st Century] CNN. Retrieved January 4 , 2007.</ref> + In the 2004 [[United States| U.S. ]] presidential campaign, [[George W. Bush]] defined opponent John Kerry as a "flip-flopper," among other characterizations, which were widely reported and repeated by the media, particularly the conservative media.<ref> John Harris, [http://www.washingtonpost.com/wp-dyn/articles/A43093-2004Sep22.html "Despite Bush Flip-Flops, Kerry Gets Label ," ] ''The Washington Post'' (September 23, 2004) . Retrieved January 4, 2007.</ref> Similarly, [[George H. W. Bush]] characterized Michael Dukakis as weak on [[crime]] and as hopelessly liberal ("a card-carrying member of the [[ American Civil Liberties Union| ACLU]]").<ref> Debra Saunders, [http://www.sfgate.com/cgi-bin/article.cgi? f =/ c / a /2002/12/12/ED194565.DTL &hw=Willie+Horton&sn=002&sc=869 " Willie Horton's legacy ," ] ''San Francisco Chronicle'' (December 12, 2002) . Retrieved September 10 , 2007.</ref> In 1996, President [[Bill Clinton]] seized upon opponent Bob Dole's promise to take America back to a simpler time, promising in contrast to "build a bridge to the twenty-first century," thus painting Dole as a person who was somehow opposed to progress.<ref>[http://www-cgi.cnn.com/ALLPOLITICS/1996/news/9608/30/clinton.speech/ " Clinton Proposes Bridge To 21st Century ," ] CNN AllPolitics (August 30, 1996) . Retrieved September 10 , 2007.</ref> − In the debate over [[abortion]], pro-abortion rights groups defined their opponents by defining themselves instead as "pro-choice." Anti-abortion rights groups responded in kind, branding themselves "pro-life." Extrapolating their respective [[rhetoric]], pro-choice groups refer to their opponents as "anti-choice," and pro-life groups refer to their opponents as "anti-life."<ref>Marcotte , Amanda , et. al. 2006. [http://alternet.org/rights/35545/ Exposing Anti-Choice Abortion Clinics] AlterNet. Retrieved January 4 , 2007.</ref><ref>[http://www.neuralgourmet.com/2006/06/15/the_anti_life_movement The Anti-Life Movement] Neural Gourmet. Retrieved January 4 , 2007.</ref> + In the debate over [[abortion]], pro-abortion rights groups defined their opponents by defining themselves instead as "pro-choice." Anti-abortion rights groups responded in kind, branding themselves "pro-life." Extrapolating their respective [[rhetoric]], pro-choice groups refer to their opponents as "anti-choice," and pro-life groups refer to their opponents as "anti-life."<ref> Amanda Marcotte, et. al. , [http://alternet.org/rights/35545/ “Exposing Anti-Choice Abortion Clinics ,” ] AlterNet (May 1, 2006) . Retrieved September 10 , 2007.</ref><ref>[http://www.neuralgourmet.com/2006/06/15/the_anti_life_movement “The Anti-Life Movement ,” ] Neural Gourmet (June 15, 2006) . Retrieved September 10 , 2007.</ref> − Opponents of [[homosexuality|same-sex]] [[marriage]] in the U.S. have declared that their opponents are not the couples suing for the right to marry in various state courts, but rather the judges who rule in their favor. They are now calling them "activist judges," implying that they impose their personal [[belief]]s instead of objectively interpreting the [[law]]. This sidesteps the thorny issue of making millions of homosexual people an "enemy," and instead focuses attention on the much smaller judiciary, who all Americans can ostensibly agree should be prevented from being "activists" on the bench.<ref>Lithwick, Dahlia. 2004. [http://seattlepi.nwsource.com/opinion/186690_lithwick18.html Activist judges? What's in a name?] Seattle PI . Retrieved January 4, 2007.</ref> + Opponents of [[homosexuality|same-sex]] [[marriage]] in the U.S. have declared that their opponents are not the couples suing for the right to marry in various state courts, but rather the judges who rule in their favor. They are now calling them "activist judges," implying that they impose their personal [[belief]]s instead of objectively interpreting the [[law]]. This sidesteps the thorny issue of making millions of homosexual people an "enemy," and instead focuses attention on the much smaller judiciary, who all Americans can ostensibly agree should be prevented from being "activists" on the bench.<ref> Dahlia Lithwick, [http://seattlepi.nwsource.com/opinion/186690_lithwick18.html “Activist judges? What's in a name? ” ] '' Seattle Post-Iintelligencer'' (August 18, 2004) . Retrieved January 4, 2007.</ref> − In [[Spain]], José Luis Rodríguez Zapatero was able to win the election for Prime Minister in 2004 after characterizing his opponents in the People's Party as weak on security following the bombing of [[Madrid]]'s Athocha Station, killing 191 people.<ref>[http://www.economist.com/world/europe/displaystory.cfm?story_id=8562022 Belated Realism] ''The Economist''. Retrieved February 6 , 2007.</ref> + In [[Spain]], José Luis Rodríguez Zapatero was able to win the election for prime minister in 2004 after characterizing his opponents in the People's Party as weak on security following the bombing of [[Madrid]]'s Athocha Station, killing 191 people.<ref>[http://www.economist.com/world/europe/displaystory.cfm?story_id=8562022 " Belated Realism ," ] ''The Economist'' (January 18, 2007) . Retrieved September 10 , 2007.</ref> ===Managing language=== ===Managing language=== Line 129: Line 133: Celebrities tend to be fans of the dictum "any publicity is good publicity." If a celebrity says or does something embarrassing, he or she will often turn it into a strength and make it part of his or her "image." This tactic is used just as much with favorable situations as much as with unfavorable ones. Celebrities tend to be fans of the dictum "any publicity is good publicity." If a celebrity says or does something embarrassing, he or she will often turn it into a strength and make it part of his or her "image." This tactic is used just as much with favorable situations as much as with unfavorable ones. − The entertainer Jessica Simpson gained nationwide prominence when she wondered aloud on a reality [[television]] show if "Chicken of the Sea" was actually [[chicken]] or [[tuna]], garnering her a reputation for being slow-witted. However, within months she was being paid to endorse a brand of breath mints called "Liquid Ice." In the product's television commercial, Simpson replicates her earlier confusion by debating whether the mint is really liquid or ice, turning her nationwide embarrassment into a lucrative endorsement deal.<ref>Rogers, Steve. 2003. [http://www.realitytvworld.com/news/jessica-simpson-gets-an-education-on-chicken-of-sea-1886.php Jessica Simpson gets an education on Chicken Of The Sea] Reality TV World. Retrieved January 4 , 2007.</ref> + Entertainer Jessica Simpson gained nationwide prominence when she wondered aloud on a reality [[television]] show if "Chicken of the Sea" was actually [[chicken]] or [[tuna]], garnering her a reputation for being slow-witted. However, within months she was being paid to endorse a brand of breath mints called "Liquid Ice." In the product's television commercial, Simpson replicated her earlier confusion by debating whether the mint is really liquid or ice, turning her nationwide embarrassment into a lucrative endorsement deal.<ref> Steve Rogers, [http://www.realitytvworld.com/news/jessica-simpson-gets-an-education-on-chicken-of-sea-1886.php " Jessica Simpson gets an education on Chicken of the Sea ," ] Reality TV World (October 21, 2003) . Retrieved September 10 , 2007.</ref> ===Branching out=== ===Branching out=== Line 136: Line 140: A number of American celebrities have transformed themselves into children's book authors, accompanied by much media coverage. A more traditional way of branching out is the celebrity restaurant. This is especially common among professional athletes, whose time in the spotlight is often limited by the physical demands of their jobs. Thus, [[basketball]] player [[Michael Jordan]] opened a restaurant in [[Chicago]]. A number of American celebrities have transformed themselves into children's book authors, accompanied by much media coverage. A more traditional way of branching out is the celebrity restaurant. This is especially common among professional athletes, whose time in the spotlight is often limited by the physical demands of their jobs. Thus, [[basketball]] player [[Michael Jordan]] opened a restaurant in [[Chicago]]. − Younger female celebrities are often drawn into the [[fashion]] world. Hotel heiress [[Paris Hilton]] recently announced that she was starting her own line of jewelry. Fading star [[Elizabeth Taylor]] launched a [[perfume]] called "White Diamonds," bringing renewed interest from the media. + Younger female celebrities are often drawn into the [[fashion]] world. Hotel heiress [[Paris Hilton]] recently announced that she was starting her own line of [[ jewelry ]] . Fading star [[Elizabeth Taylor]] launched a [[perfume]] called "White Diamonds," bringing renewed interest from the media. − Other celebrities have gravitated toward [[politics]], including film stars [[ Charleton Heston]] and notably [[Arnold Schwarzenegger]], who succeeded in being elected Governor of [[California]]. + Other celebrities have gravitated toward [[politics]], including film stars [[ Charlton Heston]] and notably [[Arnold Schwarzenegger]], who succeeded in being elected governor of [[California]]. ==Ethical and social issues== ==Ethical and social issues== − One of the most controversial practices in public relations is the use of "front groups"—organizations that purport to serve a public cause while actually serving the interests of a client whose sponsorship may be obscured or concealed. The creation of front groups is an example of what PR practitioners sometimes term the "third party technique"—the art of "putting your words in someone else's mouth." The Center for Media & Democracy, a non-profit organization that monitors PR activities it considers to be deceptive, has published numerous examples of this technique in practice, contending that public relations involves a "multi-billion dollar propaganda-for-hire industry" that works to "concoct and spin the news, organize phoney 'grassroots' front groups, spy on citizens, and conspire with lobbyists and politicians to thwart democracy."<ref>[http://www.prwatch.org/cmd/prwatch.html ''PR Watch''] Center for Media and Democracy , Publishers of ''PR Watch'' . Retrieved January 4 , 2007.</ref> + One of the most controversial practices in public relations is the use of "front groups"—organizations that purport to serve a public cause while actually serving the interests of a client whose sponsorship may be obscured or concealed. The creation of front groups is an example of what public relations practitioners sometimes term the "third party technique"—the art of "putting your words in someone else's mouth." + + The Center for Media & Democracy, a non-profit organization that monitors public relations activities it considers to be deceptive, has published numerous examples of this technique in practice, contending that public relations involves a "multi-billion dollar propaganda-for-hire industry" that works to "concoct and spin the news, organize phony 'grassroots' front groups, spy on citizens, and conspire with lobbyists and politicians to thwart democracy."<ref>[http://www.prwatch.org/cmd/prwatch.html ''PR Watch'' , ] Center for Media and Democracy. Retrieved September 10 , 2007.</ref> − Instances of the use of front groups as a PR technique have been documented in many industries. [[Coal mining]] corporations created environmental groups that contended that increased [[ carbbn dioxide]] emissions and [[global warming]] will contribute to plant growth and thus be beneficial, trade groups for bars have created and funded citizens' groups to attack anti-[[alcohol]] groups, and [[tobacco]] companies have created and funded citizens' groups to advocate for [[tort]] reform and to attack personal injury [[lawyer]]s.<ref>[http://archive.democrats.com/preview.cfm?term=corporate+front+groups Corporate front groups] Democrats.com. Retrieved January 4 , 2007.</ref> + Instances of the use of front groups as a public relations technique have been documented in many industries. [[Coal ]] [[ mining]] corporations created environmental groups that contended that increased [[ carbon dioxide]] emissions and [[global warming]] will contribute to plant growth and thus be beneficial, trade groups for bars have created and funded citizens' groups to attack anti-[[alcohol]] groups, and [[tobacco]] companies have created and funded citizens' groups to advocate for [[tort]] reform and to attack personal injury [[lawyer]]s.<ref>[http://archive.democrats.com/preview.cfm?term=corporate+front+groups Corporate front groups , ] Democrats.com. Retrieved September 10 , 2007.</ref> − Nevertheless, many of the techniques used by PR firms are drawn from the institutions and practices of [[democracy]] itself. [[Persuasion]], advocacy, and [[education]] are instruments through which individuals and organizations are entitled to express themselves in a free society, and many public relations practitioners are engaged in practices that are widely considered as beneficial, such as publicizing scientific research, promoting [[charitable organization|charities]], raising awareness of [[public health]] concerns and other issues in civil society. + Nevertheless, many of the techniques used by public relations firms are drawn from the institutions and practices of [[democracy]] itself. [[Persuasion]], advocacy, and [[education]] are instruments through which individuals and organizations are entitled to express themselves in a free society, and many public relations practitioners are engaged in practices that are widely considered as beneficial, such as publicizing scientific research, promoting [[charitable organization|charities]], raising awareness of [[public health]] concerns , and other such issues in civil society. ==Notes== ==Notes== Line 153: Line 159: ==References== ==References== − *Bernays, Edward. 1945. ''Public Relations''. Boston, MA: Bellman Publishing Company. + *Bernays, Edward. 1945. ''Public Relations''. Boston, MA: Bellman Publishing Company. *Burson, Harold. 2004. ''E pluribus unum: The Making of Burson-Marsteller''. New York: Burson-Marsteller. *Burson, Harold. 2004. ''E pluribus unum: The Making of Burson-Marsteller''. New York: Burson-Marsteller. − *Center, Allen H. & Jackson , Patrick . [1995] 2002. ''Public Relations Practices ( 5th ed .)'' . Upper Saddle, NJ: Prentice Hall. ISBN 0136138039 + *Center, Allen H. & Patrick Jackson. [1995] 2002. ''Public Relations Practices '', 5th ed. Upper Saddle River , NJ: Prentice Hall. ISBN 0136138039 − *Crifasi, Sheila C. 2000. "Everything's Coming Up Rosie , " ''Public Relations Tactics , '' Vol. 7 , Issue 9. + *Crifasi, Sheila C. 2000. "Everything's Coming Up Rosie . " ''Public Relations Tactics'' 7 ( 9 ) . − *Cutlip, Scott. 1994. ''The Unseen Power: Public Relations , A History . Hillsdale ''. Erlbaum Associates. ISBN 0-8058-1464-7. + *Cutlip, Scott. 1994. ''The Unseen Power: Public Relations : A History''. Mahwah, NJ: Lawrence Erlbaum Associates. ISBN 0805814647 − *Cutlip, Scott M. , Allen H. Center , & Glen M. Broom. 2005. ''Effective Public Relations''. Englewood Cliff , NJ: Prentice-Hall, Inc. ISBN 0130082007 + *Cutlip, Scott, Allen H. Center and Glen M. Broom. 2005. ''Effective Public Relations''. Englewood Cliffs , NJ: Prentice-Hall, Inc. ISBN 0130082007 − *Ewen, Stuart. 1996. ''PR!: A Social History of Spin''. New York: Basic Books. ISBN 0-465-06168-0. + *Ewen, Stuart. 1996. ''PR!: A Social History of Spin''. New York: Basic Books. ISBN 0465061680 − *Grunig, James E. & Todd Hunt. 1984. ''Managing Public Relations''. New York: Holt, Rinehart and Winston. ISBN 0-03-058337-3. + *Grunig, James E. & Todd Hunt. 1984. ''Managing Public Relations''. New York: Holt, Rinehart and Winston. ISBN 0030583373 − *Kelly, Kathleen S. 1998. " Effective Fund Raising Management, " Lawrence Erlbaum Associates. ISBN 0805820108 + *Kelly, Kathleen S. 1998. '' Effective Fund Raising Management ''. Mahwah , NJ: Lawrence Erlbaum Associates. ISBN 0805820108 − *Macnamara, Jim. 2005. ''Jim Macnamara's Public Relations Handbook ( 5th ed .)'' . Melbourne: Information Australia. + *Macnamara, Jim. 2005. ''Jim Macnamara's Public Relations Handbook '', 5th ed. Melbourne: Information Australia. − *Nelson, Joyce. 1989. ''Sultans of Sleaze: Public Relations and the Media''. Toronto: Between The Lines. ISBN 0-921284-22-5. + *Nelson, Joyce. 1989. ''Sultans of Sleaze: Public Relations and the Media''. Toronto: Between the Lines. ISBN 0921284225 − *Phillips, David. 2001. ''Online Public Relations''. London: Kogan Page. ISBN 0-7494-3510-0. + *Phillips, David. 2001. ''Online Public Relations''. London: Kogan Page. ISBN 0749435100 − *Stauber, John C. 1995. ''Toxic Sludge is Good for You: Lies, Damn Lies, and the Public Relations Industry''. Monroe, ME: Common Courage Press. ISBN 1-56751-061-2. + *Stauber, John C. 1995. ''Toxic Sludge is Good for You: Lies, Damn Lies, and the Public Relations Industry''. Monroe, ME: Common Courage Press. ISBN 1567510612 − *Tye, Larry. 1998. ''The Father of Spin: Edward L. Bernays & the Birth of Public Relations''. New York: Crown Publishers. ISBN 0-517-70435-8. + *Tye, Larry. 1998. ''The Father of Spin: Edward L. Bernays and the Birth of Public Relations''. New York: Crown Publishers. ISBN 0517704358 − *Stoykov, Lubomir & Valeria Pacheva. 2005. ''Public Relations and Business Communication''. Sofia: Ot Igla Do Konetz. ISBN 954-9799-09-3. + *Stoykov, Lubomir & Valeria Pacheva. 2005. ''Public Relations and Business Communication''. Sofia: Ot Igla Do Konetz. ISBN 9549799093 ==External links== ==External links== − *[http://www. prsa . org / _Resources/Profession/index.asp?ident=prof1 About Public Relations], by the Public Relations Society of America + All links retrieved December 2, 2022. − *[http://www.factcheck.org/miscreports70.html Annenberg Political Fact Check] A nonpartisan , nonprofit consumer advocate which monitors the factual accuracy of statements by political players + − *[http://http://www . bicspr.org/ Bangladesh Institute of Communication and public relations (BICSPR)([[Shobuz] ] )], Being the very first non-government organization of Bangladesh in this field, this institute has a strong desire to provide quality media education but also training, publication, research work etc. Recently the institute has commenced Diploma in Journalism as the first private institute of the country under National University + *[http://www. cprs . ca / The Canadian Public Relations Society, Inc .] − *[http://www.cipr.co.uk/ Chartered Institute of Public Relations] , the UK’s leading public relations industry professional body and the largest public relations institute in Europe + *[http://www.cipr.co.uk/ Chartered Institute of Public Relations] − * Christian Science Monitor: [http://www.csmonitor.com/2003/1212/p11s01-coop.htm The spin room - oily engine of the political meat grinder] + *[http://www.csmonitor.com/2003/1212/p11s01-coop.htm “The spin room - oily engine of the political meat grinder ,” ] by Jerry Lanson, ''Christian Science Monitor'' (December 12 , 2003) − *[http://www.corporatewatch.org.uk/?lid=1570 CorporateWatch] , a critical overview of the public relations and lobbying industry + *[http://www.prfirms.org/ Council of Public Relations Firms] − *[http://www.prfirms.org/ Council of Public Relations Firms] U.S. trade association for public relations firms + *[http://www.publicityinsider.com/freepub.asp Free Publicity] – The Newsletter for PR Hungry Businesses − *[http://www.publicityinsider.com/freepub.asp Free Publicity] , a guide to publicity for all levels + *[http://www.instituteforpr.org Institute for Public Relations] − *[http://www.instituteforpr.org Institute for Public Relations] - science beneath the art of public relations + *[http://www.iabc.com/ International Association of Business Communicators] − *[http://www.iabc.com/ International Association of Business Communicators] , an international association of 14,000 communicators, with many members from the PR profession. + *[http://www. prmuseum .com/ The Museum of Public Relations ] − *[http://www. odwyerpr .com/ O'Dwyer's PR Daily ] , another trade publication, occasionally featuring critical essays and investigative journalism about the industry + *[http://www. odwyerpr . com / O'Dwyer 's PR Daily ] − *[http://www. outfoxed . org / OUTFOXED: Rupert Murdoch 's War on Journalism ] + *[http://www.prwatch.org/ PR Watch] − *[http://www.prwatch.org/ PR Watch] , critiques deceptive PR campaigns + *[http://www.prweek.com/ PR Week] − *[http://www.prweek.com/ PR Week] , the leading PR trade weekly + *[http://www.pria.com.au/ Public Relations Institute of Australia] − *[http://www.montagecomms.com/press_releases.html/ Press release Blog for PR in the South West of England ] featuring live examples of press releases and PR photography, that have achieved results nationally and regionally. + *[http://www.prsa.org/ Public Relations Society of America] − *[http://www.pria.com.au/ Public Relations Institute of Australia] , Institute for the public relations profession in Australia. + *[http://www.sourcewatch.org SourceWatch.org] − *[http://www.prsa.org/ Public Relations Society of America] , a professional association of public relations practitioners + *[http://www.spinwatch.org Spinwatch] − *[http://www.sourcewatch.org SourceWatch.org] Provides background on PR agencies and practitioners. Focuses mostly on conservative and right-wing PR + *[http://www. factcheck .org/ Annenberg Political Fact Check ] – A nonpartisan , nonprofit consumer advocate that monitors the factual accuracy of statements by political players in the United States − *[http://www.sovetnik.ru/ Sovetnik ] The best site about public relation in Russia. − *[http://www.prwatch.org/spin Spin of the Day] - Center for Media and Democracy − *[http://www.spinwatch.org Spinwatch] monitors spin and propaganda − *[http://www.spinwatch.org Spinwatch] Monitors public relations and propaganda − *[http://www. globalpr .org/ The Global Alliance ], an international peak organisation with a mission to enhance the public relations profession and its practitioners throughout the world. − *[http://www.acpc.uts.edu.au/ The Australian Centre for Public Communication], promotes ethical practice in public relations and facilitates debate among practitioners in the field through industry liaison, research and seminars. Australia's leading postgraduate education program in communication management at UTS is linked to the Centre through the teaching staff, students, members and research projects. − *[http://www.prmuseum.com/ The Museum of Public Relations] offers a look at some of the industry's historical figures − *[http://www.cprs.ca/ The Canadian Public Relations Society, Inc.], The CPRS works to advance the professional stature of public relations and regulates its practice for the benefit and protection of the public interest. − *[http://www.icrsurvey.com/docs/MR%20for%20PR.doc Using market research for Public Relations], white paper from [[ICR/International Communications Research|ICR]] {{Credit1|Public_relations|94154739|}} {{Credit1|Public_relations|94154739|}}
Latest revision as of 18:08, 14 April 2023
In the 1890s, when gender role reversals could be caricaturized, the idea of an aggressive woman who also smoked was considered laughable. In 1929, Edward Bernays proved otherwise when he convinced women to smoke in public during an Easter parade in Manhattan as a show of defiance against male domination. The demonstrators were not aware that a tobacco company was behind the publicity stunt, a form of
public relations
.
Public relations( PR) is the art of managingcommunicationbetween an organization and its key publics to build, manage, and sustain a positive image. Public relations involves evaluation of publicattitudesandpublic opinions; formulation and implementation of an organization's procedures and policy regarding communication with its publics; coordination of communications programs; developing rapport and good-will through a two way communication process; and fostering a positive relationship between an organization and its public constituents. Public relations often involves news management—optimizing good news and forestalling bad news. Equally, good public relations managers conduct "damage control" when a disaster occurs, gathering the facts and assessing the situation to prepare appropriate information to be offered to themass media. While public relations may be criticized aspropagandaon occasion, the role of managing communication between the organization and the public is a necessary one in society. Astechnologieshave developed, it has become both more difficult to hide information and equally easier to distort it. The quality of PR material produced, and how much it reflects the truth of the situation, depend on the character and motivations of all involved.
Contents
1 History
2 The industry today
3 Public Relations Process
4 Methods, tools and tactics
4.1 Audience targeting
4.2 Press conferences
4.3 Press releases
4.4 Lobby groups
4.5 Astroturfing
4.6 Spin
4.7 Other
5 Politics and civil society
5.1 Defining the opponent
5.2 Managing language
6 Entertainment and celebrity
6.1 Playing up weaknesses
6.2 Branching out
7 Ethical and social issues
8 Notes
History
Precursors to public relationsare found in publicists who specialized in promoting circuses, theatrical performances, and other public spectacles. In theUnited States, where public relations has its origins, many early public relations practices were developed in support of the expansive power of therailroads. In fact, the first documented use of the term "public relations" appeared in the 1897 Year Book of Railway Literature.
Later, public relations practitioners were—and are still often—recruited from the ranks ofjournalism. Some journalists, concerned withethics, have criticized former colleagues for using their inside understanding of news media to help clients receive favorablemass mediacoverage. [1]
TheFirst World Waralso helped stimulate the development of public relations as a profession. Many of the first public relations professionals—includingEdward L. BernaysandCarl Byoir—got their start with the Committee on Public Information (also known as the “Creel Commission”), which organized publicity on behalf of U.S. objectives during World War I. Some historians regardIvy Leeas the first real practitioner of public relations, but Bernays is generally regarded today as the profession's founder. In describing the origin of the term “public relations,” Bernays commented, "When I came back to the United States, I decided that if you could usepropagandaforwar, you could certainly use it for peace. And propaganda got to be a bad word because of the Germans using it. So what I did was to try to find some other words, so we found the words Council on Public Relations."
Lee, who has been credited with developing the modern "news release" (or "press release"), espoused a philosophy consistent with what has sometimes been called the "two-way street" approach to public relations, in which public relations consists of helping clients listen as well as communicate messages to their publics. In the words of the Public Relations Society of America, "Public relations helps an organization and its publics adapt mutually to each other."
Bernays was the profession's first theorist. A nephew ofSigmund Freud, Bernays drew many of his ideas from Freud's theories about the irrational,unconsciousmotives that shape human behavior. One of Bernays' early clients was thetobaccoindustry. In 1929, he orchestrated a legendary publicity stunt aimed at persuading women to take up cigarette smoking, which was then considered unfeminine and inappropriate for women with any social standing. Bernays arranged forNew York Citydébutantes to march in that year's Easter Day Parade, defiantly smoking cigarettes as a statement of rebellion against the norms of a male-dominated society.
Bernays authored several books, including Crystallizing Public Opinion(1923), Propaganda(1928), and The Engineering of Consent(1947), regarding public relations as an "applied social science" that uses insights frompsychology,sociology, and other disciplines to scientifically manage and manipulate the thinking and behavior of an irrational and "herdlike" public:
The conscious and intelligent manipulation of the organized habits and opinions of the masses is an important element in democratic society. Those who manipulate this unseen mechanism of society constitute an invisible government which is the true ruling power of our country. [2]
In 1950, PRSA enacted the first "Professional Standards for the Practice of Public Relations," a forerunner to the current Code of Ethics, revised in 2000 to include six core values and six code provisions. [3]These six core values are "Advocacy, Honesty, Expertise, Independence, Loyalty, and Fairness." The six code provisions are "Free Flow of Information, Competition, Disclosure of Information, Safeguarding Confidences, Conflicts of Interest, and Enhancing the Profession."
The industry today
According to the U.S. Bureau of Labor Statistics, there were approximately 122,000 public relations specialists in theUnited Statesin 1998, while there were approximately 485,000advertising, marketing, and public relations managers working in all industries. [4]
The practice is also growing across the world. As other countries are entering into theglobalizedfree market economy, they find they would like to promote their best face to the public. Countries in the formerSoviet Unionare finding the opportunity for the first time since the fall of theBerlin Wall. Over one hundred public relations firms have emerged in the formerly SovietUkraine. [5]Similar numbers are developing all over Europe,Africa, andSouth America.
Modern public relations uses a variety of techniques including opinion polling and focus groups to evaluatepublic opinion, combined with a variety of high-tech techniques for distributing information on behalf of their clients, includingsatellitefeeds, theInternet, broadcast faxes, and database-driven phone banks to recruit supporters for a client's cause.
Although public relations professionals are stereotypically seen as corporate servants, the reality is that almost any organization that has a stake in how it is portrayed in the public arena employs at least one public relations professional. Large organizations may even have dedicated communications departments. Government agencies, trade associations, and other non-profit organizations commonly carry out public relations activities.
Public Relations Process
An effective public relations plan for an organization is designed to communicate to an audience (whether internal or external publics) in such a way that the message coincides with organizational goals and seeks to benefit mutual interests. The process of developing such a plan consists of a number of steps.
One common model has four steps. [6]The first step is "defining public relations problems," usually in terms of a "situational analysis," or what public relations professionals call a "SWOT analysis" (strengths, weaknesses, opportunities, threats). This should answer the question, "What's happening now?" The next step in the public relations process is "planning and programming," where the main focus is "strategy." This step should answer the question "what should we do and say, and why?" The third step in the public relations process is "taking action and communicating," also known as "implementation"; This step should answer the question, "How and when do we do and say it?" The final step is "evaluating the program," making a final "assessment," which should answer the question "how did we do?" This is where public relations professionals make a final analysis of the success of their campaign or communication.
Another model defines the process of public relations through four steps: "Fact-finding and data gathering; Planning and programming; Action and communication; Evaluation." [7]A different process model uses the acronym "ROSIE" to define a five-step process of research, objectives, strategies, implementation and evaluation. [8]
People who are professionals in public relations use different methods for analyzing the results of their work such as focus groups, surveys, and one-on-oneinterviews. These same methods are used in defining what medium ofcommunicationwill be used in the process of strategy and what tools will be used in relaying the message, such as press releases, brochures, websites, media packs, video news releases, news conferences, and in-house publications.
Methods, tools and tactics
Public relations and publicity are not synonyms. Publicity is the spreading of information simply to gain public awareness of a product, service, candidate, and so forth. Publicity and public relations may use similar techniques, such aspress conferencesandpress releases.
Audience targeting
A fundamental technique used in public relations is to identify the target audience, and to tailor every message to appeal to that audience. The audience can be local, nationwide, or worldwide, but it is more often a segment of a population. Marketers often refer to economy-driven "demographics," such as "white males 18-49," but in public relations an audience is more fluid, being whoever someone wants to reach. For example, political audiences may include "soccer moms" and "NASCAR dads."
In addition to audiences, there are usually stakeholders, literally people who have a "stake" in a given issue. All audiences are stakeholders (or presumptive stakeholders), but not all stakeholders are audiences. For example, acharitable organizationmay commission a public relations agency to create anadvertisingcampaign to raise money to find a cure for adisease. The charity and the people with the disease are stakeholders, but the audience is anyone who is likely to donate money.
Sometimes the interests of differing audiences and stakeholders common to a public relations effort necessitate the creation of several distinct but still complementary messages. This is not always easy to do, and sometimes—especially in politics—a spokesperson or client says something to one audience that angers another audience or group of stakeholders.
Press conferences
A press conference consists of a presentation to the news media at a predetermined time and place, usually public or quasi-public place. Press conferences provide an opportunity for speakers to control information and who has access to it; depending on the circumstances, speakers may hand-pick the journalists they invite to the conference instead of making themselves available to any journalist who wishes to attend. For example, the communist government inChinahas used regular press conferences to share the party's latest policy decisions or to afford reporters access to officials. [9]
It is also assumed that the speaker will answer journalists' questions at a press conference, although they are not obliged to. However, someone who holds several press conferences on a topic (especially a scandal) will be asked questions by the press, regardless of whether they indicate they will entertain them, and the more conferences the person holds, the more aggressive the questioning may become. Therefore, it is in a speaker's interest to answer journalists' questions at a press conference to avoid appearing as if they have something to hide.
However, questions from reporters—especially hostile reporters—detracts from the control a speaker has over the information they give out. For more control, but less interactivity, a person may choose to issue a press release.
Press releases
A press release is a written statement distributed to the media. It is a fundamental tool of public relations. Press releases are usually communicated by a newswire service to various news media and journalists may use them as they see fit. Very often the information in a press release finds its way minimally altered or verbatim to print and broadcast reports.
The text of a release is usually (but not always) written in the style of a news story, with an eye-catching headline and text written standardjournalistic"inverted pyramid" style. This style of news writing makes it easier for reporters to quickly grasp the message. Journalists are free to use the information verbatim, or alter it as they see fit. Public relations practitioners research and write releases that encourage journalists to lift the information as directly as possible.
Since press releases reflect their issuer's preferred interpretation or positive packaging of a story, journalists are often skeptical of their contents. Newsrooms receive so many press releases that, unless it is a story that the media are already paying attention to, a press release alone often is not enough to catch a journalist's attention.
With the advent of electronic media and newtechnology, press releases now have equivalents in these media—video news releases and audio news releases.
The advent of theInternethas ushered in another kind of press release known as an "optimized press release." Unlike conventional press releases of yore, written for journalists' eyes only, in hopes the editor or reporter would find the content compelling enough to turn it into print or electronic news coverage, the optimized press release is posted on an online news portal. Here the writer carefully selects keywords or keyword phrases relevant to the press release contents. If written skillfully, the press release can rank highly in searches for the chosen keyword phrases by anyone searching the news portal.
Lobby groups
Lobbygroups are established to influence government policy, corporate policy, or public opinion. These groups purport to represent a particular interest. A lobby group that hides its true purpose and support base is known as a "front group." Lobbying can take the form of private conversations with people in power, or large scale public demonstrations on behalf of a client. Lobbyists also direct people wanting to donate money to campaigns to politicians they believe would best serve those donors. These same lobbyists will also often set up meetings between influential citizens with politicians. Lobbyists are often accused of having a corrupting influence over legislators. As a result of this suspected influence, many states and countries require lobbyists to register with a central commission. Some groups that spend a lot of money on lobbying are representatives of the finance, energy, labor, transportation, and legal sectors. [10]
Astroturfing
Another public relations practice is that of "astroturfing." This is the creation of artificial "grassroots" movements in order to sway public opinion over an issue. A typical example would be the writing of letters to multiplenewspapereditors under different names to express an opinion on an issue, creating the impression of widespread public feeling but being controlled by one central entity. Another example would be if people are hired to put on a protest under the auspices of being genuinely concerned citizens.
Spin
In public relations, "spin" is a sometimes pejorative term signifying a heavily biased portrayal in one's own favor of an event or situation. While traditional public relations may also rely on creative presentation of the facts, "spin" often—though not always—implies disingenuous, deceptive and/or highly manipulative tactics. Politicians are often accused of spin by commentators and political opponents, when they produce a counter argument or position.
The term is borrowed from ball sports such ascricket, where a spin bowler may impart spin on the ball during a delivery so that it will curve through the air or bounce in an advantageous manner.
The techniques of "spin" include:
Selectively presenting facts and quotes that support one's position ("cherry picking")
Non-denial denial
Phrasing in a way that assumes unproven truths
Euphemisms to disguise or promote one's agenda
Skilled practitioners of spin are sometimes called "spin doctors." Alastair Campbell, who was involved withBritishPrime MinisterTony Blair's public relations between 1994 and 2003, and also played a controversial role as press relations officer to the British and Irish Lionsrugbyteam during their 2005 tour ofNew Zealand, has often been referred to as a "spin doctor."
State-run media in many countries also engage in spin by selectively allowing news stories that are favorable to the government while censoring anything that could be considered critical. They may also usepropagandato indoctrinate or actively influence citizens' opinions. TheRussianstate-ownednatural gasfirm Gazprom has relied on favorable coverage in newspapers loyal to the government to give it an image boost. [11]
Other
Publicity events or publicity stunts
Talk shows – a public relations spokesperson (or his/her client) "does the circuit" by being interviewed on television and radio talk shows with audiences that the client wishes to reach
Books and other writings
Direct communication (carrying messages directly to constituents, rather than through the mass media ) for example through newsletters both in print and over the internet
Collateral literature, traditionally in print and now predominantly as websites
Speeches to constituent groups and professional organizations; receptions; seminars, and other events; personal appearances
Politics and civil society
Defining the opponent
A tactic used in political campaigns is known as "defining one's opponent." Opponents can be candidates, organizations, or other groups of people.
In the 2004U.S.presidential campaign,George W. Bushdefined opponent John Kerry as a "flip-flopper," among other characterizations, which were widely reported and repeated by the media, particularly the conservative media. [12]Similarly,George H. W. Bushcharacterized Michael Dukakis as weak oncrimeand as hopelessly liberal ("a card-carrying member of theACLU"). [13]In 1996, PresidentBill Clintonseized upon opponent Bob Dole's promise to take America back to a simpler time, promising in contrast to "build a bridge to the twenty-first century," thus painting Dole as a person who was somehow opposed to progress. [14]
In the debate overabortion, pro-abortion rights groups defined their opponents by defining themselves instead as "pro-choice." Anti-abortion rights groups responded in kind, branding themselves "pro-life." Extrapolating their respective rhetoric, pro-choice groups refer to their opponents as "anti-choice," and pro-life groups refer to their opponents as "anti-life." [15] [16]
Opponents ofsame-sexmarriagein the U.S. have declared that their opponents are not the couples suing for the right to marry in various state courts, but rather the judges who rule in their favor. They are now calling them "activist judges," implying that they impose their personalbeliefsinstead of objectively interpreting the law. This sidesteps the thorny issue of making millions of homosexual people an "enemy," and instead focuses attention on the much smaller judiciary, who all Americans can ostensibly agree should be prevented from being "activists" on the bench. [17]
InSpain, José Luis Rodríguez Zapatero was able to win the election for prime minister in 2004 after characterizing his opponents in the People's Party as weak on security following the bombing of Madrid's Athocha Station, killing 191 people. [18]
Managing language
If a politician or organization can use an apt phrase in relation to an issue, such as in interviews or news releases, the news media will often repeat it verbatim, thus furthering the message. The "New Deal" became a description of PresidentFranklin D. Roosevelt's anti-Depression economic plans, and "states' rights/state sovereignty" became near-code words for anti-civil rights legislation.
Entertainment and celebrity
Playing up weaknesses
Celebrities tend to be fans of the dictum "any publicity is good publicity." If a celebrity says or does something embarrassing, he or she will often turn it into a strength and make it part of his or her "image." This tactic is used just as much with favorable situations as much as with unfavorable ones.
Entertainer Jessica Simpson gained nationwide prominence when she wondered aloud on a realitytelevisionshow if "Chicken of the Sea" was actuallychickenortuna, garnering her a reputation for being slow-witted. However, within months she was being paid to endorse a brand of breath mints called "Liquid Ice." In the product's television commercial, Simpson replicated her earlier confusion by debating whether the mint is really liquid or ice, turning her nationwide embarrassment into a lucrative endorsement deal. [19]
Branching out
AsOscar Wildeis supposed to have said, the only thing worse than being talked about is not to be talked about. Many celebrities seem to take this truism to heart, because when their popularity (and income) wane, they take on new projects that attract media attention.
A number of American celebrities have transformed themselves into children's book authors, accompanied by much media coverage. A more traditional way of branching out is the celebrity restaurant. This is especially common among professional athletes, whose time in the spotlight is often limited by the physical demands of their jobs. Thus,basketballplayer Michael Jordan opened a restaurant inChicago.
Younger female celebrities are often drawn into thefashionworld. Hotel heiress Paris Hilton recently announced that she was starting her own line ofjewelry. Fading star Elizabeth Taylor launched a perfume called "White Diamonds," bringing renewed interest from the media.
Other celebrities have gravitated toward politics, including film stars Charlton Heston and notably Arnold Schwarzenegger, who succeeded in being elected governor ofCalifornia.
Ethical and social issues
One of the most controversial practices in public relations is the use of "front groups"—organizations that purport to serve a public cause while actually serving the interests of a client whose sponsorship may be obscured or concealed. The creation of front groups is an example of what public relations practitioners sometimes term the "third party technique"—the art of "putting your words in someone else's mouth."
The Center for Media & Democracy, a non-profit organization that monitors public relations activities it considers to be deceptive, has published numerous examples of this technique in practice, contending that public relations involves a "multi-billion dollar propaganda-for-hire industry" that works to "concoct and spin the news, organize phony 'grassroots' front groups, spy on citizens, and conspire with lobbyists and politicians to thwart democracy." [20]
Instances of the use of front groups as a public relations technique have been documented in many industries.Coalminingcorporations created environmental groups that contended that increasedcarbon dioxideemissions andglobal warmingwill contribute to plant growth and thus be beneficial, trade groups for bars have created and funded citizens' groups to attack anti-alcoholgroups, andtobaccocompanies have created and funded citizens' groups to advocate for tort reform and to attack personal injury lawyers. [21]
Nevertheless, many of the techniques used by public relations firms are drawn from the institutions and practices ofdemocracyitself. Persuasion, advocacy, andeducationare instruments through which individuals and organizations are entitled to express themselves in a free society, and many public relations practitioners are engaged in practices that are widely considered as beneficial, such as publicizing scientific research, promotingcharities, raising awareness of public health concerns, and other such issues in civil society.
Notes
↑ Clarke Caywood, The Handbook of Strategic Public Relations & Integrated Communications (New York: McGraw Hill, 1997, ISBN 0786311312 ).
↑ Edward Bernays, Propaganda (1928; Brooklyn, NY: Ig Publishing, 2004, ISBN 0970312598 ).
↑ Public Relations Society of America Member Code of Ethics 2000, Public Relations Society of America. Retrieved September 10, 2007.
↑ Public Relations Specialists, U.S. Department of Labor, 2006. Retrieved September 10, 2007.
↑ Ihor Eros, “PR firms cashing in on reputation and image building,” Kyiv Post .
↑ Scott M. Cutlip, Allen H. Center, & Glen M. Broom, Effective Public Relations (Englewood Cliffs, NJ: Prentice Hall, 2005, ISBN 0130082007 ).
↑ Allen H. Center and Patrick Jackson, Public Relations Practices (Upper Saddle River, NJ: Prentice Hall, 2002, ISBN 0136138039 ).
↑ Sheila C. Crifasi, "Everything's Coming Up Rosie," Public Relations Tactics 7(9) (2000).
↑ “Foreign Ministry Spokeswoman Jiang Yu's Regular Press Conference on 30 January, 2007,” Ministry of Foreign Affairs. Retrieved September 10, 2007.
↑ Lobbying Spending Database, OpenSecrets.org.
↑ Victor Yasmann, “Russia: Rebranding The Nation,” Radio Free Europe. Retrieved September 10, 2007.
↑ John Harris, "Despite Bush Flip-Flops, Kerry Gets Label," The Washington Post (September 23, 2004). Retrieved January 4, 2007.
↑ Debra Saunders, "Willie Horton's legacy," San Francisco Chronicle (December 12, 2002). Retrieved September 10, 2007.
↑ "Clinton Proposes Bridge To 21st Century," CNN AllPolitics (August 30, 1996). Retrieved September 10, 2007.
↑ Amanda Marcotte, et. al., “Exposing Anti-Choice Abortion Clinics,” AlterNet (May 1, 2006). Retrieved September 10, 2007.
↑ “The Anti-Life Movement,” Neural Gourmet (June 15, 2006). Retrieved September 10, 2007.
↑ Dahlia Lithwick, “Activist judges? What's in a name?” Seattle Post-Iintelligencer (August 18, 2004). Retrieved January 4, 2007.
↑ "Belated Realism," The Economist (January 18, 2007). Retrieved September 10, 2007.
↑ Steve Rogers, "Jessica Simpson gets an education on Chicken of the Sea," Reality TV World (October 21, 2003). Retrieved September 10, 2007.
↑ PR Watch , Center for Media and Democracy. Retrieved September 10, 2007.
↑ Corporate front groups, Democrats.com. Retrieved September 10, 2007.
References
Bernays, Edward. 1945. Public Relations . Boston, MA: Bellman Publishing Company.
Burson, Harold. 2004. E pluribus unum: The Making of Burson-Marsteller . New York: Burson-Marsteller.
Center, Allen H. & Patrick Jackson. [1995] 2002. Public Relations Practices , 5th ed. Upper Saddle River, NJ: Prentice Hall. ISBN 0136138039
Crifasi, Sheila C. 2000. "Everything's Coming Up Rosie." Public Relations Tactics 7(9).
Cutlip, Scott. 1994. The Unseen Power: Public Relations: A History . Mahwah, NJ: Lawrence Erlbaum Associates. ISBN 0805814647
Cutlip, Scott, Allen H. Center and Glen M. Broom. 2005. Effective Public Relations . Englewood Cliffs, NJ: Prentice-Hall, Inc. ISBN 0130082007
Ewen, Stuart. 1996. PR!: A Social History of Spin . New York: Basic Books. ISBN 0465061680
Grunig, James E. & Todd Hunt. 1984. Managing Public Relations . New York: Holt, Rinehart and Winston. ISBN 0030583373
Kelly, Kathleen S. 1998. Effective Fund Raising Management . Mahwah, NJ: Lawrence Erlbaum Associates. ISBN 0805820108
Macnamara, Jim. 2005. Jim Macnamara's Public Relations Handbook , 5th ed. Melbourne: Information Australia.
Nelson, Joyce. 1989. Sultans of Sleaze: Public Relations and the Media . Toronto: Between the Lines. ISBN 0921284225
Phillips, David. 2001. Online Public Relations . London: Kogan Page. ISBN 0749435100
Stauber, John C. 1995. Toxic Sludge is Good for You: Lies, Damn Lies, and the Public Relations Industry . Monroe, ME: Common Courage Press. ISBN 1567510612
Tye, Larry. 1998. The Father of Spin: Edward L. Bernays and the Birth of Public Relations . New York: Crown Publishers. ISBN 0517704358
Stoykov, Lubomir & Valeria Pacheva. 2005. Public Relations and Business Communication . Sofia: Ot Igla Do Konetz. ISBN 9549799093
Chartered Institute of Public Relations
“The spin room - oily engine of the political meat grinder,” by Jerry Lanson, Christian Science Monitor (December 12, 2003)
Council of Public Relations Firms
Free Publicity – The Newsletter for PR Hungry Businesses
Institute for Public Relations
International Association of Business Communicators
The Museum of Public Relations
O'Dwyer's PR Daily
PR Watch
PR Week
Public Relations Institute of Australia
Public Relations Society of America
SourceWatch.org
Spinwatch
Annenberg Political Fact Check – A nonpartisan, nonprofit consumer advocate that monitors the factual accuracy of statements by political players in the United States
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Vaginal Vault Suspension
Overview
Vaginal prolapse is the herniation of the pelvic organs to or beyond the vaginal walls. It is reported to be the most common reason for hysterectomy in women over age 50 and that a half million procedures are performed for prolapse in the United States annually.[1] The number of women with pelvic organ prolapse who are managed without hospitalization and surgery and the number of women with prolapse who never seek medical treatment is not known. Incidence and prevalence estimates based on surgical procedure rates almost certainly underestimate the magnitude of the problem.
Maintenance of normal vaginal anatomy depends on the interrelationships of intact pelvic floor neuromusculature, ligaments, and fascia. This complex relationship of vaginal support is perhaps least understood at the vaginal apex or vault. Without proper identification and correction of vaginal vault prolapse, surgical correction of the other vaginal compartments is recognized to likely fail. This in part contributes to the 29.2% reoperation rate of women who undergo pelvic floor reconstruction.[2]
In a nonhysterectomized woman, the vault, or apex, is located posterior and superior to the cervix (see the image below). After a hysterectomy, the scar site assumes the position of the vaginal apex or vault.
Normal anatomy. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography © 2002-2011. All Rights Reserved.
Relevant Anatomy
The vaginal apex is the site at which multiple vaginal support structures converge. If the cervix is present, it serves as a strong attachment point for the ligaments and fascia. A woman who has had a prior hysterectomy may not have a strong attachment point, leading to vault support weakness and potential prolapse.
DeLancey described the connective tissue support of the vagina as having 3 levels. Level I support is composed of the uterosacral/cardinal ligament complex that originates at the cervix and upper vagina and inserts at the pelvic sidewall and sacrum. This ligamentous complex suspends the uterus and upper vagina in its normal orientation. It helps maintain vaginal length and normal vaginal axis. Loss of level I support contributes to prolapse of the vaginal apex.
Level II support comprises the paravaginal attachments that run the length of the vagina and are suspended by the arcus tendineus fasciae pelvis (ATFP), or lateral pelvic white line. Loss of level II support contributes to cystocele (anterior vaginal prolapse).
Level III support is provided by the perineal membrane, perineal body, and superficial and deep perineal muscles. These structures support and maintain the normal anatomical position of the urethra and distal third of the vagina. Disruption of this level of support anteriorly can result in urethral hypermobility and stress incontinence and posteriorly may result in a rectocele or perineocele.
As stated above, it is the level I support, the uterosacral/cardinal ligament complex, that plays the most important role in maintaining vaginal vault support.
The endopelvic fascia is the fibromuscular tissue layer that underlies the vaginal epithelium. This layer envelopes the entire vaginal canal, extending from apex to perineum and arcus tendineus to arcus tendineus. The endopelvic fascia helps maintain the integrity of the vaginal walls. Therefore, a tear in this layer causes herniation of the underlying tissue. If a tear exists at the level of the vaginal apex, an enterocele can develop anteriorly or posteriorly, further leading to the breakdown of apical integrity. Reconstructive surgeons need to understand the importance of this layer and its reattachment to the vaginal apex in order to correct anterior or posterior vaginal wall prolapse. If the fascia is of poor quality, a graft may be required to reinforce the repair.
Contraindications
Contraindications to prolapse correction are based on the patient’s medical comorbidities and the risk they pose to surgery. Regional anesthesia can be used to lessen risk when surgery is performed vaginally. Appropriate surgical clearance, use of pulsatile anti-embolism stockings, prophylactic antibiotics, and diligent positioning using Allen stirrups help minimize perioperative complications. Atrophic, thinned, or ulcerated vaginal mucosa should be pretreated with local estrogen for an appropriate period of time.
Problem
Multiple components to vaginal vault support exist, including uterosacral and cardinal ligaments, endopelvic fascial envelopes, and lateral paravaginal attachments. The relationship between these components is both dynamic and static, and, when they are damaged, vaginal vault prolapse ensues. In a woman with intact uterine support, all of these structures attach to the uterus and provide appropriate support. If during a hysterectomy these structures are not firmly re-attached to the vaginal cuff, vault prolapse can occur.
Frequency
Data from women enrolled in the Women’s Health Initiative reported that in women with an intact uterus, 41.1% had some form of prolapse and 14.2% had uterine prolapse. Of those women who had a prior hysterectomy, almost 38% had some form of prolapse.[3]
In women who have had a prior hysterectomy, the incidence of prolapse requiring surgical correction is 1% at 3 years and 5% at 17 years following their hysterectomy.[4]
The risk of prolapse increases with advancing age, and the incidence of prolapse likely increases as life expectancy does.
Etiology
Vaginal vault prolapse is a complex disorder not usually caused by one inciting incident. Rather, it usually results from a series of events that occur over a women’s lifetime. Collagen disorders and race can play a role in the development of vault prolapse, as can childbirth, menopause, and previous pelvic floor surgery that disrupted the apical support system. Any condition that chronically raises intra-abdominal pressure, such as chronic obstructive pulmonary disease (COPD), chronic constipation, and heavy lifting, can also contribute to the breakdown of vault support.
Presentation
A woman’s symptoms are largely based on the severity of her prolapse. With minimal or stage 1 prolapse, a woman may be asymptomatic and not need any active intervention. As the prolapse progresses, women may experience vaginal fullness, lower back pain, urinary or defecatory dysfunction, dyspareunia, and pelvic pain. As prolapse worsens, the vault becomes exteriorized with a palpable and visible bulge which may bleed from mucosal ulcerations.
Evaluation
Accurate identification of vaginal vault support is critical for the correction of vaginal prolapse. Even to the experienced clinician, identifying apical prolapse (especially in the presence of a large cystocele or enterocele) is difficult (see image below). Most importantly, if the apical prolapse is not corrected at the time of the initial prolapse repair surgery, prompt recurrence of the prolapse may occur. It is also important to help guide the surgical approach.
Cystocele and vault prolapse with visible dimples.
The presence of an exposed cervix does not necessarily mean vaginal vault prolapse exists. Cervical hypertrophy can cause the cervix to protrude from the vaginal introitus while leaving the vault well supported. To evaluate, the posterior blade of a bivalved speculum is placed in the posterior fornix, and the patient is asked to Valsalva while the blade is slowly removed. If vault prolapse exists, the uterus descends further as the speculum is removed, and reinsertion of the speculum resuspends the uterus. If the vault is well supported, the uterus stays in place despite Valsalva efforts.
In a woman who has undergone hysterectomy, the primary goal during the vaginal examination is to identify the apical scar tissue resulting from the prior hysterectomy. Significant prolapse may have stretched the apical scar tissue band making it difficult to identify. A bivalve speculum helps in visualization of the apex, but redundant vaginal mucosa associated with substantial prolapse may make this challenging. In most cases, the site of the prior uterosacral cardinal ligament complex can usually be identified as dimples on the lateral edges of the apex.
Using 2 right-angle speculum blades, or one blade to retract the anterior wall and the examiners hand to retract the posterior wall, the patient is asked to Valsalva and the degree of vault prolapse is assessed. The tip of the speculum can then be placed between the dimples to elevate the vault and assess the degree of vault prolapse. This can also be done with the examiner’s hand by identifying the dimples and elevating them to their ipsilateral spines.
As stated above, the evaluation should guide the surgeon in planning the most appropriate surgical approach. Most reconstructive surgeons prefer a vaginal approach. However, the decision should be made based on what is best for the patient and her anatomic alterations.
The importance of sexual function should be assessed. If the patient reports vaginal sexual function is a key consideration, then a sacrocolpopexy should be the primary consideration, given it will avoid any vaginal incisions and potentially avoid any vaginal shortening or narrowing.[5] The examiner should also assess vaginal length. A woman whose apex reaches the ischial spines without difficulty will likely be successful with a vaginal procedure. If the apex does not reach the spines or reaches well beyond them, she may be better served with either an obliterative procedure or abdominal colpopexy.
In today’s age of frequent graft use, the patient’s history of prior reconstructive surgery should be evaluated. This may lead to scarring or fibrosis around the sacral promontory or sacrospinous ligaments. The presence of a paravaginal defect should also be assessed, as this would be better repaired abdominally.
The quality of the patient’s tissue and the subsequent need for a graft at the time of the surgical procedure should also be assessed. Lastly, many women with pelvic organ prolapse also have coexistent colorectal problems that may require surgical correction. If this is the case, the surgical approach that would best accommodate both procedures should be considered.
Classification
Most clinicians grade prolapse based on either the Baden Walker halfway system or the Pelvic Organ Prolapse Quantification System (POP-Q) classification. The POP-Q classifications are as follows:
Stage 0 - No prolapse
Stage I - Descent of the most distal portion of the prolapse more than 1 cm above the hymen
Stage II - Descent of the most distal portion of the prolapse between 1 cm above and 1 cm below the hymen
Stage III - Descent of the most distal portion of the prolapse beyond 1 cm below the hymen but less than total vaginal length (TVL) -2 cm
Stage IV- Total or complete vaginal eversion
Surgical Treatment
The goal of surgery is the restoration of vaginal vault support, as well as correction of all pelvic floor defects in order to have the most successful outcome.[6, 7] Therefore, bladder function, sexual function, and anterior and posterior support should all be assessed prior to surgery and corrected along with apical support.
Vaginal vault support procedures can be divided into abdominal and vaginal approaches. The decision is based on the preoperative physical examination and the patient’s sexual function.
Vaginal Procedures
McCall culdoplasty
This technique was introduced by McCall in 1957 and involves plication of the uterosacral ligaments in the midline while reefing the cul-de-sac peritoneum, including full thickness of the apical vaginal mucosa, in a posterior culdoplasty. It is typically done at the time of vaginal hysterectomy and uses nonabsorbable sutures, although delayed absorbable sutures may be used. As a general rule, the authors try to place the uppermost suture on the uterosacral ligament at a distance from the cuff equal to the amount of vault prolapse present (see image below).
McCall culdoplasty.
The ureters lay approximately 1-2 cm lateral to the uterosacral ligaments at the level of the cervix, so being cautious to not kink or injure the ureters when placing the sutures is important. Cystoscopy with visualization of ureteral patency, usually with administration of intravenous indigo carmine, is recommended following the procedure.
Webb et al followed patients up to 8.8 years and reported 71% did not require any further prolapse operation. They also found 82% were "very satisfied" or "somewhat satisfied" with their results.[8]
Uterosacral ligament suspension
Reattaching the uterosacral ligaments to the vaginal apex is likely the most physiologic approach to vault prolapse (see image below). The technique involves opening the vaginal wall over the apical defect into the peritoneal cavity and identifying the pubocervical fascia, rectovaginal fascia, and uterosacral ligaments.
A permanent 1-0 suture as well as one delayed absorbable 1-0 suture is placed in the posteromedial aspect of each uterosacral ligament 1-2 cm proximal and medial to each ischial spine. Next, one arm of the permanent and the delayed absorbable suture are placed through the pubocervical and rectovaginal fascia as well as the vaginal epithelium at the apex. After any additional vaginal repairs are completed, the sutures are tied, elevating the vaginal vault. If extensive vaginal prolapse exists, redundant peritoneal tissue can sometimes make identifying the uterosacral ligaments difficult.
Uterosacral ligament suspension. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography © 2002-2011. All Rights Reserved.
Success rates for uterosacral ligament suspension are 87% to 90%, but ureteral injury has been reported to be as high as 11%, making it a limiting factor in the success of the technique.[9, 10] Given this reported high complication rate, cystoscopy following suspension is essential.
Iliococcygeus suspension
This technique involves elevating the apex to the iliococcygeus muscle overlying fascia along the lateral pelvic sidewall. It is a safe and simple procedure and can be done without any vaginal incision by placing a monofilament permanent suture into the muscle through the vaginal wall either unilaterally or bilaterally. It can be used when isolated unilateral vaginal vault prolapse occurs, which can develop following a unilateral sacrospinous fixation or as a result of a high unilateral paravaginal defect. The presence of a permanent suture at the vaginal apex can potentially cause dyspareunia, so this technique should be used with caution in women who are sexually active. It is most useful as a salvage procedure for unilateral apical prolapse.
The suspension can also be performed at the time of a posterior wall dissection in which the sutures are placed into the fascia overlying the iliococcygeus, anterior to the ischial spine along the arcus tendineus fascia pelvis, and incorporating the pubocervical fascia anteriorly and the rectovaginal fascia posteriorly.
Shull et al reported a 95% cure rate of vault prolapse following iliococcygeus suspension; however, he also found a 14% rate of prolapse at other sites during the follow-up period.[11] A randomized controlled trial comparing iliococcygeus suspension with sacrospinous fixation demonstrated similar outcomes.[12]
Sacrospinous fixation
Suspension of the vaginal apex to the sacrospinous ligaments is one of the most commonly performed vault suspension procedures (see image below). It can be performed unilaterally or bilaterally, but bilateral fixation avoids vaginal axis deviation, giving a more physiologic correction of the vaginal vault prolapse.
Bilateral sacrospinous fixation (SSF). Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography © 2002-2011. All Rights Reserved.
Sacrospinous fixation is performed by entering the pararectal space through a posterior wall dissection. The sacrospinous ligaments are identified, running from the ischial spine to the sacrum. Next, 2 nonabsorbable sutures are placed through the ligament, not around it, as the pudendal nerve and vessels sit behind the ligament and damage to these structures can cause significant morbidity. The first suture is placed 2 cm medial to the ischial spine, and the second 1 cm medial to the first. Each suture is then passed through the vaginal apex so that when tied the apex is reapproximated to the ligament. Any additional reconstructive procedures are then performed.
The success rate of sacrospinous fixation is greater than 90% in multiple series.[13] The concern lies in the exaggerated horizontal axis in which the procedure leaves the vagina, which increases force on the anterior compartment with increases in abdominal pressure. This is especially true if an anti-incontinence procedure is performed at the same time. The rate of cystocele formation following sacrospinous fixation is reported at 20%-30%.[14] Other complications of the procedure include hemorrhage, vaginal shortening, sexual dysfunction, and buttock pain.
A Danish study, which included 744 patients with a previous hysterectomy, found that significantly higher numbers of repeat surgeries were performed after sacrospinous ligament fixation than after ipsilateral uterosacral ligament suspension. After 5 years, 30.6% of patients who underwent sacrospinous fixation and 12.4% of those who underwent uterosacral ligament suspension required repeated surgery.[15]
Obliterative Procedures
Colpocleisis
This is the simplest treatment for advanced prolapse in women who are not, and will not, be sexually active. A LeFort colpocleisis involves denuding rectangles of vaginal epithelium on the anterior and posterior vaginal wall and then approximating them front to back to one another. This is combined with a high perineoplasty. The success rate for LeFort is above 95% and postoperative pain is minimal.[16]
Vaginal Kits
Vaginal mesh kits can be divided into trocar-based kits that use a transobturator or transgluteal approach to suspend the vagina and nontrocar kits that use a transvaginal fixation method. The trocar guided kits include the Prolift (Ethicon, Somerville, NJ), Apogee and Perigee (American Medical Systems, Minnetonka, MN), and Avulta (CR Bard, Murray Hill, NJ).
Trocar guided kits use a precut sheet of graft material with arms that are used for fixation.[17] Nontrocar kits include Elevate (American Medical Systems, Minnetonka, MN) and Pinnacle and Uphold (Boston Scientific, Natick, MA). With either type of kit some basic surgical principles apply; the vagina should be well estrogenized before surgery and any vaginal pessary should be removed for 2 weeks prior to surgery to avoid any vaginal epithelium irritation. Exposure of the correct vesicovaginal and rectovaginal planes can be accomplished through hydrodissection; lidocaine with epinephrine, dilute pitressin, or normal saline can be used. Correct hydrodissection should create a bubble in the avascular space. Mesh should be placed loosely because it can contract up to 20% after placement, which can compromise vaginal length and caliber.
On July 13, 2011, the US Food and Drug Administration (FDA) issued a statement that serious complications are not rare with the use of surgical mesh in transvaginal repair of pelvic organ prolapse. The FDA reviewed the literature from 1996-2011 to evaluate safety and effectiveness and found surgical mesh in the transvaginal repair of pelvic organ prolapse does not improve symptoms or quality of life more than nonmesh repair. The review found that the most common complication was erosion of the mesh through the vagina, which can take multiple surgeries to repair and can be debilitating in some women. Mesh contraction was also reported, which causes vaginal shortening, tightening, and pain.
The FDA’s update states, “Both mesh erosion and mesh contraction may lead to severe pelvic pain, painful sexual intercourse or an inability to engage in sexual intercourse. Also, men may experience irritation and pain to the penis during sexual intercourse when the mesh is exposed in mesh erosion.” The FDA is continuing to review the literature regarding surgical mesh in the treatment of stress urinary incontinence and will issue a report at a later date. See the full update regarding surgical mesh in pelvic organ prolapse here: FDA Safety Communication: Update on Serious Complications Associated with Transvaginal Placement of Surgical Mesh for Pelvic Organ Prolapse.
In 2016, the FDA reclassified surgical mesh for transvaginal repair of POP from a moderate-risk device (class II) to a high-risk one (class III) and gave manufacturers 30 months to prove that their products are safe and effective.[18]
On April 16, 2019, the FDA mandated that all manufacturers of surgical mesh intended for transvaginal repair of anterior compartment prolapse (cystocele) stop selling and distributing their products. The FDA has determined that the vaginal mesh kit manufacturers have not demonstrated reasonable assurance of safety and effectiveness for these devices, which is the premarket standard that now applies to them since the FDA reclassified them into class III (high risk) in 2016.[19]
Apogee vaginal vault suspension
The Apogee system (American Medical Systems, Minnetonka, MN) creates neoligaments that are analogous to the Cardinal by anchoring graft arms at sites adjacent to the ischial spines, at the attachment of the arcus tendineus (see the image below).
Apogee vault suspension kit: synthetic and biologic variations.
The technique is performed by accessing the pararectal space and palpating the ischial spine and arcus tendineus. A modified SPARC needle is passed through a pararectal incision that is made 3 cm lateral and 3 cm posterior to the anus. The needle is then guided through the ipsilateral levators and then through the iliococcygeus muscle, ultimately anchoring into the arcus tendineus at the level of the ischial spine. The exact anchoring point for the Apogee is 0.5-1 cm anterior to the ischial spine through the white line.
The polypropylene mesh arms are attached to the needle and brought out through the para-anal incision. The graft is secured to the vaginal apex and the perineal body by interrupted delayed absorbable sutures. This re-creates apical support from ischial spine to ischial spine and gives a physiologic vaginal axis. Vaginal length averages 7-9 cm and success rate is 88% to 100% with minimal complications[20] It is available in synthetic polypropylene mesh and biologic porcine dermis.
Prolift
The Prolift system (Ethicon, Somerville, NJ) uses a slightly curved C-shaped trocar to anchor either into the arcus tendineus fascia pelvis (ATFP) or the sacrospinous ligament, depending on the approach taken (see the images below). The graft material is then laid down in a tension-free fashion.
Elmér et al found that the anatomic cure rate at one year for anterior repair was 79%, 82% for posterior repair and for combined anterior, and posterior repair cure rate was 81% and 86%, respectively. They also found that mesh erosions occurred in 11% of the cases.[21] In another prospective trial, anatomic cure rate at 12 months was found to be 91% with a 15% mesh erosion rate.[22]
Prolift multicenter trial, Europe.
Prolift 1-year data.
Prolift 1-year data.
Avaulta
The Avaulta System (CR Bard, Covington, GA) is another trocar-based vaginal mesh kit. It is similar to the above mentioned kits as trocars are used to fixate synthetic mesh (see the image below). Dissection is also similar and is done up to the level of the ischial spines. The Anterior kit fixation point is 1-2 cm lateral and 3 cm posterior to the ATFP near the ischial spine. The Posterior fixation point is the sacrospinous ligament at the ischial spine. The Avaulta comes as a posterior or an anterior kit. The posterior kit addresses both the vaginal vault and the posterior vaginal compartment while the anterior kit is used to treat cystoceles.
A recent trial that followed patients out for an average of 14 months found a surgical cure rate of 81% using a definition of any POP-Q point greater than 0 or any reports of vaginal bulge. They reported a mesh erosion rate of 11.7% and de novo pain in 3.3% of patients.[23]
Avaulta: 1-year results.
Elevate
The Elevate apical prolapse repair system (American Medical Systems, Minnetonka, MN) is a single-incision procedure that uses small polypropylene fixation anchors to affix polypropylene mesh arms to the sacrospinous ligaments (see image below). The advantage is that the anchors are able to access the sacrospinous ligament without going through or behind it, avoiding potential neurovascular complications. Additionally, the Elevate does not use external needle passage avoiding the risk of long term postoperative pain from banding or tension.
The procedure is started with a midline vaginal incision along the anterior or posterior vaginal walls, which is used to access the sacrospinous ligaments and ischial spine through the paravaginal space. Next, using either a retractor or the operator’s hand, the rectum is swept medially for safety and the needle tip is positioned onto the ligament approximately 2 cm medial to the ischial spine to avoid neurovascular injury. The loose eyelets of the graft then slide over the fixation rods until they engage the mesh part of the fixating arms. The graft is then trimmed and the apical portion of the mesh is fixated to either the cervix or the vaginal apex. Final tensioning is then done and the fixating arms trimmed. It is important to ensure that the mesh is flat and the edges do not roll out.
A recent prospective multicenter trial demonstrated a cure rate of 92.5% at 12 months for the posterior wall and 89.2% apical cure rate. Extrusion was seen in 6.5% of subjects.[24]
Elevate posterior.
Pinnacle and Uphold
The advantage to nontrocar kits is the complete vaginal approach. These kits avoid the transobturator space so surgeons who are not familiar or comfortable with the area can still use a vaginal mesh kit for suspension of the vagina. With a total vaginal approach, no blind procedures exist; the mesh appendage placement can be done under direct visualization.
The dissection for both the Uphold[25] and the Pinnacle (Boston Scientific, Natick, MA) are similar to that described for the Elevate system (American Medical Systems, Minnetonka, MN). Once the sacrospinous ligament is palpated and the insertion point has been cleaned off, the ligament is penetrated using the Capio transvaginal capturing device (Boston Scientific, Natick, MA) to suture the mesh arms to the sacrospinous ligament and the ATFP. The mesh arms are slowly and loosely tensioned and the mesh is sutured flat. The vagina is then minimally trimmed, if needed, keeping in mind that the epithelium will contract as it heals, and closed.
Abdominal Procedures
Abdominal sacral colpopexy
This is considered by most surgeons to be the criterion standard procedure for repair of vaginal vault prolapse (see image below).[26] Although the procedure requires an abdominal incision and has a higher overall morbidity compared to vaginal procedures, its longevity and physiologic results as well as having the least risk of sexual dysfunction and dyspareunia make it very appealing.
Abdominal sacrocolpopexy. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography © 2002-2011. All Rights Reserved.
The procedure is begun through an abdominal incision then exposing the sacral promontory by incising the peritoneum between the right ureter and the sigmoid colon. Sutures (2-0 polypropylene) or bone anchors are used to place 2-3 sacral suspensory sutures. Next, the vaginal apex is identified using either the operator’s hand or the obturator of an end-to-end anastomosis rectal tool. The bladder and peritoneum are dissected off the anterior vaginal wall and any fascial tears are identified and repaired.
The graft used for the procedure is synthetic polypropylene graft with a long arm (4-5 cm) that will extend down the posterior vagina, and a shorter end (2-3 cm) that is secured to the anterior vaginal wall. Typically, 3 rows of 2-0 polypropylene sutures are placed along the back wall, and 2 rows are placed along the anterior. Once secured to the graft the vault can be suspended to the sacral promontory with minimal tension. Prior to suspending the apex, a culdoplasty should be performed to obliterate the cul-de-sac and prevent future enterocele formation.
After the vault is suspended, the abdomen is copiously irrigated and the peritoneum closed.
The major complications related to the procedure are hemorrhage from the sacral promontory and postoperative ileus. The risk of bleeding can be minimized by using bone anchors on the sacral promontory.
Postoperative details
Patients need to avoid any heavy lifting (over 5 pounds) for at least 6 weeks after surgery. At their 6-week postoperative visit, the surgical site is assessed, and, if the area is well healed, the patient is instructed to progressively return to their usual daily activities. Postmenopausal patients are instructed to use vaginal estrogen (we use 1 g twice weekly) to maintain integrity of the pelvic tissues.
Follow-up
Patients are instructed to follow-up 3 months after they return to normal activities to assess the repair. The authors also continually follow our patients to evaluate the integrity of the repair.
Complications
Abdominal approach
Bleeding is the most serious complication of sacral colpopexy through injury to the presacral venous plexus or the middle sacral artery. Other injuries includes ureteral injury and graft erosion. The erosion rate has been reported to be 3% for sacral colpopexy.
Vaginal approach
The complications associated with vaginal vault surgery are ureteral injury, injury to the lower urinary tract, fistula formation, pelvic infection, bowel injury, and graft exposure. Sacrospinous ligament fixation carries the additional risk of hemorrhage and nerve injury through the pudendal neurovascular bundle. Recurrence of vault prolapse is also a potential complication.
Mesh kits
Mesh extrusion is always a potential complication with vaginal mesh kits at a rate of approximately 10% (7%-18%).[27] Symptoms of mesh exposure or extrusion are vaginal discharge, persistent bleeding, pain, dyspareunia, partner pain, dysuria, and recurrent urinary tract infections. Examination reveals any exposed mesh. Management can be conservative with vaginal estrogen or trimming of the mesh in the office. If conservative measures fail or the exposure is too large to be managed in the office, excision with operative vaginal closure after excision of the exposed mesh may be required.
Summary
Pelvic reconstructive surgeons should be extremely familiar with the evaluation and treatment of vaginal vault prolapse. Multiple techniques are available for the restoration of vaginal vault support and most are very effective at suspending the vaginal apex. The primary challenge is identifying the vaginal vault in women with advanced degrees of vaginal prolapse. The surgical approach should be based on both patient’s needs and the surgeon’s evaluation.
Contributor Information and Disclosures
Author
G Willy Davila, MD
Chairman, Department of Gynecology, Section of Urogynecology and Reconstructive Pelvic Surgery, Cleveland Clinic Florida
G Willy Davila, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Colorado Medical Society, Florida Medical Association
Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: AMS/Astora; Astellas, Uroplasty/Cogentix<br/>Received research grant from: Pfizer; A-Cell; Coloplast; Cook Myocyte.
Chief Editor
Christine Isaacs, MD
Associate Professor, Department of Obstetrics and Gynecology, Division Head, General Obstetrics and Gynecology, Medical Director of Midwifery Services, Virginia Commonwealth University School of Medicine
Christine Isaacs, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists
Disclosure: Nothing to disclose.
References
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Hendrix SL, Clark A, Nygaard I, Aragaki A, Barnabei V, McTiernan A. Pelvic organ prolapse in the Women's Health Initiative: gravity and gravidity. Am J Obstet Gynecol. 2002 Jun. 186(6):1160-6. [QxMD MEDLINE Link].
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Rondini C, Braun H, Alvarez J, et al. High uterosacral vault suspension vs Sacrocolpopexy for treating apical defects: a randomized controlled trial with twelve months follow-up. Int Urogynecol J. 2015 Aug. 26(8):1131-8. [QxMD MEDLINE Link].
Maher C, Feiner B, Baessler K, Schmid C. Surgical management of pelvic organ prolapse in women. Cochrane Database Syst Rev. 2013 Apr 30. 4:CD004014. [QxMD MEDLINE Link].
Khunda A, Vashisht A, Cutner A. New procedures for uterine prolapse. Best Pract Res Clin Obstet Gynaecol. 2013 Jun. 27(3):363-79. [QxMD MEDLINE Link].
Webb MJ, Aronson MP, Ferguson LK, Lee RA. Posthysterectomy vaginal vault prolapse: primary repair in 693 patients. Obstet Gynecol. 1998 Aug. 92(2):281-5. [QxMD MEDLINE Link].
Barber MD, Visco AG, Weidner AC, Amundsen CL, Bump RC. Bilateral uterosacral ligament vaginal vault suspension with site-specific endopelvic fascia defect repair for treatment of pelvic organ prolapse. Am J Obstet Gynecol. 2000 Dec. 183(6):1402-10; discussion 1410-1. [QxMD MEDLINE Link].
Edenfield AL, Amundsen CL, Weidner AC, Wu JM, George A, Siddiqui NY. Vaginal prolapse recurrence after uterosacral ligament suspension in normal-weight compared with overweight and obese women. Obstet Gynecol. 2013 Mar. 121(3):554-9. [QxMD MEDLINE Link].
Shull BL, Capen CV, Riggs MW, Kuehl TJ. Bilateral attachment of the vaginal cuff to iliococcygeus fascia: an effective method of cuff suspension. Am J Obstet Gynecol. 1993 Jun. 168(6 Pt 1):1669-74; discussion 1674-7. [QxMD MEDLINE Link].
Maher CF, Murray CJ, Carey MP, Dwyer PL, Ugoni AM. Iliococcygeus or sacrospinous fixation for vaginal vault prolapse. Obstet Gynecol. 2001 Jul. 98(1):40-4. [QxMD MEDLINE Link].
Guerette N, Davila GW. Sacrospinous fixation. Does reinforcement of the vaginal vault improve outcome?. Int Urogynecol J. 2003. (suppl 1):S69.
Pollak JT, Togami J, Davila GW, Ghoniem G. Vaginal axis and vault position following vaginal vault suspension. J Pelvic Med Surg. 2004. 10(suppl 1):S39.
Husby KR, Larsen MD, Lose G, Klarskov N. Surgical repair of vaginal vault prolapse; a comparison between ipsilateral uterosacral ligament suspension and sacrospinous ligament fixation-a nationwide cohort study. Int Urogynecol J. 2020 Sep 8. [QxMD MEDLINE Link].
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Dubuisson J, Eperon I, Dällenbach P, Dubuisson JB. Laparoscopic repair of vaginal vault prolapse by lateral suspension with mesh. Arch Gynecol Obstet. 2013 Feb. 287(2):307-12. [QxMD MEDLINE Link].
FDA strengthens requirements for surgical mesh for the transvaginal repair of pelvic organ prolapse to address safety risks. U.S. Food and Drug Administration. Available at https://www.fda.gov/news-events/press-announcements/fda-strengthens-requirements-surgical-mesh-transvaginal-repair-pelvic-organ-prolapse-address-safety. 2016 Jan 04; Accessed: January 15, 2021.
Urogynecologic surgical mesh implants. U.S. Food and Drug Administration. Available at https://www.fda.gov/medical-devices/implants-and-prosthetics/urogynecologic-surgical-mesh-implants. 2019 Jul 10; Accessed: January 15, 2021.
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| https://emedicine.medscape.com/article/1848619-print |
STATE v. GORE | 901 A.2d 1251 (2006) | 2d125112082 | Leagle.com
LAVINE J. The defendant Curtis Gore was charged with assault of an employee of the department of correction in violation...2d125112082
STATE v. GORE
No. 26304.
View Case
Cited Cases
Citing Case
901 A.2d 1251 (2006)
96 Conn.App. 758
STATE of Connecticut
v.
Curtis GORE.
Appellate Court of Connecticut. https://leagle.com/images/logo.png
Argued April 20, 2006.
Decided August 1, 2006.
Attorney(s) appearing for the Case
Kent Drager, senior assistant public defender, for the appellant (defendant).
Melissa Streeto Brechlin, assistant state's attorney, with whom, on the brief, were Thomas Griffin, supervisory assistant state's attorney, and Stephen M. Carney, senior assistant state's attorney, for the appellee (state).
DIPENTIMA, GRUENDEL and LAVINE, Js.
Appellate Court of Connecticut.
LAVINE, J.
The defendant, Curtis Gore, was charged with assault of an employee of the department of correction in violation of General Statutes § 53a-167c(a)(1). The defendant pleaded not guilty and elected to be tried by the court. Following a trial, the court found him guilty of assault of an employee of the department of correction. On appeal, the defendant claims that (1) the evidence was insufficient to support his conviction, (2) the court failed to ensure that his waiver of his constitutional right to a jury trial was knowing, intelligent and voluntary, and (3) the court improperly admitted certain testimony into evidence. We agree with the defendant's second claim and conclude that the record is devoid
[901 A.2d 1253]
of any evidence that he made a knowing, intelligent and voluntary waiver of his right to a jury trial. We reverse the judgment of conviction on that basis.
The court reasonably could have found the following facts. In August, 2003, the defendant was incarcerated at the Corrigan Correctional Institution in Uncasville and assigned as an inmate to the restrictive housing unit. The unit, consisting of eleven cells that are parallel to one another, functions as a segregation area in which inmates remain confined to their cells for twenty-three hours a day. In the center of the unit is a protected glass area, known as the control station, where a correction employee monitors the inmates. During second shift duty, there is one correction employee who stays in the control station and two correction employees who patrol the outside of the cells. Each individual cell door contains a small metal rectangular sliding door that is utilized by the correction employees to deliver meals to the inmates.
On August 18, 2004, correction employees Christopher Hanney, Jason Ware and Joseph Iozzia were assigned to second shift duty at the restrictive unit. Iozzia was assigned to the control station, and Hanney and Ware were patrolling the area outside the cells. All three employees were informed prior to beginning their shift that the defendant had been disruptive all day because he was upset that he would not be receiving a vegetarian meal. The defendant had failed to put in the proper request for the vegetarian meal.
At approximately 4:05 p.m., Hanney and Ware began delivering the meals to the inmates through the sliding doors. This procedure involved Ware's unlocking the door and sliding it open, providing each inmate with a beverage and leaving the door open for Hanney to slide the meal through. When Hanney arrived at the defendant's door, he asked the defendant if he wanted his meal. The defendant initially refused to eat the regular meal but then told Hanney that he would eat it. The defendant then stuck his hands through the door, which prevented Hanney from sliding the food tray through the door. Hanney repeatedly ordered the defendant to pull his hands back through the door, so that he could deliver the food tray. The defendant refused to move his hands. Ware joined Hanney, and they both threatened to close the sliding door if the defendant did not move his hands. The defendant refused to comply with the order, prompting Hanney to attempt to close the sliding door. As he attempted to do so, the defendant grabbed Hanney's hands, and using his fingernails, cut Hanney's fingers, hands and wrist. Hanney was able to remove his hands from the defendant's grip and closed the sliding door. The defendant was charged with assault of an employee of the department of correction, tried, convicted and ultimately sentenced. This appeal followed. Additional facts will be set forth as necessary.
I
The defendant claims that the evidence was insufficient to support the court's finding of guilt on the charge of assault of an employee of the department of correction. Specifically, the defendant argues that the state failed to prove beyond a reasonable doubt that he had the specific intent to prevent Hanney from performing his duty. 1We are not persuaded.
[901 A.2d 1254]
The defendant failed to move for a judgment of acquittal at the conclusion of the state's case or before the case was submitted to the court or to move to set aside the finding of guilt and now seeks to prevail on appeal under State v. Golding,213 Conn. 233, 239-40, 567 A.2d 823 (1989). Goldingreview is not necessary to resolve the defendant's claim. See State v. Ashe,74 Conn.App. 511, 514, 812 A.2d 194, cert. denied,262 Conn. 949, 817 A.2d 108 (2003). "Unpreserved sufficiency claims are reviewable on appeal because such claims implicate a defendant's federal constitutional right not to be convicted of a crime upon insufficient proof. . . . Our Supreme Court has stated that Jackson v. Virginia,[443 U.S. 307, 99 S.Ct. 2781, 61 L.Ed.2d 560 (1979)], compels the conclusion that any defendant found guilty on the basis of insufficient evidence has been deprived of a constitutional right, and would therefore necessarily meet the four prongs of [Golding]. . . . Thus . . . there is no practical reason for engaging in a Goldinganalysis of a claim based on the sufficiency of the evidence. . . ." (Internal quotation marks omitted.) State v. Ashe,supra, at 514, 812 A.2d 194.
The standard of review for sufficiency of the evidence claims has been stated frequently and is well established. "In reviewing a sufficiency of the evidence claim, we apply a two-part test. First, we construe the evidence in the light most favorable to sustaining the verdict. Second, we determine whether upon the facts so construed and the inferences reasonably drawn therefrom the [trier of fact] reasonably could have concluded that the cumulative force of the evidence established guilt beyond a reasonable doubt. . . . In evaluating evidence, the trier of fact is not required to accept as dispositive those inferences that are consistent with the defendant's innocence. . . . The trier may draw whatever inferences from the evidence or facts established by the evidence it deems to be reasonable and logical. . . . This does not require that each subordinate conclusion established by or inferred from the evidence, or even from other inferences, be proved beyond a reasonable doubt . . . because this court has held that a [trier's] factual inferences that support a guilty verdict need only be reasonable.. . .
"[A]s we have often noted, proof beyond a reasonable doubt does not mean proof beyond all possible doubt . . . nor does proof beyond a reasonable doubt require acceptance of every hypothesis of innocence posed by the defendant that, had it been found credible by the trier, would have resulted in an acquittal. . . . On appeal, we do not ask whether there is a reasonable view of the evidence that would support a reasonable hypothesis of innocence. We ask, instead, whether there is a reasonable view of the evidence that supports the [trier's] verdict of guilty. . . . Furthermore, [i]n [our] process of review, it does not diminish the probative force of the evidence that it consists, in whole or in part, of evidence that is circumstantial rather than direct. . . . It is not one fact, but the cumulative impact of a multitude of facts which establishes guilt in a case involving substantial circumstantial evidence." (Citations omitted; internal quotation marks omitted.) State v. Padua,273 Conn. 138, 146-47,869 A.2d 192(2005).
[901 A.2d 1255]
"It is well established that the question of intent is purely a question of fact. . . . Intent may be, and usually is, inferred from the defendant's verbal or physical conduct. . . . Intent may also be inferred from the surrounding circumstances. . . . The use of inferences based on circumstantial evidence is necessary because direct evidence of the accused's state of mind is rarely available. . . . Furthermore, it is a permissible, albeit not a necessary or mandatory, inference that a defendant intended the natural consequences of his voluntary conduct." (Citation omitted; internal quotation marks omitted.) State v. Porter,76 Conn.App. 477, 487-88, 819 A.2d 909, cert. denied,264 Conn. 910, 826 A.2d 181 (2003).
Pursuant to § 53a-167c(a), to prove assault of an employee of the department of correction, the state must prove beyond a reasonable doubt that the defendant "with intent to prevent a reasonably identifiable. . . employee of the Department of Correction. . . from performing his . . . duties, and while such . . . employee . . . is acting in the performance of his . . . duties, (1) such person causes physical injury to such . . . employee . . . ." General Statutes 53a-167c(a)(1). In the present case, the defendant contends that the evidence was not sufficient to prove that he had the specific intent to prevent Hanney from performing his duties. The defendant's claim appears to be that while the evidence may have been sufficient to permit the court to conclude that he intended to harm Hanney, it was not sufficient to permit the court to conclude that he intended to prevent Hanney from performing his duties.
The cumulative impact of the evidence in this case sufficiently enabled the court to conclude beyond a reasonable doubt that the defendant was guilty of assault of a department of correction employee. The evidence indicates that Hanney was in uniform at the time of the incident and that the defendant knew that he was a department of correction employee. The evidence further indicates that Hanney was carrying out his lawful duty in an orderly manner at the time the defendant became angry, grabbed Hanney's hands outside the sliding door and scratched his wrist, hand and fingers. Under those circumstances, the court reasonably could have found that when the defendant grabbed Hanney's hands and scratched him, causing injury, he intended not only to harm Hanney, but also to prevent him from performing his duties. The fact that the defendant may have been actuated by two separate intents does not diminish either one individually. "Given the complexity of human behavior, the existence of the intent required for commission of a crime may be blurred by the presence of multiple intents. An intent is forward looking; it is the end in view, the object to be accomplished by the action taken, which is its criterion. (See Anscombe, Intention [2d ed.1976]). An action may be taken with many ends in view. Where one of them is an element of the offense, it satisfies the scienter required for the offense, notwithstanding the presence of additional and extraneous intents."
People v. Brady,
190 Cal.App.3d 124
, 136 n. 4,
235 Cal.Rptr. 248
(1987); see also 1 W. LaFave, Substantive Criminal Law (2d Ed.2003) § 5.2(d), pp. 351-52.
2
We conclude that the evidence was sufficient to persuade the court that the state had proved beyond a reasonable doubt that the
[901 A.2d 1256]
defendant had the specific intent to prevent Hanney from performing his duty and that, therefore, the evidence was sufficient to support a conviction of assault of an employee of the department of correction.
II
The defendant next claims that the court improperly found that he effectively waived his right to a jury trial. The defendant concedes that this claim was not raised at trial and, thus, was not preserved for our review. He now seeks review under State v. Golding,supra, 213 Conn. at 239-40, 567 A.2d 823. 3We will review the defendant's claim, as the record is adequate for review and the alleged violation is of constitutional magnitude because it involves his constitutional right to a jury trial.
We begin by setting forth the applicable standard of review. "The right to a jury trial in a criminal case is among those constitutional rights which are related to the procedure for the determination of guilt or innocence. The standard for an effective waiver of such a right is that it must be knowing and intelligent, as well as voluntary. . . . Relying on the standard articulated in Johnson v. Zerbst,304 U.S. 458, 464, 58 S.Ct. 1019, 82 L.Ed. 1461(1938), we have adopted the definition of a valid waiver of a constitutional right as the intentional relinquishment or abandonment of a known right. . . . This strict standard precludes a court from presuming a waiver of the right to a trial by jury from a silent record. . . . In determining whether this strict standard has been met, a court must inquire into the totality of the circumstances of each case. . . . When such a claim is first raised on appeal, our focus is on compliance with these constitutional requirements rather than on observance of analogous procedural rules prescribed by [General Statutes § 54-82b(b)] or by . . . Practice Book [§ 42-1]." 4(Citations omitted; internal quotation marks omitted.) State v. Ouellette,271 Conn. 740, 751-52,859 A.2d 907(2004).
The following additional facts are necessary for the resolution of the defendant's claim. The defendant entered a pro forma not guilty plea and a jury election on September 23, 2004. Prior to the defendant's entering his plea, the court gave a general
[901 A.2d 1257]
advisement of rights on two occasions when the defendant's case was on the court calendar. 5When the case was called for trial on November 17, 2004, the following colloquy took place between the court and defense counsel:
"[Defense Counsel]: Your Honor, [the defendant] and I had a lengthy discussion a few moments ago about how to proceed in this case, and at this point, I believe, we're changing our election, if election was made, from a jury trial to a court trial.
"The Court: All right.
"[Defense Counsel]: December 9, Your Honor.
"The Court: All right. We'll set this matter for a trial on December 9. Be a two o'clock trial?
"[Defense Counsel]: Yes.
"The Court: All right. Two o'clock."
The court did not address the defendant personally concerning the waiver of a jury trial. The defendant argues that the failure of the court to conduct such an examination and to advise him of his constitutional right to a jury trial made the waiver invalid. The state contends that the two general advisements made by the court, coupled with the assertion made by defense counsel create a record that shows that the defendant affirmatively waived his right to a jury trial. We disagree with the state.
It is an established principle in this state that "a waiver of a fundamental constitutional right is not to be presumed from a silent record. See Boykin v. Alabama,395 U.S. 238, 243, 89 S.Ct. 1709, 23 L.Ed.2d 274 (1969)." State v. Shockley,188 Conn. 697, 707, 453 A.2d 441 (1982). Contrary to the assertion put forth by the state that the record is not silent, the mere election by defense counsel of a court trial and the recitation of the advisement of rights by the court made prior to defense counsel's subsequent assertion of the defendant's election of a court trial are not sufficient to indicate that the defendant knowingly, intelligently and voluntarily waived a jury trial. "[C]ourts indulge every reasonable presumption against waiver of fundamental constitutional rights and. . . do not presume acquiescence in the loss of fundamental rights." (Internal quotation marks omitted.) Id.We do not base our conclusion merely on the absence of a verbal exchange between the court and the defendant; see State v. Crump,201 Conn. 489, 503, 518 A.2d 378 (1986); but rather on the court's failure to discern whether the defendant was aware of the rights his counsel was purporting to waive on his behalf by electing a court trial. 6Such a fundamental right cannot be waived on the basis of defense counsel's assertion. See Taylor v. Illinois,484 U.S. 400, 417-18, 108 S.Ct. 646, 98 L.Ed.2d 798 (1988).
We conclude, in light of the totality of the circumstances on the record, that the waiver made by defense counsel on the defendant's behalf was constitutionally deficient. Accordingly, we reverse the judgment of the trial court and remand the case for a new trial. In light of our resolution
[901 A.2d 1258]
of this issue, we need not reach the defendant's final claim on appeal.
The judgment is reversed and the case is remanded for a new trial.
In this opinion the other judges concurred.
FootNotes
1. As our Supreme Court has stated, "[i]nterests of judicial efficiency, sound appellate policy and fundamental fairness require a reviewing court to address a defendant's insufficiency of the evidence claim prior to remanding a matter for retrial because of trial error. Pursuant to
Burks v. United States,
437 U.S. 1
, 18, 98 S.Ct. 2141, 57 L.Ed.2d 1 (1978), a defendant is entitled to a judgment of acquittal and retrial is barred if an appellate court determines that the evidence is insufficient to support the conviction."
State v. Padua,
273 Conn. 138
, 178,
869 A.2d 192
(2005).
2. "A person often acts with two or more intentions. These intentions may consist of an immediate intention (intent) and an ulterior one (motive). . . . [S]o long as the defendant has the intention required by the definition of the crime, it is immaterial that he may also have had some other intention." 1 W. LaFave, supra, § 5.2(d), at pp. 351-52.
3. "[A] defendant can prevail on a claim of constitutional error not preserved at trial only if
all
of the following conditions are met: (1) the record is adequate to review the alleged claim of error; (2) the claim is of constitutional magnitude alleging the violation of a fundamental right; (3) the alleged constitutional violation clearly exists and clearly deprived the defendant of a fair trial; and (4) if subject to harmless error analysis, the state has failed to demonstrate harmlessness of the alleged constitutional violation beyond a reasonable doubt." (Emphasis in original.)
State v. Golding,
supra, 213 Conn. at 239-40, 567 A.2d 823.
4. General Statutes § 54-82b(b) provides: "In criminal proceedings the judge shall advise the accused of his right to trial by jury at the time he is put to plea and, if the accused does not then claim a jury, his right thereto shall be deemed waived, but if a judge acting on motion made by the accused within ten days after judgment finds that such waiver was made when the accused was not fully cognizant of his rights or when, in the opinion of the judge, the proper administration of justice requires it, the judge shall vacate the judgment and cause the proceeding to be set for jury trial."
Practice Book § 42-1 provides: "The defendant in a criminal action may demand a trial by jury of issues which are triable of right by jury. If at the time the defendant is put to plea, he or she elects a trial by the court, the judicial authority shall advise the defendant of his or her right to a trial by jury and that a failure to elect a jury trial at that time may constitute a waiver of that right. If the defendant does not then elect a jury trial, the defendant's right thereto may be deemed to have been waived."
5. The court gave a general advisement of rights on September 2, 2004, and then again on September 23, 2004. The record does not reveal, however, whether the defendant was actually in the courtroom during those advisements. Nor does it indicate that the defendant was individually addressed with respect to his rights generally or with respect to his right to a jury trial, specifically.
6. We note that there is no evidence in the record that a written waiver was sought or obtained from the defendant. See
State v. Crump,
supra, 201 Conn. at 504, 518 A.2d 378.
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Government Workers - C08528003 - Means of Transportation to Work by Class of Worker for Workplace Geography - American Community Survey 2010 (ACS10) - Survey ACS 2010 (1-Year Estimates) - Social Explorer
Data Dictionary - Survey ACS 2010 (1-Year Estimates); American Community Survey 2010 (ACS10); Means of Transportation to Work by Class of Worker for Workplace Geography; C08528003; Government Workers
Survey: ACS 2010 (1-Year Estimates)
Data Source:
Table:
C08528. Means of Transportation to Work by Class of Worker for Workplace Geography [30]
Universe: Universe: Workers 16 years and Over
Variable Details
C08528.
Means of Transportation to Work by Class of Worker for Workplace Geography
Universe: Universe: Workers 16 years and Over
C08528001 Universe: Workers 16 years and Over C08528003 Government Workers
Percent base:
Workers 16 Years and Over (ACS10:C08528001)
Aggregation method:
Addition
Relevant Documentation:
Excerpt from: Social Explorer; U.S. Census Bureau; American Community Survey 2010 Summary File: Technical Documentation. ACS 2010-1yr Summary File: Technical Documentation -> Appendix A. Supplemental Documentation -> 2010 Subject Definitions -> Population Variables -> Journey to Work Journey to Work Place of Work back to top The data on place of work were derived from answers to Question 30, which was asked of people who indicated in Question 29 that they worked at some time during the reference week. (See "Reference Week.") Data were tabulated for workers 16 years old and over, that is, members of the Armed Forces and civilians who were at work during the reference week. Data on place of work refer to the geographic location at which workers carried out their occupational activities during the reference week. In the American Community Survey, the exact address (number and street name) of the place of work was asked, as well as the place (city, town, or post office); whether the place of work was inside or outside the limits of that city or town; and the county, state or foreign country, and ZIP Code. In the Puerto Rico Community Survey, the question asked for the exact address, including the development or condominium name, as well as the place; whether or not the place of work was inside or outside the limits of that city or town; the municipio or U.S. county. Respondents also were asked to "enter Puerto Rico or name of U.S. state or foreign country" and the ZIP Code. If the respondent's employer operated in more than one location, the exact address of the location or branch where he or she worked was requested. When the number and street name were unknown, a description of the location, such as the building name or nearest street or intersection, was to be entered. People who worked at more than one location during the reference week were asked to report the location at which they worked the greatest number of hours. People who regularly worked in several locations each day during the reference week were requested to give the address at which they began work each day. For cases in which daily work did not begin at a central place each day, the respondent was asked to provide as much information as possible to describe the area in which he or she worked most during the reference week. Place-of-work data may show a few workers who made unlikely daily work trips (e.g., workers who lived in New York and worked in California). This result is attributable to people who worked during the reference week at a location that was different from their usual place of work, such as people away from home on business. In areas where the workplace address was geographically coded to the block level, people were tabulated as working inside or outside a specific place based on the location of that address regardless of the response to Question 30c concerning city/town limits. In areas where it was impossible to code the workplace address to the block level, or the coding system was unable to match the employer name and street address responses, people were tabulated as working inside or outside a specific place based on the combination of state, county, ZIP Code, place name, and city limits indicator. The city limits indicator was used only in coding decisions when there were multiple geographic codes to select from, after matching on the state, county, place, and ZIP Code responses. The accuracy of place-of- work data for census designated places (CDPs) may be affected by the extent to which their census names were familiar to respondents, and by coding problems caused by similarities between the CDP name and the names of other geographic jurisdictions in the same vicinity. Place-of-work data are given for selected minor civil divisions (MCDs), (generally cities, towns, and townships) in the 12 strong MCD states (Connecticut, Maine, Massachusetts, Michigan, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, and Wisconsin), based on the responses to the place of work question. Many towns and townships are regarded locally as equivalent to a place, and therefore, were reported as the place of work. When a respondent reported a locality or incorporated place that formed a part of a township or town, the coding and tabulating procedure was designed to include the response in the total for the township or town. Workplace-based Geography back to top The characteristics of workers may be shown using either residence-based or workplace-based geography. If you are interested in the number and characteristics of workers living in a specific area, you should use the standard (residence- based) journey-to-work tables. If you are interested in the number and characteristics of workers who work in a specific area, you should use the workplace-based journey-to-work tables. Because place-of-work information for workers cannot always be specified below the place level, the workplace-based tables are presented only for selected geographic areas. Means of Transportation to Work back to top The data on means of transportation to work were derived from answers to Question 31, which was asked of people who indicated in Question 29 that they worked at some time during the reference week. (See "Reference Week.") Means of transportation to work refers to the principal mode of travel or type of conveyance that the worker usually used to get from home to work during the reference week. People who used different means of transportation on different days of the week were asked to specify the one they used most often, that is, the greatest number of days. People who used more than one means of transportation to get to work each day were asked to report the one used for the longest distance during the work trip. The category, "Car, truck, or van," includes workers using a car (including company cars but excluding taxicabs), a truck of one-ton capacity or less, or a van. The category, "Public transportation," includes workers who used a bus or trolley bus, streetcar or trolley car, subway or elevated, railroad, or ferryboat, even if each mode is not shown separately in the tabulation. "Carro publico" is included in the public transportation category in Puerto Rico. The category, "Other means," includes workers who used a mode of travel that is not identified separately within the data distribution. The category, "Other means," may vary from table to table, depending on the amount of detail shown in a particular distribution. The means of transportation data for some areas may show workers using modes of public transportation that are not available in those areas (for example, subway or elevated riders in a metropolitan area where there is no subway or elevated service). This result is largely due to people who worked during the reference week at a location that was different from their usual place of work (such as people away from home on business in an area where subway service was available), and people who used more than one means of transportation each day but whose principal means was unavailable where they lived (for example, residents of nonmetropolitan areas who drove to the fringe of a metropolitan area, and took the commuter railroad most of the distance to work). Private Vehicle Occupancy back to top The data on private vehicle occupancy were derived from answers to Question 32. This question was asked of people who indicated in Question 29 that they worked at some time during the reference week and who reported in Question 31 that their means of transportation to work was "Car, truck, or van." Data were tabulated for workers 16 years old and over, that is, members of the Armed Forces and civilians who were at work during the reference week. (See "Reference Week.") Private vehicle occupancy refers to the number of people who usually rode to work in the vehicle during the reference week. The category, "Drove alone," includes people who usually drove alone to work as well as people who were driven to work by someone who then drove back home or to a non-work destination. The category, "Carpooled," includes workers who reported that two or more people usually rode to work in the vehicle during the reference week. Workers Per Car, Truck, or Van back to top Workers per car, truck, or van is a ratio obtained by dividing the aggregate number of workers who reported using a car, truck, or van to get to work by the number of such vehicles that they used. Workers per car, truck, or van is rounded to the nearest hundredth. This measure also may be known as "Workers per private vehicle." Aggregate Number of Vehicles (Car, Truck, or Van) Used in Commuting back to top The aggregate number of vehicles used in commuting is derived by counting each person who drove alone as occupying one vehicle, each person who reported being in a two-person carpool as occupying one-half of a vehicle, each person who reported being in a three-person carpool as occupying one-third of a vehicle, and so on, then summing all the vehicles. This aggregate is used in the calculation for "workers per car, truck, or van." Time Leaving Home to Go to Work back to top The data on time leaving home to go to work were derived from answers to Question 33. This question was asked of people who indicated in Question 29 that they worked at some time during the reference week, and who reported in Question 31 that they worked outside their home. The departure time refers to the time of day that the respondent usually left home to go to work during the reference week. (See "Reference Week.") Travel Time to Work back to top The data on travel time to work were derived from answers to Question 34. This question was asked of people who indicated in Question 29 that they worked at some time during the reference week, and who reported in Question 31 that they worked outside their home. Travel time to work refers to the total number of minutes that it usually took the worker to get from home to work during the reference week. The elapsed time includes time spent waiting for public transportation, picking up passengers in carpools, and time spent in other activities related to getting to work. (See "Reference Week.") Aggregate Travel Time to Work (in Minutes) back to top Aggregate travel time to work is calculated by adding all of the travel times (in minutes) for workers who did not work at home. Aggregate travel times of workers having specific characteristics also are computed. The aggregate travel time is subject to rounding, which means that all cells in a matrix are rounded to the nearest 5 minutes. (For more information, see "Aggregate" under "Derived Measures.") Mean Travel Time to Work (in Minutes) back to top Mean travel time to work (in minutes) is the average travel time that workers usually took to get from home to work (one way) during the reference week. This measure is obtained by dividing the total number of minutes taken to get from home to work (the aggregate travel time) by the number of workers 16 years old and over who did not work at home. The travel time includes time spent waiting for public transportation, picking up passengers and carpools, and time spent in other activities related to getting to work. Mean travel times of workers having specific characteristics also are computed. For example, the mean travel time of workers traveling 45 or more minutes to work is computed by dividing the aggregate travel time of workers whose travel times were 45 or more minutes by the number of workers whose travel times were 45 or more minutes. The aggregate travel time to work used to calculate mean travel time to work is rounded. (For more information, see "Aggregate Travel Time to Work (in Minutes).") Mean travel time is rounded to the nearest tenth of a minute. (For more information on means, see "Derived Measures.") Time Arriving at Work from Home back to top The data on time arriving at work from home were derived from answers to Question 33 (Time Leaving Home to Go to Work) and from answers to Question 34 (Travel Time to Work). These questions were asked of people who indicated in Question 29 that they worked at some time during the reference week, and who reported in Question 31 that they worked outside their home. The arrival time is calculated by adding the travel time to work to the reported time leaving home to go to work. These data are presented with other characteristics of workers at their workplace. (See "Time Leaving Home to Go to Work" and "Travel Time to Work.") The responses to the place of work and journey to work questions provide basic knowledge about commuting patterns and the characteristics of commuter travel. The communting data are essential for planning highway improvement and developing public transportation sevices, as well as for designing programs to ease traffic problems during peak periods, conserve energy, reduce pollution, and estimate and project the demand for alternative-fueled vehicles. These data are required to develop standards for reducing work-related vehicle trips and increasing passenger occupancy during peak period of travel. The Bureau of Economic Analysis (BEA) plans to use county-level data in computing gross commuting flows to develop place-of-residence earning estimates from place-of-work estimates by industry. In addition, BEA also plans to use these data for state personal income estimates for determining federal fund allocations. Question/Concept History back to top Starting in 1999, the American Community Survey questions differ from the 1996-1998 questions in that the labels on the write-in spaces and format of the skip instructions were modified to provide clarifications. Beginning in 2004, the category, "Public transportation" for means of transportation was tabulated to exclude workers who used taxicab as their means of transportation. The 2004 American Community Survey marked the first time that workplace-based tables were released as a part of a standard census data product. Limitation of the Data back to top Beginning in 2006, the group quarters (GQ) population is included in the ACS. Some types of GQ populations have place of work distributions that are different from the household population. The inclusion of the GQ population could therefore have a noticeable impact on the place of work distribution. This is particularly true for areas with a substantial GQ population. The data on place of work is related to a reference week, that is, the calendar week preceding the date on which the respondents completed their questionnaires or were interviewed. This week is not the same for all respondents because data were collected over a 12-month period. The lack of a uniform reference week means that the place-of-work data reported in the survey will not exactly match the distribution of workplace locations observed or measured during an actual workweek. The place-of-work data are estimates of people 16 years and over who were both employed and at work during the reference week (including people in the Armed Forces). People who did not work during the reference week but had jobs or businesses from which they were temporarily absent due to illness, bad weather, industrial dispute, vacation, or other personal reasons are not included in the place-of-work data. Therefore, the data on place of work understate the total number of jobs or total employment in a geographic area during the reference week. It also should be noted that people who had irregular, casual, or unstructured jobs during the reference week might have erroneously reported themselves as not working. The address where the individual worked most often during the reference week was recorded on the questionnaire. If a worker held two jobs, only data about the primary job (the job where one worked the greatest number of hours during the preceding week) was requested. People who regularly worked in several locations during the reference week were requested to give the address at which they began work each day. For cases in which daily work was not begun at a central place each day, the respondent was asked to provide as much information as possible to describe the area in which he or she worked most during the reference week. Comparability back to top This data source is comparable to the decennial censuses for all journey to work variables. Since both the American Community Survey and the decennial censuses are related to a "reference week" that has some variability, the data do not reflect any single week. Since the American Community Survey data are collected over 12 months, the reference week in American Community Survey has a greater range of variation. (See "Reference Week.") For more detailed information regarding the difference of place of work and journey to work in the ACS and Census 2000, see Estimates about Journey to Work from the 2005 ACS, C2SS, and Census 2000 on the ACS website. See the 2010 Code List for Place of Work Code List.Labor Force Status See Employment Status. Excerpt from: Social Explorer; U.S. Census Bureau; American Community Survey 2010 Summary File: Technical Documentation. ACS 2010-1yr Summary File: Technical Documentation -> Appendix A. Supplemental Documentation -> 2010 Subject Definitions -> Population Variables -> Class of Worker Class of Worker Class of worker categorizes people according to the type of ownership of the employing organization. Class of worker data were derived from answers to question 41. Question 41 provides respondents with 8 class of worker categories from which they are to select one. These categories are: An employee of a private, for-profit company or business, or of an individual, for wages, salary, or commissions. An employee of a private, not-for-profit, tax-exempt, or charitable organization. A local government employee (city, county, etc.). A state government employee. A Federal government employee. Self-employed in own not incorporated business, professional practice, or farm. Self-employed in own incorporated business, professional practice, or farm. Working without pay in a family business or farm. These questions were asked of all people 15 years old and over who had worked in the past 5 years. For employed people, the data refer to the person's job during the previous week. For those who worked two or more jobs, the data refer to the job where the person worked the greatest number of hours. For unemployed people and people who are not currently employed but report having a job within the last five years, the data refer to their last job. The class of worker categories are defined as follows: Private wage and salary workers back to top Includes people who worked for wages, salary, commission, tips, pay-in-kind, or piece rates for a private, for-profit employer or a private not-for-profit, tax-exempt or charitable organization. Self-employed people whose business was incorporated are included with private wage and salary workers because they are paid employees of their own companies. ACS tabulations present data separately for these subcategories: "Employee of private company workers," "Private not-for-profit wage and salary workers," and "Self-employed in own incorporated business workers." Government workers back to top Includes people who were employees of any local, state, or Federal governmental unit, regardless of the activity of the particular agency. For ACS tabulations, the data are presented separately for the three levels of government. Employees of Indian tribal governments, foreign governments, the United Nations, or other formal international organizations controlled by governments were classified as "Federal government workers." The government categories include all government workers, though government workers may work in different industries. For example, people who work in a public elementary school or city owned bus line are coded as local government class of workers. Self-employed in own not incorporated business workers back to top Includes people who worked for profit or fees in their own unincorporated business, profession, or trade, or who operated a farm. Unpaid family workers back to top Includes people who worked without pay in a business or on a farm operated by a relative. Editing Procedures back to top A computer edit and allocation process excludes all responses that should not be included in the universe and evaluates the consistency of the remaining responses. Class of worker responses are checked for consistency with the industry and occupation data provided for that respondent. Occasionally respondents do not report a response for class of worker, industry, or occupation. Certain types of incomplete entries are corrected using the Alphabetical Index of Industries and Occupations. If one or more of the three codes (occupation, industry, or class of worker) is blank after the edit, a code is assigned from a donor respondent who is a "similar" person based on questions such as age, sex, educational attainment, income, employment status, and weeks worked. If all of the labor force and income data are blank, all of these economic questions are assigned from a "similar" person who had provided all the necessary data. These data are used to formulate policy and programs for employment and career development and training. Companies use these data to decide where to locate new plants, stores, or offices. Question/Concept History back to top Class of worker data have been collected during decennial censuses since 1910. Starting with the 2010 Census, class of worker data will no longer be collected during the decennial census. Long form data collection has transitioned to the American Community Survey. The American Community Survey began collecting data on class of worker in 1996. The questions on class of worker were designed to be consistent with the 1990 Census questions on class of worker. The 1996-1998 ACS class of worker question had an additional response category for "Active duty U.S. Armed Forces member." People who marked this category were tabulated as Federal government workers. A check box was added to the employer name questionnaire item in 1999. This check box is to be marked by anyone "now on active duty in the Armed Forces..." This information is used by the industry and occupation coders to assist in assigning proper industry codes for active duty military. Limitation of the Data back to top Beginning in 2006, the population in group quarters (GQ) was included in the ACS. Some types of GQ populations have class of worker distributions that are different from the household population. The inclusion of the GQ population could therefore have a noticeable impact on the class of worker distribution in some geographic areas with a substantial GQ population. Data on occupation, industry, and class of worker are collected for the respondent's current primary job or the most recent job for those who are not employed but have worked in the last 5 years. Other labor force questions, such as questions on earnings or work hours, may have different reference periods and may not limit the response to the primary job. Although the prevalence of multiple jobs is low, data on some labor force items may not exactly correspond to the reported occupation, industry, or class of worker of a respondent. Comparability back to top Class of worker categories have remained consistent since the implementation of the American Community Survey in 1996. The 1996-1998 ACS class of worker question had an additional response category for "Active duty U.S. Armed Forces member" in order to assist industry and occupation coders in assigning proper industry codes for active duty military. People who selected this category were tabulated as Federal government workers. Active duty U.S. Armed Forces have been coded as Federal government workers from 1996 to 2010. See also, Industry and Occupation. Excerpt from: Social Explorer; U.S. Census Bureau; American Community Survey 2010 Summary File: Technical Documentation. ACS 2010-1yr Summary File: Technical Documentation -> Appendix A. Supplemental Documentation -> 2010 Subject Definitions -> Population Variables -> Journey to Work -> Workplace-based Geography Workplace-based Geography The characteristics of workers may be shown using either residence-based or workplace-based geography. If you are interested in the number and characteristics of workers living in a specific area, you should use the standard (residence- based) journey-to-work tables. If you are interested in the number and characteristics of workers who work in a specific area, you should use the workplace-based journey-to-work tables. Because place-of-work information for workers cannot always be specified below the place level, the workplace-based tables are presented only for selected geographic areas.
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Facts about "Casablanca" : Classic Movie Hub (CMH)
Browse Fun Facts and Trivia about at Classic Movie Hub (CMH).
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Casablanca
"As Time Goes By" was written by lifelong bachelorHerman Hupfeldand debuted in 1931's Broadway show "Everybody's Welcome", sung byFrances Williams, It had been a personal favorite of playwright and high school teacherMurray Burnettwho, seven years later, visited Vienna just after the Nazis had entered. Later, after visiting a café in south France where a black pianist had entertained a mixed crowd of Nazis, French and refugees, Burnett was inspired to write the melodrama "Everybody Comes to Rick's", which was optioned for production byMartin GabelandCarly Wharton, and later, Warners. After the film's release, "As Time Goes By" stayed on radio's "Hit Parade" for 21 weeks. However, because of the coincidental musicians' union recording ban, the 1931Rudy Valleeversion became the smash hit. (It contains the rarely-sung introductory verse, not heard in the film.)Max Steiner, in a 1943 interview, admitted that the song "must have had something to attract so much attention".
"Here's looking at you, kid" was improvised by
Humphrey Bogart
in the Parisian scenes and worked so well that it was used later on again in the film. He originally used the same line in
Midnight
. It is also rumored that during breaks,
Ingrid Bergman
would play poker with other cast members. Since she was still learning English, Bogart would occasionally watch the game, and he added "Here's looking at you" to her poker repertoire.
"Rick's Café Américain" was modeled after Hotel El Minzah in Tangiers.
Humphrey Bogarthad to wear platform shoes to play alongsideIngrid Bergman.
Humphrey Bogart
,
Ingrid Bergman
and
Paul Henreid
later reprised their roles for a radio performance of on the CBS radio program "The Screen Guild Players", a war benefit show on April 26, 1943.
Humphrey Bogart
's wife
Mayo Methot
continually accused him of having an affair with
Ingrid Bergman
, often confronting him in his dressing room before a shot. Bogart would come onto the set in a rage. In fact, despite the undeniable on-screen chemistry between Bogart and Bergman, they hardly spoke, and the only time they bonded was when the two had lunch with
Geraldine Fitzgerald
. According to Fitzgerald, "the whole subject at lunch was how they could get out of that movie. They thought the dialogue was ridiculous and the situations were unbelievable... I knew Bogart very well, and I think he wanted to join forces with Bergman, to make sure they both said the same things." For whatever reasons, Bogart and Bergman rarely spoke after that.
S.Z. Sakall, who plays the maitre d' at Rick's Cafe, actually has more screen time thanPeter LorreorSydney Greenstreet.
Madeleine Lebeau
, who plays Yvonne, and
Marcel Dalio
, who plays croupier Emil, were husband and wife at the time of filming. They had not long before escaped the Nazis by fleeing their native France.
Dooley Wilson
(Sam) was a professional drummer who faked playing the piano. As the music was recorded at the same time as the film, the piano playing was actually a recording of a performance by
Elliot Carpenter
who was playing behind a curtain but who was positioned such that Dooley could watch, and copy, his hand movements.
Dooley Wilsonwas borrowed from Paramount at $500 a week.
Dooley Wilsonwas, in fact, the only member of the cast to have ever actually visited the city of Casablanca.
Joy Page
, who played the young Bulgarian wife, was the stepdaughter of studio head
Jack L. Warner
. She,
Humphrey Bogart
and
Dooley Wilson
were the only American-born people in the credited cast. This film was her debut.
Hal B. Wallisdidn't wantHumphrey Bogartwearing a hat too often in the film, as he thought it made Bogart look like a gangster.
Hal B. Wallis's first choice for director wasWilliam Wyler.
Sydney Greenstreet
wanted to wear something more ethnic to show that his character had assimilated into the Moroccan lifestyle. This idea was nixed by producer
Hal B. Wallis
who insisted that he wear his now-iconic white suit.
Ingrid BergmanandPaul Henreidmake their first appearance 24 minutes into the film.
Ingrid Bergman
considered her left side as her better side, and to the extent possible that was the side photographed throughout the film, so she is almost always on the right side of the screen looking towards the left regardless of who is in the shot with her. However, there are several shots where she is to the left and
Humphrey Bogart
is on the right, including the flashbacks to the street scene in Paris (0:41:50) and the scene at the window (0:43:40). There are also several scenes where Bergman is centered between
Paul Henreid
and Bogart, suggesting the triangle nature of their relationship; in these shots Henreid is usually to the left and Bogart is usually on the right, including the scene where she and Henreid enter the café at just before the famous "Battle of the Anthems" (1:07:40); the scene where Captain Renault arrests Victor Laszlo (1:34:00); and at the end of the final airport scene (1:39:00).
Ingrid Bergman's contract was owned by producerDavid O. Selznick, and producerHal B. Wallissent the film's writers,Philip G. EpsteinandJulius J. Epstein, to persuade Selznick to loan her to Warner Bros. for the picture. After 20 minutes of describing the plot to Selznick, Julius gave up and said, "Oh, what the hell! It's a lot of shit likeAlgiers!" Selznick nodded and agreed to the loan.
Ingrid Bergman
's line "Victor Laszlo is my husband, and was, even when I knew you in Paris" was almost cut from the film because during that time it was deemed inappropriate for a film to depict or suggest a woman romancing with another man if she were already married. However, it was pointed out that later in the film she explains that she had thought Laszlo was dead at the time, and the censors allowed the line to stay in.
Howard Hawks
had said in interviews that he was supposed to direct
Casablanca
and
Michael Curtiz
was supposed to direct
Sergeant York
. The directors had lunch together, where Hawks said he didn't know how to make this "musical comedy", while Curtiz didn't know anything about "those hill people." They switched projects. Hawks struggled on how to direct the scenes that involved singing, namely the "La Marseillaise" scene. It is ironic to note that most of his other films involved at least one singing scene.
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Agronomy | Free Full-Text | Arbuscular Mycorrhizal Fungi as Potential Agents in Ameliorating Heavy Metal Stress in Plants
Heavy metal accumulation in plants is a severe environmental problem, rising at an expeditious rate. Heavy metals such as cadmium, arsenic, mercury and lead are known environmental pollutants that exert noxious effects on the morpho-physiological and biological attributes of a plant. Due to their mobile nature, they have become an extended part of the food chain and affect human health. Arbuscular mycorrhizal fungi ameliorate metal toxicity as they intensify the plant& rsquo;s ability to tolerate metal stress. Mycorrhizal fungi have vesicles, which are analogous to fungal vacuoles and accumulate massive amount of heavy metals in them. With the help of a pervasive hyphal network, arbuscular mycorrhizal fungi help in the uptake of water and nutrients, thereby abating the use of chemical fertilizers on the plants. They also promote resistance parameters in the plants, secrete a glycoprotein named glomalin that reduces the metal uptake in plants by forming glycoprotein& ndash;metal complexes, and improve the quality of the soil. They also assist plants in phytoremediation by increasing the absorptive area, increase the antioxidant response, chelate heavy metals and stimulate genes for protein synthesis that reduce the damage caused by free radicals. The current manuscript focuses on the uptake of heavy metals, accumulation, and arbuscular mycorrhizal impact in ameliorating heavy metal stress in plants.
Arbuscular Mycorrhizal Fungi as Potential Agents in Ameliorating Heavy Metal Stress in Plants
by
Rajni Dhalaria 1 ,
Dinesh Kumar 2 ,
Harsh Kumar 2 ,
Eugenie Nepovimova 3 ,
Kamil Kuča 3,* ,
Muhammad Torequl Islam 4 and
Rachna Verma 1,*
1
School of Biological and Environmental Sciences, Shoolini University of Biotechnology and Management Sciences, Solan 173229 (H.P.), India
2
Faculty of Applied Sciences and Biotechnology, Shoolini University of Biotechnology and Management Sciences, Solan 173229 (H.P.), India
3
Department of Chemistry, Faculty of Science, University of Hradec Kralove, 50003 Hradec Kralove, Czech Republic
4
Department of Pharmacy, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj (Dhaka)-8100, Bangladesh
*
Authors to whom correspondence should be addressed.
Agronomy 2020 , 10 (6), 815; https://doi.org/10.3390/agronomy10060815
Received: 25 April 2020 / Revised: 30 May 2020 / Accepted: 3 June 2020 / Published: 9 June 2020
Abstract
:
Heavy metal accumulation in plants is a severe environmental problem, rising at an expeditious rate. Heavy metals such as cadmium, arsenic, mercury and lead are known environmental pollutants that exert noxious effects on the morpho-physiological and biological attributes of a plant. Due to their mobile nature, they have become an extended part of the food chain and affect human health. Arbuscular mycorrhizal fungi ameliorate metal toxicity as they intensify the plant’s ability to tolerate metal stress. Mycorrhizal fungi have vesicles, which are analogous to fungal vacuoles and accumulate massive amount of heavy metals in them. With the help of a pervasive hyphal network, arbuscular mycorrhizal fungi help in the uptake of water and nutrients, thereby abating the use of chemical fertilizers on the plants. They also promote resistance parameters in the plants, secrete a glycoprotein named glomalin that reduces the metal uptake in plants by forming glycoprotein–metal complexes, and improve the quality of the soil. They also assist plants in phytoremediation by increasing the absorptive area, increase the antioxidant response, chelate heavy metals and stimulate genes for protein synthesis that reduce the damage caused by free radicals. The current manuscript focuses on the uptake of heavy metals, accumulation, and arbuscular mycorrhizal impact in ameliorating heavy metal stress in plants.
Keywords:
mycorrhizal fungi
;
translocation
;
heavy metals
;
toxic effects
;
plant–microbe interactions
;
amelioration
1. Introduction
A “heavy metal” is any element having metallic properties, with relatively high density, and is harmful at even low concentrations [ 1 ]. The most phytotoxic and non-essential heavy metals (HMs) found in the soil are lead (Pb), arsenic (As), cadmium (Cd) and mercury (Hg), which are highly mobile and are promptly absorbed by the plants. Besides these, there are other HMs (copper, chromium, zinc, selenium, molybdenum, tin, nickel etc.), which cause environmental contamination and health risks [ 2 , 3 , 4 ]. Generally, metal concentration is assessed by the amount of metal in the bedrock and its deposition from the atmosphere. Small amounts of these HMs are already present in the soil and atmosphere, but other things keep on adding these to the environment and include industrial and natural anthropogenic activities, fertilizers, polluted water, sewage sludge, the weathering of soil and minerals [ 5 ]. HMs have detrimental impacts on the plant metabolism, soil fertility, terrestrial ecosystems and human health [ 6 ]. The HMs get transferred to the human body through soil–plant–food interactions and cause exigent defects [ 7 ]. HMs cause harmful impacts on plant growth and productivity by many mechanisms, such as (i) interference with the activity of nutrients, which are essential for plant growth; (ii) effects on plant morphology and physiology; (iii) negative impacts on the soil microbes’ growth, including that of symbiotic microbes such as rhizobia; and (iv) effects on soil properties [ 8 , 9 ].
Most of the HMs on the soil surface occur naturally, but the condition becomes worse when these metals are added in surplus amounts in the surrounding atmosphere [ 10 ]. High amounts of HMs in plant tissue exert toxicity in plants, disrupt cell membrane permeability, inhibit photosynthesis and mineral uptake, affect plant morpho-physiological and biological processes and ultimately inhibit the growth rate [ 1 , 11 ]. They also result in the production of free radicals such as hydrogen peroxide (H 2 O 2 ), superoxide radical (O 2− ) and hydroxyl radical ( ● OH), which further react with cellular organelles and cause damage to the cell and DNA, inhibit ATP (adenosine triphosphate) production and cause lipid peroxidation [ 12 , 13 ]. HMs’ ability to cause damage relies on the already existing stage of stress exposure, its duration, the concentration of HMs and their bioavailability in plant organs [ 1 , 14 ]. Plants possess indigenous defense mechanisms, i.e., they have antioxidant enzymes that are involved in warding off HM stress. HMs produce ROS (reactive oxygen species), so at their highest concentration, these enzymes do not function. Numerous physical and chemical strategies have been used to ameliorate HM ion concentrations in soil [ 15 , 16 ]. These include soil washing, excavation, acidification, vitrification and land filling. These methods are observed to be expensive and alter the quality of the soil, which makes it unsuitable for the growth of rhizospheric microbial communities. Meanwhile, biological methods (the use of plants and microbes) have been proved to be an innovative solution as they are cost-effective, easy to implement and maintain the natural properties of the environment [ 9 ].
In a natural ecosystem, plants continually interact with a large number of microorganisms in the rhizosphere and create mutually beneficial alliances with them. Arbuscular mycorrhizal fungi (AMF)-like beneficial fungi develop a symbiotic association with the plant roots where photosynthetic products prepared by the plants are received by the fungus and, in turn, it helps the plant by enhancing nutrient uptake, protecting them from HM toxicity, enhancing biomass accumulation and improving photosynthesis [ 17 , 18 ]. Approximately 80% of terrestrial plant roots form symbiotic relations with fungi, where fungal hyphae percolate in the cortical cells of plant roots forming arbuscules, vesicles and hyphae [ 19 ]. They also render HMs immobile at the cortical region of roots by binding with them, prevent their translocation towards aerial parts of the plant and prevent leaf tissues from damage. AMF are a type of endomycorrhizal fungus (phylum Glomeromycota) that provides nutrients for plant growth, by ameliorating water uptake and controlling stomatal conductance [ 20 ]. AMF is considered as one of the best biological tools for enhancing plant growth and shoot biomass as it can detoxify HM-induced stress. AMF reduces HM stress by HM immobilization in fungal structure, precipitation and chelation in the rhizosphere, sequestration in vacuoles and activation of antioxidant mechanisms in plants [ 16 ]. The utilization of AMF is an ecofriendly approach and a useful component to attain sustainable productivity by improving soil health and protecting plants against abiotic and biotic stresses [ 18 ]. Thus, the main objective of this study is to review the role of AMF in maintaining a sustainable environment in an HM-contaminated ecosystem. It includes the HMs’ impact on human health and plants. At the same time, it also highlights various ways in which AMF minimizes the HMs’ impact on plants.
2. Heavy Metals (HMs) and Their Impacts
Heavy metals (HMs) such as As, Pb, Hg, Cd, Cr, Ni and Cu are the toxic metals that are listed as the 1st, 2nd, 3rd, 7th, 17th, 58th and 120th most harmful substances by the Agency for Toxic Substances and Disease Registry, respectively, on the basis of their toxic effects on human beings [ 21 ]. Different sources of HMs and their impacts on human health are described in Table 1 .
In the biological processes of organisms, metals play a vital role. Some metals serve as micronutrients and are essential, while others are toxic and have no biological role in organisms. Moreover, non-essential metal have a bad impact on the environment, thus decreasing the biological activity of the soil. They enter the food chain and affect human health. A worldwide map of heavy metals showing the countries where significant impact has been observed is represented in Figure 1 .
Generally, HMs at their lowest concentrations have the potential to cause intense damage to plants as well as to human beings through the food chain [ 56 ]. According to the European Commission, the maximum levels of different HMs permitted in food items are as depicted in Table 2 .
In the case of As, there is no maximum level, but the European Food Safety Authority (EFSA) Panel recommended to reduce the use of inorganic As for dietary exposure. According to EFSA, 0.20–0.30 µg kg
−1
is the optimum/maximum level of As that should be present in food.
3. Sources of HMs
The HMs are naturally available in the soil, but their concentrations rise in the environment because of human activities that have an adverse impact on plants and humans. They are mobile between soil–plant systems and are frequently being added to the soil via several agricultural activities like agrochemical usage. Besides the natural weathering process, there are different sources of HMs in the soil like chimney emissions from factories, the excessive supplementation of phosphate fertilizers, additives in pigments and gasoline, pesticides, metal-polluted water and effluent from storage batteries [ 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 ]. A major source of Hg in the soil is power plants that burn coal for energy generation. The exhaust fumes of automobiles in urban areas contribute to atmospheric pollution. Plants growing along roadsides constitute a large quantity of HMs due to the combustion of gasoline in vehicles. The contamination of soils occurs by HM compounds like lead arsenate (PbHAsO 4 ) and bordeaux mixture (CuSO 4 ), which are used as a pesticides in orchards. The mining and smelting of metalliferous ores with fossil fuel combustion have globally increased the risk associated with HMs in the soil over the past few centuries.
4. Uptake, Translocation and Accumulation of HMs in Plants
Initially, HMs present in the soil are absorbed by the roots and can be translocated to the other parts of the plant. Very often, heavy metals remain in the roots because of the barrier effect. The uptake of HMs by plant roots depends on the bioavailability of the metal ions (i.e., not co-precipitated with oxides or adsorbed to organic matter) in the soil solution and is regulated by soil pH and carbonate contents [ 68 ]. The pathways through which HMs enter the roots include H + ATPase/pumps, which help in maintaining the negative potential across the epidermal membrane in the roots; HM ions present in the soil make their entry into the plant epidermis either through ion channels or as organic compounds formed after combination with chelates released by plant roots in the soil, thus entering as metal–ligand complexes into the root epidermal layer [ 69 ]. Different transporters including members of the HM ATPases (HMA) family, Zrt/Irt protein (ZIP) family and natural resistance-associated macrophage protein (NRAMP) family are also involved in the uptake of HM ions in plants. Generally, root hairs enhance the surface area of roots for HM absorption so that ions migrate quickly inside the apoplast [ 70 , 71 , 72 ]. HM ions, once absorbed by the roots, are bound directly to the carboxyl groups of mucilage uronic acid or to the polysaccharides on the rhizodermis and show apoplastic movement from the root epidermis to the cortex region [ 73 , 74 ]. These ions primarily accumulate in root cells because of the obstruction in the apoplastic pathway at the endodermis by casparian strips. Later, after crossing the endodermis, HM ions travel by the symplastic pathway through vascular tissues, i.e., xylem and phloem and are translocated to the above-ground parts of the plant, as shown in Figure 2 .
The absorption of HM ions does not remain uniform along the plant roots, as their concentration varies in root apices and other regions of the root. In the case of a HM such as Pb, the highest concentration of this HM was found in the young root cells having thin cell walls [
75
]. Limited transport of metal occurs from the roots to the above-ground parts of the plant, as during the translocation of HM ions between the roots and shoots, the endodermis acts as a partial barrier [
76
]. Some plant species transfer a large amount of Pb to their shoots [
77
]. Pb in the wheat roots remains in the cell wall and can only be isolated as a complex with citric acid [
78
]. Different Pb complexes were also observed in the stem and leaves of alfalfa [
79
]. In addition to this, Pb is transferred to the stem and leaves in
Sesbania drummondii
[
80
]. Pb transportation is limited in the different parts of the plant due to the immobilization of insoluble Pb salts as precipitates in intercellular spaces, fixation in the cell wall by negatively charged pectins, and accumulation in the vacuoles of cortical and rhizodermal cells and the plasma membranes of cells [
81
,
82
,
83
,
84
,
85
,
86
,
87
]. The minimum availability of heavy metals at higher trophic levels can be possible by their minimum uptake. Hyperaccumulator plants (e.g.,
Pteris vittata
,
P. cretica
,
P. biaurita
,
Sesbania drummondii
,
Helianthus annuus
,
Sedum alfredii
,
Atriplex halimus
,
Amanita muscaria
and
Polygonum aviculare
) are required for soil remediation as these plants are capable of growing in high metal concentrations, absorbing them through their roots and translocating them with minimal or no toxicity to the aerial parts of the plant. The amount of HM ions that is taken up from the soil by the plants is measured by the transfer factor [
88
,
89
].
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A higher TF (Transfer Factor) value is observed in non-mycorrhizal fenugreek plants than in mycorrhizal ones [ 90 ]. Plants are classified on the basis of the transfer factor as its values are different in both hyperaccumulators (TF > 1) and non-hyperaccumulators (TF < 1) [ 91 ].
5. Impact of HMs on Plants in the Absence of AMF
Soil contaminated by toxic metals causes acute and chronic impacts on plant growth and productivity. Extreme concentrations of HMs affect the morphology of plants, which results in a decreased transpiration rate and damage to the root system [ 92 , 93 ]. Generally, HMs interact with the sulfhydryl group (–SH) of enzymes, which agitates chloroplast functioning by restricting the activities of enzymes related to chlorophyll biosynthesis, the aggregation of protein complexes involved in photosystems (PS), and carbon dioxide (CO 2 ) fixation [ 94 ]. Metal stress decreases chlorophyll synthesis, which is an imperative pigment in photosynthesis, by reducing the supply of essential elements like magnesium, zinc and iron, eventually affecting the plant–nutrient relationship [ 90 ]. It has been reported that the level of chlorophyll decreased when the seedlings of Phaseolus vulgaris were treated with Cd [ 95 , 96 , 97 ]. Photosynthetic plants, upon exposure to HMs, experience harmful effects in respiration and adenosine triphosphate (ATP) content. With the increasing metal stress, the ratio of chlorophyll a/chlorophyll b decreases, which implies a shift in the ratio of PSII/PSI. The experimental results indicate that Cd and Pb stress decreases the photosynthetic pigments (chlorophyll and carotenoids content) in the host plant in the absence of AMF [ 98 , 99 ].
HMs interfere with protease and amylase enzymes, which prevents germination and the development of seedlings [ 100 ]. Pb exposure causes inhibition of the germination of seeds as reported in Oryza sativa , Pinus halepensis and Hordeum vulgare , whereas mercury also affects seed germination as described in the case of Enhalus Acoroides and Vigna radiata [ 81 , 100 , 101 , 102 , 103 ]. It is recorded that a high concentration of Cd affects the growth of lettuce plants [ 104 ]. Many changes take place in mitochondria as they lose cristae and undergo swelling, nuclei becomes deep-colored, plasma membranes get injured, and vacuolization takes place in dictyosomes and endoplasmic reticulum after 42–72 h of Pb exposure, particularly in Allium sativum . HMs also interact with the cytoplasmic proteins of the plant and decrease protein synthesis, which leads to physiological changes in the plant [ 85 ]. A reduction in protein pool also results from the different actions of Pb such as the oxidation of proteins, the stimulation of protein activity, an increase in ribonuclease activity and the modification of gene expression [ 105 , 106 , 107 , 108 , 109 ]. Some reports indicate that in the absence of AMF, Cd stress decreases chlorophyll content and growth and increases the accumulation of H 2 O 2 in Solanum lycopersicum [ 110 ].
HMs reduce essential mineral uptake and the plasticity of the plant cell wall, which further influences the turgor pressure of the cell. In Helianthus annus , a reduction in mineral uptake was observed when the plant was exposed to cadmium stress [ 111 ]. Metal toxicity leads to the production of free radicals like ROS that are formed during cellular metabolic processes, and the overproduction of these species is considered as oxidative stress. Free radicals react with cell organelles, membranes, biomolecules like lipids, proteins and nucleic acids (e.g., DNA, RNA); reduce the normal functions of cells; and induce abnormality. Free radicals cause DNA damage and the inhibition of ATP and lipid peroxidation, thereby generating oxidative stress [ 112 , 113 ]. They also damage electron transport chains in chloroplasts and mitochondria, which leads to the disruption of proteins by oxidative reactions or proteolytic activity. A high concentration of toxic metals causes the membrane to rupture and results in cell death. Abscisic acid is a phytohormone responsible for the opening and closing of stomata [ 114 ]. HM ions cause the accumulation of abscisic acid in aerial plant parts and roots, which leads to the closing of stomata, limits gaseous exchange with the atmosphere and reduces the transpiration rate [ 115 , 116 ]. Various impacts of heavy metals on plants are shown in Figure 3 .
6. Role of AMF in HM Detoxification in Plants
Once HMs have entered the soil, they have long-term effects on plants. AMF are an essential bioagent, as they can significantly enhance the efficiency of the ecosystem by producing fungal structures like arbuscules and aid in the exchange of inorganic compounds and minerals required for the growth of plants, thereby providing considerable strength to plants. They also act as a biological filter for HMs and help in mitigating them. They help the plant to grow actively under stressful conditions by assisting the plant through increased water uptake, photosynthetic rate and nutrition [
118
]. Generally, HMs get immobilized in the fungal hyphae living in symbiotic association with plants, which reduce their availability to plants by retaining the HMs in the cell wall, vacuole or cytoplasm by chelation, thus decreasing metal toxicity in the plants [
119
,
120
]. Several different strategies have been ratified for how AMF influence the uptake, translocation and accumulation of HMs and enhance plant tolerance to HM stress. These strategies include various steps viz. the retention of HMs in the mycorrhizal roots and external hyphae, the stimulation of nutrient absorption, the sequestration of HMs in vacuoles, the binding of HMs on the fungal cell wall, the protection of the reaction center and the rectification of gas exchange capacity, the increasing of the antioxidant response of plants, the chelation of HMs in the cytosol of fungi and the induction of glomalin by AMF, and AMF-mediated phytoremediation.
6.1. Retention of HMs in Mycorrhizal Roots and External Hyphae of AMF
AMF colonization with higher plant roots enables the plant to retain HMs in their roots and external mycelium. AMF shows a mechanism to ameliorate HM toxicity in plants by retaining HMs in mycorrhizal structures such as the fungal mycelium and vesicles, where high amounts of HMs are concentrated, which further prevents their mobilization to aerial plant tissues as shown in Figure 4 [ 122 ].
The fungal vesicles in mycorrhizal plants are analogous to the plant vacuoles, which are implicated in accumulating toxic compounds. The external mycelium of roots has a predominant effect on the immobilization of metals in the stressed soil because of its wider surface area, which makes them more efficient than the plant roots for absorbing metals. This retention mechanism by AMF decreases the translocation of HMs and protects leaf tissues from injury by retaining them in roots, therefore contributing to phytostabilization. In mycorrhizal plants, the HM tolerance potential is correlated with the yield of mycelial biomass and fungal growth, as metals remain accommodated in the fungal mycelium. Moreover, the vesicles in the fungi also increase with the increase in the concentration of HMs [
99
]. Pakchoi shoots were observed with significantly decreased concentrations of Pb upon the addition of mycorrhizal fungi, e.g.,
Rhizophagus intraradices
,
Glomus versiforme
and
Funneliformis mosseae
[
124
]. The AMF colonization of
Aster tripolium
roots enabled the fungi to retain Cd in the mycelium and promoted plant tolerance to Cd [
125
]. The AMF inoculation of
Melastoma malabathricum
plants led to an increase in the absorption area of the roots in the soil and resulted in better plant growth [
126
].
6.2. AMF Promotes Nutrient Absorption in Plants
The AMF stimulate plant growth even in stressed conditions by modifying the soil structure. Generally, nutrients are absorbed from the soil by fungal hyphae and directed to the fungus–plant interface, where bidirectional exchange take place [ 127 ]. Under the influence of AMF, some enzyme characteristics are altered viz. the activity, quantity and number of enzymes in the soil, particularly the activity of acid phosphatase, which improves growth and nutrient uptake in the host plants [ 128 ]. A phosphate transporter is present in mycorrhizal fungi for the direct transport of inorganic phosphate (Pi) from the soil to the plants [ 129 ]. On the extraradial mycelium of Glomus mosseae , G. intraradices and G. versiforme , several genes encoding transporter proteins such as GmosPT , GiPT and GvPT have been identified that are involved in the uptake of phosphate [ 130 , 131 , 132 ]. AMF raise the concentration of phosphorus and other essential mineral nutrients in plants with enhancement in the uptake from soil, by extending beyond the limits of the plant roots and increasing the absorption area [ 133 ]. Higher contents of nitrogen, potassium and phosphorus have been observed in host plants subjected to HM stress in the presence of AMF [ 134 , 135 , 136 ].
6.3. AMF Sequester HMs in Vacuoles
Once HMs reach their target site, the mechanism of metal sequestration by polyphosphate granules in fungal vacuoles is activated [ 90 , 137 ]. Generally, sequestration limits the harmful effects of HMs, as the main compartment of HM storage in fungal and plant cells is the vacuole. Various reports have suggested that H + pumps in the vacuole, especially vacuolar proton ATPase (V-ATPase) and vacuolar proton-pyrophosphatase (V-PPase), aid in the uptake of HMs in vacuoles. Symbiosis increases the phosphorus content in the host plant, which provides metabolic energy as adenosine triphosphate (ATP) for the sequestration of metals within the vacuoles of the cells, thus restricting them to a smaller area and preventing their translocation to the other parts of the plant, as shown in Figure 4 [ 138 , 139 , 140 , 141 , 142 ]. Sequestration allows the concentration of a large amount of HMs in the above-ground parts without any phytotoxic effects on the plants. The vacuoles of leaf cells are the sequestration sites for non-essential and essential HMs [ 143 ]. The regulation of metal transport across the membrane is a decisive element in the control of metal homeostasis.
6.4. AMF Assist in HM Binding on the Fungal Cell Walls
The fungal cell wall also helps in the adsorption of HM ions. The fungal cell wall is made up of chitin and polysaccharides that are used as a barricade for HM ions and other solutes to get into the cells, thereby regulating their adsorption. Various functional groups such as imidazole carboxyl groups, amino groups and free hydroxyl groups provide binding sites for HMs and form negatively charged structures that adsorb most of the metals in the soil and block their movement in plants [ 144 ]. In addition, AMF store metals in the spores [ 145 , 146 ]. Several authors have reported that with the increase in metal concentrations, the cell walls of fungi act as a first line of defense as they obstruct the entry of HMs [ 11 , 138 ]. AMF induces the biosynthesis of cell wall in the roots of the host plant, which promotes metal reduction because with the increase in the thickness of cell wall, the area for metal absorption also increases [ 147 ]. At high concentrations of metal ions, a few of them pass through the cell wall, get deposited in the cell membrane of the fungus or are transported to the fungal cytoplasm, thereby reducing the amount of metal ions in the plants.
6.5. AMF Protects the PSII Reaction Center and Rectifies the Gas Exchange Capacity
A high amount of HMs in the soil is translocated to other plant parts and affects the enzyme activity alliance with chlorophyll biosynthesis, which further affects the photosynthesis process, mainly the photosystem II reaction center. The inoculation of AMF increases the chlorophyll content, especially chlorophyll a, which is responsible for photosynthesis in the host plant. Several findings indicate higher chlorophyll synthesis in plants inoculated with AMF that results in improved photosynthesis [
110
,
134
]. It has also been studied that AMF promote the enhancement of chlorophyll biosynthesis by increasing the de novo synthesis of proteins, which has a direct impact on the uptake of essential elements such as Mg and Fe, which constitute an imperative part of the chlorophyll molecule [
111
]. AMF symbiosis ameliorates the photosynthetic capacity and phytochemical efficiency of the host plants. It also improves the gas exchange capacity by stomatal opening and increasing the transcription fluxes.
6.6. Heavy Metals Enhance the Antioxidant Responses of Plants
Plants have antioxidative defense systems to protect themselves against heavy metal stress. These defense systems of plants include various enzymatic ROS scavengers such as glutathione peroxidase (GPX), catalase (CAT), superoxidase dismutase (SOD), glutathione reductase (GR), peroxidase (POD) and ascorbate peroxidase (APX), which protect against disruption and dysfunction in plant cells [ 90 , 148 ]. These antioxidant enzymes are highly active during metal stress. Generally, SOD detoxifies superoxide radicals (O 2− ), thereby averting stress-induced cellular damage. SOD activity generates H 2 O 2 , which is transformed into water by APX or CAT [ 111 , 128 ]. Studies performed by various researchers have demonstrated that AMF have the ability to promote the synthesis of antioxidants and increase their activity under metal stress. For instance, Garg et al. (2013) reported that AMF, under oxidative stress, upregulate antioxidant enzyme activity and reduce ROS production in the host plant Cajanus cajan and aid in mitigating metal stress [ 149 ]. It has also been observed that the level of the antioxidant enzyme activities of APX, GR, CAT and SOD increases under cadmium stress [ 150 ]. Yang et al. (2015) demonstrated that AMF symbiosis with Robinia pseudoacacia improves ROS-scavenging capabilities and enhances the enzymatic activities under different concentrations of Pb stress [ 99 ]. It has also been reported that AMF activate and stimulate the antioxidant system in Cd-stressed soil in Trigonella plants [ 151 ].
6.7. AMF-Assisted HM Chelation
A unique amelioration strategy adopted by AMF is the chelation of HMs with ligands having high affinity for metal ions in the cytosol. The production of chelating compounds occurs if the concentration of toxic metals exceeds the threshold value inside the cells. Chelation helps in warding off HMs by rendering them less available in the cytoplasm and also by decreasing their solubility and reactivity. Various chelating agents are present in AMF and plants such as metallothioneins (MTs), organic acids, phytochelatins (PCs) and amino acids, which play a crucial role in the tolerance to HMs in plants by chelating these substances [ 2 , 152 ]. Generally, HMs enter the cytoplasm of plant cells through the Zrt-Irt proteins (ZIP) belonging to the family of metal transporters. The HM tolerance mechanism relates to the synthesis of thiol peptides called phytochelatins, which form complexes with HMs. AMF are capable of enhancing the synthesis of phytochelatins [ 153 , 154 ]. These peptides are synthesized enzymatically with glutathione (GSH) as a substrate, in the presence of the enzyme phytochelatin synthase (PCS), which is activated by the existence of HMs [ 155 ]. Phytochelatin (PC) is involved in metal–thiol binding. The metal chelator (HM-PC) complexes are destined to reach cell vacuoles by moving through cytoplasm and then tonoplasts [ 138 ]. The excess metal ions in plants and fungi are stored in cell vacuoles, and phytochelatin–metal complexes are pumped into the vacuoles, whereby the complexed metals are made inert by the P1B-ATPase transporter (ABC-P1B) and ATP-binding-cassette, as shown in Figure 5 [ 156 ].
Zhang et al. reported that mycorrhizal inoculation in Zea mays decreases Cd toxicity and mobility by transforming Cd into an inactive form, which might be ascribed to the increased content of PC and GSH [ 147 ]. As AMF increases the PCs biosynthesis so more PC-Cd complexes are formed and transferred to the vacuole, thereby decreasing their negative effect [ 157 ]. Reports indicate that inoculation with F. mosseae enhances the level of GSH in Nicotiana tabacum , further reducing the Cd and As content in the leaves and roots of the plant [ 158 ].
Another group, i.e., metallothioneins (MTs), is also involved in the sequestration of HMs. MTs are a group of proteins having a low molecular weight, high metal content and non-enzymatic, cysteine-rich, long polypeptide chains that consist of a large number of amino acids. They have a common sequence pattern, i.e., Cys-X-Cys where X is an amino acid other than cysteine. These are the metal ligands that bind metal ions in a metal thiolate in clusters in the cytosol or sub-cellular compartments for the accumulation and sequestration of HMs in plant vacuoles, as shown in Figure 4 . Metallothioneins also have the competence to bind to HMs through the thiol group (-SH) of cysteine residues and help in protection against oxidative stress [ 159 ]. They are biosynthesized in mycorrhizal plants and AMF by certain hormones and HMs. Hasegawa et al. reported an increased Cd tolerance in cauliflower upon the insertion of CUP1 genes from yeast that, in response, enhanced its accumulation by 16-fold in plant tissues [ 160 ]. Some authors have found that various classes of MT genes are activated by HMs [ 161 , 162 ].
6.8. Glomalin-Induced Soil Metal Complexes
Glomalins are the glycoproteins produced by AMF and exist as homologs of heat shock protein 60 (hsp 60) that play a role in the immobilization of HMs [ 163 ]. Glomalin-related soil protein (GRSP) also exists as an alkaline soluble protein material with AMF. These are stable compounds impervious to heat degradation, generated mostly in the inner layer of the cell walls of mycorrhiza, and are released into the soil during hyphal turnover or after the death of the fungus [ 164 ]. Besides Glomeromycota, no other fungal group generates these glycoproteins in significant quantity [ 165 ]. The production of glomalin depends upon the level of metal ions present in the soil [ 165 , 166 ]. The symbiotic association between plants and the glomalin producers AMF enhances atmospheric CO 2 , which leads to an increase in the production of glomalin. When glomalin is released in the soil, it performs several functions such as improving the stability of soil aggregates, reducing soil erosion, enhances soil quality and forming protein–metal complexes, as shown in Figure 4 , which decrease the content of metal ions in the soil. These proteins further aid in the wall binding and influence the plants and AMF to withstand metal stress. The presence of certain functional groups in the glomalin protein structure assists in binding with HMs. Glomalins help in retaining the water content in the soil by adjusting the frequency of water transport between plants and the soil, and ultimately increases the development of the plant. Different studies carried out by Chern et al. (2007) and Gonzalez-Chavez et al. (2009) explained the involvement of glomalin in reducing the toxicity of HMs [ 167 , 168 ].
6.9. AMF-Assisted Phytoremediation of HMs
Phytoremediation is a technique in which plant species known as hyper-accumulators are used for growing in HM-contaminated soil. Metal ions are absorbed through plant roots and translocated in plants with no or minimal toxicity. Plants used in the phytoremediation of As are Pteris vittata , P. cretica and P. biaurita [ 169 ]. Hyper-accumulator plants for Pb are Sesbania drummondii and Helianthus annuus , and, for Cd, Sedum alfredii, Sesbania drummondii and Atriplex halimus. Amanita muscaria and Polygonum aviculare are the known hyperaccumulator plants that can accumulate a large amount of Hg from the soil [ 170 ]. The efficiency of phytoremediation is increased by inoculating phytoremediator plants with the AMF (as they are considered as a biological tool for improving phytoremediation). AMF are the components of the soil microbiome that play a vital role in the mobilization and immobilization of metal ions and alter their availability to plants. Their contribution to the process of phytoremediation is assistance in the phytostabilization and phytoextraction steps [ 171 , 172 ]. Phytostabilization includes the immobilization of HMs in the roots or soil, thus decreasing their bioavailability and mobility, while phytoextraction identifies the HMs for uptake and transports them to above-ground parts of the plant [ 173 ]. Mycorrhizal colonization in plant roots allows the stabilization and retention of HMs in the plant roots and rhizospheric region. Several factors of AMF play a role in this process such as glomalin production, which helps in binding the soil–metal complexes, and extended hyphal growth, which increases the absorptive area of the plant roots. In AMF-colonized plants, the effectiveness of phytostabilization and phytoextraction also depends on the extent of colonization of AMF, the AMF species, growth, the biomass yield and the ability of hyperaccumulator plants [ 174 ].
7. Impact of AMF-Induced Genes on Metal Toxicity
Heavy metal efflux is a strategy used by AMF to protect plants from metal toxicity [ 137 , 175 ]. Several transcriptional genes from fungal cells are involved in HM efflux and get activated upon metal exposure. GmarMT1 , a cDna-encoding metallothionein-like functional polypeptide was identified from the germinating spores of Gigaspora margarita to provide tolerance against Cu and Cd [ 176 ]. Furthermore, it has also been reported that exposure to HMs upregulates the expression of GmarMT1 in the symbiotic mycelium. GintABC1 was isolated as a putative ABC transporter from the extraradial mycelium of Glomus intraradices, involved in Cu and Cd mitigation [ 177 ]. Several genes are also involved in the maintenance of cellular homeostasis against HMs; those include GmarMT1 , GintABC1 , GrosMT1 and RintZnT1 [ 178 ]. GmarMT1 codes for MTs reported in G. margarita (BEG34), maintains the redox potential of the fungus and safeguards against oxidative stress. GintABC1 aids in the detoxification of zinc and copper [ 179 ]. A zinc transporter, RintZnT1 , isolated from Rhizophagus intraradices is involved in the vacuolar sequestration of Zn [ 180 ]. In Gigaspora rosea , the expression of GrosMT1 was reported [ 181 ]. Benabdellah et al. (2009) indicated GintGRX1 as a multifunctional enzyme and the first glomeromycotan glutaredoxin that responds to oxidative stress [ 182 ]. RintPDX1 was isolated from Rhizophagus intraradices and is involved in the reduction of Cu and hydrogen peroxide [ 183 ]. The upregulation of various transcriptional factors activating zinc transporter and glutathione S-transferase was observed in the extra- and intra-mycelia of the AMF Glomus intraradices in response to metal stress [ 184 ].
Altogether, these results indicate that the molecular regulation of genes plays an important role in HM accumulation and detoxification in fungal cells, which further prevents their translocation toward the host plant.
8. Conclusions and Future Prospects
In the twenty-first century, one of the biggest challenges of humanity is to feed the growing population of the world without an increase in the present environmental problems. However, due to the advancement of industrialization and human-induced activities, HM toxicity in soil is increasing rapidly, which further affects morpho-physiological processes in plants. There are few metals that are beneficial, while some impart negative effects on the plant and also on human health through the food chain.
Under HM stress, an excessive amount of ROS is produced that reacts with cellular organelles and results in oxidative damage to plant cellular structures. In response, plants activate several antioxidant enzymes, which scavenge the generated ROS to protect the cells from damage. Moreover, several soil engineers and environmentalists have approved different strategies to overcome the challenges and ameliorate the adverse impacts of HMs on plants. Among these approaches, the use of AMF is considered as one of the most promising and effective strategies.
Several changes such as the enhancement of the antioxidant response and modification in root morphology are seen in plants due to the influence of AMF, and their symbiotic relations improve the growth of the plant by enhancing nutrient acquisition. They also act as a biofertilizer for plants and biosorbant for HMs and enhance plant performance via specific intrinsic molecular mechanisms. They help in improving soil aggregation by secreting glomalin, which forms protein–metal complexes, thereby restricting the entry of HMs into the plant. AMF also adsorb a large amount of HMs onto the fungal walls and also sequester them in fungal vacuoles (biological barriers). They also help in enhancing the phytoremediation of HMs and play a key role in the mobilization and immobilization of HMs. However, the signaling pathways and molecular mechanisms that are linked to the formation of successful mycorrhizal symbiosis need better understanding. Genomic knowledge regarding AMF is poor and needs to be unraveled.
Author Contributions
Conceptualization, R.V., E.N. and K.K.; manuscript writing, R.D. and H.K.; manuscript editing, M.T.I. and D.K.; critical revising, R.V., E.N., K.K., M.T.I. and D.K. All authors have read and agreed to the published version of the manuscript.
Funding
Supported by University of Hradec Kralove (Faculty of Science, VT2019-2021).
Conflicts of Interest
The authors declare that they have no competing interests.
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Figure 1. Global map of heavy metals showing countries where significant impact has been observed.
Figure 1. Global map of heavy metals showing countries where significant impact has been observed.
Figure 2. Uptake, translocation and accumulation of heavy metal (HM) in plants.
Figure 3. Effects of heavy metals on plants [ 100 , 117 ].
Figure 3. Effects of heavy metals on plants [ 100 , 117 ].
Figure 4. Mechanism of heavy metal (HM) detoxification in plants by arbuscular mycorrhizal symbiosis. (1) Chelating agents (phytochelatins and organic acids from the plant and glomalins from the fungus) bind with HM ions in the soil. (2–4) Transport of metal ions across the cell wall and plasma membrane (acting as selective barrier and with the help of transporters) of plants and fungi. (5) Chelation of HM ions in the cytosol. (6) Export of HMs via active or passive transport from plant or fungal cells. (7) Sequestration of HM ions in the vacuoles of plant and fungal cells. (8) Transport of HM ions in the fungal hyphae. (9) Export of HM ions from the fungus to plant cells via transporters in arbuscules. Modified from [ 123 ] with permission.
Figure 4. Mechanism of heavy metal (HM) detoxification in plants by arbuscular mycorrhizal symbiosis. (1) Chelating agents (phytochelatins and organic acids from the plant and glomalins from the fungus) bind with HM ions in the soil. (2–4) Transport of metal ions across the cell wall and plasma membrane (acting as selective barrier and with the help of transporters) of plants and fungi. (5) Chelation of HM ions in the cytosol. (6) Export of HMs via active or passive transport from plant or fungal cells. (7) Sequestration of HM ions in the vacuoles of plant and fungal cells. (8) Transport of HM ions in the fungal hyphae. (9) Export of HM ions from the fungus to plant cells via transporters in arbuscules. Modified from [ 123 ] with permission.
Figure 5.
Mitigation of heavy metal (HM) stress by chelating agents. The figure shows the uptake of HM that is mediated via zinc and iron like protein (ZIP) transporter and other ion channels; HM ions, when entering the cytosol, activate the enzyme phytochelatin synthase (PCS) and catalyze the formation of phytochelatins (PCs) from glutathione (GSH), which is synthesized from glutamate (Glu) and cysteine (Cys) by the transfer of γ glutamyl-cysteinyl (γ Glu-Cys) conjugates onto GSH via glutathione synthetase (GS); PCs binds with the cytosolic HM ions and form heavy metal–phytochelatin (HM-PC) complexes, which enter the vacuole via ATP-binding-cassette (ABC), P1B ATPase (P1B) and other transporters such as heavy metal ATPases (HMA), natural resistance-associated macrophage protein (NRAMP) and ZIP transporters. HM ions also lead to the production of reactive oxygen species (ROS) such as superoxide radical (O
2−
), which is dismutated by superoxide dismutase (SOD) and produces hydrogen peroxide (H
2
O
2
), which is further broken down into water (H
2
O) by ascorbate peroxidase (APX) and catalase (CAT). Peroxidase (POD); glutathione peroxidase (GPX); glutathione reductase (GR).
Figure 5. Mitigation of heavy metal (HM) stress by chelating agents. The figure shows the uptake of HM that is mediated via zinc and iron like protein (ZIP) transporter and other ion channels; HM ions, when entering the cytosol, activate the enzyme phytochelatin synthase (PCS) and catalyze the formation of phytochelatins (PCs) from glutathione (GSH), which is synthesized from glutamate (Glu) and cysteine (Cys) by the transfer of γ glutamyl-cysteinyl (γ Glu-Cys) conjugates onto GSH via glutathione synthetase (GS); PCs binds with the cytosolic HM ions and form heavy metal–phytochelatin (HM-PC) complexes, which enter the vacuole via ATP-binding-cassette (ABC), P1B ATPase (P1B) and other transporters such as heavy metal ATPases (HMA), natural resistance-associated macrophage protein (NRAMP) and ZIP transporters. HM ions also lead to the production of reactive oxygen species (ROS) such as superoxide radical (O 2− ), which is dismutated by superoxide dismutase (SOD) and produces hydrogen peroxide (H 2 O 2 ), which is further broken down into water (H 2 O) by ascorbate peroxidase (APX) and catalase (CAT). Peroxidase (POD); glutathione peroxidase (GPX); glutathione reductase (GR).
Table 1. Health effects on humans of different heavy metals (NS—not specified).
Table 1. Health effects on humans of different heavy metals (NS—not specified).
Heavy Metal Source Country Biological Effects Ref Arsenic (As) Drinking water Hungary Increase in stillbirths and spontaneous abortion [ 22 ] Drinking water Chile Increase in stillbirths and infant mortality [ 23 ] Drinking water Bangladesh Increase in spontaneous abortions, stillbirths and preterm births [ 24 ] Drinking water Taiwan Reduced birth rate [ 25 ] Drinking water India Increase in stillbirths [ 26 ] Drinking water Chile Increased liver cancer mortality for ages 10–19 [ 27 ] Drinking water Chile Increased lung cancer and chronic obstructive pulmonary disease (COPD) deaths for ages 30–39 [ 28 ] Drinking water Bangladesh Chronic cough, breathing problems or blood in the sputum of 39 aged people [ 29 ] Drinking water Mongolia Skin hyperkeratosis, hyperpigmentation and depigmentation and other skin lesions among men [ 30 ] Soil and vegetables Nigeria Liver damage, gastro-intestinal effects, lung cancer and skin lesions [ 31 ] Rice and edible mushrooms China NS [ 32 ] Food Spain NS [ 33 ] Cadmium (Cd) Soil Thailand High prevalence of renal dysfunction, bone mineral loss, hypertension and urinary stones [ 34 ] NS Sweden Tubular and glomerular kidney effects in women [ 35 ] Industrial plants Italy Delayed onset of puberty in male adolescents and impaired testicular growth [ 36 ] Soil and vegetables Turkey Gastro-intestinal, renal prostate and ovarian cancer [ 37 ] Soil Nigeria Damage to central nervous system [ 31 ] Rice and edible mushrooms China NS [ 32 ] Vegetables and Fish China NS [ 38 ] Food Spain NS [ 33 ] Smelting China Renal dysfunction [ 39 ] Rice Thailand Kidney, lung and liver problems [ 40 ] Food South west china Bone damage, kidney injury and cancer [ 41 ] Mining areas South china Renal effects, particularly in children [ 42 ] Drinking water Iran NS [ 43 ] Chromium (Cr) Ground water India Gastrointestinal and dermatological complaints and abnormal hematological function [ 44 ] Chromate production plant USA Nasal irritation and nasal ulceration [ 45 ] Vegetables Nigeria Respiratory problems, lung cancer and skin rashes [ 31 ] Vegetables China NS [ 38 ] Copper (Cu) Drinking water Chile Nausea, abdominal pain or vomiting [ 46 ] Vegetables Bangladesh Kidney damage or tumors [ 47 ] Vegetables China NS [ 38 ] Drinking water Iran NS [ 43 ] Mercury (Hg) Mercury mining sites China Postural sway, as well as hand tremor, may be affected by elemental mercury vapor exposure [ 48 ] Mercury mines China Finger and eyelid tremor, gingivitis, and typical darkline on gums [ 49 ] Tapajos river basin Brazil Sensory disturbance (especially glove-and-stocking type, which is characteristic of Minamata disease), tremor, failure in two-point discrimination, and slight balancing failure [ 50 ] Rice and edible mushrooms China NS [ 32 ] Lead (Pb) Glass work plant China Susceptible autonomic nervous function [ 51 ] Battery plant Turkey Increased erythrocyte malondialdehyde (MDA) levels, catalase and glucose-6-phosphate dehydrogenase (G6PD) activities, and decreased blood glutathione/glutathione disulfide ratio [ 52 ] Automobile plant India High blood pressure, less heme biosynthesis [ 53 ] Soil China Renal dysfunction [ 54 ] Vegetables Nigeria Neurological, immunological effects [ 31 ] Vegetables China NS [ 38 ] Food Spain NS [ 33 ] Battery plant China Neurological damage [ 55 ] Drinking water Iran NS [ 43 ]
Table 2. Maximum level of heavy metals in food components (European Commission, 2006, 2015/1005, June 2015 and National Food Safety Standard (GB 2762-2012)).
Table 2. Maximum level of heavy metals in food components (European Commission, 2006, 2015/1005, June 2015 and National Food Safety Standard (GB 2762-2012)).
Heavy Metals Food Components Maximum Levels (mg kg −1 wet weight) Ref. Lead (Pb) Leafy vegetables, brassica vegetables and a few fungi like Pleurotus ostreatus (oyster mushroom), Agaricus bisporus (common mushroom) and Lentinula edodes (shiitake mushroom) 0.3 [ 57 ] with permission Vegetables (excluding fresh herbs and fungi, leafy vegetables and brassica vegetables) 0.1 Berries and small fruits 0.2 Cereals, pulses and legumes 0.2 Fruits (excluding small fruits and berries) 0.1 Mercury (Hg) Muscle meat of fish and fishery products 0.50 Cadmium (Cd) Fresh herbs, leafy vegetables, celeriac and some fungi like Pleurotus ostreatus (oyster mushroom) and Agaricus bisporus (common mushroom) 0.2 Potatoes and root and stem vegetables (excluding celeriac plants) 0.1 Fruits and vegetables (excluding fresh herbs, root and stem vegetables, fungi, potatoes and leafy vegetables) 0.05 Soybeans 0.2 Cereals (excluding rice, wheat, germ and bran) 0.1 Rice, wheat, germ and bran 0.2 Tin (Sn) Canned food (except beverages) 200 Canned beverages (including vegetable and fruit juices) 100 Processed cereal based products (excluding powdered and dried products) 50 Chromium (Cr) Fresh vegetables 0.5 [ 58 ] Grains and its products 1.0 Beans 1.0 Meat and its products 1.0 Nickel (Ni) Oil and its products (mainly hydrogenated vegetable oil) 1.0
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THE J-CURVE THEORY AND THE BLACK URBAN RIOTS: AN EMPIRICAL TEST OF PROGRESSIVE RELATIVE DEPRIVATION THEORY* | CIA FOIA (foia.cia.gov)
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THE J-CURVE THEORY AND THE BLACK URBAN RIOTS: AN EMPIRICAL TEST OF PROGRESSIVE RELATIVE DEPRIVATION THEORY*
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Reprinted from THE AMERICAN POLITICAL SCIENCE REVIEW
Vol. LXXI, No. 3, September, 1977
The J-Curve Theory and the Black Urban Riots:
An Empirical Test of Progressive Relative Deprivation Theory
ABRAHAM H. MILLER
University of Cincinnati
Louis H. BOLCE
Fordham University, Lincoln Center
and
MARK HALLIGAN
Northwestern University Law School
Introduction
In the intellectual quest for a systematic
understanding of the etiology of political and
collective violence, relative deprivation theory
has emerged as a prevalent explanatory device.
One form of relative deprivation theory has
received particularly strong scholarly attention
through theoretical elaboration and empirical
application to a variety of significant episodes
of political and collective violence. This form is
the progressive variety of relative deprivation
and is most commonly referred to as the
"J-curve.
"1
*This research was funded by the University of
Concinnati Research Council through an award to
Professor Miller. The data were obtained from the
Inter-University Consortium for Political Research
through the facilities of the University of Cincinnati
Behavioral Sciences Laboratory. The authors alone are
responsible for the use and interpretation of the data.
At the time of this study, Louis H. Bocce was a Charles
Phelps Taft Graduate Fellow in Political Science and
Mark Halligan was an Undergraduate Fellow in Politi-
cal Science. William Klecka and Alfred Tuchfarber,
University of Cincinnati, Ted Robert Gun, North-
western University, and four anonymous reviewers
contributed useful and insightful suggestions which are
gratefully acknowledged.
I James C. Davies, "Toward a Theory of Revolu-
tion," in Studies in Social Movements, ed. Barry
McLaughlin (New York: The Free Press, 1969), pp.
85-109. Hardly an anthology on revolution or social
movements exists without including this work. James
A. Geschwender, "Explorations in the Theory of
Social Movements and Revolutions," Social Forces 47,
2 (December, 1968), 127-135, has attempted to
elaborate the theory in terms of cognitive dissonance.
The J-curve resulted from an attempt by
James C. Davies to reconcile what he perceived
as two antithetical explanations of the phenom-
enon of revolution. According to Davies, two of
the most famous students of revolution, Karl
Marx and Alexis de Tocqueville, had arrived at
completely opposite conclusions about the
causes of revolution. Drawing on Marx's work
in The Communist Manifesto, Davies argued
that Marx perceived revolutions as most likely
to occur when things get worse, when the
misery of the proletariate increased relative to
the economic standard of living of the bour-
geoise. In contrast, Tocqueville had advanced
the theory that revolutions occurred when a
previously oppressive regime released the yoke
and 'created expectations it could not fulfill.2
Davies attempted to reconcile these diver-
gent explanations by arguing that each of these
perspicacious students of revolution had ac-
curately rendered part of the picture of revolu-
2Alexis de Tocqueville, The Old Regime and the
French Revolution, translated by Stuart Gilbert (Gar-
den City, N.J.: Doubleday Anchor, 1955), p. 177.
Tocqueville's observation that those parts of France
which experienced the greatest degree of positive
change also showed the greatest popular discontent is
sometimes referred to as Tocqueville's paradox. Two
different explanations of the paradox exist. The most
common, and the one used by Davies and in this
research, is the rising expectations thesis. A less
well-known interpretation is referred to as "the
present value of the past." This argues that present
achievement is devaluated by the perception of~ past
costs. See, in this regard, Charles Wolf, Jr., "The
Present Value of the Past," mimeo (Santa Monica: The
Rand Corporation, 1969).
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%AW
1977 The J-Curve Theory and the Black Urban Riots 965
tion, but not the total picture. The complete
depiction of the causes of revolution awaited
the fashioning of both components into a single
entity, which Davies engagingly accomplished.
Davies argued that revolutions occur when a
period of progress is followed by a period of
sharp reversal and decline.
This rise-an.d-decline phenomenon can be
read as: first Tocqueville then Marx. As Davies
notes:. "Revolutions are most likely to occur
when a prolonged period of objective economic
and social development is followed by a short
period of sharp reversal. The all-important
effect on the minds of people in a particular
society is to produce, during the former period,
an expectation of continued ability to satisfy
needs - which continue to rise - and, during
the latter, a mental state of anxiety and
frustration when manifest reality breaks away
from anticipated reality."3 The theory is de-
picted in Figure 1 below.
3Davies, "Toward a Theory of Revolution," p. 86.
At a conceptual level the theory has a great
deal of appeal. It is the type of theory that is
very attractive to social scientists. It reconciles
apparent contradictions in the work of two
leading theorists and creates a parsimonious
explanatory structure. In the search for con-
ceptual simplicity, clarity and phenom-
enological regularity, it yields, at a minimum,
heuristic success and beyond that has had
ostensible empirical corroboration.
From the perspective of empirical theory,
however, there are several primary empirical,
methodological, and conceptual problems in-
herent in the structure and application of the
J-curve. These problems have consequences for
the J-curve theory specifically and relative
deprivation theory generally.
It is the purpose of this research to examine
some of these problems in the context of the
application of the J-curve to the black urban
riots. Although the primary objective of the
research is to test the J-curve theory, considera-
tion will also be given to the substantive
EXPECTED NEED SATISFACTION
U)
w
W
z
1956
ACTUAL NEED
SATISFACTION
1
A TOLERABLE GAP
AN INTOLERABLE
GAP BETWEEN WHAT
PEOPLE WANT AND
WHAT THEY GET
BETWEEN WHAT PEOPLE
WANT AND WHAT THEY GET
1964
TIME
1968
Figure 1.
Pictorial Representation of Davies's J-Curve
(Adapted from James C. Davies, "The J-Curve...," p. 691)
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966 The American Political Science Review
implications of the analysis as it affects our research designs based on relative deprivation
understanding of the riots. theory have played a prominent role in the
Seemingly, a number of different events attempts to explain these events. The results of
could have been chosen to examine the theo- these studies, in making a case for relative
retical and empirical application of the J-curve. deprivation as. a primary explanation of the
The black urban riots were chosen, in part, riots, have been largely disappointing, despite
because Davies, himself, has applied his theory some rather sophisticated and well-conceived
to this set of events.4 Consequently, it is methodological procedures.8 As McPhail notes
possible to follow his operationalizations, ". . . there is considerable reason for rejecting
avoiding questions of operational comparabili- the sociological and popular cliche that abso-
ty, and to assess the theory in an appropriate lute or relative deprivation and the ensuing
empirical setting. Moreover, one of the major frustration or discontent or despair is the root
criticisms which we level against the application cause of rebellion."9 On the basis of his
of the J-curve, and most relative deprivation observations, McPhail suggests reconsideration
theories, is the problem of reductionism, some- of Guff's assertion that relative deprivation is
times referred to in the philosophy of science as ". . . as fundamental to understanding civil
the level-of-analysis issue: the validity of using strife as the law of gravity is to atmospheric
data and concepts developed at one level of physics......10
analysis to test theories formulated at a differ- Davies, in his assessment of the urban riots,
ent level.5 (This problem is comparable to the strikes a more confident note: "The Negro
one raised by W. S. Robinson's6 criticism of the rebellion appears to have been preceded by the
use of aggregate correlations to draw inferences same J-curve of expectations that are first
concerning the behavior of individuals.) A gratified and then frustrated."11 In contrast to
variety of data exists for the study of the black Davies's work, the studies cited by McPhail are
urban riots, making it possible to conduct generally based on analyses of socioeconomic
analytical comparisons and reconstruct oper- and political characteristics of riot versus non-
utionalizations at various analytical levels. As a riot cities. Relative deprivation is usually rnea-
result, the level-of-analysis problem can be sured in these studies by comparing various
empirically assessed rather than simply noted as socioeconomic, census data characteristics of
a caveat affecting the research. the black community with those of the white
The Black Urban Riots and community. The underlying logic is that the
Relative Deprivation Theory riot cities should manifest greater disparities
along these dimensions than the nonriot cities.
In his revrew of the sociological literature on Davies's work is based on population charac-
the black urban riots, Clark McPhail7 notes that tarictire? nnnn14-1-
4James C. Davies, "The J-Curve of Rising and
Declining Satisfactions as a Cause of S P.
ea' Sociological Review, 36 (December, 1971),
Revolutions and a Contained Rebellion," in The 1058-1073.
history of Violence in America, ed. Hugh Davis
Graham and Ted Robert Gurr (New York: Bantam 8See, in this regard, Milton Bloombaum, "The
Books, 1970), pp. 690-731. Conditions Underlying, Race Riots as Portrayed by
Sin the philosophy of science this problem is Multidimensional Scalogram Analysis: A Reanalysis of
sometimes alluded to as a problem in reductionism. Lieberson and Silverman's Data," American S'oci-
See, for example, May Brodbeck, "Methodological ological Review, 33 (February, 1968), 76-91; Bryan
Individualism: Definition and Reduction," in Readings T. Downes, "Social Characteristics of Riot Cities: A
in the Philosophy of the Social Sciences, ed. May (D
Comparative ecember, r96Study, 504-520; Stanley Quarterly, 49
Brodbeck (New York: The MacMillian Co., 1968). Arnold Silverman, "The Precipitants Lieberson and
6W. S. Robinson, "Ecological Correlations and the Conditions of Race Riots," AmericandSociological
Behavior of Individuals," American Sociological Re- Review, 30 (December, 1965), 887-898; Seymour
view, 15 (June, 1950), 351-357. See also: L. A. Spilerman, "The Causes of Racial Disturbances: A
Goodman, "Some Alternatives to Ecological Correla- Comparison of Alternative Explanations," American
tion," American Journal of Sociology, 64 (May, Sociological Review, 35 (August, 1970), 627-649;
1959), 610-625; 0. D. Duncan and B. Davis, "An and Jules Wanderer, "An Index of Riot Severity and
Alternative to Ecological Correlation," American Soci- Some Correlates," American Journal of Sociology, 74
ological Review, 18 (December, 1953), 665-666. 0. (March, 1969), 500-505.
1). Duncan, R. P. Cuzzort, and B. Duncan, Statistical q
Geography (Glencoe: The Free Press, 1961), note, as McPhail, "Civil Disorder Participation," p. 1064.
we do, that the problem arises wherever the units of t 0Ted Robert Gurr, "Urban Disorder: Perspectives
analysis are changed. The change need not be from From the Comparative Study of Civil Strife," in Riots
one distinct type of unit (e.g., individual) to a and Rebellion: Civil Violence in the Urban Com-
d i fferent type (e.g., group). munity, ed. Louis H. Mascotti and Don R. Bowen
70ark McPhail, "Civil Disorder Participation: A (Beverly Hills: Sage Publications, 1968), p. 52.
Critical Examination of Recent Research," American 11Davies, "The J-curve," p. 717.
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1977 The J-Curve Theory and the Black Urban Riots 967
The index for measuring relative deprivation is This eclectic interpretation of the data raises
constructed by dividing family income by issues concerning the validity of the J-curve as
average years of schooling for the total and an explanation of the urban riots. Moreover,
nonwhite populations. The ratio of the result- Davies's logic, as that of his compeers in
ing nonwhite quotient to the white quotient is
described as a measure of nonwhite satisfaction.
The nonwhite satisfaction ratio is then plotted
from 1940 to 1967 to determine whether a
J-curve can be traced for the period of the riots.
The numeric data and plot are presented in
Table 1 and Figure 2 below.
Although in some remote fashion Figure 2
might be construed to illustrate a J-curve, the
reversal in need fulfillment takes place during
the wrong years - predicting a peak of unrest
in the mid-1950s. Despite this, the data from
the black urban riots are not seen as disconfirm-
ing the theory. Davies simply argues that the
riots needed the exacerbation of southern
violence a decade later to produce the aggres-
sion that began with the frustration demon-
strated by the ratio of education to income.12
12Jbid., p. 724.
TIME
Figure 2.
Index of Nonwhite Economic Satisfaction
(Adapted from James C. Davies,
"The JCurve... ," p. 724)
Table 1. Davies's Origin and Time Sequence of Black Frustration
(adapted from James C. Davies, "The J-Curve... ," p. 726)
Average Family Income Divided by
Average Years of Schooling
Nonwhite
Satisfaction
Nonwhite
Frustration
Year
Total
Population
Nonwhite
Population
Column 2 as
% of Column I
Column 3
from 100%
1940
$1231
= 146.3
$ 489
= 84.3
57.5
42.5
8.4
5.8
3031
= 336.8
1614
= 233.9
69.4
30.6
9.0
6.9
1950
3319
= 356.9
1869
= 274.9
77.0
23.0
9.3
6.8
3890
= 385.1
2338
= 329.3
85.8
14.5
10.1
7.1
4971
= 469.0
2764
= 359.0
76.5
23.5
10.6
7.7
5620
= 530.2
3233
= 394.3
74.4
25.6
10.6
8.2
5956
= 522.5
3330
= 387.2
74.1
25.9
11.4
8.6
6559
= 560.6
3839
= 431.3
77.0
23.0
11.7
8.9
3995
= 443.8
75.3
23.7
11.8
9.0
7436
= 619.7
4628
= 503.0
81.2
18.8
12.0
9.2
a
a
78.9
20.2
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968 The American Political Science Review
sociology cited by McPhail,' 3 is not congruent
with the empirical and theoretical requirements
of relative deprivation theory. The requisite
level of analysis has been violated in the
assertion that the presence of aggregate, non-
perceptual characteristics ostensibly related to
black frustration is an appropriate indication
that individual black people are indeed exper-
iencing frustration.
The importance of this logical gap is best
understood by looking at the psychological
basis of relative deprivation theory. Relative
deprivation theory claims theoretical descent
from the psychological research of John Dol-
lard and his Yale colleagues.14 The Yale team
established what has come to be known as the
frustration-aggression hypothesis. This hypoth-
esis, as it has evolved, proposes that frustration
produces various responses, one of which is
aggression, and if nonaggressive responses do
not relieve the frustration, the probability of an
aggressive response increases. 15
Relative deprivation theory has built upon
this hypothesis in viewing relative deprivation
as a major component of the chain of events
leading to aggression. It is this deprivation that
produces frustration; frustration produces ag-
gression; aggression produces civil violence; and
civil violence can be translated into political
violence. 16
The language of relative deprivation theory
is replete with reference to this psychological
foundation. As Davies notes:-"Political stability
and instability are ultimately dependent on a
state of mind, a mood, in a society. Satisfied or
apathetic people who are poor in goods, status,
and power can remain politically quiet and
their opposites can revolt .... 1117
Relative deprivation is, thus, an individual
experience, and, despite objective, aggregate
indicators, relative deprivation can only take
place if people perceive themselves to be
deprived. Economic indicators may demon-
strate that the availability of goods, status, or
power may be low or may have diminished
13McPhail, "Civil Disorder Participation," p. 1059.
14John Dollard et al., Frustration and Aggression
(New Haven: Yale University Press, 1939).
15This statement is based on the elaboration of
Dollard's work by Neal E. Miller et al., "The Frustra-
tion-Aggression Hypothesis," Psychological Review,
48 (July, 1941), 337-342. See also: Leonard Berko-
witz, Aggression: A Social Psychological Analysis
(New York: McGraw Hill, 1962), in Advances in
Experimental Social Psychology, Volume 2, ed. Leon-
ard Berkowitz (New York: Academic Press, 1965).
t6Gurr, Why Men Rebel (Princeton: Princeton
University Press, paperback, 1970).
1 Davies, "The J-curve," pp. 86-87.
from some previous level, but this does not
demonstrate that people perceive themselves to
have been deprived and are consequently dis-
content.
With .the exception of work by Grofman and
Muller,' 8 relative deprivation theorists general-
ly use the language and theoretical foundation
of individual data but perform their empirical
testing with aggregate social and economic
indicators. The chasm that separates objective
societal conditions from subjective perceptions
seems to have trapped many researchers who
have made enthusiastic and confident assertions
about the perceptual basis of individual be-
havior from theoretically remote aggregate in-
dicators.19
Given the above considerations, how would
Davies's index appear if he had obtained indi-
vidual-level data (overlooking momentarily the
entire question of perceptual vs. nonperceptual
data and simply looking at the difference in the
unit of analysis)? From our individual data,
taken from the Michigan Survey Research
Center election studies from 1956-1968,
Davies's operationalizations were replicated and
his index was reconstructed. The data are
displayed below for both whites and blacks and
by region in Table 2 and Figure 3.
The above data and Figure 3 do not demon-
strate anything as parsimonious as a J-curve.
The index of black frustration varies without
consistent pattern, and the overall impression it
imparts is that the differences between blacks
and whites are so trivial as to be substantively
inconsequential. In four out of the seven years
analyzed, blacks, contrary to the interpretation
originally derived from Davies's data, receive a
slightly higher income return for years of
"Bernard N. Grofman and Edward N. Muller,
"The Strange Case of Relative Gratification and
Potential for Political Violence: The V-Curve Hy-
pothesis," The American Political Science Review, 67
(August, 1973), 514-539.
191n addition to the sociological literature noted
above in footnote 8, see, for example: Iva K.
Feierabend, R. L. Feierabend, and B. A. Nesvold,
"Social Change and Political Violence: Cross-National
Patterns," in Anger, Violence and Politics: Theories
and Research, ed. No K. Feierabend, Rosalind L.
Feierabend, and Ted Robert Gurr (Englewood Cliffs,
N.J.: Prentice Hall, No K. Feierabend, Rosalind L.
Feierabend, "Aggressive Behaviors within Polities
1948-1962: A Cross-National Study," Journal of
Conflict Resolution, 10 (September, 1966), 249-271;
Raymond Tanter and Manus Midlarsky, "A Theory of
Revolution," Journal of Conflict Resolution, 11 (Sep-
tember, 1967), 264-280; and Ted Robert Gurr, "A
Causal Model of Civil Strife: Using New Indices," in
Anger, Violence and Politics, ed. I. K. Feierabend et
al. Much to his credit, of all the authors cited, Gurr,
Ibid., p. 210, is the only one to acknowledge the
level-of-analysis problem.
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Approved For Release 2005/07/01 : CIA-RDP86B009R000100070018-6
1977 The J-Curve Theory and the Black Urban Riots 969
66 58 60 62 64 66 68
TIME
TOTAL BLACKS
NORTHERN BLACKS
SOUTHERN BLACKS
Figure 3.
Index of Black Economic Satisfaction
from Individual Data
education than do whites. This is not as
surprising a finding as it first appears (as we will
demonstrate below), but is rather a penetrating
commentary on the inappropriateness of the
index as a measure of black frustration. Al-
though income generally varies with education,
it is those with lower education who receive a
higher per annum income return for unit of
education. Higher education yields a con-
siderable amount more money over a working
lifetime. On a per annum basis, however, it
takes many increments in years of schooling to
produce modest increments in income. Black
people tend to cluster at the bottom end of the
education distribution where the ratio of in-
come to education is highest. As a result, black
people have higher income to education ratios.
This is not to argue the absurd position that
whites are frustrated relative to blacks. Rather,
what is discerned from this finding is the
futility of attempting to measure a perceptual
concept such as frustration with aggregate,
objective indicators. Moreover, it is solely be-
cause Davies's index is based on a ratio of two
aggregates that the inappropriateness of the
index is not readily discernible. The manner in
which the aggregations conceal what is occur-
ring can be readily observed in Table 3 below.
In Table 3 the level of education is controlled
by partition design, and the data indicate that it
is the lower levels of education that yield the
best ratio of income to years of schooling.
Having demonstrated the inappropriateness
of Davies's index for testing the J-curve theory
in the context of the urban riots, we attempted
a refinement of the operationalization. Given
relative deprivation theorists' reliance on objec-
tive data, we were interested in whether chang-
ing the unit of analysis, from aggregate to
individual, and refining the measurement might
yield something similar to a J-curve or other
theoretically parsimonious configuration. Also,
we were interested in observing if more so-
phisticated operationalizations of the objective
but individual-level data would correspond to
our perceptual measures (see below).
To accomplish this refinement in measure-
ment, two objective measures based on the
regression of income on education, after parti-
Table 2. Individual-Level Objective Data Measures of
Davies's Operationalization of Black Economic Satisfaction'
Average of Each Head's Income Score
Divided by Each Head's Years of Schooling Scoreb
Black Satisfaction Ratio of
Column 2 to Column 1
Year
Total
White
North
White
South
White
Total
Black
North
Black
South
Black
Total
Black
North
Black
South
Black
1956
1.68
1.72
1.55
1.72
1.99
1.47
1.02
1.15
.95
1958
1.62
1.62
1.61
1.66
1.60
1.74
1.02
.98
1.08
1960
.55
.55
.51
.47
.54
.40
.85
.99
.71
1962
1.84
1.91
1.70
2.01
2.20
1.88
1.09
1.15
1.10
1964
.59
.59
.59
.53
.56
.52
.90
.93
.88
1966
.54
.55
.52
.55
.59
.46
1.01
1.08
.88
1968
.70
.70
.70
.58
.63
.52
.83
.90
.75
'Scores are not translatable into dollar terms as they reflect the relationship between measurements on coding
categories. Codes are not always comparable from year to year, but this is of no consequence since we are inter-
ested in the differences in any one year between whites and blacks and how these differences vary longitudinally.
Column 3, the nonwhite satisfaction index, multiplied by 100 is similar to the nonwhite satisfaction index in
Table 1.
bOnly heads of household were used.
Approved For Release 2005/07/01 : CIA-RDP86B00985R000100070018-6
Aft
Approved For Release 2005/07/01 : CIA-RDP86B00985RM0100070018-6
970 The American Political Science Review
All
Educatiopal
Groups
Grade
School
High
School
College
and
Above
Total white
1.84c
3.10
1.53
0.86
North white
1.91
3.13
1.57
0.8.5
South white
1.70
3.00
1.43
0.88
Total black
2.01
2.67
1.08
0.85
North black
2.20
3.77
1.11
0.98
South black
1.87
2.17
1.05
0.55
aData are from 1962 only since the issue is a cross-sectional one and not a longitudinal one. The year was
chosen at random.
bHeads of household only.
cScore is the average of each head's income score divided by each head's year of schooling score.
tioning race and region, were created. One of
these is called the "differ variable," and it
computes the difference between predicted
income for blacks subtracted from predicted
income for whites, when income is regressed
against education. The second and more
elaborate measure is called the "discrim vari-
able," and it is constructed by subtracting a
black individual's actual income from the in-
come he would expect if he were white.20 This
20This latter operationalizations was suggested, in
part, by Otis D. Duncan, "Discrimination Against
TOTAL BLACKS
NORTHERN BLACKS
SOUTHERN BLACKS
Figure 4.
Differ Operationalization of
Black Economic Satisfaction
creates two objective individual-level measures
of black relative deprivation. The results of
these operationalizations are displayed below in
Table 4 and Figures 4 and 5.
Regardless of operational differences, the
trends for Figures 4 and 5 demonstrate the
same time-series pattern. In neither case do we
observe a J-curve. It is also important to note
the divergences between the black population
in each of the two regions. The national
configuration is often an averaging of radically
different trends between northern blacks and
southern blacks. (This demonstrates the im-
portance of looking at specific groups rather
than treating the society as a monolith, or
failing to make important distinctions within
Negroes," in Social Intelligence for America's Future,
ed. Bertram M. Gross (Boston: Allyn and Bacon,
1969). Discrimination is measured by taking the slope
and intercept of the regression equation for whites and
plugging in the observed independent variable (educa-
tion) scores for blacks. The resultant predicted depen-
dent variable (income) scores for blacks are subtracted
from the blacks' actual score on the dependent
variable. The residual [Yp (if respondent were white)
- Ya] is the measure of deprivation.
A wholly individual measure, based on differences
between actual and predicted income, was desired for
the "differ" operationalization. Such a measure would
have been very similar to the one used for the
"discrim" operationalization. In the calculation of
measures of association, the type of measure is
feasible. In calculating summary measures for the
purpose of obtaining averages for blacks, this is not
possible. In the case of any individual black., the
"differ" is the residual between predicted income and
actual income. The average of the residuals
[E (Yi-Ya)/N ] however, always equals zero.. The
operationalization
| https://www.cia.gov/readingroom/document/cia-rdp86b00985r000100070018-6 |
Comment: Will William Hague turn hope into action?
In opposition William Hague was a vocal campaigner for the people of Burma. Now he has power, will he follow through?
* un / William Hague
Comment: Will William Hague turn hope into action?
*Comment & Analysis
* un / William Hague
Comment: Will William Hague turn hope into action?
In opposition William Hague was a vocal campaigner for the people of Burma. Now he has power, will he follow through?
By Zoya Phan
I remember how I walked onto the huge stage, wearing my ethnic Karen traditional white dress, and saw what seemed like thousands of people in the hall. I knew this was an opportunity to raise awareness about what was going on in my country – I had to seize it.
I talked about how the Burmese army attacked ethnic Karen villages in eastern Burma, shooting children, burning homes, beheading people and raping women, even girls as young as five.
I told delegates: "The opportunity to speak to you today has given me hope. Promoting human rights is not a cultural issue, it is everyone's business and should be a priority for every country."
In 2007 I was invited back again, speaking in the aftermath of the shooting of monks on the streets of Rangoon. The following year, as shadow foreign secretary, William Hague even came to the launch of my autobiography, 'Little Daughter', in the House of Commons.
I think it will be hard for most people to understand how much these events meant. For senior politicians in the UK to invite me to speak, and take the time to offer support, when the world usually seems to be looking the other way, it means a lot to a girl from the jungle. I am aware British MPs won't win many extra votes for supporting democracy in Burma.
When William Hague became foreign secretary after the election I was pleased he continued to support a UN Commission of Inquiry into war crimes and crimes against humanity in Burma. Such an inquiry had been recommended by the United Nations special rapporteur on Burma and is strongly supported by Burma's democracy movement.
The need for such an inquiry has now become one of the main issues facing the international community with regard to Burma. Rigged elections last year have been followed by a new constitution which legalises dictatorship. While two of the most senior generals have retired, their right-hand men are now running the government. And for many ethnic people, they have unleashed hell. Longstanding ceasefire agreements with some armed ethnic groups have been broken. Thousands of Burmese army soldiers have been sent to attack ethnic minority civilian populations, mortar-bombing villages, just as mine was mortar bombed so many years ago.
Every week at Burma Campaign UK we receive more reports of how the Burmese Army is using gang-rape as a weapon of war. Women are being raped, sometimes in front of their husbands and children, and often then mutilated and killed. Thousands of people are used as slave labour to carry military supplies, and forced to walk in front of army columns as human minesweepers. Since the elections in Burma in November last year, around a hundred thousand people have been forced to flee their homes. At the same time torture continues in Burma's jails, with almost 2,000 political prisoners still in jail, and the government denying they even exist.
But to my horror, governments and the United Nations have been virtually silent about what is taking place. Instead they seem to be falling for a charm offensive by the new rebranded dictatorship. They talk about regime promises of economic reform, they talk about how it is easier for diplomats to get visas to visit. They even praised the regime for not following through on its threat to attack Aung San Suu Kyi's supporters if she left the capital. Apparently this is progress. How can they have such short memories? They have been lied to over and over again by the same rulers. They might have taken off their soldiers uniforms, but it is the same people and the same lies. They always dangle the prospect of change round the corner, and the international community then says we must wait and see.
While they wait my people are being slaughtered.
Foreign secretary William Hague now has the chance to turn the hope he gave me into concrete action. A UN Inquiry into war crimes and crimes against humanity can be established by the United Nations General Assembly resolution on Burma, which is passed every year. Officials from the European Union will table the resolution by the end of September. William Hague has the influence to persuade his fellow EU ministers and put text establishing an inquiry into the draft resolution. Then at last there will be some concrete action. A UN inquiry will not only expose the truth about what is happening in Burma, it will also end the dictatorship's perception that they can act with impunity. This will lead to a reduction in human rights abuses taking place, as for the first time they will be afraid of consequences for their actions.
So please foreign secretary William Hague, take this concrete action for my people. You have it in your power to make sure the General Assembly establishes a UN inquiry. You have given me hope. Now please turn hope into action.
Zoya Phan is campaigns manager at Burma Campaign UK. Her autobiography is published as 'Undaunted' in the USA, and 'Little Daughter' in the rest of the world. You can watch her 2006 speeech to the Conservative party conference hereand her 2007 speech here.
| https://www.politics.co.uk/comment-analysis/2011/09/11/comment-will-william-hague-turn-hope-into-action/ |
McWilson Warren, PhD (1929–2021), Scientist, Malaria Researcher, and ASTMH Editor in: The American Journal of Tropical Medicine and Hygiene Volume 104 Issue 4 (2021)
" McWilson Warren, PhD (1929–2021), Scientist, Malaria Researcher, and ASTMH Editor" published on 07 Apr 2021 by The American Society of Tropical Medicine and Hygiene.
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The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
Online ISSN:
1476-1645
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McWilson Warren, PhD (1929–2021), scientist, malaria researcher, and ASTMH Editor.
McWilson Warren, PhD (1929–2021), scientist, malaria researcher, and ASTMH Editor.
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McWilson Warren, PhD (1929–2021), Scientist, Malaria Researcher, and ASTMH Editor
Mark L. Eberhard
Mark L. Eberhard Division of Parasitic Diseases, CDC, Atlanta, Georgia (Retired);
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Barnett L. Cline Professor Emeritus, Tulane University, New Orleans, Louisiana;
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Peter F. Weller Harvard Medical School, Harvard T.H. Chan School of Public Health, Beth Israel Deaconess Medical Center, Boston, Massachusetts;
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DOI:
https://doi.org/10.4269/ajtmh.21-1929
Volume/Issue:
Volume 104: Issue 4
Page(s):
1602–1603
McWilson Warren, a long-standing member of the ASTMH, passed away in January of this year at the age of 91 years. Mac, as he was affectionately known, was born on a small tobacco farm outside Clinton, NC, where he grew up and attended local schools. He earned both his bachelor and master’s degrees at the University of North Carolina. An undergraduate course in parasitology sparked what was to be a most exciting and extraordinary career. Mac earned his master’s under the guidance of John Larsh, becoming intrigued with malaria and the biological complexity of parasites. Larsh steered Mac to Martin Young’s NIH laboratory in Columbia, SC, where he learned to rear and dissect mosquitoes, and prepare blood films on patients undergoing malaria therapy for neurosyphilis. After 2 years in Young’s laboratory, Mac enrolled in the PhD program at Rice University in 1954 under the guidance of Asa Chandler, where he worked on dwarf tapeworm biology. Mac then took a position in the Preventive Medicine Program at the University of Oklahoma School of Medicine from 1957 to 1961 where, among other things, he worked on hospital acquired Staphylococcusinfections.
During his tenure in Oklahoma, Mac enrolled in a Rockefeller-funded program at Tulane for a 2-month tour of Central American countries to learn more about tropical diseases. During this trip, Mac realized an intense desire to work overseas full time. Happily, Robert (Bob) Coatney at the NIH recruited Mac to join a team in Malaysia that was studying primate malaria. This checked both of Mac’s boxes – going overseas and returning to the study of malaria. In concert with Don Eyles, but also working side by side with eminent malariologists such as Arthur Sandosham, Harry Wharton, and Pete Contacos in addition to Martin Young and Bob Coatney, lasting scientific contributions were made. Frequent visitors to Malaysia included other malaria luminaries such as P. C. C. Garnham, Leonard Bruce Chwatt, Bill Bray, and Robert Desowitz. The purpose of the undertaking, in a nutshell, was to determine what primate malarias existed, to what extent they could infect humans, and whether the anopheline vectors of these primate species would feed on and transmit infection to humans—in other words, what impact would primate malaria have on the success of the malaria eradication program being undertaken at that time. This story is wonderfully captured in the book The Primate Malarias (Coatney, Collins, Warren, Contacos 1971), where the species of primate malaria are described and illustrated, their vectors elucidated, and their biology detailed, including how readily they infected various other primates, including humans. The information generated in those studies from 1961 to 1965 has served malaria research well in vaccine development, chemotherapy studies, and understanding and appreciation of the rise in human cases of Plasmodium knowlesiin Southeast Asia recently documented in this and other journals.
After leaving Malaysia, Mac returned briefly to the NIH from 1965 to 1967, where he was contacted by P. C. C. Garnham at the London School of Hygiene and Tropical Medicine about doing a postdoctorate year in his laboratory working on, among other things, irradiated sporozoites. Following his time in London, Mac spent several years at the NIH, but with his continued interest in overseas assignments, in 1970, he was transferred to the CDC and sent to help establish the new field station in El Salvador. It was here that he met Mary Keany, whom he married in 1975. During their time in Salvador, they had one son, James. Following Mac’s tenure in El Salvador and on his return to Atlanta, Mac did malaria work in Haiti, Pakistan, and then back to Malaysia from 1981 to 1984 on secondment to the WHO to train the trainers for the malaria control program that encompassed the entire Pacific region. Mac finally returned to the CDC and Atlanta in 1985 to finish out his 32-year U.S. Public Health Service career.
Shortly before retiring from the CDC, Mac became Editor-in-Chief of the AJTMH in 1991, a position he continued for 7 years. It was at the Journalthat Mac was able to blend his vast experience working in the tropics, engaging with networks of colleagues and collaborators, and pursuing scientific discovery. When Mac took over as Editor, the Society and Journalwere both on the verge of major changes. Mac navigated the transition from paper submissions to a totally electronic process, including a format change from 7 × 10 to the contemporary 8.5 × 11, but throughout, he kept a laser attention to keeping the Journalscientifically focused and publishing the highest quality articles. Ultimately, the Society and Journalcame out much stronger, with a major increase in membership as well as readership of the Journal, becoming an internationally recognized top-tier medical journal. Mac kept a keen focus on scientific quality and integrity, and widening manuscript submission to a broader range of topics. He was always attentive and supportive of the efforts of young scientists to publish, including selfless assistance to scientists for whom English was not their first language. Another personal interest of Mac’s was snakebite, and he was always excited to get another manuscript dealing with some aspect of this topic. This was probably stimulated in great measure by his many years spent in the tropics and firsthand experience with victims, and recognition of the terrible toll of this underappreciated, underreported problem on rural populations. Mac found his time as Editor to be both stimulating and enormously rewarding.
Mac also made other profound contributions to the Society, both scientific and programmatic, including serving as the first ASTMH Scientific Program chair from 1978 to 1980. His intellect, scientific curiosity, appreciation of biological complexities, and love of the tropics served him well throughout his distinguished career. In particular, Mac took it upon himself to encourage and support promising young scientists, particularly those at the CDC.
During their years in Atlanta, the Warrens’ home was a unique gathering spot for colleagues and visitors, and their hospitality was widely appreciated. The warmth of his home and wealth of editorial experience was opened to Jim Kazura, the newly named Editor, when he succeeded him in 1997–1998. In 2000, the Warrens moved to rural New Hampshire, where they owned a home that had been in Mary’s family. Mac enjoyed retirement, and the two of them were actively involved in the town of Grafton. Mac’s enthusiasm, intellectual endeavors, and physical activity continued. He relished long country walks, including in wintertime, always with an eye toward the study of local flora and fauna. Mac was preceded in death by his wife Mary, and is survived by son James. His infectious passion for tropical medicine research and immense contributions to the ASTMH will be greatly missed.
<here is a image e2d9eeba045d4445-2697972c058ccb8f
McWilson Warren, PhD (1929–2021), scientist, malaria researcher, and ASTMH Editor.
Citation: The American Journal of Tropical Medicine and Hygiene 104, 4;10.4269/ajtmh.21-1929
McWilson Warren, PhD (1929–2021), scientist, malaria researcher, and ASTMH Editor.
Citation: The American Journal of Tropical Medicine and Hygiene 104, 4;10.4269/ajtmh.21-1929
McWilson Warren, PhD (1929–2021), scientist, malaria researcher, and ASTMH Editor.
Citation: The American Journal of Tropical Medicine and Hygiene 104, 4;10.4269/ajtmh.21-1929
McWilson Warren, PhD (1929–2021), scientist, malaria researcher, and ASTMH Editor.
Citation: The American Journal of Tropical Medicine and Hygiene 104, 4;10.4269/ajtmh.21-1929
| https://www.ajtmh.org/view/journals/tpmd/104/4/article-p1602.xml?result=17&rskey=5DCzBm |
PA44 pilot has loss of electric power; executes a gear up landing. - NASA ASRS
PA44 pilot has loss of electric power; executes a gear up landing.
PA44 pilot has loss of electric power; executes a gear up landing.
Attributes ACN 723088 Time Date 200701 Local Time Of Day 1801 To 2400 Place Locale Reference airport : l45.airport State Reference CA Altitude msl single value : 10000 Environment Flight Conditions VMC Light Dusk Aircraft 1 Controlling Facilities artcc : zla.artcc Operator general aviation : personal Make Model Name PA-44 Seminole Turbo Seminole Operating Under FAR Part Part 91 Flight Phase cruise : level Flight Plan IFR Person 1 Affiliation other Function flight crew : single pilot Qualification pilot : commercial pilot : instrument pilot : multi engine Experience flight time last 90 days : 44 flight time total : 1147 flight time type : 22 ASRS Report 723088 Events Anomaly aircraft equipment problem : critical ground encounters : gear up landing Independent Detector other flight crewa Resolutory Action none taken : detected after the fact Supplementary Problem Areas Aircraft Flight Crew Human Performance
Narrative:
I checked the WXonce again; filed a flight plan on duats and headed back to lgb. I did a full preflight and run-up. Aside from the placarded instruments; everything else seemed to be working fine and I decided to proceed with my trip. Long beach clearance delivery could not pull up my flight plan and suggested tower en route towards santa barbara; and I accepted the clearance. The flight proceeded without incident until 5 or 10 mins south of the ventura VORwhen I noticed that my #1 VORand the associated DMEhad failed. This problem had occurred in this aircraft a few times during my flight training; had been intermittent at times with the localizer working but not the GS; etc. I checked and everything else was working at the time; circuit breakers were all in; ammeter was working. I tried turning the avionics switch off and back on and did not see a change in the VORor DME. Before reaching ventura; I requested a deviation towards gorman and the valley but the controller told me they would be unable to send me there; and suggested direct towards paso robles. I did not sense an emergency at that time; accepted the heading and continued trying to make the VORwork. I checked all the fuses; the ammeter and all the switches. I checked all circuit breakers; recycled the avionics; master; alternator; collision light switches; etc; but to no avail. Then; well north of ventura; now in pitch black darkness; to my surprise; I lost the second VORas well. I concentrated on maintaining my heading; made another check to make sure that the avionics switch was in the proper location and now realized that I would probably not have either VORfor the rest of the trip. I tried to call ATCbut could not transmit. A few mins later I heard ATCcalling me; and asking another aircraft to call me; but I could not reach them. I heard ATCask me to identify if I could hear them. I placed 7700 on the transponder (I realized after I landed that 7600 was the lost communication frequency) and pressed the identify button. Realizing that I was over mountainous terrain with few airports; I decided to deviate from my ATCflight plan and headed east towards the valley; reasoning that I was more familiar with the terrain over the valley; knew there were multiple airports along the valley; and worse-come-to-worse; a forced landing would be safer over agricultural areas than over the mountains. I focused on flying the airplane; saw the lights of bakersfield and headed towards the south end of town towards L45 so as to stay away from the bfl traffic as I could not transmit on my radio. I saw the rotating beacon and headed for the south end of the field; lining up with runway 34. I did not see any other traffic in the vicinity and decided to land. I went through my pre-landing checklist; gumps; both fuel tanks and electric fuel pumps were on; pressed the gear lever down; mixture full forward; propellers forward and landing lights on. I knew that the radio/ VOR's were not working but some of the panel lights were functioning; I could still hear ATCxmissions and I did not realize that I had a near total electrical failure and that the gear had not come down -- I was so focused on flying the airplane and did not pull the emergency gear extension lever. I landed on the centerline and came to a relatively smooth but rather sudden stop; and realized I had landed gear up. I turned off all the switches and exited the aircraft.
Original NASA ASRS Text
Title:
PA44 PLT HAS LOSS OF ELECTRIC PWR; EXECUTES A GEAR UP LNDG.
Narrative:
I CHKED THE WX ONCE AGAIN; FILED A FLT PLAN ON DUATS AND HEADED BACK TO LGB. I DID A FULL PREFLT AND RUN-UP. ASIDE FROM THE PLACARDED INSTS; EVERYTHING ELSE SEEMED TO BE WORKING FINE AND I DECIDED TO PROCEED WITH MY TRIP. LONG BEACH CLRNC DELIVERY COULD NOT PULL UP MY FLT PLAN AND SUGGESTED TWR ENRTE TOWARDS SANTA BARBARA; AND I ACCEPTED THE CLRNC. THE FLT PROCEEDED WITHOUT INCIDENT UNTIL 5 OR 10 MINS S OF THE VENTURA VOR WHEN I NOTICED THAT MY #1 VOR AND THE ASSOCIATED DME HAD FAILED. THIS PROB HAD OCCURRED IN THIS ACFT A FEW TIMES DURING MY FLT TRAINING; HAD BEEN INTERMITTENT AT TIMES WITH THE LOC WORKING BUT NOT THE GS; ETC. I CHKED AND EVERYTHING ELSE WAS WORKING AT THE TIME; CIRCUIT BREAKERS WERE ALL IN; AMMETER WAS WORKING. I TRIED TURNING THE AVIONICS SWITCH OFF AND BACK ON AND DID NOT SEE A CHANGE IN THE VOR OR DME. BEFORE REACHING VENTURA; I REQUESTED A DEV TOWARDS GORMAN AND THE VALLEY BUT THE CTLR TOLD ME THEY WOULD BE UNABLE TO SEND ME THERE; AND SUGGESTED DIRECT TOWARDS PASO ROBLES. I DID NOT SENSE AN EMER AT THAT TIME; ACCEPTED THE HDG AND CONTINUED TRYING TO MAKE THE VOR WORK. I CHKED ALL THE FUSES; THE AMMETER AND ALL THE SWITCHES. I CHKED ALL CIRCUIT BREAKERS; RECYCLED THE AVIONICS; MASTER; ALTERNATOR; COLLISION LIGHT SWITCHES; ETC; BUT TO NO AVAIL. THEN; WELL N OF VENTURA; NOW IN PITCH BLACK DARKNESS; TO MY SURPRISE; I LOST THE SECOND VOR AS WELL. I CONCENTRATED ON MAINTAINING MY HDG; MADE ANOTHER CHK TO MAKE SURE THAT THE AVIONICS SWITCH WAS IN THE PROPER LOCATION AND NOW REALIZED THAT I WOULD PROBABLY NOT HAVE EITHER VOR FOR THE REST OF THE TRIP. I TRIED TO CALL ATC BUT COULD NOT XMIT. A FEW MINS LATER I HEARD ATC CALLING ME; AND ASKING ANOTHER ACFT TO CALL ME; BUT I COULD NOT REACH THEM. I HEARD ATC ASK ME TO IDENT IF I COULD HEAR THEM. I PLACED 7700 ON THE XPONDER (I REALIZED AFTER I LANDED THAT 7600 WAS THE LOST COM FREQ) AND PRESSED THE IDENT BUTTON. REALIZING THAT I WAS OVER MOUNTAINOUS TERRAIN WITH FEW ARPTS; I DECIDED TO DEVIATE FROM MY ATC FLT PLAN AND HEADED E TOWARDS THE VALLEY; REASONING THAT I WAS MORE FAMILIAR WITH THE TERRAIN OVER THE VALLEY; KNEW THERE WERE MULTIPLE ARPTS ALONG THE VALLEY; AND WORSE-COME-TO-WORSE; A FORCED LNDG WOULD BE SAFER OVER AGRICULTURAL AREAS THAN OVER THE MOUNTAINS. I FOCUSED ON FLYING THE AIRPLANE; SAW THE LIGHTS OF BAKERSFIELD AND HEADED TOWARDS THE S END OF TOWN TOWARDS L45 SO AS TO STAY AWAY FROM THE BFL TFC AS I COULD NOT XMIT ON MY RADIO. I SAW THE ROTATING BEACON AND HEADED FOR THE S END OF THE FIELD; LINING UP WITH RWY 34. I DID NOT SEE ANY OTHER TFC IN THE VICINITY AND DECIDED TO LAND. I WENT THROUGH MY PRE-LNDG CHKLIST; GUMPS; BOTH FUEL TANKS AND ELECTRIC FUEL PUMPS WERE ON; PRESSED THE GEAR LEVER DOWN; MIXTURE FULL FORWARD; PROPS FORWARD AND LNDG LIGHTS ON. I KNEW THAT THE RADIO/VOR'S WERE NOT WORKING BUT SOME OF THE PANEL LIGHTS WERE FUNCTIONING; I COULD STILL HEAR ATC XMISSIONS AND I DID NOT REALIZE THAT I HAD A NEAR TOTAL ELECTRICAL FAILURE AND THAT THE GEAR HAD NOT COME DOWN -- I WAS SO FOCUSED ON FLYING THE AIRPLANE AND DID NOT PULL THE EMER GEAR EXTENSION LEVER. I LANDED ON THE CTRLINE AND CAME TO A RELATIVELY SMOOTH BUT RATHER SUDDEN STOP; AND REALIZED I HAD LANDED GEAR UP. I TURNED OFF ALL THE SWITCHES AND EXITED THE ACFT.
| http://www.37000feet.com/report/723088/PA44-pilot-has-loss-of-electric-power-executes-a-gear-up-landing |
Barriers to solidarity in Lebanon’s 2019 uprising, by Anne Kirstine Rønn
" Barriers to solidarity in Lebanon’s 2019 uprising, by Anne Kirstine Rønn" published on 30 May 2023 by Brill.
Barriers to solidarity in Lebanon’s 2019 uprising: How should we understand them, and what can be learned from them?
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Anne Kirstine Rønn
Carlsberg Postdoctoral Fellow in the Middle East Centre at the London School of Economics and Political Science
While conducting field research for my PhD dissertation on Lebanon's 2019 October Uprising, I frequently asked my interlocutors what they considered to be the uprising's most important characteristic. One of the common answers I received was "diversity." According to many of the protesters I spoke to, the uprising was remarkable because it united individuals from different walks of life. Street vendors and lawyers suddenly stood side by side and chanted slogans against Lebanon's corrupt sectarian elites that have governed the country since the civil war.
The celebration of diversity, inclusivity and solidarity across societal fault lines was also evident in the news coverage of the uprising, and asstudies and survey dataconfirm, protesters did indeed come from all corners of Lebanon. They were old and young, women and men, and they broke boundaries between regions, sects, and classes.
However, the October Uprising was not solely a display of unity; it also reflected underlying divisions and exclusionary practices that constitute barriers to solidarity between protesters. Like in any other popular protest movement, there were disagreements regarding tactics and political goals. Prejudices and fears also persisted, resulting in negative attitudes and suspicions toward certain segments of the population in the streets and squares of the uprising. Specifically, individuals belonging to marginalized groups in society faced such biases.
I delve into the barriers to solidarity within the Lebanese uprising in my recentarticlein Middle East Law and Governance, entitled “Promoting Inclusivity in Anti-Sectarian Protests: Understanding the Dilemmas of Organizers in Lebanon's 2019 October Uprising”. The article draws on interviews with twenty-two individuals who represented a diverse range of key organizers in the protests that took place in Beirut. Its objective is to understand the dilemmas faced by these organizers when attempting to address the persistence of negative discourses concerning a particular segment of the lower classes in Lebanon, namely young men from the areas of Dahiyeh and Khandak el Ghamiq.
Dahiyeh and Khandak el Ghamiq are known to be stronghold areas of Hezbollah and Amal Movement, Lebanon's two major Shiite political actors. Dahiyeh, located south of Beirut, has a population of approximately 500,000 people and comprises various impoverished and more affluent neighborhoods predominantly controlled by Hezbollah. Khandak el Ghamiq is a smaller working-class neighborhood in downtown Beirut associated with the Amal Movement.
A general stereotype exists regarding people from these two areas: a man dressed in black, adorned with tattoos, and exhibiting a hypermasculine attitude. He rides a cheap motorbike and is assumed to be a supporter of Hezbollah or Amal. Allegedly brainwashed by the propaganda of these political parties, he is believed to be willing to defend them with violence. Whenever such individuals are present at demonstrations against the Lebanese regime, they are assumed to have ulterior motives, aiming to infiltrate and intimidate the crowds rather than expressing genuine discontent with the political elites.
Early in the uprising, protesters encountered several attacks by people who matched this stereotype and were often identified as individuals from Khandak or Dahiyeh. Although such claims were frequently difficult to substantiate, they led to a general fear and suspicion towards men who appeared to be "infiltrators" from the two areas. Moreover, they perpetuated a negative and reductionist image of Khandak el Ghamiq and Dahiyeh, which had existed for years – an image that disregarded the political agency of people from these areas and ignored the fact that they were among the first to join the demonstrations at the beginning
The organizers interviewed in the study, some of whom lived in or had relatives in Khandak el Ghamiq and Dahiyeh, generally found the stereotype problematic. They wanted to promote an alternative and more holistic image of the areas and wished to advocate for solidarity with the communities, including those who held skeptical attitudes toward the uprising or were deterred from participating.
During my interviews with the organizers, several potential discursive strategies were discussed that could have demonstrated such understanding. However, all of these strategies shared a common problem: they could be interpreted as favoritism toward a particular sectarian group. Implementing them would therefore jeopardize the integrity of the October Uprising as a movement against sectarianism, as argued by the vast majority of organizers in my study.
The article not only sheds light on a sensitive issue within the October Uprising but also highlights broader challenges related to solidarity, and inclusion in popular protests. Firstly, it reminds us that these challenges should be understood through an intersectional lens, which pays attention to the intersections of class, gender, sect, ethnicity, and geography.
This might seem self-evident. However, assessments of inclusivity of popular protests often tend to focus on singular identities. Especially in popular, mediatized narratives, descriptions such as cross-class and cross-sectarian are frequently used. If we examine the October Uprising through such one-dimensional lenses, we might overlook or fail to understand the complex challenges to solidarity.
As the article shows, we can only fully grasp why it was difficult for the uprising to promote discourses of solidarity with the people of Khandak el Ghamiq and Dahiyeh with reference to their combined position as lower-class Shiites (and males) from geographical areas that carry specific historical, cultural, and political connotations.
When a protest movement is described as cross-class, we must therefore remember to ask whether it truly includes all segments of the lower classes. When it is said to have women at the forefront, which specific women are being referred to?
The article also provides lessons about the structural obstacles to protest solidarity in the context of Lebanon. More specifically, it illustrates how theomnipresence of sectarianismlimited the discursive and tactical opportunities of organizers in the October Uprising. It is, of course, possible that organizers in potential future Lebanese uprisings may learn from past experiences and find ways to enhance solidarity with the communities of Khandak el Ghamiq and Dahiyeh. However, as I discuss, mass protests in Lebanon, as well as in any other society, are unlikely to promote inclusivity of all groups.
Because of this, I argue we need to pay attention to the smaller-scale and more localized forms of grassroots mobilization. How can such types of mobilization complement and compensate for the limitations of mass uprisings? In the Lebanese case, a main task for future research is to explore whether environmental campaigns, alternative labor unions, and student movements can cultivate solidarity ties that the October Uprising struggled to establish. By engaging with this question, we might reach a better understanding of the prospects for citizens to challenge the country's ingrained political and economic regime.
| https://blog.brill.com/display/post/guest-post/barriers-to-solidarity-in-lebanon-s-2019-uprising--how-should-we-understand-them--and-what-can-be-learned-from-them-.xml?result=1&rskey=xefOGB |
Tibbetts v. Job - Illinois - Case Law - VLEX 891930364
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Tibbetts v. Job
<table><tbody><tr><td> Court</td><td> Supreme Court of Illinois</td></tr><tr><td> Writing for the Court</td><td> TREAT</td></tr><tr><td> Citation</td><td> 1 Peck 453,11 Ill. 453,1849 WL 4305</td></tr><tr><td> Parties</td><td> ALBERT TIBBETTSv.JEREMIAH JOB et al.</td></tr><tr><td> Decision Date</td><td> 31 December 1849</td></tr></tbody></table>
11 Ill. 453
1849 WL 4305 (Ill.)
1 Peck (IL) 453
ALBERT TIBBETTS
v.
JEREMIAH JOB et al.
Supreme Court of Illinois.
December Term, 1849.
This was an action of ejectment, brought in the Madison circuit court, to recover the south fractional half section thirty-three, in township five north, range nine west, of said county.
The cause was heard before Underwood, judge, and a jury, at August term, 1849, of said court. The jury found for the defendants, a motion for a new trial was denied, and the plaintiff below brings the cause to this court, upon the following agreed state of facts:
Plaintiff, to sustain his case, introduced a deed from the auditor to John Dement, of date January 24, 1835, reciting the sale of said land for the sum of three dollars and fifty-one cents, the amount of tax for the year 1832, with interest and costs. It was admitted by defendants, that plaintiff connected himself with Dement's title for eleven-thirteenths of said land,
[11 Ill. 454]
excepting forty acres to be taken off the east side of said land, which plaintiff did not claim. Defendants admitted possession, claiming title to the whole of the land at the time of suit brought.
The defendants then offered in evidence the deposition of Thomas H. Campbell, contained in the record of this case, when before the supreme court at its December term, 1848, together with the diagrams from the auditor's office, thereto attached; to the admission of which in evidence to the jury the plaintiff objected. Objection overruled, and deposition read. The plaintiff at the time excepted to the decision of the court. It was agreed by the parties that the depositions contained in the record, heretofore before the supreme court, might be referred to, and taken as part of this record.
Deposition of Thomas H. Campbell. --I am auditor of public accounts--have held the office since March, 1846--was clerk in said office from February, 1843, to March, 1846. The land in controversy was entered in the book containing a list of the district lands subject to taxation from the year 1828 to 1834, as appears from the diagram marked A, and taxed as is therein represented. Diagram A is correctly copied from the tax book in my office, and contains every thing in said book relating to said land. There is no heading to any of the columns of said book, except for the year's tax, as is shown in the diagram. The first entry in the diagram is copied from, and is the first entry on page 177, of said book. This land is not listed in any other book for taxation, from the year 1828 to 1834. It no where appears in said book that said land was classed or listed as first, second or third rate, unless the figure (1) in the ninth column of the diagram marked A, checked with red ink, denotes the rate or class.
Cross-examination.--The figures 204, immediately succeeding the figure (1) in the ninth column of diagram A, refer to page 204 of Non-resident Land Book C, as will more fully appear by diagram marked B. Diagram B is a correct copy from book C, page 204, so far as relates to the tracts of land therein described. The headings to the columns, as represented by diagram B, are the same as in book C, except that in said book the name of land district is written at the head of some of the pages. The letter A, and the figures 7 and 108, in the tenth column of diagram B, refer--the letter A to
[11 Ill. 455]
Non-resident Land Book A, figure 7, of said book, and figure 108 refers to page 108, of said book--as will more fully appear by reference to diagram marked C; the same being a correct transcript from said pages of said book, so far as relates to the lands described in the diagram. The books from which the diagrams A, B and C are made are the books in which non resident lands were listed by the auditor. Figure (1) in the ninth column of the diagrams marked A and B, in my opinion, denotes the rate or class in which the land was listed for taxation. The original lists, with the affidavits accompanying them, furnished by non residents previous to the year 1833, are not among the files of my office. Think that for the tax of 1832 this land was not taxed in the first class, on account of the amount of tax charged.
*DIAGRAM A.
A Critical Assessment of the Originalist Case Against Administrative Regulatory Power: New Evidence from the Federal Tax on Private Real Estate in the 1790s. United States Yale Law Journal Vol. 130 Nbr. 6, April 2021 April 1, 2021 ...part of officials to make the required descriptions and categorizations. See Graves v. Bruen, 11 Ill. 431, 439-41 (1849); Tibbetts v. Job, 11 Ill. 453, 460-61 (625.) BLACKWELL, supra note 613, at 183. (626.) Thurston v. Little, 3 Mass. (1 Tyng) 429, 432-33 (1807). (627.) Thayer v. Stearns, ......
The Chicago v. People Ex Rel. Joseph Dennison United States Supreme Court of Illinois March 21, 1881 ...69; Fowler v. People, 93 Ill. 116. 8. If land is listed in one class and assessed in another, the assessment is void. Tibbetts v. Job, 11 Ill. 453; Graves v. Bruen, Id. 431. 9. A decree of court of competent jurisdiction is binding on the parties till reversed. Mr. C. BECKWITH, also for the......
Austin v. People of State United States Illinois Supreme Court December 31, 1849 ...a further sum of one hundred dollars. S. T. LOGAN and C. EMERSON, for plaintiff in error. LINCOLN & HERNDON, for defendants in error. [11 Ill. 453]TREAT, C. J. The cases of Frazier v. Laughlin, 1 Gilman, 347, and Hinckley v. West, 4 Gilman, 136, are directly in point, and decisive of this c......
2 cases
The Chicago v. People Ex Rel. Joseph Dennison United States Supreme Court of Illinois March 21, 1881 ...69; Fowler v. People, 93 Ill. 116. 8. If land is listed in one class and assessed in another, the assessment is void. Tibbetts v. Job, 11 Ill. 453; Graves v. Bruen, Id. 431. 9. A decree of court of competent jurisdiction is binding on the parties till reversed. Mr. C. BECKWITH, also for the......
Austin v. People of State United States Supreme Court of Illinois December 31, 1849 ...a further sum of one hundred dollars. S. T. LOGAN and C. EMERSON, for plaintiff in error. LINCOLN & HERNDON, for defendants in error. [11 Ill. 453]TREAT, C. J. The cases of Frazier v. Laughlin, 1 Gilman, 347, and Hinckley v. West, 4 Gilman, 136, are directly in point, and decisive of this c......
1 books & journal articles
A Critical Assessment of the Originalist Case Against Administrative Regulatory Power: New Evidence from the Federal Tax on Private Real Estate in the 1790s. United States Yale Law Journal Vol. 130 No. 6, April 2021 April 1, 2021 ...part of officials to make the required descriptions and categorizations. See Graves v. Bruen, 11 Ill. 431, 439-41 (1849); Tibbetts v. Job, 11 Ill. 453, 460-61 (625.) BLACKWELL, supra note 613, at 183. (626.) Thurston v. Little, 3 Mass. (1 Tyng) 429, 432-33 (1807). (627.) Thayer v. Stearns, ......
| https://case-law.vlex.com/vid/tibbetts-v-job-891930364 |
1 Creating the Institute of Medicine | To Improve Human Health: A History of the Institute of Medicine | The National Academies Press
Read chapter 1 Creating the Institute of Medicine: Since its founding in 1970, the Institute of Medicine has become an internationally recognized source o...
To Improve Human Health: A History of the Institute of Medicine (1998)
Chapter: 1 Creating the Institute of Medicine
1 Creating the Institute of Medicine
In the summer of 1964, Dr. Irvine Page, who edited a journal that was widely distributed to members of the medical profession, wrote an editorial on the need for a National Academy of Medicine. With the appearance of this editorial, Irvine Page began a concerted campaign to create the National Academy of Medicine (NAM). Although he was ultimately unsuccessful in creating an entity with this name, he set in motion the forces that would lead to the creation of the Institute of Medicine (IOM) in 1970.
Between 1964 and 1970, key government officials and leaders of academic medicine agreed on the need for an organization concerned with health policy but disagreed over what form that organization should take. Irvine Page had the idea of an advocacy group that would represent the best collective wisdom of the medical profession. In his mind, such a group should be composed primarily of physicians. James Shannon, director of the National Institutes of Health (NIH), thought that the organization's primary mission should be to support scientific research in medicine. Walsh McDermott, a prominent practitioner of academic medicine with a deep interest in public health, believed that the organization should serve as a forum where physicians and other professionals concerned with health policy could work toward the solution of health-related social problems.
Although profound differences divided these three men, they concurred in the belief that the organization should do more than bestow an honor on its members. Each favored an entity composed of working members. Each also realized that the primary reason for forming a new organization lay in the changed relationship between the federal government and medicine. They understood that the federal government, the nation's primary source of funds for the conduct of medical research and the payment of medical care, could not be ignored as a factor in health policy.
The discussions in which Page, Shannon, and McDermott engaged took place in two main settings. Beginning in 1967, Irvine Page organized a series of meetings in Cleveland to discuss the formation of
Suggested Citation:
a National Academy of Medicine. These gave way in November 1967 to the activities of the Board on Medicine, a group convened in Washington by the National Academy of Sciences. What emerged in 1970 was the Institute of Medicine. An institute not an academy, the new organization nonetheless reflected the ideas of all three men.
The Page Discussion Group
Between 1964 and 1967, Irvine Page had the field pretty much to himself, although he was not alone in proposing a National Academy of Medicine. In the fall of 1960, a six-person task force, which contained no fewer than four future members of the Institute of Medicine, advised President-elect Kennedy of the need to establish a National Academy of Medicine ''comparable to the National Academy of Sciences.'' President Kennedy showed little interest in this recommendation, preferring to concentrate instead on the creation of Medicare, as the expansion of Social Security to pay the hospital bills of Social Security recipients became known. When Irvine Page wrote his editorial on the need for a National Academy of Medicine in 1964, Medicare was a hotly contested issue. On September 2, 1964, within weeks of the appearance of Page's editorial, the Senate approved a version of the measure.
It was no wonder, then, that Page led his editorial by calling attention to the "important trend linking medicine to government." A group from the medical profession was needed to provide the government with the impartial yet expert advice necessary to make "decisions of wisdom" on questions of medical policy. The American Medical Association, according to Page, approached the federal government with a "grumbling hostility" that limited its effectiveness. The Association of American Medical Colleges, a similarly venerable organization that was in the process of transforming itself from a "congenial 'deans' club' into a powerful lobby for academic medicine," represented the interests of academic health centers, not the medical profession. Few other organizations were large or influential enough to speak for the profession. Page believed that the solution was a National Academy of Medicine, located in Washington, D.C., that would be "truly representative of excellence in all branches of medicine." 1
Irvine Page was the logical leader of a campaign to create a National Academy of Medicine. Like nearly everyone who helped found the Institute of Medicine, he came from the fields of academic medicine and scientific research. He combined a high academic
pedigree (degrees from Cornell and the Cornell Medical School) and scientific prowess with a talent for organization that enabled him to publicize his causes effectively. Born in 1901, he was older than most of the Institute of Medicine's other founding mothers and fathers, more than 65 years of age by the time serious discussions began. His career reflected many of the major developments in American academic medicine. He began by studying the chemistry of the brain and in 1928 received an invitation from the prestigious Kaiser Wilhelm Institute in Munich to begin a department in brain chemistry. After the rise of Hitler made working in Germany uncomfortable, he secured a position at the Rockefeller Institute for Medical Research in New York. These aspects of Page's career illustrated the influence of German models on American science and demonstrated that in the prewar era, support for medical research came as much from private philanthropy as from government grants.
Working at the Rockefeller Institute between 1931 and 1937, Page became interested in the phenomenon of high blood pressure. He both demonstrated the harmful effects of hypertension and showed that the disease could be treated effectively. In 1937, moving to the Lilly Laboratory for Clinical Research, he continued his efforts to "identify and isolate the compounds that affected blood pressure." After the Second World War, he started a research division at the Cleveland Clinic that attracted many topflight doctors and scientists. Not content to limit his work to the laboratory, Page also made rounds at the clinic and became a public health advocate, stressing the importance of exercise and diet in the prevention of heart disease. To further his goals, he helped create such organizations as the American Foundation for High Blood Pressure and the American Society for the Study of Arteriosclerosis. 2
Irvine Page, then, was far from a typical physician engaged in the full-time practice of clinical medicine; rather, he was a representative of a branch of the profession that enjoyed close relations with academia. Not surprisingly, Page communicated the results of his research by publishing, writing textbooks on the chemistry of the brain, editing books on treatment techniques for stroke and high blood pressure, and producing scientific papers and laboratory reports. Because of his academic prominence and ability to communicate his ideas, he received opportunities to serve in advisory capacities for influential organizations, such as NIH. If he obtained support from the Rockefellers at the beginning of his career, he, in common with many of his colleagues, switched to the National Institutes of Health, whose budget grew from $3 million to $400 million between 1941 and 1960, in the postwar era. Over the course of
To Improve Human Health: A History of the Institute of Medicine
a long career, therefore, Page had observed the changing relationship between government and medicine at close hand. 3
At the end of the summer of 1964, Page wrote a letter to his many contacts in the medical profession and in the world of science and asked for their reactions to his proposal to create a National Academy of Medicine. In the letter, he noted that the National Academy of Sciences (NAS) did a good job in representing the interests of science and that engineers appeared well on their way to establishing a National Academy of Engineering within the larger NAS. He wanted to know if a National Academy of Medicine would serve a similarly useful purpose.
Page's correspondents presented him with a bewildering variety of views. Some wanted to wait to see how the National Academy of Engineering turned out. Others expressed skepticism about finding an exact purpose for the organization. Some advocated a close alliance with the National Academy of Sciences, but others felt just as strongly that the new organization should have nothing to do with the NAS. They criticized the NAS as a "self-perpetuating" body. It was a great honor to join, and the "main function ... is to decide who deserves the honor." "Let us proceed slowly and thoughtfully, but let us proceed," Page concluded. 4In private, he told a colleague that no one needed to be pushed ''but if the thinking about it is open and moves along, the whole thing will gel." 5
In public, he wrote another editorial for Modern Medicinethat appeared in March 1965. In this piece, Page again cited the gap between the American Medical Association, which at the moment was leading a last-gasp effort to prevent the passage of Medicare, and the various federal agencies concerned with medicine. Something had to be done to close this gap, because "no serious-minded person denies the role that medicine must play if we plan to have a 'Great Society'." Summarizing the letters that he had received, he wrote that they demonstrated a need for a National Academy of Medicine and indicated that the material was "certainly there to form it."
In July 1965, Page refined his ideas about the proper membership for a National Academy of Medicine and once again solicited the views of his colleagues. He had no doubt that unlike the democratic and relatively ineffectual American Medical Association, the new organization should draw "from the upper, relatively thin layer of the best medical and scientific and lay talent." There should, however, be no limit on the number of members because the subject of medicine was "constantly growing." Further, membership should depend on a person's capabilities, without regard to degrees or titles. These
capable members would be expected to work, not just to participate in "an honorary society for the greater glory of the individual."
For the most part, his correspondents agreed, Dr. Julius H. Comroe, Jr., director of the Cardiovascular Research Institute of the San Francisco Medical Center and later an influential figure in the creation of the Institute of Medicine, argued for the importance of "real working committees picked from individuals best able to give advice on specific problems." Fred Robbins, a Nobel laureate in medicine who worked up the road from Page at Case Western Reserve University and would later be president of the Institute of Medicine, emphasized the need to choose people who commanded respect at the national level and suggested that practitioners of the biological, behavioral, and social sciences be represented. Each of these ideas would influence the subsequent development of the Institute of Medicine. 6
External events motivated Page to go from ideas to action. Signing Medicare into law on July 30, 1965, President Lyndon Johnson set in motion forces that would lead to a rise in medical expenditures—from 6.2 to 7.6 percent of gross national product between 1965 and 1970—and a fall in the percentage of these expenditures paid by the private sector—from 75 to 63.5 percent in the same five years. Although these trends created opportunities for collaboration between the medical profession and the federal government, they also produced tensions. Similarly, federal support of medical research, although lavish, bred its share of problems among members of Congress, the executive branch, and representatives of medical schools. In June 1966, President Johnson convened a meeting of his top health policy officials and asked them whether "too much energy was being spent on basic research and not enough on translating laboratory findings into tangible benefits for the American people." The mere fact that the President posed the question, according to Stephen Strickland, "fell like a bombshell" on NIH officials and created a ripple of panic among the scientists in medical schools. 7Not long after this meeting, Scienceprinted an item in which it attributed a desire to create a National Academy of Medicine to "reform-minded top officials of the Department of Health, Education, and Welfare." The new organization "would supply the profession with another set of spokesmen and provide the government with a more congenial source of authoritative advice.'' 8
Only a short time after President Johnson's meeting with his science advisers, Page used his local connections to secure a grant of $6,000 from the Cleveland Foundation that enabled a group of leading physicians to travel to Cleveland, Ohio and discuss strategy. The
To Improve Human Health: A History of the Institute of Medicine
meeting took place on January 17, 1967. In addition to Page, 15 physicians, nearly all of whom were on the faculties of medical schools or attached in some capacity to the National Institutes of Health, attended the meeting. 9
It was Page's show. He set the agenda, hosted the meeting, chaired the sessions, and gave an opening talk, to which he devoted substantial preparation, on the need for a National Academy of Medicine. The new organization, Page said, should be the "voice of moderation, wisdom, and integrity," and it should be "free and beholden to no one" as it ''provided advice ... to any who want to listen." Above all, Page stressed the fact that advice on medical questions could no longer be left to amateurs: medicine's growing scientific base and its increasingly complicated relationship with the government necessitated the creation of a group that could mobilize the best professional opinion in the country. 10
Although Page dominated the meeting, James Shannon also made his presence felt. Only three years younger than Page, James Augustine Shannon was something of a Washington legend because of his extraordinary success at running the National Institutes of Health. Like Page, Shannon combined interests in science and medicine. He received a medical degree from New York University (NYU) and a Ph.D. in physiology. During the war, he became the director of an NYU research service at Goldwater Memorial Hospital and did work on malaria that led to a Presidential Medal of Merit. After flirting with private industry after the war, Shannon arrived at the National Institutes of Health in 1949 as associate director for intramural research of the National Heart Institute. On August 1, 1955, he became the director of the National Institutes of Health. In this position, he held what Donald S. Fredrickson, himself an NIH director and an IOM president, described as an "uncomplicated philosophy of science" that consisted of "unfettered support of good science and rejection of the bad." Good science tended to mean basic research, rather than research targeted on finding a cure for a particular disease. He blended this uncomplicated philosophy with a sophisticated understanding of congressional relations and of the policy process. 11Shannon, whose career bore so many similarities to Page's, was just the sort of person whom Page hoped to interest in a National Academy of Medicine.
Addressing the group in Cleveland, Shannon said that a National Academy of Medicine should be able to speak to government and to conduct sound studies. It should be highly professional and not be formed unless it could isolate four or five broad areas of inquiry, because its initial studies would determine its reputation. An
overarching purpose of the organization, according to Shannon, would be to "define, enunciate, and promote the health sciences." As a practical matter, Shannon advised that representatives of the group should sit down with Fred Seitz, the physicist who served as president of the National Academy of Sciences, and with Harvey Brooks, a Harvard academic who chaired the Academy's influential Committee on Science and Public Policy, and gauge the NAS's level of interest in a National Academy of Medicine. 12
A second meeting, held on March 7, 1967, satisfied Page that the need existed for a National Academy of Medicine. Still, he wondered, as had James Shannon, whether the group should proceed on its own or whether it should "come under the umbrella of a chartered organization such as the NAS." In fact, the Cleveland group was already in contact with the NAS. After the first meeting, Shannon and Ivan Bennett had arranged a Washington conference with Frederick Seitz, president of the NAS. They had no trouble getting an appointment. An NAS member, Shannon was one of the federal government's most influential bureaucrats concerned with science. Although a generation younger than Shannon or Page, Ivan Bennett was an academic physician with impressive Washington connections, who had worked at Yale and as the Baxley Professor of Pathology at Johns Hopkins before accepting an appointment as deputy director of the Office of Science and Technology in the Johnson White House.
Talking with Shannon and Bennett, Seitz had offered the possibility of establishing a "board" within the Academy that could begin to do the sorts of studies the Cleveland group wanted and, according to Shannon, "give us a base from which we could begin to operate and to study what sort of organization should emerge." Shannon believed that Page's group should take advantage of the NAS's generosity, even though he thought that there ultimately should be a National Academy of Medicine that was independent of the National Academy of Sciences. Bennett pointed to the advantages of working with a group as prestigious as the Academy. If things turned out badly, the doctors could always back out gracefully and form their own group.
Colin MacLeod, who played a key role in discussions at the second meeting of Page's group, agreed with this assessment, and like the others in attendance, he spoke with considerable authority on the subject of medical policy. He came from an academic and scientific background that was far removed from the daily practice of clinical medicine. A doctor with a strong interest in science, MacLeod had worked at the Rockefeller Institute during the 1930s, just as Page had. From there he had gone on to chair the Microbiology
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Departments at New York University and the University of Pennsylvania. In 1963, he took a job in the White House at the Office of Science and Technology, which he later yielded to Ivan Bennett. In 1967, he served as the vice president of medical affairs at the Commonwealth Fund, an important dispenser of funds for medical research and public health. Highly regarded as a scientist, MacLeod, like James Shannon, was a member of the National Academy of Sciences. 13
Walsh McDermott and the Board on Medicine
As Ivan Bennett noted, the prestige of the National Academy of Sciences, with its federal charter and its proud history that stretched back to the presidency of Abraham Lincoln, was beyond dispute. In 1967, it consisted of about 800 members, each of whom had undergone rigorous nomination and election procedures. Almost all of the members owed their selection to the quality of their published research in the "hard sciences." Upon election to the Academy, a member voluntarily joined one of 18 discipline-specific sections. Physics and chemistry formed the two largest sections. Attempts to increase the number of physicians in the Academy had met with repeated failure. In 1941, for example, Ross Harrison of the Yale Medical School called attention to the "urgent need for the Academy to have in its membership a larger proportion of the distinguished clinicians of the country than at present." He was told that creating a section of medical scientists would result in attracting people who were "merely clinicians,'' and the idea was dropped for the next 27 years. 14In the interim, the few medical doctors elected to the Academy were found in the microbiology, physiology, and biochemistry sections. It was not a young crowd; the median age of the microbiologists was 66.5. Very few social scientists belonged to the Academy, and those who did were concentrated in the anthropology and applied mathematics sections. Beyond the prestige that came from joining the Academy, members also enjoyed the benefit of two yearly meetings at which they discussed NAS governance, awarded medals to one another, and listened to scientific papers.
The Academy also contained what observers called an "operational arm" in the form of the National Research Council (NRC). Established in 1916 during the period of mobilization before the country's entry into the First World War, it responded to requests for studies or advice from Congress, the executive branch, and a variety of other
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private and public sources. The periods of greatest activity for the NRC came during the two world wars. In the Second World War, for example, the NRC's Division of Medical Sciences had advised the surgeons general of the Army and Navy on medical research and other matters related to wartime care. Between 1940 and 1946, the division's advisory committees on war services held more than 700 meetings and 243 conferences and played an important role in shaping the nation's wartime medical policy. 15In 1946, however, the National Research Council contemplated an end to these emergency activities. The advent of the cold war once again increased the demand for the NRC's services, yet the Division of Medical Sciences initiated little work of its own. As a result of the policy to respond to requests from others, the division contained a bewildering variety of committees, offices, research boards, and panels such as an Office of Tropical Health, an advisory committee to the Federal Radiation Council, the Atomic Bomb Casualty Commission, and the Committee on Radiology. To do its work, the National Research Council drew on the resources of large numbers of scientists in academia and private industry; its reach extended well beyond that of the Academy itself. 16
Beyond the formal Academy and the National Research Council, the National Academy of Sciences also housed the National Academy of Engineering (NAE). Established in 1963, it marked an outgrowth of the engineering section within the NAS. Engineers felt that the scientists in the Academy failed to accord the engineering profession the respect it deserved. After the engineers received a grant from the Sloan Foundation, the NAS agreed to form what Fred Seitz called "a sister academy under the original NAS Charter." The possibility remained that the National Academy of Engineering would eventually split away from the NAS. By the end of the decade, however, the NAE remained entrenched within the Academy, and the exact relationship between the National Academy of Engineering and other parts of the NAS was a matter of constant negotiation. Engineers continued to feel that they were not first-class citizens of the NAS. Officers of the NAS believed that the engineers elected people to their Academy who were better known as executives of large private firms than as scientists. 17
Although NAS leaders who served on the Academy's governing council regarded the National Academy of Engineering as less than a hopeful precedent, they nonetheless listened to Colin MacLeod, who reported to them in April 1967 on the events in Cleveland, with considerable sympathy. Seitz told the Executive Committee of the NAS Council that he had already talked with Bennett and Shannon and suggested the creation of an advisory board on medicine. Such a
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board, Seitz felt, could provide advice on policy questions related to medicine and health and consider the question of whether to form a National Academy of Medicine. For the NAS, it was a way of bringing discussion about a National Academy of Medicine in-house. Furthermore, an ad hoc advisory board of the sort Seitz proposed would involve a minimum of bureaucratic disruption and avoid the time-consuming and often contentious matter of a vote by the membership. Council members agreed with Seitz. If nothing else, creation of an advisory board on medicine would prevent the Carnegie Corporation and the Commonwealth Fund from taking independent action on the matter, as they threatened to do. Seitz felt confident enough about the matter to inform NAS members at their 1967 spring meeting that it appeared "fairly clear" that an advisory board on medicine would be created. 18
Early in June, the NAS Council approved a motion to establish this advisory Board on Medicine and Public Health. The new Board, charged with the responsibility to "formulate recommendations on matters of policy related to medicine and public health," would report directly to the Council. Seitz told the division heads of the National Research Council that the Board could "possibly lead to the formation of a National Academy of Medicine somewhat analogous to the NAE." 19The Page group hoped this would be the case and made plans to hold a third meeting.
These plans received a serious setback on June 12, 1967, when Irvine Page suffered what his secretary described as a "mild coronary." Page, the expert on heart disease, now found himself looking at the condition "from inside out." After his heart attack, Page, despite his relative vigor, occupied a less prominent place in the movement to create a National Academy of Medicine. His role changed from that of primary advocate to chief critic of the Board on Medicine. 20
Seitz realized that the chairman of the Board on Medicine and Public Health would have to be a physician who was also a member of the National Academy of Sciences. His choice was Walsh McDermott, a 56-year-old professor of medicine and public health at Cornell Medical School who recently had been elected to the Academy. McDermott belonged to Page's discussion group, although he had missed both meetings and told Page of his ambivalence toward a National Academy of Medicine. 21The appeal of his selection lay not only in his familiarity with the movement to create a National Academy of Medicine but also in his unquestioned prominence as a doctor and a public health official.
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McDermott was an American aristocrat—"white shoe," in the words of one of his colleagues. The son of a New Haven physician, he attended Andover, Princeton, and Columbia Medical School. During his residency at New York Hospital in 1935, he developed tuberculosis and had to go to the tuberculosis sanitarium in Saranac Lake, New York. Over the course of the next few years he eased his way back into work until he accepted an appointment in 1942 as the head of the Division of Infectious Diseases at New York Hospital. In this post, he performed important clinical trials on penicillin, streptomycin, and other so-called wonder drugs. He also engaged in laboratory work on the effects of antimicrobial therapy on animals, despite the fact that he had never had formal training in either microbiology or experimental pathology. In the 1950s, he shifted directions and became interested in bringing medical treatment to underserved populations, earning substantial fame for organizing a successful tuberculosis treatment program for the Navajos living in Arizona and New Mexico. This experience sparked a continuing interest in public health and led him to become involved in other public health projects both in the inner-city neighborhoods of New York and the developing nations of the world. In the course of these activities, McDermott acquired a plethora of contacts and honors. He served, for example, as a member of the NIH's National Advisory Health Council between 1955 and 1959 and of New York City's Board of Health. 22
McDermott accepted the appointment as head of the NAS Board on Medicine and Public Health at the end of June. Both he and Seitz hoped that the Board would develop into "a widely respected voice of American medicine." He proceeded to negotiate with Seitz over other members of the Board. They agreed that Ivan Bennett, Colin MacLeod, James Shannon, and Irvine Page, the prime movers behind Page's efforts to launch a National Academy of Medicine, should all be members. Seitz suggested other names, making it a point not to limit membership to physicians. For example, he mentioned Rashi Fein, an economist at Brookings, who had served as a staff member on the President's Council of Economic Advisors and, according to Seitz, "has a deep interest in the social problems connected with medicine," as a potential member of the Board. 23
Despite Page's illness and the preemptive action of the NAS, the Page group held a third and final meeting on June 28. Colin MacLeod chaired the meeting in Page's absence. Some of the nine physicians present wondered if the Board on Medicine and Public Health would really be able to do anything constructive, because it started from the narrow base of doctors within the NAS. The participants conveyed a sense of regret that Page's group no longer controlled the action on a
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National Academy of Medicine. MacLeod urged the group to develop a list of people who should be involved in the Board on Medicine. Those present obliged by coming up with no fewer than 41 names. 24
The business of constructing a Board on Medicine and Public Health began in earnest on September 13, 1967, at a meeting called by Fred Seitz. Those present included McDermott, Colin MacLeod, Ivan Bennett, and Page. Joseph Murtaugh, chief of the Office of Program Planning at NIH, represented the interests of Jim Shannon. Keith Cannan, who worked for the Division of Medical Sciences of the National Research Council, attended as an NAS staff member. Irving London, chairman of the Department of Medicine at Albert Einstein College of Medicine; Eugene Stead, a professor of medicine at Duke; and Robert J. Glaser, dean of Stanford's School of Medicine, completed the group. All of the people in the room, with the exception of Seitz and NAS staffers, were medical doctors, and each had connections with an academic medical center. It was their task to complete the list of Board members. As Page put it, ''Each one of the members appointed to the Board will represent different aspects of social and scientific medicine, such as economics, poverty, etc."
As a practical matter, members of the group agreed on themselves and on Dwight Wilbur, a San Francisco physician who was president-elect of the American Medical Association, and then got bogged down. In the social science fields, for example, the group had only the most cursory knowledge of current practitioners. James Tobin, Milton Friedman, and Carl Kaysen were suggested as economists, even though none of the people in the room was familiar with their work. As for a sociologist, someone in the room offered the name of Daniel Bell, not because of his work in the field of medicine but because he was well known. For the most part, the group concentrated on occupational and demographic categories, such as dentists or people who worked in the pharmaceutical industry, and it acknowledged the need for "at least two Negroes." 25
The group agreed to ask 22 people to serve, and by the end of September, Seitz reported to the Council that the Board on Medicine "was taking shape." McDermott told Seitz that it was a good list but that it was weighted toward the two coasts and contained almost no private practitioners. Given the people doing the selecting, this was a natural bias. In addition, the Academy had trouble recruiting people from outside the medical profession. A string of distinguished economists declined the offer, as did sociologist Daniel Bell who cited "a lack of competence" on questions related to medicine. Pure scientists approached by the group also were reluctant to become involved with the Board. When Kermit Gordon, the economist from
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the Brookings Institution declined to be named to the Board, he quickly suggested Rashi Fein of the Brookings staff, whom Seitz had mentioned earlier, as a logical substitute. As Fein recalled, Gordon urged him to accept the position, and he did so with alacrity, pleased to join a "disinterested group that would be able to examine ... the issues facing the American medical system." 26
The National Academy of Sciences made a public announcement of the new Board, now called simply the Board on Medicine, on November 13, 1967. In its final form, the Board contained 21 men and one woman (Lucile Petry Leone of the Texas Woman's University's School of Nursing). Two of the Board members were black. Although a majority of Board members were physicians, the group also included two economists, one of whom later resigned, a nurse, a lawyer, an engineer, and at least two people identified primarily as social scientists. Only two of the physicians devoted the bulk of their time to private practice, and one was something of a "ringer." The son of Ray Lyman Wilbur, Herbert Hoover's Secretary of Commerce and a Stanford University president, Dwight Wilbur, although a clinician engaged in private medical practice, nonetheless knew many of the leaders of academic medicine. The rest of the Board on Medicine members either served as medical administrators, did research in academic settings, or both. Twelve held formal academic appointments.
Members of the Board on Medicine, June 1969Walsh McDermott, M.D.*,**Joseph S. Murtaugh**Ivan L. Bennett, Jr., M.D.**Samuel M. Nabrit, Ph.D.Charles G. Child III, M.D.**Irvine H. Page, M.D.**Julius H. Comroe, Jr., M.D.**Henry W. Riecken, Ph.D.John T. Dunlop, Ph.D.Walter A. Rosenblith, Ing. Rad.Rashi Fein, Ph.D.Eugene A. Stead, Jr., M.D.Robert J. Glaser, M.D.Dwight L. Wilbur, M.D.**Lucile P. Leone, M.A.Bryan Williams, M.D.Irving M. London, M.D.Adam Yarmolinsky, LL.B.Colin M. MacLeod, M.D.**;Alonzo S. Yerby, M.D.*** Chairman** Deceased
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The appointment of the group made a large splash in the media. The New York Timesran a page one story that featured quotations from Seitz and McDermott. Seitz cited the need to apply biomedical knowledge to "critical human needs." He specifically mentioned experimentation on human beings, the role of medicine in attacking rural and urban slum problems, improvement of the quality of medical care, and the reform of medical education as matters that the Board might investigate. McDermott spoke of the "good balanced mix of people who could be counted on for dispassionate and expert judgments about a broad range of problems." 27
Despite the high hopes, the Board on Medicine faced the difficult task of simultaneously undertaking scientific studies and exploring the feasibility of a National Academy of Medicine. McDermott hoped to build the Board's reputation on the scientific studies it would undertake. For Irvine Page and Julius Comroe, however, the National Academy of Medicine was a constant preoccupation that demanded the Board's total attention. From the beginning, Page worried that the Board would somehow, as he put it, prevent "the evolvement of a freestanding NAM." Although he often contemplated dropping out of the Board on Medicine, he never disbanded his own group of physicians and scientists interested in a National Academy of Medicine, writing reports for them on Board on Medicine activities that, by their mention of confidential discussions, often annoyed McDermott.
"Don't think for a moment that our original group is disbanded," Page told one of his medical acquaintances soon after the creation of the Board on Medicine. He urged fellow Board member Jim Shannon to keep "our ultimate objectives in mind" and informed Shannon that Walsh McDermott ''is an extremely capable and nice person but I do not think he is in a class with you." Indeed, Page hoped Shannon would become the first president of a National Academy of Medicine. As these sentiments implied, Page had many criticisms of the way in which the National Academy of Sciences handled the Board on Medicine. He objected to the lack of clarity in the Board's objective and to the mixed nature of its membership. "I am not sure if as unhomogeneous a board as we now have can even begin to fulfill the promises a NAM can make,'' he wrote Colin MacLeod. 28
Beyond the matter of a medical academy, the Board faced the problem of meeting high expectations with a group of only 22 people and one professional staff member. He was Joseph Murtaugh, a former staff member at NIH, who had agreed to leave the government and come to work for the National Academy of Sciences. To be successful, the group had to make recommendations that commanded the respect of both government officials and practicing doctors. Yet
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the group itself contained only one full-time clinician and a few people with recent government experience. Furthermore, the Board hoped to look at the social aspects of medical problems, despite the fact that only four of its members had training in social sciences. Many of the problems on which the Board hoped to focus, such as the plight of inner cities, were large and complex; it would be difficult to define the Board's contributions to their solution.
The Board on Medicine held its first formal meeting on November 15, 1967. All but four of the members attended. Fred Seitz greeted the group and expressed his hope that it might address some of the problems caused by the growing complexity of medicine. Page added his wish that the Board be a place to consider complex problems in a setting free from emotion, professional politics, and other forms of distortion and bias. For all that the Board was supposed to be a professional tribunal whose members were guided only by the facts, the members inevitably brought their own preferences, formed by their unique experiences, to the discussion. Dr. Dwight Wilbur, whose primary institutional experience was with the American Medical Association, wanted the group to consider the problems caused by the importation of foreign physicians. James Shannon noted the profusion of groups already concerned with medical care and policy and compared the result to a "floating crap game." The Board on Medicine should bring institutional stability to this situation and should make it less of a game of chance and more a matter of putting the best minds in contact with the hardest issues. Adam Yarmolinsky, a lawyer by training with a strong interest in problems related to poverty, noted that his prior contacts with medicine were primarily those of a patient, yet he hoped the Board would address the distribution of medical care in the inner cities. Samuel Nabrit, executive director of the Southern Fellowships Fund who was very involved with questions related to civil rights, agreed that the Board should consider how "to meet immediately and directly the ghetto's needs." The meeting ended with agreement only on the need for more discussion of the types of problems the Board should address. 29
When the Board reconvened in December, it adopted a seminar format. Board members lectured to one another on such topics as the personal physician delivery system, the functions of the modern hospital, medical education, and the funding of medical research. 30McDermott believed that these sorts of sessions served the useful purpose of establishing a common language and arriving at a consensus about current conditions that would lead to policy recommendations. 31Reporting to the members of his group, Page described the tone of the meetings as "pedagogic." "At the moment we
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are all trying to get our breath, get used to one another, and in due coursecome to grips with these major organizational problems." Page worried, however, that the nonmedical members of the panel did not share his concerns about forming a National Academy of Medicine. 32It was clear that the Board on Medicine had not yet found its rhythm.
The Heart Transplant Statement
Then, in the second month of 1968, the Board caught a break. 33On February 2, McDermott brought up the matter of organ transplantation. All of the Board members were aware that only a few months before, the first heart transplant operation had been performed by Dr. Christian Barnard in South Africa. The operation, quickly followed by others performed in the United States, captured public interest at a time when much of the other news, such as the beginnings of the Tet Offensive in South Vietnam, was depressing. Eugene Stead, the Board on Medicine member from Duke, called McDermott and told him that the American Heart Association was prepared to issue a guideline on the use of heart transplants. Stead said that the Board on Medicine would be a much more appropriate organization to issue such a guideline. McDermott reminded Board members that they had already been attacked in the popular press for being inactive. If the Board came up with a statement on heart transplants, it could counter its image. No one appreciated the need for slow deliberation on weighty topics more than McDermott, but as he put it, "we are trying to establish an institution" and certain issues should be seized.
The group held a brief discussion on the subject. McDermott emphasized the fact that heart transplants were experimental procedures that required a careful recording of the operation and its results. Informed consent of the patient should be obtained, and the procedure should be done only on people who would otherwise die. It followed that not all hospitals should undertake heart transplants. When Christian Barnard performed his heart transplant, he lacked, according to Julius Comroe, a proper team of immunologists to assist him. Robert J. Glaser, the dean of the Stanford Medical School that had performed a heart transplant only weeks before, claimed that Barnard had no background in, and little appreciation of, the immunological aspects of heart transplantation, in contrast to Stanford's Dr. Rose Payne, who was a topnotch immunologist. As a result, the radiation in Barnard's operation, according to Glaser, was
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"given ineptly and in excess." Such practices, the Board agreed, should not be allowed to occur. The Board should therefore caution the medical profession that heart transplants should be done only as an experiment in a proper setting. The public should know that heart transplants were not a therapy that could be relied on until more data had been gathered. Such a statement, Glaser hoped, might serve as a deterrent to adventurous surgeons who wanted to be on the cutting edge of medical practice yet knew little about how to prevent rejection of the transplanted heart. McDermott then turned to Glaser and asked him to draft a statement, with an emphasis on the experimental nature of heart transplants. 34
Working with Joseph Murtaugh and Walsh McDermott, Glaser prepared a short statement that was ready for circulation by February 20. Instead of waiting for the next Board meeting to discuss the statement, McDermott decided to solicit members' opinions by phone. As he saw it, the statement hinged on two basic principles. Heart transplants could not yet be justified as therapy because no one knew their relative advantages over other forms of therapy. In other words, controlled experiments had not yet been performed, and the public should understand that in the absence of these experiments, heart transplants could not be regarded as a miracle cure. As a second basic principle, McDermott believed that heart transplants should be conducted only in institutions "in which the total array of scientific expertise necessary for the proper conduct of the whole experimentcan be brought to bear in every case." In other words, heart transplants were more than a matter of surgery; they also involved complicated issues related to immunology. If McDermott's two principles were implemented, the total number of transplants would be small. 35
Moving with incredible speed, the Board issued what was billed as its first public statement on February 27. The statement polished the rhetoric of the previous discussions. "Cardiac transplantation raises new, complex issues that must be faced promptly," the Board asserted. It could not yet "be regarded as an accepted form of therapy, even as a heroic one." Instead, "it must be clearly viewed for what it is, a scientific exploration of the unknown, only the very first step of which is the actual surgical feat of transplanting the organ.'' The procedure, in other words, required much more than a surgeon with good hands. Instead, it demanded a "surgical team" that ''should have extensive laboratory experience in cardiac transplantation." Furthermore, the "overall plan of study should be carefully recorded in advance and arrangements made to continue the systematic observations throughout the whole lifetime of the recipient." 36
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The media gave the statement prominent play. Walsh McDermott told the New York Timesthat the Board felt comfortable with the statement because heart transplants were "a more clear cut example of all the problems involved in human experimentation" than medicine usually afforded. McDermott said that the Board realized that there were many surgeons who had the necessary skill to perform the operation and who faced a "terrible temptation ... to embark on the avant garde with ... the tremendous satisfaction of exercising one's skill." With its statement, the Board hoped to discourage such surgeons. McDermott said that the statement illustrated the Board's mission to consider situations in which medical knowledge outstripped its application to critical human needs. 37
If the Board wanted to publicize its work, heart transplantation served as the perfect vehicle. The Board used clear and concise language that any layperson could understand to address a pressing matter in a timely fashion. As a consequence, word of the Board's actions spread not just to centers of elite opinion, such as New York and Washington, but also to smaller cities across the nation. Nearly every major newspaper in the country carried a story about the Board's stance on heart transplants. "Don't Try Heart Transplants too Soon, Scientists Warn," read a typical headline. 38
The statement made a deep impression on intellectuals who followed the transplantation debate and on government officials responsible for funding medical research. In April 1968, the Saturday Reviewprinted the statement in full. 39Senator Lister Hill (D-Ala.), who both authorized and appropriated money for medical research programs, inserted the Board's statement into the Congressional Record. In the White House, Joseph Califano, the staff member most responsible for President Johnson's domestic policy, read and commented on the statement. In the Department of Health, Education, and Welfare (HEW), Dr. Philip Lee, Assistant Secretary for Health, called the statement "timely and very appropriate." Wilbur Cohen, about to become HEW Secretary, praised the Board for "bringing a sense of reality and caution into a very complex set of matters." The statement even received international recognition. The State Department's Office of International Scientific Affairs sent the statement to major embassies across the world in the "Friday bag.'' The United States Information Agency interviewed McDermott for the Voice of America. 40
Not everyone, even at the elite medical schools, approved of the statement. Some saw it casting doubt on a promising area of medical inquiry. Francis D. Moore, a prominent surgeon at Harvard Medical School, said he was shocked to see such a statement coming from a
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Board that contained not a single surgeon or any immunologists who had experience with heart transplantation. He also could not understand why the Board chose to single out heart transplants from the transplantation of other organs. At Brigham and Women's Hospital, a Harvard teaching hospital, surgeons had done their first kidney transplant in 1951, although the procedure had involved identical twins and posed no immunological problems. Ignoring the fact that Glaser had contacted the members of his faculty who had performed heart transplant surgery, Moore thought it would have been prudent "for the National Academy of Sciences to seek some consultation from those who have been intimately concerned with these problems for almost twenty years." He felt that the Board did not make it sufficiently clear that heart transplants could "rest secure in the scientific, ethical and moral climate which has already been characteristic of the transplantation of other organs in the United States." 41
In a sense, Moore accused McDermott of exploiting the interest in heart transplants in an opportunistic manner. In reply, McDermott argued that the statement was intended to be a positive one, not meant to eliminate heart transplants but rather to make sure that such procedures were performed in places that had the "capability to make all the relevant observations." Most of the cardiac surgeons with whom McDermott had discussed the statement regarded it as "sensible and helpful," setting down guidelines that they themselves followed. 42The statement, according to McDermott, exemplified the Board's mission of acting as a "disinterested group'' that sought ''to be helpful on the more important issues as they arise considering both medicine itself and its relationship to our society." 43
Still, the heart transplant statement, for all of McDermott's lofty ideals, possessed elements of self-interest that were difficult for members of the Board on Medicine to perceive. As a pragmatic matter, the statement counted as a great success. As Irvine Page noted, the Board was "well ahead of the game" and could only hope to do "as well next time." 44It did not trouble either Page or McDermott that the statement favored the types of institutions with which they were associated over other institutions; they simply assumed that their institutions were superior. Robert J. Glaser, chief author of the heart transplant statement, worked for a medical institution that had already performed such transplants, one whose scientific expertise, according to the Board on Medicine, should allow it to continue to do these operations. To put it more bluntly, the head of the Stanford Medical School had helped draft a statement saying that complicated operations such as heart transplants should be done only in places
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To Improve Human Health: A History of the Institute of Medicine
like the Stanford Medical School. No one on the Board on Medicine was likely to challenge such a statement.
Business of the Board
The heart transplant statement gave a sense of momentum to the operations of the Board on Medicine. As if in direct response, the Commonwealth Fund announced that it would give $150,000 to the National Academy of Sciences to support the Board on Medicine. It marked the start of what would be a long-standing philanthropic relationship between the fund and the Institute of Medicine. In awarding the money, the head of the Commonwealth Fund spoke of the "urgent need for an institutional entity of authoritative standing to serve as an independent, objective resource for dealing comprehensively with the problems and decisions confronting medicine and health in American society." 45Even when the hyperbolic foundation rhetoric is discounted, such a statement showed the hope that the Board engendered in elite medical policy circles.
Although a lack of funds would become one of the Board on Medicine's and the Institute of Medicine's chronic problems, it looked at first as if raising money would be easy. The Board, unlike other voluntary organizations that served a social purpose, enjoyed the backing and prestige of the National Academy of Sciences. Its mission, although vague, appeared to be related to America's social problems at a time when the mid-1960s optimism about solving these problems through Great Society programs had begun to wane. The combination of pedigree and relevance was very attractive to private foundations. As if this were not enough, the Board had some direct connections to the foundation world. Colin MacLeod, the same person who pleaded the Board's case to the NAS Council, worked for the Commonwealth Fund, which became an early supporter of the Board. Many Board on Medicine members served on foundation boards, and some, such as Walsh McDermott and Robert J. Glaser, went on to play major roles in the foundations that supported medical research. In Jim Shannon, the head of NIH, the Board maintained a connection to the largest supporter of medical research in the world. Although Shannon left NIH in 1968, he nonetheless kept the Board abreast of NIH and other government activities. 46
Colin MacLeod took a direct role in the Board's outreach to the philanthropic community. He arranged a meeting at the Commonwealth Fund in New York that allowed Seitz, McDermott, and Murtaugh to discuss the Board's work with representatives of five
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large foundations. McDermott looked to the foundations represented at the meeting, such as the Carnegie Foundation and the Rockefeller Foundation, to provide core support for the Board. He wanted to increase the Board's staff by at least three professional staff members. At the end of the meeting, Margaret Mahoney of the Carnegie Corporation took McDermott aside and told him that her foundation would be very interested in participating in a study of urban health services. She also told McDermott that the foundations worried about the widespread dispersal of their funds, which limited their effectiveness. She advised McDermott to get several foundations to work in concert to support the Board on Medicine. 47The Board on Medicine followed her advice and secured initial backing from Commonwealth, the Rockefeller Foundation, the Milbank Memorial Fund, Carnegie, and the Association for Aid to Crippled Children. 48
A good part of the attraction for these foundations was the fact that the Board worked on social, and not merely medical, problems. If the Board needed a reminder of the urgency of America's social problems, it received it during its April meeting. Originally scheduled for the downtown offices of the National Academy of Sciences, the meeting took place in the suburbs to avoid the disruptions caused by the riots that followed the death of Martin Luther King, Jr. At this meeting, the Board faced the fact that despite the heart transplantation statement, it had still not initiated any substantive studies. In partial response, members decided to create two study panels. One, on medical education, came at the urging of Jim Shannon, who sought nothing less than a major redesign of medical education to incorporate changes in science into the curriculum. McDermott asked Ivan Bennett to head a five-person subcommittee charged with developing a proposal. The other study panel, on health services, had the daunting task of examining "existing programs, mechanisms, and laws" that related to the delivery of health services and of somehow formulating "a creative diagnosis" of the issues in the field. McDermott chose economist Rashi Fein to head this five-person panel. 49
Both panels made initial progress. In June, the Board gained NAS approval to enter into a $40,000 contract with the National Institutes of Health for the initial phase of a study of medical education. 50The Board also refined its proposal in the area of health services, concentrating on the topic of health and the poor. It proposed to define the problem by asking if the health conditions of the poor were different, to examine how the poor were being served, to analyze government health programs that served the poor, to project the future medical needs of center-city dwellers, to test the effect of
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income transfers or vouchers on improving access to health care, and to design government programs that might better serve the poor. If the project lacked focus and appeared to be overly ambitious, it nonetheless represented a tangible product of the Board's long discussions. 51By the fall, a Board Panel on Health and the Disadvantaged, chaired by Samuel Nabrit and containing five other Board members and four outside experts, had met in Washington for further consideration of the study. 52
Despite this semblance of progress, the Board faced many internal and external challenges. In the first place, it drew criticism from within the National Academy of Sciences. One epidemiologist, a member of the NAS since 1948, questioned whether the Academy was qualified to appoint a Board on Medicine. He noted that the Academy itself still did not have a functioning Section on Medicine (although one would be formed in 1968) and that Board members were not "primarily people who have been involved in the provision of medical care to the public." The Board's social mission, so attractive to outside funders, also drew criticism from inside the Academy. 53Second, the very attractiveness of the Board's mission, combined with the slow pace at which it moved, invited competition from other entities that claimed to speak in the public interest. Senator Walter Mondale (D-Minn.), for example, hoped to create a Commission on Health, Science, and Society to "study and evaluate research in medicine." Such a commission could provide competition for the Board. 54Third, the Board still had to deal with the question of forming a National Academy of Medicine.
Neither Julius Comroe nor Irvine Page would let go of this issue. Comroe argued that the Board was placing too much emphasis on its social mission and too little on forming a National Academy of Medicine. Suggesting that the Board change its name to the "NAS Board on Social Medicine," he thought another group should organize a National Academy of Medicine. Comroe was worried that the Board spent its time on large and intractable problems, such as the conditions in urban and rural slums, that required the entire nation's attention and to which the Board could contribute little. Comroe, a blunt man, did not hide his feelings from Walsh McDermott. "I think that it is very nice for 22 men in a wide variety of disciplines to meet once a month and move at a relatively slow pace toward solution of major problems," he told McDermott, "but the work could go very much faster ... if a large prestigious group, more representative of medicine were formed to do the work....'' Page agreed with Comroe. In Page's opinion, the Board had become "the McDermott Committee of the NRC" and he hoped that Comroe, Colin MacLeod, and Jim
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Shannon could save the organization from "becoming a small, self-satisfied outfit which can never properly undertake the problems I think we all had in mind when we got the thing started." 55
Debate over a National Academy of Medicine
By July 1968, McDermott believed that it was time to begin a serious discussion on whether to form a National Academy of Medicine. He arranged a special one-day meeting to consider the matter and asked Comroe and Page to lead the discussion. In a paper prepared for the meeting, Page critiqued the Board on Medicine as too small, too narrow, and too concerned with the socioeconomic dimension of medical problems. With the socially minded Board on Medicine and the scientifically minded National Research Council, medicine found itself in a "schizophrenic state," a "split appendage" of an organization in which it had "no voice." Page concluded that a National Academy of Medicine should be formed, with or without the help of the National Academy of Sciences. 56Comroe, for his part, prepared for the discussion by asking the opinions of 20 prominent physicians. All 12 of those who responded believed that there should be a National Academy of Medicine, although they differed on whether it should be affiliated with the NAS. Comroe emphasized that his correspondents felt a National Academy of Medicine should be organized by people actively engaged in medical practice, education, research, or administration. As for his vision of a National Academy of Medicine, Comroe thought it should have a permanent home, a full-time president, and at least 20 members in full-time residence, many of whom would be on sabbatical. 57Not surprisingly, he saw the NAM as a place to which academics would come to write and do research.
From the moment of Comroe's and Page's presentations on a National Academy of Medicine, the Board on Medicine concerned itself with little else. At the end of six hours of conversation, McDermott said he detected neither a consensus in favor of an academy nor one against it. He decided to appoint a subcommittee to investigate the matter. Headed by Irving London, a summa cum laude graduate of Harvard and a Harvard-trained doctor who chaired the Department of Medicine at Albert Einstein College of Medicine, the group contained six other Board on Medicine members. Because the group included Shannon, Comroe, Wilbur, and Page, it was comprised, as Comroe conceded, of "a very clear majority dedicated to
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the formation of an academy." McDermott served in an ex officio capacity. 58
This group, with the unwieldy title of the Ad Hoc Panel on Further Institutional Forms for the Board on Medicine, met at the end of September 1968. The political climate lent a sense of urgency to the proceedings. When the Board started its work, the Democrats were in firm control of the White House and Congress. It now appeared as if Republican Richard Nixon might win the election and federal support for medical research and for social welfare programs, such as Medicaid, might weaken. As Adam Yarmolinsky told the Board, "Whoever is President of the United States—Humphrey, Nixon, Wallace, it is less likely that the kind of advice that we have to offer which involves spending money and doing things will be accepted." 59
Whatever the urgency of the political situation, the Ad Hoc Panel moved at a very deliberate pace. A first meeting served only to set the stage for a second. "The discussions were quite tentative," Joseph Murtaugh reported to Fred Seitz, "with a great deal of uncertainty being reflected by the members in respect to many important points." 60One of Page's allies wrote that he sensed a "foot-dragging attitude" on the part of McDermott. He urged Page to act independently of the National Academy of Sciences. He suggested that if nothing happened in the next few months, Page's original committee should be reactivated and a National Academy of Medicine should be organized on an independent basis. 61The head of the Dartmouth Medical School told Page that he was "bullheadedly holding to my original bias'' in favor of a National Academy of Medicine. ''The more I have thought about it ... the more I feel the academy is the only position to take," Page replied. He attributed opposition to the NAM to "public health people" and those "concerned with economics" who believed that "if medicine had the upper hand, we would all revert to our antediluvian days of which they are so highly critical." 62
Walsh McDermott, whom Page would have classified as one of the public health people, refused to be stampeded. In a letter to London he tried to set the intellectual tone for the discussion. He began by pointing out that everyone agreed on the need for an institution, free of special interest, that included nonphysician professionals as well as physicians. The disagreement came over what purpose the institution should serve. The Page and Comroe faction favored an organization that spoke formedicine; McDermott wanted one that spoke aboutmedicine. The first concept involved a group that addressed problems within medicine and expressed the medical viewpoint. The second concept addressed the need for an entity that "would speak to the
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issues from the position of all-round competency rather than one that would speak from within medicine." This concept reflected McDermott's belief that the major problems facing medicine extended beyond the professional boundaries of medical doctors. Because McDermott admitted that he favored the second concept, he came down on the side of expanding the number of people on the Board on Medicine without changing its basic shape or character, rather than creating a National Academy of Medicine. It seemed to him that the Board represented the best hope of interdisciplinary collaboration, in which physicians could work with social scientists on such problems as the reform of medicine and medical education. An Academy of Medicine would develop a tendency to be overprotective of the medical profession and to shy away from the most critical problems. 63
In a rebuttal to Walsh McDermott, Page charged that McDermott had stacked the intellectual deck. McDermott assumed that physicians would act in a biased and defensive manner without any evidence to support those assertions. Page argued that McDermott's was "the counsel of timidity" that expressed a "lack of faith in the competence of selected physicians." Physicians, according to Page, must have a "strong voice in determining the destiny of medicine," and anything less was ''a weak compromise for which interest will soon flag." 64
The next meeting of London's committee took place in the midst of considerable confusion. First, the presidential election turned out as many Board on Medicine members had feared. Second, the National Academy of Sciences was undergoing its own change of administration. Fred Seitz would leave at the end of the fiscal year (July 1969), and the Board would have to deal with a new NAS president. In addition, the NAS was forming a section on medical sciences that could conceivably sap some of the energy from the campaign to create the National Academy of Medicine. Because these changes made the future seem less than clear, the second meeting of London's committee, like the first, ended with little substantive agreement except that each member would write down his preferences about a new institutional form for the Board on Medicine and send the results to Dr. London. 65
When the full Board on Medicine convened on November 20, 1968, London could offer his colleagues only a status report on the deliberations of his subcommittee. Despite the uncertainty, some ideas appeared to be taking shape. Membership in whatever organization evolved should be on a short-term basis. Each of the members would be expected to work; no one wanted a purely honorific organization. There should be a full-time staff, headed by a full-time
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officer or officers. The majority of the people on the Ad Hoc Panel appeared to be heading toward the use of the word "academy" in the organization's title. Most people agreed that the Board on Medicine in its present form had failed to meet the expectations generated by Page's discussion group and other advocates of a National Academy of Medicine. Still, profound differences remained between the Page-Comroe faction and McDermott. As Comroe put it, "Some of us believe very strongly that if it is to be a Board on Medicine or an Academy of Medicine, then it must be predominantly made up of medical people." If such a board or an academy were to be accepted, it had to be accepted among medical practitioners. This meant it had to overcome the stereotype that physicians always acted in their self-interest, desired nothing more than a trade union, and exhibited no concern for the country's future. 66
Irvine Page aptly summarized the situation at the end of 1968. In an unguarded moment, he wrote that "there have been many, many arguments over the past year and a great deal of soul searching going on and there is no way of knowing how it is going to come out." To Dwight Wilbur, Page's friend and ally on the Board, it appeared that Walsh McDermott was "doing his best to fan the flames in his direction or on his behalf." 67
As Wilbur's comment suggested, the Page faction spent much of the next year and a half in a state of frustration. One source was the inevitable delay. Another, more enduring source of frustration came with the announcement that Philip Handler, chairman of the Department of Biochemistry at Duke, would become president of the National Academy of Sciences on July 1, 1969. Unlike Seitz, Handler held no particular brief for a National Academy of Medicine. High on his list of priorities was a desire to strengthen the life sciences within the Academy. As part of this agenda, he hoped to elect more practitioners of medical sciences to the Academy and to strengthen the management of the National Research Council. None of this meshed with Page's plans. 68
McDermott, too, experienced his share of aggravation. As the meetings of the Board on Medicine became more contentious, his job became more difficult. His finely honed sense of obligation did not permit him to retire from the Board until he had settled its future. This commitment forced him to attend endless rounds of meetings with Board members and NAS officials. Because McDermott regarded it as his duty to serve as an honorable intermediary between the Board and the NAS, he was often the bearer of bad news.
Nor did the Board's research projects bring much encouragement to Page, McDermott, or anyone else. The project to reform medical
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education gradually unraveled. It had been tacitly agreed with Jim Shannon that the National Institutes of Health would support the project. On the strength of the initial $40,000 from NIH, the Board recruited a study director and assembled a number of panels. By the beginning of 1969, it had become clear that NIH had developed different priorities since Shannon's departure. The study director resigned, and efforts began to secure funds from other sources. The project on medical services for the poor experienced a similarly rocky start. 69
London's panel to decide on a National Academy of Medicine appeared to be the only Board on Medicine activity that mattered. The group met for a third time at the end of February in Palo Alto, California. 70This time the group managed to get past its previous impasse and reach a decision. The group had already decided on the need for an "institutional framework in medicine" that could confront medicine's problems. The questions centered on what form such an institution should take. The panel debated three options: (1) continuation of the Board on Medicine, (2) transformation of the Board on Medicine into a National Academy of Medicine under the Charter of the NAS, and (3) creation of a free-standing National Academy of Medicine. In the end, the panel decided on the second alternative. It recommended that the "Board on Medicine take the steps necessary to secure the creation, under the Charter of the National Academy of Sciences, of an autonomous National Academy of Medicine." The panel even included a timetable that culminated in the formal creation of the National Academy of Medicine by July 1, 1970. 71Joseph Murtaugh hastily drew up a proposal for a National Academy of Medicine that included members who would serve for no more than 10 years; it would have an initial membership of 250 people, a balance of three to one between medical professionals and others, and a full-time elected president. 72Although Murtaugh could not have known it, he had, in fact, written the first draft of a plan for the Institute of Medicine.
At first glance the London panel's report appeared to be a victory for Irvine Page, who favored the creation of a National Academy of Medicine, and a defeat for Walsh McDermott, who opposed it. As always, however, it was the details that mattered. If London's group had its way, the National Academy of Medicine would be part of the National Academy of Sciences, a prospect more congenial to NAS member McDermott than to Page. Nor did the panel specify how much of a social, as opposed to a medical, content the new academy would have. Therefore, although Page felt a cautious sense of optimism, he warned Dwight Wilbur that "our troubles aren't over." 73
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The Board on Medicine debated London's report on March 12, 1969. In his presentation to the Board, London emphasized the advantages in terms of prestige and financial support that would come from linking the NAM to the established National Academy of Sciences. When Philip Handler dropped in on the meeting, he too argued against what he described as a free-standing academy. "I am afraid it would be thought of in the world at large as a guild of some sort," and it would be encumbered with the "stigma that guilds have in the world," he said. McDermott agreed that "the greatest single trap in which this campaign can be caught is guildism.''
Listening to the discussion with relative complacency, Board members voted to accept the panel's main recommendation. With a unanimous vote, the Board put itself on record as favoring an autonomous National Academy of Medicine under the National Academy of Sciences. In Comroe's account of the meeting to the absent Irvine Page, "there were only a few feeble arguments opposing the proposal for a National Academy of Medicine and these were dealt with very ably by those around the table." During the rest of the meeting, the Board attended to some of the details. If the Council of the National Academy of Sciences approved the proposal, then the president of the NAS would appoint an organizing committee to write what amounted to a constitution for the new organization. The Board on Medicine would then be expanded to 50 members who would select the first members of the National Academy of Medicine. Within three years of the founding of the National Academy of Medicine, three-quarters of the members would come from medicine and the medical sciences, and one-quarter would come from the social sciences, administration, law, and engineering. 74
Rejection by the National Academy of Sciences
Once again, the campaign to create a National Academy of Medicine accelerated. Walsh McDermott presented the Board's plan to the Executive Committee of the NAS Council at the end of March. The NAS officers asked him a lot of pointed questions. They wondered just how members would be chosen, how the new academy might develop a working relationship with the National Research Council, and whether the NAM might take positions on public controversies that would put it at odds with the impartial National Academy of Sciences. In the end, the Executive Committee "accepted in principle the concept of a National Academy of Medicine" and agreed that the full NAS Council would take up the matter in June. However,
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preliminary discussions in the Council, conducted behind closed doors, showed that many NAS Council members remained skeptical of the venture. They questioned the need for a new academy's autonomy. As far as Philip Handler and the NAS Council were concerned, the matter was far from settled. 75
In the course of the May discussions of the Board, Walsh McDermott confided that he was having his own crisis of confidence. Although he would do his best to argue the case for a National Academy of Medicine to the Council in June, he still had doubts about the wisdom of this approach. Two things were essential to him—that the NAM not be solely honorific and that it contain a mixture of disciplines. "I have serious questions that anything that is called an academy is the proper instrument to meet these two purposes," he said. Irving London, who sympathized with McDermott's position, explained why he nonetheless favored a national academy. If the Board followed McDermott's advice and established something like a "National Medical Council" or the "National Board on Medicine," then "quite another group in this country would come along calling itself the National Academy of Medicine and would create enormous confusion in the public mind." 76
Setting his doubts aside, McDermott issued the final assignments for the presentation to the NAS Council. He, London, and Adam Yarmolinsky would draft a document that would be presented to the Council. A delegation from the Board on Medicine comprised of McDermott, Glaser, London, and Yarmolinsky would make the formal presentation. There was nothing surprising about these assignments, except perhaps for the inclusion of Yarmolinsky. His selection reflected the Board's growing dependence on Yarmolinsky as a draftsman and, because he was quick thinking, as a spokesman. Yarmolinsky became the Board's informal counselor, advising the group on legal matters and matters of organizational design. His experiences in the Kennedy and Johnson administrations made this Harvard law professor the closest thing the Board had to a Washington insider. 77
Jim Shannon, the Board's consultant and other certified Washington insider, took the case for a National Academy of Medicine to the public. Speaking in Chicago, Shannon told the American College of Physicians that the National Academy of Medicine would be a super agency that would reorganize America's "nonsystem" of health care. It would do for medicine what the National Academy of Sciences had done for science and technology. Addressing a Travelers Research Corporation seminar in Hartford, Connecticut, Shannon said that the members of the National Academy of Medicine would be
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broadly informed and "objective enough to give true leadership." Naturereported that there was a good chance that a National Academy of Medicine would exist by 1970 and that Shannon "seems to have been the chief instrument in planning the new academy." 78
Shannon joined the Board's representatives when they made their pitch to the NAS Council on June 7, 1969. The two-hour session resembled a Supreme Court hearing, with NAS Council members taking the part of judges. Scientists on the Council peppered the physician and lawyer who stood before them with questions. Would it not be better to expand the Board on Medicine? How could the National Academy of Medicine ensure that its members would be of high stature? Would the inclusion of medical practitioners debase the status and prestige of the new academy?
Although Shannon and the others did their best to respond, the answers seemed only to create more questions. The Council should not look on an Academy of Medicine as a threat or as competition, argued Shannon, but rather as a "complementary institution necessary for the further evolution of science." It would be a source of disinterested advice. This led George Kistiakowsky, the Harvard chemist and NAS vice-president, to wonder if offering such advice would make the new academy a lobbying organization and threaten the NAS Charter. Phil Handler also stressed the differences between the two sorts of academies. The National Academy of Medicine would initiate views on public policy rather than limiting itself, in the traditional NAS manner, to responding to requests for advice. The broad scope of the NAM mission also troubled the scientists, who wanted the disciplinary borders of the new academy to be clearly drawn. At the end of the discussion, Alvin Weinberg, an applied physicist who worked at the Oak Ridge National Laboratory, said that he would have a difficult time voting for the proposal because of what he called a substantial "impedance mismatch" between "some of the concepts set forth for the NAM and those which have been traditional for the NAS." 79
When the Board on Medicine representatives left the room, Council members expressed serious misgivings about establishing a National Academy of Medicine. Handler said that demands to create separate academies would proliferate and soon the social scientists would ask that they too have an academy. The National Academy of Sciences might then become so diluted that its prestige would disappear. Wallace Fenn, a physiologist who worked at the University of Rochester's medical school, thought it would be much better to expand the Academy's Medical Sciences Section and the NRC's Division of Medical Sciences than to create a new academy. Council
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members agreed that the Board's proposal should be examined with "great care and deliberation." Handler, who was about to take over as NAS president, proposed—and the Council agreed—that action on the proposal be put off until the Executive Committee meeting in July. 80
Soon after the June meeting, Handler wrote the NAS Council a letter that further revealed his doubts about a National Academy of Medicine. He realized that there was a mismatch between the qualifications of the distinguished scientists elected to the NAS and the practical expertise needed to respond to requests for advice on policy questions related to science. The Academy had too few clinical medical scientists, applied agricultural scientists, engineers, and social scientists. This put many pressures on the Academy, such as the request to form the National Academy of Medicine. The advocates of an NAM wanted to "undertake a type of lobbying activity which is not in keeping with the history of the Academy" and to have a "mixed membership which would, in effect, make them independent of this Academy for advisory functions." If the federal government turned to the NAM and similar entities for advice, the NAS would "be left with only minor advisory functions. Its role in our national life will have been very markedly diluted and its prestige very significantly eroded." Handler proposed to create a Division of Medical Sciences, one of five such divisions in a reorganized NAS, that could elect its own members. Such a division might preempt the campaign to create a National Academy of Medicine. 81
Although Joseph Murtaugh called the Council's reception of the Board on Medicine "cordial," the proposal for a National Academy of Medicine came at a sensitive time in NAS history. 82The resulting dispute reflected in part the differences in outlook between the hard and applied sciences. The physicists, chemists, and mathematicians who made up the bulk of the National Academy of Sciences regarded most social problems as too imprecise to define in a meaningful way. Because social problems did not lend themselves to the formulation and testing of hypotheses, they could not be solved through the scientific method and hence were not the legitimate business of the National Academy of Sciences. The economists and sociologists who might have disagreed with this proposition were too few in number in the NAS to influence its outlook.
Both McDermott and the Page contingent differed in their views from NAS scientists. For McDermott, the social aspects of medicine were the most important things for a National Academy of Medicine to address. Shannon, Page, and Comroe, each of whom became NAS members, were closer to the outlook of pure scientists. They, too, had doubts about the social aspects of the Board on Medicine's work—in
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part because they came from the world of medical research, rather than the fields of public health, health services, or health care financing. Still, they believed that an effective National Academy of Medicine required participation from a broad cross-section of the medical profession. This put them at odds with the scientists who regarded an academy as a place for researchers, not mere clinicians; for thinkers, not policy activists. Furthermore, the scientists at the National Academy of Sciences, led by Handler, were protective of the Academy as a place where merit alone secured membership. In the Nixon era, with both academia and the undirected nature of scientific research under attack, preserving the Academy as a sanctuary from ephemeral politics seemed all the more important.
When the Executive Committee of the NAS Council met on July 19 in the Academy's facilities at Woods Hole, Massachusetts, to make a final decision on the Board's proposal, Handler's views prevailed. Although the NAS was generally sympathetic to the objectives of the Board proposal, it objected to the issuance of policy statements on political questions and to the "variable criteria" for membership. The Executive Committee hoped to work toward increasing the number of NAS members and, in doing so, to meet many of the Board's objectives. If the Board wished to proceed with an independent NAM, it should feel free to do so but without the help of the NAS. Finally, the fact that engineers had gained their own academy should "not be followed as a precedent." 83
On the following day, McDermott and his group met with the NAS Executive Committee and learned of its decision: the NAS Council had rejected the concept of a National Academy of Medicine. Any hope of achieving the Board's objectives would have to occur in a reorganized NAS. In the meantime, the Executive Committee advised the Board to continue with its activities and to have faith in the committee's goodwill. Somewhat stunned, Yarmolinsky and London asked how the movement to create an independent National Academy of Medicine could be contained as the NAS reorganization process proceeded. There could be no way of preventing this from happening, Handler replied. He thought that in the long run, however, the prestige and status of the NAS would prevail. 84
Handler tried to put a positive spin on the Council's actions. He emphasized that the NAS Council "warmly" approved of the Board's objectives. The Council's differences with the Board came over the mechanism of a National Academy of Medicine, which was "not welcomed by the Council at this time." Rather, the Council proposed to restructure the NAS, and whatever structures emerged would involve "increased membership of clinical investigators and of
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individuals in other disciplines related to the problems of health care." Handler hoped that the process could be completed by the following spring. He concluded by thanking the Board for its proposal, which "has heightened our consciousness of the need for early reforms of our structure and mechanisms." 85
The Diplomacy of Reconciliation
At a July postmortem meeting of the Board, Page said that the movement to start an independent National Academy of Medicine could no longer be contained. Dr. London believed that the group was the victim of timing. If Fred Seitz were still the NAS president, things would have turned out differently. McDermott tried to move beyond the anger and get the Board to decide on what to do now. Should the Board continue, or should its energy be put into forming an independent National Academy of Medicine? Dr. Bryan Williams, the physician from Dallas, said he did not want to wait any longer; it was time to form a National Academy of Medicine. Dr. Comroe urged the group to go back to Page's original conception of a National Academy of Medicine. Ivan Bennett agreed that the group had lost both time and money by working with the National Academy of Sciences. For all of the anger, however, the group could still not make a clean break from the NAS. Instead, McDermott was instructed to tell Philip Handler that it looked as though "the road is going to be that of an Academy of Medicine, that it is our hope that this can be done in a way that represents a natural disengagement from NAS with a lot of help from NAS." McDermott, meanwhile, clung to his hope that something could be worked out with the National Academy of Sciences. 86
The situation had turned out as Page had thought. "It looks now as though the NAM is going to be formed independent of the NAS," he told a friend, "We are wiser but just about where we left off when the meetings were transferred to Washington." It was time to reunite the Cleveland group and get down to business. On August 15, Page sent a form letter to the leaders of his original Cleveland discussion group in which he announced tentative plans for another small meeting. The whole experience, he explained to Jim Shannon, demonstrated that a "chairman unsympathetic with the purposes of a group can really hamstring the progress of a committee." 87
It was not a good time for the Board on Medicine. Within a week, it became clear that the study of medical education, which had received a final rejection from the National Institutes of Health,
Suggested Citation:
To Improve Human Health: A History of the Institute of Medicine
would be disbanded. The staff hired for this study began to put their resumes in the mail. With the loss of this project, the rationale for continuing the Board on Medicine looked even weaker. 88
In this deteriorating situation, Handler and McDermott engaged in a confrontational form of diplomacy. McDermott advised Handler that at least 14 members of the Board doubted whether an accord could be worked out with the Academy. Some of these, however, still believed that it would be more worthwhile to maintain some sort of link with the Academy. Handler informed his executive board that the Board on Medicine had decided to go ahead with the initial planning for a National Academy of Medicine and wondered what, if anything, the NAS should do in response. Members of the Council's Executive Board told him to hold firm. George Kistiakowsky recommended that the NAS do nothing to oppose the creation of a National Academy of Medicine. It should, however, insist that the Board undertake this activity on its own time or through other organizations. Wishing the Board well, the NAS should go about its business of increasing the number of physicians in the Academy and restructuring the National Research Council. Encouraged by this advice, Handler did not appear willing to make many concessions to the Board. ''I feel rather strongly that, in the end, creation of an independent National Academy of Medicine is not in the national interest," he told Joseph Murtaugh. The National Academy of Sciences would not be blackmailed by the threat of an independent National Academy of Medicine. At this point, the situation resembled the sorts of power struggles that scientists were beginning to witness over such things as the creation of black studies programs on their campuses. 89
As the summer continued, both sides retreated from their harsh positions and began to engage in pragmatic bargaining. Walsh McDermott did all he could to soften Handler's position through a series of phone calls and telegrams. Working closely with McDermott, Handler drafted a letter in which he offered McDermott a chance to participate actively in the NAS committee charged with reorganizing the National Research Council. He also raised the possibility that a series of what he called "institutes" might be formed within the National Academy of Sciences, "one of which might well be an institute on medicine or health affairs." As he made these suggestions, Handler, along with the Executive Committee of the Council, urged that "the Board not take precipitate action at this time with respect to the planning of an external Academy of Medicine." Instead, all alternative plans should be examined and an "acceptable accommodation" found. In this manner, health affairs could assume "a suitable, highly visible, and decidedly dignified position within this
Suggested Citation:
To Improve Human Health: A History of the Institute of Medicine
total body" and the fragmentation of the NAS could be avoided. "Your ... letter to me was splendid," McDermott replied. 90
In September 1969, negotiations continued at a 12-hour meeting attended by Handler and all the principal players from the Board on Medicine, a sort of executive committee. Board on Medicine participants tried to determine which of their conditions were nonnegotiable. Merely adding members to the Board, they agreed, was unacceptable. At a minimum, they required a large institution with freedom to develop its own program, a diverse membership, and the word "academy" in the title. Handler, for his part, tried to be as conciliatory as he could, yet he admitted that the issue of a title for the new medical organization still presented considerable difficulties. He once again mentioned the possibility of an institute and hoped that this might provide "a sufficiently prestigious image." He also speculated that the entire NAS might be reorganized to contain five different subacademies, including the Academy of Medicine. Because such an academy (or subacademy) would maintain the NAS's membership standards, only scientists would be allowed to join. This left no room for the mixed membership coveted by McDermott. As for a completely independent National Academy of Medicine within the NAS, Handler saw no possibility of this. "If the Board insists on going down that road, we are at an impasse," he said.
After listening to Handler, the exhausted group identified three options, each of which meant giving up something. One was to proceed with an independent NAM and abandon the discussions with the NAS (the Page solution). Another was to find a place for medicine within a reorganized NAS structure and abandon McDermott's notion of a group with a mixed membership (the Handler solution). A third involved creating a new institution within the NAS, with a mixed membership, and abandoning the title "National Academy of Medicine" (the McDermott solution). These would be the options that the smaller group would present to the full Board on Medicine when it met in September. 91
Page and Comroe were less than enthusiastic about the chances for progress. Page described Handler's mood as "flippant" at some times and "fairly harsh" at others. McDermott, he felt, sparred with the Board and represented it "very poorly indeed." Julius Comroe thought that "we are witnessing a last-ditch struggle to retain Walsh McDermott in the leadership (or controlling) position in the affairs of a Board on Medicine or its successor." Page agreed that "most of us have had enough of this cat-and-mouse game, so the field is again wide open, and I am not at all sure that anything profitable will come out of the meeting at the end of the month.'' 92
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Not much did. Nearly all of the Board members were weary of the long struggle to create a National Academy of Medicine. As one put it, "We have all lost that pleasant little glow ... because we are haggling over what we are going to call ourselves." "The words are becoming very stale" because "we have not been doing anything for quite some time," London said. To stir things up, the Board agreed that it should return to its program of studies. Even as it tried to get back into the substance of medical policy, however, it kept stumbling over lingering antagonisms. Ivan Bennett mentioned that the Board had failed to advance the torch that the Page group had handed it, and Comroe placed the blame on Walsh McDermott. If the Board had not taken over, Comroe believed, a National Academy of Medicine would have been formed two years earlier. 93
McDermott told Handler that little of substance had emerged from the meeting, except for a request that the Board meet with the NAS Council, a desire that the Board return to its substantive studies, and a commitment to continue to work with the NAS as the reorganization process progressed. Some Board members, McDermott emphasized, wanted to go further and draw up articles of incorporation for an Academy of Medicine. McDermott thought that support for this action was waning, yet the sentiment persisted. Handler replied that there was little point in the NAS Council meeting with the Board. The Council preferred to wait for the report of the Reorganization Committee, chaired by Franklin Long of Cornell University, before such a meeting. 94
At this point, neither group knew if it could trust the other. Handler and the NAS Council regarded the creation of a National Academy of Medicine as a real threat to the integrity of the NAS. Ivan Bennett, who was becoming increasingly militant in his quest for a National Academy of Medicine, believed that the NAS had always been "reserved and academic in making studies and proposals," with little "activism in trying to see to it that these proposals are heard in the proper circles and that measures are taken to insure their implementation." Irvine Page thought that there was "little hope of coming to any sensible agreement with NAS without sacrificing the larger objectives of a National Academy of Medicine. I have no enthusiasm whatever to be dominated by Phil Handler and Walsh McDermott, who insist on treating us as second class citizens." The notion of trying to get back to the substantive work of the Board was only a "ploy" to silence Page and his allies. 95
If so, it worked. For a time in late 1969, the Board concentrated on such substantive issues as the movement to pass national health insurance and the increased use of physician's assistants. A spurt of
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
renewed 1960s optimism attended this phase of the Board's work. It appeared likely that Congress would approve some form of national health insurance and that troop reductions in Vietnam would create a peace dividend that could be spent on social programs. At a time of fears of a shortage of physicians, nurses, and other key health professionals, de-escalation of the war also had the salutary effect of increasing the number of medical doctors and nurses at home. Caught up in the spirit, one Board member talked of opening "up for this nation and our society a whole new vista of progress." 96Buoyed by this optimistic feeling, the members made a crucial concession to the NAS and agreed to wait for the report of the Long Reorganization Committee before taking action on an independent National Academy of Medicine. "In my judgment," a relieved McDermott told Handler, "the immediate crisis has been weathered." For his part, Handler believed that "our problems are not solved and that we have simply bought time to bring the house in order. But that is all that I had hoped to accomplish at this period." 97
Some of the fallout from the protracted struggle began to appear in early 1970 in the form of critical articles in the professional press. The standard line was that the Board had failed to live up to its expectations, as demonstrated by the rejection of its plan to investigate medical education. The rebuff of the academy idea by the NAS had "shattered the morale of many board members and staff." As further evidence of the low morale, the press pointed to the fact that both Shannon and his protégé Joseph Murtaugh were planning to leave the National Academy of Sciences. Shannon, who had been acting as an NAS consultant since his 1968 departure from the Academy, took a job with former NAS president Fred Seitz at Rockefeller University. Murtaugh, who had done a heroic amount of staff work for the Board, accepted a position with the Association of American Medical Colleges. 98
Despite bad press notices, the Board made real progress toward the resolution of its issues in January 1970. For one thing, Ivan Bennett met with the members of the Long committee and came away impressed. Although he had been an outspoken critic of Walsh McDermott, he began to believe that some sort of accommodation with the NAS might be possible. For another, Handler, stressing that the NAS had not vetoed the idea—as opposed to the title—of a National Academy of Medicine, worked at selling the concept of what McDermott called an "Institute of Health Sciences" to Board members.
Page began to give ground. If there could be a broadly based organization that "subtended all of medicine in its broadest sense"
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
and if money could be raised for such an organization, he ''would see no reason particularly for starting anything outside" of the Board on Medicine. To be sure, Page remained skeptical, yet he felt he had no alternative but to give the initiative a chance. 99When he left the January Board meeting, Page told Comroe that he had the strong impression he "would have to play along with it," in part because Robert J. Glaser and Irving London had gone "over to the other side completely." "I suppose in common decency that we have to wait," Page advised. 100
As Joseph Murtaugh cleared off his desk before leaving the Board on Medicine, he too detected some progress. The Board had decided to turn its energy toward examining the implications of national health insurance for medicine, medical education, and health services. It was the usual broad and diffuse Board inquiry, yet it indicated that at least some members were beginning to think of something other than a National Academy of Medicine. In addition, Dr. Eugene Stead had started a small study of the role of the physician's assistant in medicine. Even better, Murtaugh thought that Page would call off a planning meeting of his "Cleveland group." 101
In May, the Board on Medicine received a full briefing on the Long committee report. Although the report contained many suggestions about dividing the NAS membership among several subacademies, it also included the idea of creating institutes within the NAS structure. Most of the committee's recommendation required approval of the membership, which could take at least a year. McDermott stressed, however, that the Board could proceed with the creation of an institute immediately. Much like the old Board on Medicine, the new institute would survey the field, generate its own agenda, and undertake its own studies with its own staff. If the Board wished to go this route, "we are in a position to pretty much carve it out the way we want it," said McDermott. Adding his support, London noted that if Page gave his approval and the members approached the task with enthusiasm, the necessary money could be raised to make a go of this institute. McDermott persuaded the Board to put together a proposal for an institute that he could bring to the NAS Council. 102
The Institute of Medicine
Once again, the Board on Medicine dusted off a proposal and presented it to the Council of the National Academy of Sciences. In this proposal, the Board asked that it be converted to an Institute of Medicine, reporting directly to the NAS Council. It would be
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Save
"qualitatively similar to the Board but sufficiently expanded ... to meet the great needs revealed by 2.5 years of Board experience." The Institute would conduct its own studies, provided they were less than a year in duration. Longer studies would be conducted jointly by the NRC and the Institute. As in the previous proposals for an academy, the Institute would have fixed terms of membership and be able to select its own members, most of whom would not be NAS members. At least 25 percent of the members would have degrees in fields other than medicine or biomedical sciences. All members would be selected for their personal attributes, not because they represented a particular constituency. Soon after the Institute started, it would have about 100 members, and ultimately it might grow to 250 members. 103
Walsh McDermott and a delegation from the Board on Medicine presented this "draft charter" to the NAS Council on June 5, 1970. Yarmolinsky, the principal writer, hastened to reassure Council members that the Charter marked a revision of, but not a departure from, the Board on Medicine. It would not establish a propaganda body, as some Council members feared. On the contrary, it represented the culmination of long years of discussion and established a workable relationship with the NAS. If the Academy rejected this approach, McDermott warned, it would lose "the medical constituency."
The following day, the Council voted to authorize the president of the National Academy of Sciences "to take the necessary steps to create an Institute of Medicine." The Council specified that it would have final authority over the Institute, including the right to review publications and the right to add or delete names of those nominated for membership. It also asked to see a "specific detailed plan describing the organization and operation of the Institute." It regarded this plan as little more than a formality, however, because it authorized Handler to announce the Council decision to the public. 104
On June 10, 1970, the National Academy of Sciences made a formal announcement that it would create an Institute of Medicine "to address the larger problems of medicine and health care." In a letter to McDermott, Handler cited the design of the health care delivery systems, the role of university medical schools, the mechanisms for funding medical care, and the support and nature of biomedical research as the types of problems the Institute might address. He also requested McDermott to prepare a document containing the bylaws of the organization in time for the NAS Council meeting in August. 105
Appearing before the Board on Medicine in June, Handler assured the group that the NAS Council had given the Board on Medicine the
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
"broadest kind of hunting license" to establish the new Institute. The head of the Institute would be "someone of stature who would command a commensurate salary." The Board envisioned such a person to be about 45 years old. ''If you find the best man for it, we are just going to be delighted," Handler said, using the conventional sexist language of the era. He added that he did not foresee any problems with NAS Council approval. 106
A draft of the constitution and bylaws received the Board's approval on July 22. The next step was for Irving London, Adam Yarmolinsky, Walsh McDermott, and James Shannon to present these documents to the NAS Council on August 24. In the meantime, Handler offered his suggestions. Among other things, he changed the title of the president of the IOM to the director, and the name "executive council" to "executive committee." In making these suggestions, Handler hoped to avoid confusion between the IOM and the NAS itself.
The August 24 meeting of the NAS Council went smoothly. On nearly all matters of dispute between the Board and the NAS, the Council yielded. The Council wanted to restrict the total number of members, but McDermott assured them that the Institute's work required more than 200 people. The Council agreed that the IOM should have a president, not a director. Both sides concurred in the provision that all members of the Medical Sciences Section of the National Academy of Sciences would receive an invitation to join the Institute.
On September 9, 1970, Walsh McDermott wrote that he, Adam Yarmolinsky, and Irving London were all quite pleased with the final version of the Institute of Medicine's Charter and Bylaws. The Charter contained a ringing statement that reflected McDermott's point of view: "The problems posed in provision of health services are so large, complex and important as to require, for their solution, the concern and competences not only of medicine but also of other disciplines and professions." 107In the terms of the earlier debate with Irvine Page, the Institute would speak about, not for, medicine.
Irvine Page retreated as gracefully as he could. In an editorial that appeared in October, he stated that he had once believed that only a freestanding National Academy of Medicine would do. Recently, however, he had been persuaded that the "N.A.S sincerely wishes to fulfill those needs through an Institute of Medicine. The immediate plans have taken more than two years to evolve, and the institute deserves a fair trial." Robert J. Glaser called Page's statement "excellent.... I believe we are now well on our way to creating the kind of organization you and others envisioned from the start."
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Although Glaser warned that much would depend on securing financial backing, the initial signals from the foundation community were encouraging. Independently of Glaser, Page learned that foundation money for the sort of national academy he had wanted to form was no longer obtainable. As Page put it, the Carnegie Foundation and Commonwealth Fund planned to let the Institute "have a try and fail before big money will be available for NAM." 108
Conclusion
Between 1967 and 1970, the Board on Medicine spent most of its time trying to reconcile the conflicting points of view of its members and negotiating with the National Academy of Sciences. As a consequence, it completed few studies and gained fame only for a short statement that it issued on heart transplants. An initial round of enthusiasm for the venture went largely unexploited, because the members of the Board could never quite agree on its final form. An almost superhuman form of patience was required on Walsh McDermott's part to bring the process to conclusion.
In the end, however, the Institute of Medicine reflected McDermott's vision as much as anyone else's. When Irvine Page wrote the 1964 editorial launching the process that ultimately led to the Institute of Medicine, he did not envision that the result would be an organization in which a quarter of the membership would be composed of people from outside the health sciences. Nor did he foresee an entity concerned not only with the problems of medical research but also with the larger social problems surrounding health. The Institute of Medicine was created at a time when health policy experts and even some of those in the realm of heath sciences research, such as McDermott, emphasized the social aspects of medical problems and people thought these problems were amenable to solution. The optimism of the era was stamped on the Institute of Medicine's Charter and Bylaws and on its initial agenda.
So were the organizational tensions that had developed in the National Academy of Sciences. These tensions created ambiguities that would continue to plague the Institute. Exactly how much autonomy did the Institute have? How did the Institute relate to the rest of the Academy structure? Few people wished to probe these questions too deeply for fear of upsetting the delicate set of understandings on which the IOM rested.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
On December 17, 1970, Philip Handler appeared before the Board on Medicine, functioning as the Executive Committee of the Institute of Medicine, and announced that Dr. Robert J. Glaser would serve as acting president of the Institute. He would volunteer his time and keep his regular job. Until recently the dean of Stanford's School of Medicine, Dr. Glaser currently worked as a vice president of the Commonwealth Fund in New York, a position previously held by Board member Colin MacLeod. Four days later, the NAS issued a press release announcing the "formal activation of the Institute of Medicine." 109The Institute of Medicine was launched.
Notes
1.Irvine H. Page, "Needed—A National Academy of Medicine," Modern Medicine, July 20, 1964, pp. 77–79; Wilbur Cohen, "Health and Security for the American People," reprinted in U.S. Senate, Committee on Finance, Nomination of Wilbur J. Cohen, March 22 and 23, 1961. The description of the Association of American Medical Colleges comes from Robert Ebert, "The Changing Role of the Physician," in Carl J. Schramm, ed., Health Care and Its Costs(New York: W.W. Norton and Company, 1987), p. 163. For a historical overview of the many organizations concerned with health policy, see Paul Starr, The Social Transformation of American Medicine(New York: Basic Books, 1982).2. Lawrence K. Altman, "Dr. Irvine H. Page Is Dead at 90: Pioneered Hypertension Research," New York Times, June 12, 1991; Curriculum Vitae of Irvine H. Page, M.D., Box 8, Irvine Page Papers, National Library of Medicine, Bethesda, Md.3.Paul Starr, The Social Transformation of American Medicine, p. 347; Stephen P. Strickland, Politics, Science, and Dread Disease: A Short History of United States Medical Research Policy(Cambridge, Mass.: Harvard University Press, 1972); Daniel M. Fox, Health Policies, Health Politics: The British and American Experience, 1911–1965(Princeton, N.J.: Princeton University Press, 1986).4.Irvine H. Page, "More on a National Academy of Medicine," Modern Medicine, March 15, 1965, pp. 89–90; materials in File IOM: 1965, Box 1, Page Papers.5.Irvine Page to Dr. Karl Folkner, President, Stanford Research Institute, April 6, 1964, File IOM: 1965, Page Papers.6.Irvine Page, "Membership in a National Academy of Medicine," and "Replies to July 1965 Query re: Membership in a N.A.M.," both in Container 1, File IOM: 1965, Page Papers.7.Edward D. Berkowitz, America's Welfare State: From Roosevelt to Reagan(Baltimore, Md.: Johns Hopkins University Press, 1991), p. 178; Stephen P. Strickland, Politics, Science, and Dread Disease, p. 207.8."News in Brief," Science, September 23, 1966, p. 1508.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
9.Irvine Page to Robert Aldrich, September 6, 1966, and "Agenda of First Organizational Meeting," January 17, 1966, both in Page Papers.10.Irvine Page, "Is There a Need?" Notes for first organizational meeting, Page Papers.11.Donald S. Fredrickson, "James Augustine Shannon," Proceedings of the American Philosophical Society, 140 (March 1966), pp. 107–114; Stephen P. Strickland, Politics, Science, and Dread Disease, pp. 100–101.12."Minutes of Organizational Meeting of National Academy of Medicine," January 7, 1967, Board on Medicine Files, National Academy of Sciences (NAS) Archives.13."Minutes of Second Organizational Meeting for a National Academy of Medicine," March 7, 1967, Board on Medicine Files, NAS Archives.14.Ross Harrison to George H. Whipple, September 6, 1941, and E. B. Wilson to Harrison, September 12, 1941, Box 80, Ross Harrison Papers, Yale University.15. Report of the National Academy of Sciences, National Research Council, Fiscal Year 1945–46 (Washington, D.C.: U.S. Government Printing Office, 1947), p. 52.16.See, for example, National Academy of Sciences, National Academy of Engineering, National Research Council, Annual Report Fiscal Year 1967–68(Washington, D.C.: U.S. Government Printing Office, 1970).17. Frederick K. Seitz Memoir, p. 289; J. F. A. McManus, M.D., "Why a National Academy of Medicine?" Medical Science, April 1967, in Agenda Book, Background Materials on Further Institutional Forms for the Board on Medicine, Board on Medicine Files.18.Council Meeting, Executive Session, April 22–23, 1967, and Business Session, April 25, 1967, both in Board on Medicine: General 1967 file, NAS Records.19.Council Meeting, June 3 and 4, 1967, and Governing Board Meeting, June 4, 1967, both in Board on Medicine: General 1967 file, NAS Records.20.Betty Libby to Robert Aldrich, June 15, 1967, and Irvine Page to Philip Lee, June 23, 1967, both in Page Papers.21.Walsh McDermott to Irvine Page, October 5, 1966, File IOM: 1966, Page Papers.22.Paul B. Beeson, "Walsh McDermott, October 24, 1909–October 17, 1981," NAS Biographical Memoirs, pp. 283–299, enclosed in Beeson to Samuel Thier, May 10, 1990, Wallace Waterfall Materials, National Academy of Sciences.23.Frederick Seitz to Dr. Walsh McDermott, June 28, 1967, and McDermott to Seitz, July 22, 1967, NAS, Committee and Boards, Board on Medicine, General, NAS Records, NAS Archives.24.Minutes of Meeting, June 28, 1967, Board on Medicine Meetings, Minutes, 1967–1968, Board on Medicine Files, NAS Records, NAS Archives.25.Irvine H. Page to Dr. Robert Aldrich et al., September 13, 1967, Container I, File IOM: August–December 1967, Page Papers; Diary Note, September 14, 1967, Meeting of Organizing Group, September 12, 1967, NAS Records.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
26.Minutes of Council Meeting, September 30, 1967, NAS Records; Walsh McDermott to Frederick Seitz, September 18, 1967, NAS Records; Daniel Bell to Seitz, October 3, 1967; Kermit Gordon to Seitz, October 26, 1967; Milton Friedman to Seitz, October 13, 1967; and James Tobin to Seitz, October 5, 1967, all in Board on Medicine: Membership, NAS Records; Seitz to Rashi Fein, October 31, 1967, and Fein to Seitz, November 6, 1967, both in Rashi Fein Papers (privately held); Interview with Rashi Fein, August 2, 1997, Lake George, New York.27.Evert Clark, "Medical Board Set Up to Speed Benefits of Research to Public," New York Times, November 14, 1967, p. 1. Other media coverage included articles in the Journal of the American Medical Association, December 4, 1967; Medical World News, November 24, 1967; U.S. Medicine, December 15, 1967, Medical Tribune, November 27, 1967; and Science, 158 (1967), p. 891. Each of these stories is carefully collected in the Page Papers.28.Irvine Page to Colin MacLeod, July 2, 1967; Page to Fred Seitz, October 3, 1967; Page to Stuart M. Sessoms, December 4, 1967; Page to James A. Shannon, December 8, 1967; Page to Julius Comroe, January 2, 1968; and Page to MacLeod, January 2, 1968, all in Page Papers.29."First Meeting of the Board on Medicine, National Academy of Sciences, November 15, 1967: Summary of Discussion" (prepared by Joseph Murtaugh), Board on Medicine Meetings, Minutes, 1967–1968, Board on Medicine Files.30."Summary Minutes of the Second Meeting of the Board on Medicine, Washington, D.C.," December 14 and 15, 1967, File Board on Medicine Meetings: Minutes 1967–1968, Board on Medicine Files, NAS Records, NAS Archives.31.Walsh McDermott to Dr. Julius H. Comroe, Jr., January 16, 1968, File Functional Statement: Proposed, Board on Medicine Files.32.Irvine H. Page to Drs. R. A. Aldrich et al., December 18, 1967, File Board on Medicine: Meeting: December 14–15, 1967, Board on Medicine Files.33.Irvine H. Page to Drs. R. A. Aldrich et al., February 6, 1968, Container 1, Page Papers.34.Minutes of Board on Medicine Meeting, February 2, 1968, Board on Medicine Files.35.Walsh McDermott to Board on Medicine, February 20, 1968, Board on Medicine Files.36."Board on Medicine Recommends Criteria for Heart Transplants," press statement for release on February 28, 1968, File Draft Annual Report, August 1969, Board on Medicine Files.37.Evert Clark, "Guidelines Urged for Transplants," New York Times, February 27, 1968.38.Rudy Abramson, "Don't Try Heart Transplants too Soon, Scientists Warn," Atlanta Journal, February 29, 1968.39."Appraising Heart Transplants," Saturday Review, April 6, 1968, pp. 59 ff.40.Alberto Z. Romualdez, M.D., Secretary General, World Medical Association, to Walsh McDermott, February 2, 1968, Heart Transplant
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Material, Board on Medicine Records; Congressional Record, March 5, 1968, pp. S 22212–22213; Joseph A. Califano, Jr., to McDermott, March 5, 1968; Wilbur Cohen to McDermott, March 11, 1968; and Joseph Murtaugh to McDermott, April 21, 1968, all in File Transplant Statement: Correspondence, Board on Medicine Records.41.Dr. Francis Moore to Walsh McDermott, March 14, 1968, File Transplant Statement: Correspondence, Board on Medicine Records.42.Walsh McDermott to Dr. Francis D. Moore, April 3, 1968, File Transplant Statement: Correspondence, Board on Medicine Records.43.Walsh McDermott to Dr. Henry K. Beecher, Department of Anaesthesia, Harvard Medical School, April 27, 1965, File Transplant Statement: Correspondence, Board on Medicine Records.44.Irvine Page to Walsh McDermott, March 18, 1969, File Transplant Statement: Correspondence, Board on Medicine Records.45.Quigg Newton, Commonwealth Fund, to Fred Seitz, May 9, 1968, Board on Medicine Records.46.James Shannon to Fred Seitz, May 23, 1968, Committee and Boards: Board on Medicine, General, 1968, NAS Records.47.Joseph Murtaugh to the record, Meeting at the Commonwealth Fund, June 10, 1968, Committees and Boards, 1968, Board on Medicine, Panels, Further Institutional Forms Ad Hoc, NAS Records.48.See ''Source of Funds, Board on Medicine, 1968–1969," Board on Medicine Records.49."Summary Report of Meetings April 10 and 11, at Stone House, Bethesda, Maryland," April 15, 1968, and Joseph Murtaugh to John S. Coleman, April 22, 1968, File Meeting April 10–11, 1968, Agenda, Attendance, Draft Minutes, both in Board on Medicine Files;50.Task Order 49, Medical Education for the Future, Board on Medicine Records.51."Health and the Poor" (Proposal for a Study), June 10, 1968, Study of Health and the Disadvantaged File, Board on Medicine Files.52."Summary Report of the Meeting of the Panel on Health and the Disadvantaged," September 11, 1968, Study of Health and the Disadvantaged File, Board on Medicine Records.53.Thomas Francis, Jr., M.D., Professor and Chairman, Department of Epidemiology, University of Michigan, to Fred Seitz, January 5, 1968, Committee and Boards: Board on Medicine: General, 1968, NAS Records,54.Internal Health, Education, and Welfare memorandum from Jane E. Fullerton to the Record, March 25, 1968, included in Joseph Murtaugh to Members, Board on Medicine, April 4, 1968, Drawer 1, Board on Medicine Files; Julius Comroe to McDermott, April 8, 1968, File Board on Medicine Functional Statement: Proposal, Board on Medicine Files.55.Julius Comroe to Joseph Murtaugh, March 14, 1968, and Irvine Page to Comroe, March 19, 1968, File NAS-Board on Medicine Correspondence, March 1968, Page Papers.56.Irvine Page, "Needed—A National Academy of Medicine," July 3, 1968, in Joseph Murtaugh to Members, Board on Medicine, July 16, 1968,
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
NAS Committees and Boards (1968), Board on Medicine: Panels, Further Institutional Forms Ad Hoc, NAS Records.57.Julius Comroe form letter, July 8, 1968, in Meeting July 22, 1968: Agenda, Attendance File, Board on Medicine Records; Comroe to Board on Medicine, July 26, 1968, in Agenda Book, Background Materials on Further Institutional Forms for the Board on Medicine, Board on Medicine Records; File July 22, 1968, Meeting Transcript, p. 42, Board on Medicine Records.58.Julius Comroe to Irvine Page, August 16, 1968, File NAS-Board on Medicine, July–September 1968, Page Papers. The members of the panel were Irving London, Julius Comroe, Robert J. Glaser, Henry Riecken, Walter Rosenblith, and Dwight Wilbur, with James Shannon listed as a consultant.59.Board on Medicine Meeting Transcript, September 25, 1968, p. 164, Board on Medicine Files, "Notes on the Meeting of the Ad Hoc Panel of Further Institutional Forms for the Board on Medicine," September 27, 1968, 1968, NAS Records.60.Joseph Murtaugh to Fred Seitz, October 8, 1968, NAS Records.61.Irving S. Wright to Irvine Page, November 13, 1968, Container 2, File NAS-Board on Medicine Correspondence, November-December 1968, Page Papers.62.Carleton B. Chapman, M.D., Dean, Dartmouth Medical School, to Irvine Page, December 18, 1968; Page to Chapman, December 27, 1968; and Page to Francis D. Moore, December 26, 1968, all in File NAS-Board on Medicine Correspondence, November–December 1968, Page Papers.63.Irvine Page to Irving London, November 14, 1968, NAS Committees and Board, Future Institutional Forms, NAS Records.64.Irvine Page, "The Two-Concept Idea," Background Materials for Further Institutional Forms, Board on Medicine Files.65."Notes on the Meeting in Boston, November 18, 1968, of the Ad Hoc Panel on Further Institutional Forms, Agenda Book, Background Materials for Further Institutional Forms, Board on Medicine Files.66.Transcript of Board on Medicine Meeting, November 20–21, 1968, Board on Medicine Records. See particularly pp. 133–134.67.Irvine Page to Francis Moore, December 26, 1968, and Dwight Wilbur to Page, January 3, 1969, both in File NAS-Board on Medicine Correspondence, January-February 1969, Page Papers.68.Joseph S. Murtaugh to Members, Board on Medicine, January 9, 1969, in Drawer One, Board on Medicine Records; NAS Press Release, January 17, 1969, Drawer One, Board on Medicine Records.69."Summary Notes on the Meeting of January 20, 1969," January 27, 1969, and Robert A. Kevan to Joseph Murtaugh, January 28, 1969, both in Study on Biomedical Education for the Future File, Board on Medicine Records.70.Robert Glaser to Irvine Page, February 13, 1969, and Page to Glaser, February 20, 1969, both in File NAS-Board on Medicine Correspondence January-February 1969, Page Papers.71.Irving M. London to Walsh McDermott, March 7, 1969, NAS Records.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
×
72."A Proposal for a National Academy of Medicine," February 28, 1969, Committee and Boards, Panel: Further Institutional Forms, Ad Hoc, General, 1969, NAS Records.73.Irvine Page to Dwight Wilbur, March 3, 1969, File NAS-Board on Medicine Correspondence March-April 1969, Page Papers.74.Transcript of Board on Medicine Meeting, March 12, 1969, pp. 113, 126–127, 256, Board on Medicine Records; Walsh McDermott to Irvine Page, March 21, 1969, and Julius Comroe to Page, March 17, 1969, both in File NAS-Board on Medicine Correspondence March-April 1969, Page Papers.75.Walsh McDermott to Fred Seitz, March 24, 1969, NAS Council, Executive Committee Meeting, March 29, 1969, NAS Records; McDermott to Board on Medicine, May 22, 1969, NAS Records; McDermott to Irving London, April 15, 1969, NAS Records; Minutes of NAS Council, April 26–27, 1969, NAS Records.76.Transcript of Board on Medicine Meeting, May 7–8, 1969, pp. 53, 105–108, Board on Medicine Files.77.Joseph S. Murtaugh to Members, Board on Medicine, "Summary Report on Board on Medicine Meeting, May 7–8, 1969," McDermott Files, Board on Medicine Records; McDermott to the President and Members of the Council of the National Academy of Sciences, May 29, 1969, Agenda Book, June 25–26, 1969, Meeting, Board on Medicine Records.78.Ronald Kotulak, "Plan Super Agency to Advise on Health," Chicago Tribune, April 25, 1969; David Rhinelander, "Health Expert Wants Medicine Academy," Hartford Courant, May 4, 1969; and "Scheme for Medical Academy," Nature, 223 (August 9, 1969).79.Minutes of the Council Meeting, June 7, 1969, NAS Records; Joseph Murtaugh to McDermott, Glaser, London, Yarmolinsky, and Shannon, June 12, 1969, NAS Records.80.Council Meeting, June 7, 1969, Executive Session, Restricted, NAS Records.81.Philip Handler to the Council, National Academy of Sciences, June 17, 1990, McDermott Files, Board on Medicine Records.82.Joseph Murtaugh to Members, Board on Medicine, June 11, 1969, NAS Records.83.NAS Executive Committee Meeting, July 19, 1969, NAS Records.84.Joseph Murtaugh, "Notes on the Meeting of the Delegation of the Board on Medicine with the Executive Committee of the NAS Council, July 20, 1969, at Woods Hole, Massachusetts," July 28, 1969, NAS Records.85.Philip Handler to Walsh McDermott, July 29, 1969, NAS Records.86.Transcript of Board on Medicine Meeting, July 30, 1969, Board on Medicine Records.87.Irvine Page to James Shannon, August 1, 1969, and Page to Cecil Andrus, August 6, 1969, both in File NAS-Board on Medicine Correspondence July-August 1969, Page Papers.88.Robert Q. Marston to Ivan Bennett, June 20, 1969, Meeting File for September 29–30, 1969, Board on Medicine Records; Robert A. Kevan to C. H.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
William Ruhe, August 7, 1969, Reorganization File for the Study on Biomedical Education for the Future, Board on Medicine Records.89.Philip Handler to Philip H. Abelson et al., August 1, 1969, "Background Materials," September 9–10, 1969, Meeting of the Ad Hoc Committee on Further Institutional Forms of the Board on Medicine, Board on Medicine Records; Telegram from Walsh McDermott to Philip Handler, August 5, 1969, National Academy of Medicine Proposal File, 1969, Board on Medicine Records; Handler to Joseph Murtaugh, August 5, 1969, McDermott Files, Board on Medicine Records; Handler, memoranda for file, August 12 and August 13, 1969, NAS Records.90.Philip Handler to Walsh McDermott, August 12, 1969, Board on Medicine: Meetings, Resolution to Create National Academy of Medicine, July 1969 File, NAS Records; McDermott to Handler, n.d., NAS Records.91."Meeting of the Ad Hoc Panel on Further Institutional Forms, New York City, September 9–10, 1969," Board on Medicine Records.92.Irvine Page to Julius Comroe, September 11, 1969, Container 2, File NAS-Board on Medicine Correspondence September-December 1969, Page Papers; Comroe to Page, August 25, 1969, NAS-Board on Medicine Correspondence July-August 1969, Page Papers.93.Transcript of Board on Medicine Meeting, September 29–30, 1969, Board on Medicine Records.94.Walsh McDermott to Philip Handler, October 6, 1969, Bennett Committee File, Board on Medicine Records; Handler to McDermott, September 8, 1969, McDermott Files, Board on Medicine Records; NAS Council Minutes, September 27, 1969, NAS Records.95.Ivan Bennett to Irvine Page, October 16, 1969, File NAS-Board on Medicine Correspondence September-December 1969, Page Papers; Page to Bennett, November 4, 1969, File NAS-Board on Medicine Correspondence November-December 1969, Page Papers.96."Summary Report of the Meeting of the Board on Medicine," November 12, 1969, Board on Medicine Records.97.Walsh McDermott to Philip Handler, November 13, 1969, and Handler to McDermott, November 25, 1969, NAS Records.98."NAS Spikes Proposal for Academy of Medicine," Biomedical News, January 1970; "Ivory Tower of Medicine: Is 'No' Final?" Medical World News, January 2, 1970, both in Institute of Medicine Proposed, 1970 File, NAS Records; Research Notes, January 7, 1970, Institute of Medicine—General File, NAS Records.99.Transcript of Board on Medicine Meeting, January 21–22, 1970, Board on Medicine Records.100.Irvine Page to Julius Comroe, January 22, 1970, and Page to Gerald S. Berenson, M.D., February 19, 1970, both in File NAS-Board on Medicine Correspondence, January-April 1970, Page Papers.101.Joseph Murtaugh to John Coleman, January 30, 1970, Loose File, Board on Medicine Records.102.Transcript of Board on Medicine Meeting, May 13–14, 1970, Board on Medicine Records.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Save
Cancel
103."Proposal to Council of NAS by Board on Medicine," June 5, 1970, NAS Records.104.Minutes of the Council Meeting, June 5–6, 1970, NAS Records.105.NAS Press Release, June 10, 1970, NAS Records; Philip Handler to Walsh McDermott, June 10, 1970, NAS Records.106.Transcript of Board on Medicine Meeting, June 24, 1970, Board on Medicine Records; "Brief Minutes," June 29, 1970, McDermott Files, Board on Medicine Records.107.Institute of Medicine, Charter and Bylaws, 1970, NAS Records.108.Douglas Bond, M.D., President, Grant Foundation, to Irvine Page, July 21, 1970, and Robert Glaser to Page, August 10, 1970, both in File NAS-Board on Medicine July-September 1970, Page Papers; Irvine Page, "The Institute of Medicine of the National Academy of Sciences," Modern Medicine, October 5, 1970, pp. 95–97.109."Dr. Robert J. Glaser Named Acting President of Institute of Medicine," NAS Press Release, December 21, 1970, NAS Records; Institute of Medicine, Meeting of Executive Committee, December 17, 1970, NAS Records.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Suggested Citation:
"1 Creating the Institute of Medicine." Institute of Medicine. 1998.
To Improve Human Health: A History of the Institute of Medicine
. Washington, DC: The National Academies Press. doi: 10.17226/6382.
Since its founding in 1970, the Institute of Medicine has become an internationally recognized source of independent advice and expertise on a broad spectrum of topics and issues related to the advancement of the health sciences and education and public health. Institute activities, reports, and policy statements have gained a wide audience both in the United States and throughout the world.
In this first formal history of the Institute, Professor Edward D. Berkowitz describes many of the important individuals and events associated with the Institute's creation, operation, development, and accomplishments since its founding, as well as the issues and challenges the Institute has confronted over the years that have helped shape it and to which it has contributed potential solutions and responses.
| https://nap.nationalacademies.org/read/6382/chapter/2 |
RE: [Histonet] Tissue-Tek Express
RE: [Histonet] Tissue-Tek Express
OK, Who's channeling Lee Greenwood!?!
Claire Ingles
________________________________
From: histonet-bounces@lists.utsouthwestern.edu on behalf of Lim, Langston (NIH/NCI) [E]
Sent: Fri 6/30/2006 12:03 PM
To: Timothy Macatee; Bartlett, Jeanine H. (CDC); Goodwin, Diana; Dennis Hahn; HistoNet@Pathology.swmed.edu; kemlo.rogerson@waht.swest.nhs.uk
Subject: RE: [Histonet] Tissue-Tek Express
To my fellow Americans and veterans:
If tomorrow all the things were gone I'd worked for all my life,
And I had to start again with just my children and my wife.
I'd thank my lucky stars to be living here today,
'Cause the flag still stands for freedom and they can't take that away.
And I'm proud to be an American where at least I know I'm free.
And I won't forget the men who died, who gave that right to me.
And I'd gladly stand up next to you and defend her still today.
'Cause there ain't no doubt I love this land God bless the U.S.A.
>From the lakes of Minnesota, to the hills of Tennessee,
across the plains of Texas, from sea to shining sea,
>From Detroit down to Houston and New York to LA,
Well, there's pride in every American heart,
and it's time to stand and say:
I'm proud to be an American where at least I know I'm free.
And I won't forget the men who died, who gave that right to me.
And I'd gladly stand up next to you and defend her still today.
'Cause there ain't no doubt I love this land God bless the U.S.A.
Langston Lim, HT (ASCP)
Tissue Array Research Program
DHHS/NIH/NCI/CCR/LP
-----Original Message-----
From: Timothy Macatee [mailto:timothy.macatee@med.nyu.edu]
Sent: Friday, June 30, 2006 12:49 PM
To: Bartlett, Jeanine H. (CDC); Goodwin, Diana; Dennis Hahn;
HistoNet@Pathology.swmed.edu; kemlo.rogerson@waht.swest.nhs.uk
Subject: Re: [Histonet] Tissue-Tek Express
Just for anyone who is interested, I found this web site on the American
Flag a nice overview. Happy Independent 4th.
http://www.ushistory.org/betsy/flagetiq.html#1
Tim
On 6/30/06 12:24 PM, "Bartlett, Jeanine (CDC/NCID/VR)"
wrote:
> Is it okay that I am GOP but don't have a gun?
>
>
> Jeanine Bartlett, BS, HT(ASCP)
> (404) 639-3590
> jeanine.bartlett@cdc.hhs.gov
>
>
> -----Original Message-----
> From: histonet-bounces@lists.utsouthwestern.edu
> [mailto:histonet-bounces@lists.utsouthwestern.edu] On Behalf Of
Goodwin,
> Diana
> Sent: Friday, June 30, 2006 12:08 PM
> To: Dennis Hahn; HistoNet@Pathology.swmed.edu;
> kemlo.rogerson@waht.swest.nhs.uk
> Subject: RE: [Histonet] Tissue-Tek Express
>
> Here, Here, and a resounding "Huzzah!" So nice that we bleeding-heart
> liberals can wholeheartedly agree and identify with our gun-toting GOP
> brethren now and again.
>
> Now I'm going home to hoist an ice-cold Coors and rent "The Patriot".
>
> Best Regards to ALL,
> Diana Goodwin
>
> ________________________________
>
> From: Dennis Hahn [mailto:DennisH@cookchildrens.org]
> Sent: Friday, June 30, 2006 11:56 AM
> To: Goodwin, Diana; HistoNet@Pathology.swmed.edu;
> kemlo.rogerson@waht.swest.nhs.uk
> Subject: RE: [Histonet] Tissue-Tek Express
>
>
> Histo Net,
>
> Climbs upon his American, gun-toting soap-box....
>
> Let the Friday flaming begin. This is not meant to offend any one
> nationality. I usually just pick up tid-bits of information from the
> histonet, and ignore all the usual comments or flamings.
>
> However, maybe the wording was not meant to be what I interpret it as,
> but...
>
> 1) We were not "made" independent from anyone. No other country, or
> king, gave us our independence. We fought for it. I served in our
armed
> forces for 6 years active duty, including the "first" gulf "conflict"
as
> it is referred to. I fly an American flag in my front yard and do my
> best to explain to my children each time we take it down and burn it
> (Yes, you SHOULD burn the American flag when it is worn out, and no
> longer usable...it represents our country, a living, breathing entity)
> that many men, and women, have died so that the people in our nation,
> and others, may vote for our representatives both locally and
> nationally, say what we want, when we want, come and go throughout our
> country and the world as we please, all without the fear of any
> retaliation when we lay our heads down at night to sleep because of
it.
>
> 2) I'm not saying that anyone should be sad, but in less than 230
years,
> the US did GAIN it's independence, survive a brief civil war,
establish
> a free, and hopefully, equal society, spearhead many of the industrial
> revolution ideas (That cotton gin thing really had the world stumped,
> didn't it?) and create the most sophisticated military the planet has
> ever known. Yes, we do have our problems...The elderly, poor, and many
> children do not have access to adequate health care.
>
> 3) I do believe that Diana Goodwin stated, and I quote, "Happy
> Independence Day to all my fellow Americans!" Why respond at all if it
> doesn't apply to you?
>
> 4) Let all of my fellow Americans remember ALL the soldiers this
weekend
> that are currently scattered throughout the world. Many are in places
> and battles that we will never know about.
>
> Climbs down off his soapbox, gets some BBQ to eat, and is ready for
> fireworks.
>
> Dennis Hahn
> dennish@cookchildrens.org
>
>
>>>> Kemlo Rogerson
6/30/2006 8:52 AM
>>>>
>
> Question? Can we say 'Happy Independence Day'? It was from us you were
> made
> independent from, so should we be sad?
>
> Kemlo Rogerson
> Pathology Manager
> Ext 3311
> DD 01934 647057
> Mob 07749 754194
> Pager 07659 597107
>
> Distance is meant to relate, not separate. --Satish Kumar
>
>
>
> This e-mail is confidential and privileged. If you are not the
intended
> recipient please accept my apologies; please do not disclose, copy or
> distribute information in this e-mail or take any action in reliance
on
> its
> contents: to do so is strictly prohibited and may be unlawful. Please
> inform
> me that this message has gone astray before deleting it. Thank you for
> your
> co-operation
>
>
>
>
>
> _______________________________________________
> Histonet mailing list
> Histonet@lists.utsouthwestern.edu
> http://lists.utsouthwestern.edu/mailman/listinfo/histonet
>
>
>
>
>
>
------------------------------------------------------------------------
> ------------------------------------
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| http://www.histosearch.com/histonet/Jul06/RE.HistonetTissue-TekExprA.html |
060331SE
Page 159
1 Friday, 31 March 2006
2 [Status Conference]
3 [The accused not present in court]
4 --- Upon commencing at 10.10 a.m.
5 JUDGE BONOMY: Will the registrar please call the case.
6 THE REGISTRAR: Good morning, Your Honour. This is case number
7 IT-05-87-PT, the Prosecutor versus Milutinovic et al. Thank you.
8 JUDGE BONOMY: Thank you.
9 Mr. Hannis, can I take the appearance for the Prosecution.
10 MR. HANNIS: Thank you, Your Honour. I'm Tom Hannis, appearing on
11 behalf of the Office of the Prosecutor. I'm joined today by our case
12 manager Tamara Margitic on my right; on my left, trial attorney Christina
13 Moeller; and behind me, trial attorney Mathias Marcussen.
14 JUDGE BONOMY: Thank you, Mr. Hannis. This is a Status Conference
15 in the conjoined case of Milutinovic and others and it involves, at the
16 moment, six accused, all of whom are on provisional release. So as I take
17 the appearances for the Defence, I would like to confirm your appearance
18 and also assure me that your client is aware of the Status Conference
19 taking place and has authorised you to conduct it on his behalf in his
20 absence. So can I take the appearances in turn, please.
21 MR. O'SULLIVAN: Good morning, Your Honour. Eugene O'Sullivan and
22 Slobodan Zecevic, appearing for Mr. Milutinovic, who is not present this
23 morning, who is aware of this Status Conference and waives his right to be
24 present.
25 JUDGE BONOMY: Thank you, Mr. O'Sullivan. Mr. Fila.
Page 160
1 MR. FILA: [Interpretation] Good morning, Your Honour. My name is
2 Toma Fila and I appear with Mr. Vladimir Petrovic, representing the
3 Defence counsel of Mr. Sainovic, who is aware that we're holding a Status
4 Conference today and has authorised to us conduct the proceedings on his
5 behalf. Thank you.
6 JUDGE BONOMY: Thank you. Mr. Visnjic.
7 MR. VISNJIC: [Interpretation] Good morning, Your Honour. My name
8 is Tomislav Visnjic, an attorney, and I represent General Ojdanic, who is
9 aware of the Status Conference being held today and has waived his right
10 to attend in person.
11 JUDGE BONOMY: Mr. Ackerman.
12 MR. ACKERMAN: Good morning, Your Honour. I'm John Ackerman and
13 I'm here with Aleksandar Aleksic, my co-counsel, and General Pavkovic is
14 aware of this conference and has authorised us to proceed on his behalf.
15 JUDGE BONOMY: Thank you. Mr. Bakrac.
16 MR. BAKRAC: [Interpretation] Good morning, Your Honour. My name
17 is Mihajlo Bakrac. I represent General Vladimir Lazarevic. Together with
18 me is my colleague Mr. Milan Petrovic. General Lazarevic is aware of this
19 Status Conference being held today, and he is waiving his right to attend
20 in person and has authorised me to represent him at today's Status
21 Conference. Thank you.
22 JUDGE BONOMY: Mr. Bakrac. Mr. Ivetic.
23 MR. IVETIC: Good morning, Your Honour. Dragan Ivetic on behalf
24 of the Defence of General Sreten Lukic. General Lukic is apprised of
25 today's proceedings. He, with full knowledge, has waived his appearance
Page 161
1 and has authorised myself to appear on his behalf for today's proceedings.
2 JUDGE BONOMY: Thank you, Mr. Ivetic.
3 And I should record also that Mr. Scudder contacted me personally
4 to indicate the difficulty about his attendance today, and I authorised
5 the Status Conference to proceed in his absence also.
6 Now, yesterday afternoon we had a 65 ter Conference. I suppose
7 it's fairly easy in the atmosphere of fruitful discussion to say just how
8 cooperative things appeared to be at that time among everyone, but having
9 reflected on the matter overnight, I think it right to record now publicly
10 what seemed to me to be an extremely successful discussion and to
11 acknowledge the cooperation of all parties on both sides in efforts to get
12 this case underway as a trial at the earliest reasonable opportunity.
13 In saying that, I don't mean for a minute to pre-judge what I know
14 will be submissions that counsel will wish to make about the projected
15 dates. I simply at this stage acknowledge I think everyone's goodwill
16 towards achieving as early a trial date as is reasonable and fair.
17 A number of matters were discussed yesterday, and the position in
18 most of them was fairly clear. I think it right, though, to deal with a
19 number of them in the context of the Status Conference just to give each
20 of us an opportunity to review what appeared to be decided yesterday.
21 The first thing I think I want to do is acknowledge what's
22 outstanding. A recent decision of the Trial Chamber dealt with challenges
23 to the proposed amended indictment or objections to the proposed amended
24 indictment, and at the moment the ball is in the court of the Prosecution
25 on that one to produce a further revised indictment. Mr. Hannis indicated
Page 162
1 yesterday that that would be forthcoming within the next few days.
2 MR. HANNIS: Well, Your Honour, I believe our date is Wednesday,
3 the 5th of April, and we anticipate filing on that date.
4 JUDGE BONOMY: Thank you very much. It was also noted that the
5 additional features in this indictment would be clearly identified with
6 translation in mind, and I indicated that I would discuss the question of
7 translation with CLSS with a view to ensuring that all counsel have a copy
8 of the indictment in its entirety in B/C/S as quickly as possible, and I
9 shall undertake that at the beginning of the week, once I see what is
10 actually involved.
11 The second thing that is outstanding is an appeal by the United
12 States, I think, in relation to one interlocutory matter, and I will
13 simply report to the Appeals Chamber the importance of having the matter
14 dealt with as quickly as possible. My understanding is that there is
15 nothing required of the parties, that everything is in hand, and it's
16 simply a question of producing a decision.
17 The third outstanding matter was one raised by Mr. Ackerman, who
18 indicated to me that there had been discussions among counsel with a view
19 to formulating specific and all-inclusive requests for material,
20 documentary material, on behalf of the Defence and that within the next
21 ten days appropriate requests would be made. And I indicated to him then
22 that he should bear in mind the impending nature of the trial when
23 deciding whether it might be necessary to invoke the Court's assistance in
24 terms of Rule 54 bis in relation to any requests made. So that is a
25 matter of which the Court has notice.
Page 163
1 And the fourth outstanding matter, I think the final one, related
2 to certain protective measures already requested and then withdrawn, and
3 that matter was left on the basis that Mr. Hannis would revive it by
4 making a fresh filing in the light of the up-to-date information he
5 indicated he had. He also indicated that there may be protective measures
6 sought for other witnesses not yet intimated in full to the Defence, and I
7 urged him, and he agreed, to treat that as a matter of urgency.
8 Now, unless counsel can recollect any outstanding issue that
9 requires a determination, then I think that covers the matters we
10 discussed which yet require resolution. All right.
11 Mr. O'Sullivan.
12 MR. O'SULLIVAN: There was one other matter that you asked us on
13 the Defence side to consider. That was a date for the next 65 ter.
14 JUDGE BONOMY: Can I come back to that, if you don't mind?
15 MR. O'SULLIVAN: Yes.
16 JUDGE BONOMY: I've got that particularly in mind. I was thinking
17 more of things that require action over which I don't at the moment have
18 any control.
19 That takes me to the question of Prosecution witnesses. There
20 were a few loose ends, I think, left yesterday, Mr. Hannis, so I think
21 everyone would be grateful for as specific an indication as you can give
22 now of the number of witnesses you anticipate.
23 MR. HANNIS: Your Honour, our most recent calculation had us
24 anticipating calling some 80, 8-0, witnesses as live witnesses. We had
25 another 90 witnesses we proposed to submit under Rule 92 bis. And in
Page 164
1 addition, we have now, I believe, 11 experts we're proposing. As we
2 indicated to you yesterday, we do no longer intend to call Mr. Torkildsen.
3 JUDGE BONOMY: That may actually be ten. Does that not reduce it
4 to ten?
5 MR. HANNIS: You're right, Your Honour. I did my math wrong.
7 I can note now that you have apparently disclosed all the anticipated
8 material in relation to each of the experts.
9 MR. HANNIS: That's correct, Your Honour. I did indicate
10 yesterday that with Mr. Coo we might file a supplement based on some of
11 the new documents.
12 JUDGE BONOMY: He was the only one. Now, going back to your other
13 witnesses, how many of these witnesses have not yet been disclosed to the
14 Defence? Can you tell me roughly even the number?
15 MR. HANNIS: Your Honour, of -- I haven't calculated that because
16 as some of what we were doing was replacing some witnesses. I know that
17 previously we had said I think we were going to have 66 live witnesses and
18 about the same number of viva voce -- of 92 bis. That number increased so
19 the number may be something in the neighbourhood of 20 live and 20 or 30
20 92 bis, but that's a very tentative number, Your Honour.
21 JUDGE BONOMY: That's quite a large number of witnesses, and it
22 seems to me that there can be no justification for not disclosing
23 immediately all the material, all the supporting material relating to
24 these witnesses unless there are issues of protection involved. Now, do
25 you accept that?
Page 165
1 MR. HANNIS: I do accept that, Your Honour. I would indicate that
2 for these additional numbers I'm confident that a number of them, their
4 identified as a witness we intended to call at that time.
5 JUDGE BONOMY: Now, I can immediately understand the concern of
6 Defence counsel about the vagueness of this, so I really need to have an
7 undertaking from you, Mr. Hannis, that within a week of today they'll have
8 everything in relation to which you do not envisage seeking protective
9 measures.
10 MR. HANNIS: I will undertake to do that, Your Honour, and if I
11 have a time problem, I will seek relief from you, if there's any problem.
12 JUDGE BONOMY: Okay. I think you also owe it to everyone now to
13 make it clear within the same time scale the number of witnesses and the
14 general nature of their evidence for whom protective measures are to be
15 sought and to take steps to have that resolved now so that appropriate
16 disclosure can be made at the earliest possible date. Now, do you accept
17 that?
18 MR. HANNIS: I do.
19 JUDGE BONOMY: Well, would you -- would you try to please apply
20 the same time scale to at least indicating what the position is and
21 formulating an application.
22 MR. HANNIS: I will, Your Honour.
23 JUDGE BONOMY: Thank you. Now, we also discussed the potential
24 length of the trial, and I think that there are loose ends in respect of
1 happened yesterday when I say that you are unlikely to have 80 witnesses
2 whose evidence in chief is given viva voce in its entirety.
3 MR. HANNIS: That's correct, Your Honour. We anticipate trying to
4 make good use of Rule 89(F).
5 JUDGE BONOMY: Yes. And we had, I hope, a -- I indicated to you
6 my understanding of where difficulties can arise when a witness's evidence
7 appears to be unbalanced in the sense that the bulk of his oral evidence
8 is given in cross-examination, but I indicated that the Court would be
9 alert to that, and we'd expect that where issues had been raised in
10 cross-examination, the Prosecution would deal with any foreseen
11 difficulties about the way in which a witness was apparently presented by
12 dealing with the matter in re-examination.
13 MR. HANNIS: I take your point on that, Your Honour, and that's a
14 matter that we intend to deal with. Part of it will depend on the
15 personalities involved in the actual trial.
16 JUDGE BONOMY: Now, you also gave me an estimate of the time that
17 you envisaged using to present the Prosecution case. Can you remind me of
18 that?
19 MR. HANNIS: I believe we said that was 18 weeks, Your Honour.
20 That's simply for the direct examination.
21 JUDGE BONOMY: Now, is that on the basis of the 80 viva voce
22 witnesses?
24 JUDGE BONOMY: Yes. So that matter is obviously subject to
25 review.
Page 167
1 MR. HANNIS: It is.
2 JUDGE BONOMY: And I invited you to have particular regard to the
3 fact that the Prosecution, in presenting the Kosovo phase of the Milosevic
4 indictment, took only 122 hours.
5 MR. HANNIS: I recall that, Your Honour.
6 JUDGE BONOMY: As against 18 weeks I think is 360 hours.
7 MR. HANNIS: Yes, based on a calculation of 20-hour weeks.
8 JUDGE BONOMY: So I think it's an important factor to bear in mind
9 that the whole of the Prosecution case over the three indictments in
10 Milosevic took 360 hours, roughly the equivalent of what you envisage for
11 the presentation of the Prosecution case in this case. I appreciate we
12 have six accused, but I think I reminded you yesterday that the crime
13 scenes are the same for all of them and the only separate individual issue
14 will be criminal responsibility, and it's not clear to me that that's by
15 any means the bulk of the case.
16 MR. HANNIS: You did, Your Honour.
17 JUDGE BONOMY: Yes. Very well. So I make it clear to you now
18 that I have a different view of the likely time scale of the Prosecution
19 case, even allowing for cross-examination. Mr. Fila made it clear that
21 of each witness which counsel will take principal responsibility for
22 cross-examining the witness with a view to the expeditious presentation of
23 that evidence. And having that in mind, it does seem to me that 360 hours
24 may be a closer estimate of the time necessary for the whole Prosecution
25 case, including cross-examination and re-examination.
Page 168
1 MR. HANNIS: I agree, and I was pleased to hear that, Your Honour.
2 JUDGE BONOMY: All right. Thank you. So we're now looking, I
3 think, at a rather different picture from the one that has been in mind
4 for this case. The 28 months that were envisaged I expect to be
5 substantially reduced.
6 Nothing more, I think, need be said about Prosecution expert
7 witnesses, but I would like, I think, Mr. O'Sullivan to remind me of the
8 position taken by the Defence in relation to their preparation of expert
9 witnesses. Mr. O'Sullivan.
10 MR. O'SULLIVAN: Yesterday the counsel for the Defence met, and we
11 now know that there are ten experts proposed by the Prosecution, and for
12 six of those experts we agree that we can call one expert in reply. For
13 six of the ten. The other four, we're still -- we still have to work
14 among us to see whether we will have one or more experts in the other four
15 areas.
16 JUDGE BONOMY: Yes. I suggested to you that you might reflect
18 whether disclosure of the Defence expert position before the Prosecution
19 expert gave evidence might be conducive to cutting down the areas in
20 dispute. Now, have you given any more consideration to that?
21 MR. O'SULLIVAN: We haven't discussed that jointly, and quite
22 frankly, I'm opposed to that, speaking for myself at this point.
23 JUDGE BONOMY: How do you envisage dealing with an expert? By
24 that I mean instructing him finally before he gives you his final report?
25 You envisage doing that after the Prosecution expert has given evidence or
Page 169
1 at some earlier stage?
2 MR. O'SULLIVAN: At an earlier stage.
3 JUDGE BONOMY: Yes.
4 MR. O'SULLIVAN: Yes.
5 JUDGE BONOMY: But holding on to the material until you've heard
6 the Prosecution's expert.
7 MR. O'SULLIVAN: Well, that -- that fits into a -- it depends. I
8 can only speak for myself and my client in relation to this at this point.
9 That is our -- that will fit into our trial and Defence strategy, yes,
10 that determination.
11 JUDGE BONOMY: There are --
12 MR. O'SULLIVAN: Under the Rules, of course, our expert can follow
13 the proceedings when the Prosecution's expert is testifying. That much is
15 JUDGE BONOMY: Well, jurisdictions all over the world have
16 different approaches, as I understand it, to the extent to which one
17 expert can follow the evidence of another. I see no difficulty with the
18 idea that a Defence expert should follow the evidence of a Prosecution
19 expert, but I have a bit more difficulty with the idea that in every case
20 it should be, well, let's wait and see before we try to cut down the areas
21 in dispute, and I think I do have certain power in relation to experts
22 which I don't have in relation to the disclosure of other Defence
23 witnesses which I may decide to exercise, and I'm interested to have your
24 comments before I make any decision on this. And what I'm -- the message
25 I'm getting is, no, we'll be fully prepared by the time the Prosecution
Page 170
1 expert gives evidence. We'll have our report, but we think it's right to
2 hold on to it until afterwards.
3 MR. O'SULLIVAN: Well --
4 JUDGE BONOMY: I'm not criticising, I'm just trying to get the
5 picture. And I understand you clearly on that, do you?
6 MR. O'SULLIVAN: I can't say that the report -- a Defence expert
7 report will necessarily be completed by the time the Prosecution expert
8 testifies.
9 JUDGE BONOMY: Okay.
10 MR. O'SULLIVAN: I can't say that. That's the only proviso I
11 would add to what you said.
12 JUDGE BONOMY: Well, I acknowledge certainly the cooperation among
13 counsel to try to cut down the number of experts. That's encouraging.
14 But there may even be cases, I suggest to you, as you prepare in which
15 there may be scope for mutual disclosure with the Prosecution with a view
16 to identifying how little is actually in dispute between you. And indeed,
17 even if it doesn't involve disclosure, it might be a good idea, once you
18 have more or less finalised your own expert's position, to tell the
19 Prosecution what's not in dispute so that -- and hold back, if you think
20 tactically that's the right thing to do, as little as possible in
21 everyone's interest. I just encourage you to think about these things as
22 we make progress.
23 Now, does any other Defence counsel wish to comment on expert
24 witnesses at all? Mr. Visnjic.
25 MR. VISNJIC: [Interpretation] Your Honour, I just wish to give a
Page 171
1 clarification regarding the comment you made just now about the mutual
2 agreement among counsel, that only one Defence counsel will be
3 cross-examining on behalf of all.
4 I wish to say on behalf of our client that we did not reach such
5 an agreement. Of course we will discuss it among us, but at this point no
6 such agreement has been reached among us, and we will probably act on a
7 witness-by-witness basis.
8 JUDGE BONOMY: If that's the way I put it, then it was a
9 misrepresentation of what Mr. Ackerman actually said. What I hope I said
10 was that he indicated that you would get together and decide which counsel
11 should be the lead cross-examiner in relation to each witness, reserving
12 the right - and I should have made that absolutely clear - reserving the
13 right to all other Defence counsel to raise issues that they felt had to
14 be individually explored on behalf of their clients. So I fully
15 understand that and I'm sorry about the misunderstanding.
16 MR. VISNJIC: Thank you.
17 JUDGE BONOMY: There was one other thing I wanted you to make
18 clear about Defence experts, and I think it was you that raised it
19 yesterday, and that was the question of funding and whether there are
20 advantages to be gained in relation to funding by combining your
21 resources. Now, can you clarify that for me again, please.
22 MR. VISNJIC: [Interpretation] Yes.
23 THE INTERPRETER: Microphone, please.
24 MR. VISNJIC: [Interpretation] We will make a submission to the
25 Registry requesting some sort of merging of funds available to Defence
Page 172
1 regarding experts. But the comment you just made leads me to think of my
2 reasoning, previous reasoning, about the financing of experts. The
3 Tribunal limits the financing of expert evidence in pre-trial stage and
4 the trial stage, according to the information we got from the Registry.
5 For instance, experts are financed with one lump sum in the pre-trial
6 stage, another lump sum during the trial stage, depending on the size and
7 contents of the report. We will probably need to consult again with the
8 Registry whether the system indeed allows for this.
9 This adds only one technical difficulty to the idea you voiced
10 just now. Otherwise, I completely agree with it, and I don't think there
11 will be any obstacles to doing it in this trial in the way you suggested.
12 JUDGE BONOMY: Well, I just -- I just want to record my
13 appreciation of the efforts that are being made to cut down the number of
14 experts used in this case, and I hope the Registry are alert to the
15 importance of assisting counsel so far as they can in that exercise. I
16 appreciate the difficulty for all concerned but I would encourage them to
17 recognise particularly the efforts that have been made in this case.
18 Now, that concludes my review of the position in relation to
19 witnesses, subject to anything any counsel wishes to say on the matter
20 before I move to a completely separate issue. All right. I take it that
21 silence indicates there's nothing else to be reviewed on that score.
22 I want now to turn to, as I say, a completely separate issue which
23 I alerted three of the counsel here to be in a position to address today,
24 and I did so for a particular reason. The Registry has drawn to the
25 attention of the Trial Chamber what might be seen as activity on the part
Page 173
1 of three of the accused which may not be consistent with the terms on
2 which they were provisionally released.
3 Now, I'm raising it with you as a general point. I'm purely
4 concerned about any misunderstanding that there may be in general about
5 the terms on which there is provisional release and how these terms are
6 dealt with should there be a need to review them because of unexpected
7 events or developments. I'm not regarding this at this stage as a
8 complaint that I have to address, but I was anxious to have as much
9 information as you feel able to give me about the circumstances so that I
10 can reassure myself that there isn't a general problem which requires to
11 be addressed in relation to the future position of the accused or indeed
12 any other accused on provisional release in Serbia.
13 Now, the three accused referred to were Sainovic, Ojdanic, and
14 Pavkovic. So, Mr. Fila, can I ask you if you can be of assistance to me
15 in clarifying this issue.
16 MR. FILA: [Interpretation] Mr. President, we are here in this
17 courtroom in order to tell each other the truth and to respect one
18 another. I'm saying this at the outset meaning that if any error has been
19 made, I am responsible for one part of that error and the government of
20 Serbia for another.
21 I am unable to provide any additional documents because we were
22 only notified on Tuesday and we were flying on Wednesday, and at the
23 request of the Interior Ministry -- when I made the request to the
24 Ministry of the Interior and the Ministry of Defence, they said the
25 documents were confidential and they would provide them to you if
Page 174
1 necessary. Namely, those are police reports confirming that all the three
2 accused had police escort when they travelled and that the distance in
3 question is 30 kilometres, not 60, as you were notified. It's the
4 territory of the city of Belgrade, which is 20 kilometres away from the
5 site in Pozarevac, 20 kilometres.
6 I do wish to assist you in clarifying this matter. As you can
7 see, the letter addressed to the Ministry of Justice was signed by me
8 because I am the one who is responsible for the possible violation of
9 your --
10 JUDGE BONOMY: I know there is a letter but I have deliberately
11 not read it yet because there was too much happening before I came in here
12 this morning. Let me have a moment to read the letter that you're talking
13 about.
14 MR. FILA: [Interpretation] You don't have their letter. You have
15 only the letter that I wrote, and you are -- you also have the reply from
16 the government.
17 JUDGE BONOMY: Well, Mr. Fila, I have a copy of the letter to the
18 Ministry of Justice. That's the document you're referring to?
19 MR. FILA: [Interpretation] That's correct. And you should also
20 have the reply from the Ministry of Justice granting me approval, and I
21 will now explain, if you allow me.
22 JUDGE BONOMY: I haven't been given that.
23 MR. FILA: [Interpretation] The reply is in the bundle given you by
24 the Registry. Page 1710. That's the material sent to you by the
25 Registry. I have a copy if you need one.
Page 175
1 MR. ACKERMAN: Your Honour, just to clear up confusion, if you
2 look at the original document provided by the Registry, the letter is
3 attached to it. It's not something that was supplied today.
4 JUDGE BONOMY: I'm sorry. Yes, thank you.
5 MR. ACKERMAN: If you just look at the Registry's --
6 JUDGE BONOMY: Yes. Mr. Fila, the page number again, please?
7 MR. FILA: [Interpretation] 1710. That's a reply. Before I
8 embarked on writing that letter, I asked verbally if there had been such
9 precedence before, and I was told that the interpretation of your
10 decisions is such that when emergencies are in question - baptism,
11 funeral, wedding, or something similar which requires an absence of
12 several hours or maybe a night - it is the discretionary right of the
13 Ministry of Justice, together with the Ministry of the Interior, to grant
14 approval. Let me correct myself: It is allowed for the accused to be
15 absent for a day, but not a night. And in that case they are given police
16 escort, which has been observed in this case.
17 After receiving this clarification, I wrote to the minister of
18 justice, and now I am being asked why I hadn't asked for your approval as
19 well. That's my mistake. The death of Mr. Milosevic was sudden. It
20 created enormous outcry in the media. And I believe that under the
21 circumstances this travel of 20 kilometres cannot be considered as a grave
22 violation of the terms of provisional release, and I think you have
23 better, more urgent business to attend to than dealing with this travel,
24 this journey of only 20 kilometres of half an hour.
25 JUDGE BONOMY: I hope I made it clear to you at the outset that
Page 176
1 I'm not looking at it from that point of view. I'm looking at it from the
2 general issue point of view. In other words, is there a problem here in
3 general about how these conditions are being interpreted? This -- I
4 express no view on what happened in this instance, but I can envisage that
5 if this sort of thing is not addressed and the position clarified, that
6 something unfortunate could happen, and I want to avoid that eventuality.
7 MR. FILA: [Interpretation] I understand.
8 JUDGE BONOMY: Yes. Now, is there anything --
9 MR. FILA: [Interpretation] I just wish to tell you what it looks
10 like. The Ministry of Justice believes that it is possible to grant
11 approval for several hours, but certainly not more than 12. The minister
12 of police is then notified, and he designates police escort. Generally
13 speaking, they are under police supervision, under surveillance, round the
14 clock. They cannot leave their apartments without police escort, even
15 when they are going to see their counsel. When Mr. Sainovic is going to
16 meetings with me, he goes under police escort. That not only provides
17 surveillance but also prevents attacks, et cetera.
18 So the way we understand it, it is not necessary to summon the
19 Trial Chamber to decide on matters like this for such a small, short
20 absence. You will see from the report that you will receive and that I
21 haven't received because they explained it's confidential and it's not our
22 business to know how the police organises their work.
23 That is all I can tell you. And if there are any omissions on our
24 part, I am entirely responsible, not Mr. Sainovic. Death is a -- an
25 important occasion in our Orthodox Christian church. And if Slobodan
Page 177
1 Milosevic hadn't been in question, this would never have occurred.
2 Can I be of assistance in any other way?
3 JUDGE BONOMY: If you're right, that it shouldn't be necessary to
4 summon the Trial Chamber to decide on matters like this, then it's
5 important that that is well known and that the ground rules for such
6 situations are clear. On the other hand, if they weren't clear, then it
7 could be said that the strict terms of the -- of the conditions apply, and
8 it's that sort of uncertainty that I'm anxious to avoid.
9 As it turns out, for all I -- from all I have heard, the funeral
10 passed off reasonably well, but you could imagine other circumstances in
11 the -- anywhere in the Balkan region where something unfortunate happened.
12 Gosh, it happens at football matches every night. So there are
14 and therefore I think it is important that the position is clear and that
15 the matter's not left in doubt. However, I'm grateful to you for
16 explaining the position to me.
17 Mr. Visnjic, is there anything you need to add to this or do you
18 feel the need to explain the position of Mr. Ojdanic in particular?
19 MR. VISNJIC: [Interpretation] Your Honour, very briefly. On
20 behalf of General Ojdanic, I submitted my request on the 16th of March
21 around 1400 hours to the Ministry of Justice, and around 1600 hours I
22 received their reply on the same date, granting approval for him to attend
23 the funeral that was held on the 17th of March. I submitted that
24 document. I filed it.
25 What I wish to say is that I actually support this position of the
Page 178
1 Ministry of Justice, although it's the first time that my client has
2 availed myself of that particular possibility in almost one year that he
3 has been on provisional release. On one previous occasion, my client
4 absented himself from Belgrade for treatment, and on that occasion we had
5 approval from the Trial Chamber.
6 However, under these circumstances, I believe the position of the
7 Ministry of Justice is completely reasonable, because otherwise I think
8 this Trial Chamber would be completely snowed under similar requests, very
9 minor, and would cause unnecessary outlay of resources that can be much
11 the one I recently found about. One of the accused on provisional
12 release, for instance, had to visit a doctor that is only one kilometre
13 away from what is formally considered the territory of the city of
| https://www.icty.org/x/cases/milutinovic/trans/en/060331SE.htm |
continued | Download Scientific Diagram
Download scientific diagram | continued from publication: New Aspects of Cholecystokinin Processing and Visualisation in the Rat Brain by Using Antibodies Raised in Chickens and Rabbits | Neuropeptides such as cholecystokinin (CCK) are subjected to a stepwise enzymic degradation (peptide processing) during axonal transport from the somata to the nerve terminals. This results in a continual change in the primary, secondary and tertiary structures of the... | Antibodies, Chickens and Immunoglobulin Y | ResearchGate, the professional network for scientists.
Figure 3
continued
Source publication
New Aspects of Cholecystokinin Processing and Visualisation in the Rat Brain by Using Antibodies Raised in Chickens and Rabbits
Article
Full-text available
Jul 2000
Rüdiger Schade
Peter Henklein
Christoph Harms
[...]
Heide Hörtnagl
Neuropeptides such as cholecystokinin (CCK) are subjected to a stepwise enzymic degradation (peptide processing) during axonal transport from the somata to the nerve terminals. This results in a continual change in the primary, secondary and tertiary structures of the peptide. Thus, an antibody raised against a selected sequence of the propeptide m...
Contexts in source publication
Context 1
... order to study the CCK-IR in brain sec- tions from the cortex region, three rabbit antibodies (R2, R4 and R18) were used in the IHC. As shown in Figures 3 and 4, all the rabbit antibodies showed similar CCK- IRs with specific signals in somata, termi- nals and varicosities of various kinds of neu- rons. Cortical pyramidal neurons could not be made visible by any of the three rabbit antibodies. ...
Context 2
... and showed specific CCK-IR in neu- ronal somata, terminals and dendrites (Figures 3 and 4). In contrast to the find- ings with the rabbit antibodies, IHC with antibodies Ch22 ( Figure 5) and ChB4 (Fig- ures 6d and 6f) also displayed specific CCK-IR signals in pyramidal neurons. ...
Citations
Veterinary Applications of IgY
Full-text available
Jan 2006
Yosef Daniel Huberman
The production of antibodies (Ab) in chicken and the extraction of specific Ab from egg yolk are increasingly attracting the interest of the scientific community as well as the animal welfare organizations. The IgY technology was approved as an alternative method for supporting the animal welfare and it is recommended as a replacement for the usage of IgG – Ab extracted from mammals, in order to minimize pains due to invasive Ab-sampling from serum of rabbits, horses, ruminants or small rodents. The immune system of chicken consists of primary organs (bursa of Fabricius and thymus) and secondary organs (spleen, Harderian gland, lymph nodes, bone marrow and lymphoid tissues of the alimentary tract). The bone marrow is the source of thymus and bursal stem cells. The bursa of Fabricius is the site of differentiation of stem calls into B-cells whereas the thymus is the site of differentiation of stem cells into T-cells. The spleen is the organ for plasma cell proliferation and memory B-cells. Like in mammals, three classes of immunoglobulins exist in chicken: IgA, IgM and IgY. The IgY, is the analogue of the mammalian IgG, in its function and its concentration. The IgY consists of two light and two heavy chains. The heavy chain contains one variable domain and four constant domains. The light chain consists of one variable and one constant domain. The molecular weight of IgY is 167,250 Dalton. IgY is transferred to the eggs yolk by receptor-mediated processes. The amount of IgY that is transferred is related to the IgY serum concentration. The final concentration in the egg yolk varies between 10-20 mg/ml and a total of 100-400 mg per egg. This variation is attributed to the existing difference between the antigen and its form of application and genetic lines or breeds.
Replacement of Fetal Calf Serum in Cell Cultures by an Egg Yolk Factor with Cholecystokinin/Gastrin-like Immunoreactivity
Article
Nov 2000
ATLA-ALTERN LAB ANIM
Mirko Sasse
Thomas Lengwinat
Peter Henklein
Andreas Hlinak
Rüdiger Schade
The in vitro culture of various cell types is an important scientific tool and is becoming increasingly acceptable as a viable alternative to animal experiments. Fetal calf serum (FCS) is a supplement used in many cell culture media, and provides cells with growth factors and cytokines necessary for successful culture. In view of the animal welfare issues surrounding the production of FCS, an alternative agent allowing the replacement or reduction in the use of FCS is desirable. A yolk extract factor (EYF-X) obtained from chicken eggs is described, which facilitates the in vitro culture of a variety of cell types. When the extract was added to a culture medium used for in vitro fertilisation, the number of successful fertilisations was significantly increased. In a further in vitro model (permanent neuronal cell line N2A), the yolk extract significantly stimulated cell proliferation as well as the growth of cell processes. A set of specific antibodies against different parts of the prepro-cholecystokinin reacted with the extract. The intensity of the reaction depends on the age of the egg (time after the laying date). Analysis by gel chromatography recorded a main protein fraction with an apparent molecular mass of 20-30kDa. This fraction was labelled by Western blot with an antibody with specificity against CCK-octapeptide. These findings suggest that the yolk factor may be a CCK/gastrin-like molecule. Since CCK/gastrin-like molecules have also been detected in the spermatozoa of mammals, the influence on in vitro fertilisation could be explained by the yolk factor replacing the endogenous CCK/gastrin-like molecule destroyed in sperm freezing. The results of this study suggest that it might be possible to replace FCS with EYF-X. The application of the yolk factor to a broad spectrum of cell types remains to be investigated.
Production, purification, and characterization of rat pro-CCK from serum-free adapted Drosophila cells
Article
Oct 2003
PROTEIN EXPRES PURIF
Petra Kleditzsch
John Pratt
Daesety Vishnuvardhan
Peter Henklein
Margery C Beinfeld
The precursor of cholecystokinin (pro-CCK) was expressed and purified from media of stably transfected D.Mel-2 cell as an V5-His tagged fusion protein. Its identity was confirmed using SDS-PAGE, immunoblotting, gel filtration chromatography, HPLC, and Mass Spectroscopy. Two major forms of pro-CCK were found with a molecular weight of about 14.4 and 11.3 kDa. The smaller form represents the V5-His tagged pro-CCK after cleavage at a single arginine residue at CCK-58. This cleavage is probably being performed by endogenous proteases in these cells. Purification of the desired larger form of pro-CCK is possible using a nickel column with a recovery of about 20%, yielding 500 microg/L media. The purified protein is stable for several months and can be used for further functional studies of pro-CCK.
Chicken Egg Yolk Antibodies (IgY-technology): A Review of Progress in Production and Use in Research and Human and Veterinary Medicine
Article
Full-text available
May 2005
ATLA-ALTERN LAB ANIM
Rüdiger Schade
Esteban Gutierrez Calzado
Rodolfo Sarmiento
Pablo Anibal Chacana
Horacio Raul Terzolo
The production of antibodies (Abs) in chickens and the extraction of specific Abs from egg yolk (IgY Abs) are increasingly attracting the interest of the scientific community, as demonstrated by the significant growth of the IgY literature. This review offers detailed and comprehensive information about IgY-technology, including: a) possibilities for hen keeping in accordance with the Three Rs principles; b) new insights into the IgY transfer mechanism from blood to yolk as a biological basis for the technology; c) the comparative characteristics of IgY Abs and IgG Abs; d) the high efficacy of the technique, in view of the extraordinary amount of IgY Ab produced by one hen in one year (between 20 g and 40 g IgY in total); e) comparisons between the efficacies of IgY Abs and IgG Abs (rabbit, sheep, mouse) in several immunological assays; f) immunisation protocols, as well as the most commonly used IgY-extraction procedures; g) new possibilities for application in human and veterinary medicine, including strategies for the treatment of Helicobacter pylori infection or fatal intestinal diseases in children, particularly in poor countries, for reducing the use of antibiotics, and, in Asia and South America, for producing Abs against snake, spider and scorpion venoms; and h) the use of IgY Abs in various fields of research, also taking into consideration recent developments in South America (particularly Argentina and Cuba) and in Asia.
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| https://www.researchgate.net/figure/continued_fig1_224937455 |
Filter response curves | aavso
Filter response curves
Affiliation
Variable Stars South (VSS)
Hi All,
I recently purchased a Star Analyser diffraction grating with the aim of measuring spectral response curves (is this the right terminology?) of my DSLR cameras. What I want to determine is the individual red, green and blue channel curves and compare these with standard BVRc filters. Does anyone have a step by step tutorial for doing this?
From these filter response curves it should be possible to calculate coefficients for transforming instrumental magnitudes to standard BVRc magnitudes. I've determined emprical transformation coefficients from observations of standard stars but it would be an interesting exercise to calculate them from filter response curves. Cheers,
Mark
DSLR response curves
Hi Mark,
You have a good idea, but I think a transmission grating isn't the right answer. These units don't give a very good absolute response - there is different efficiency depending on the wavelength, and the DSLR will have vignetting, etc. so that the spread of the spectrum across the sensor will include these aspects.
The best way IMHO (and I've never seen it done - it would be an excellent paper) is to illuminate the DSLR with a monochromator. These are sorta inverse spectrographs - they use a blackbody source (like a tungsten lamp), feed the light through a prism, and then use a slit to isolate one wavelength of light to exit through the system. If you used that to illuminate the DSLR, and then took lots of images, one for each "step" of the monochromator, you would see the response vs. wavelength for the red,green,blue pixels, including any red/blue leak that their filters might have.
Arne
Actually I've seen it done well with the Star Analyser. You do need to do a spectral calibration of the system first. This is done by using a tungsen lamp to show the spectral response of the system. This can then be used with a filter to show the filter response across the spectrum. While a DSLR camera can be used, a monochrome camera would be much better.
Jeff
Hi Jeff,
it is the DSLR's inbuilt Bayer matrix filters I'm trying to measure. I was thinking of recording a spectrum of, say, an A0 star, calibrating wavelength axis using the zero order spectrum and a known absorption feature then dividing by a library spectrum of the same (or similar?) star. Does this sound feasible? Cheers,
Mark
Hi Mark,
You can practice on Vega, an excellent star to experiment with. Wavelength calibrating the line profile should be very easy. I've attached a calibrated line profile of Vega taken with a Star Analyser.
Jeff
Spectral Response Curve
Hi Mark,
Here is an attachement showing the original Vega spectrum line profile, the wavelength calibrated line profile and finally the instrument response corrected line profile.
Jeff
Star Analyser
Hi Jeff,
Vega unfortunately is not an option for me. I'm at about 34 S latitude and Vega culminates at less than 20 degrees altitude - and behind buildings as viewed from my observatory. I'd have to use much fainter A0 stars, but thats ok since my setup can accommodate unguided exposures up to 2 minutes. If necessary multiple images could be stacked. Cheers,
Mark
DSLR reponse curves
Hi Arne,
some months ago Ed Budding and I discussed using a monochromatic light source to measure DSLR response curves. Ed made some enquiries with contacts in New Zealand (a unversity I believe) however they weren't interested.
I read a paper recently by Munari and Moretti about characterising photometric filters in the ANS collaboration program. The UV-Vis spectrometer they used would be ideal. I might make a few enquiries with Australian labs.
The Star Analyser approach is definitely a poor mans option but might prove useful. Cheers,
Mark
Pass-band response
Hi Mark,
Yes, you can do it easily with the star analyser. I do it and I have submitted a paper to the JAAVSO about a simulation based on the response curves of the DSLR and using the Pickles spectra library. I have no news about that paper, I have no idea when it would be published. You can contact me through the "contact" flap of my profile.
The setup to make the pass-band response (the combination of all filters and the sensor) is simple. I put the SA100 in front of a 85 mm lens (or 200 also) with a slit about 1 meter away at the end of a carton tube, black inside and adding some baffles. The light source could be the sun reflected by a white paper target (never in direct). The spectrum of the sun is published at proper air-mass by the ASTM and other sources. The lines will enable you to calibrate the wavelength. Then you divide your DSLR spectrum by the sun spectrum (needs to be filtered at the same resolution). You shall also convert the sun spectrum to photon-count instead energy (our CMOS sensors are photon-count sensitive, not energy). Some correction of the efficiency curve of the SA100 should be applied too (The SA100 is a very specific case and its efficiency varies few between 400 and 700 nm). In the involved SA100 configuration vignetting is no problem. The results are in very good agreement with other sources for similar DSLR.
For this simple work you can use the simple tools of IRIS (http://www.astrosurf.com/buil/index.htm) or ISIS, or VSpec... You could find tutorials and number of papers on the Buil's site and the ARAS site (http://www.astrosurf.com/aras/)
Clear Skies !
Roger
Pass-band response
Hi Roger,
thanks for your detailed reply. Sounds like a nice experiment but I need to digest this info. Cheers,
Mark
DSLR RGB spectral response
Hi Mark,
Is this what you are looking for ?
By Christian Buil comparing with a previously spectrophotometrically calibrated camera.
Note he used a LISA slit spectrograph. If you plan to use the Star Analyser, you need to arrange for the light source to be a point (or slit) and as Arne pointed out you should (as for any spectrum you are going to make quantitative measurements on) apply a flat field correction to the spectrum.
EDIT :
(Except in this case you can't use a flat as a spectroscopic flat contains the very thing you are trying to measure and therefore removes it - tricky)
Cheers
Robin
Vignetting, efficiency
Hi Robin, Mark,
In fact the vignetting is not an issue with the SA100. In any case it's ok to make a classical DSLR flat like we do for photometry (not a spectro flat as denoted by Robin ! ).
In addition the vignetting should be negligible given the F# and the low dispersion of this grating. With my Nikkor 85mm F1.8 used with the SA100 in front, we get only F4 and the corner/center vignetting is <10%. Then the 400-700 nm spectrum extends on about 700 pixels in a image width of 4290 by the way a quadratic vignetting is < 0.2% at the spectrum level ! No issue...
The point that needs more consideration is the efficiency curve of the grating. The SA100 is a transmissive grating at low dispersion, such grating doesn't have significant s-p polarization problems (reflective have). Then it is well blazed for a DSLR pass-band. The efficiency of such grating is very high and the curve smooth. We do not have (confirmed by Robin) a curve measured in lab, but the modelization and measures made on similar gratings show the max transmission at 500~550 nm is ~80% , ~60% at 400 nm, ~70% at 700 nm. Those points can be interpolated at second order, fitting well the curve. I made an indirect check by comparing the R,G and B integrated output of the DSLR with and without the SA100 and this confirmed the assumption. Anyhow we don't need much accuracy around 400 and 700 nm, the transmission of the DSLR being very low at those wavelengths.
Checking further the efficiency curve of the SA100 should be very interesting, we need only a couple of points, I think 5 is enough given the smooth curve.
Cheers,
Roger
Video showing the how to calibrate for instrument response
Although I'm a bit late to this thread, I thought the link below might be helpful. It shows the steps to do instrument response calibration.
Although this video is specific to the RSpec software (of which I'm the author) it should be useful to anyone interested in the topic, since the concepts and general work-flow would be the same in other software too.
http://www.rspec-astro.com/more-videos
Selectvideo 15, entitled "Adjustment for Instrument Response"
Tom
| https://www.aavso.org/comment/110413 |
Should invasive coronary angiography be performed by non-cardiologist operators? - The British Journal of Cardiology
Future role? This study by Yasin et al. suggests that there could be a role for experienced nurse operators in the future. However, since the inception of nurse-led angiography in the late 1980s, there have been considerable advancements in the technology and infrastructure within interventional cardiology centres. ...
Should invasive coronary angiography be performed by non-cardiologist operators?
Tiffany PattersonNIHR Academic Clinical Lecturer in Interventional Cardiology
Simon R RedwoodProfessor of Interventional Cardiology and Honorary Consultant Cardiologist
Cardiovascular Department, British Heart Foundation Centre of Research Excellence, King’s College London, St. Thomas’ Hospital, Westminster Bridge Road, London, SE1 7EH
Correspondence to:Dr T Patterson ( Tiffanypatterson05@gmail.com )
The concept of nurse-led angiography was first introduced in the UK just over two decades ago. This was in response to concerns raised following implementation of the Calman report. 1The Calman report recommended a structured training programme for cardiology registrars, thus, achieving clinical competence at a faster rate, with a view to filling anticipated consultant vacancies. However, it was presumed that this would negatively impact clinical service delivery. One particular concern was that there would be a reduced number of registrars available and able to perform coronary angiography. There was a fear that this shortfall would lead to reduced throughput within cardiology centres. Boulton et al.described a potential solution to this shortfall: the training of a clinical nurse specialist to perform coronary angiography. 2The aim was to teach the nurse-angiographer the technical skills to undertake coronary angiography, with a head-to-head comparison of procedural time, radiation exposure, and complication rate. The results were impressive with the nurse-angiographer demonstrating a numerical reduction in complication rate and fluoroscopy time. These results were similar to those of DeMots et al., who trained a physician assistant in Portland, Oregon to perform coronary angiography with a view to reducing the workload of trainee cardiologists. 3
This study by Yasin et al. suggests that there could be a role for experienced nurse operators in the future. However, since the inception of nurse-led angiography in the late 1980s, there have been considerable advancements in the technology and infrastructure within interventional cardiology centres. The number of centres now performing coronary angiography and percutaneous coronary interventions (PCI) has considerably increased, forming part of a larger group of strategic cardiac networks. 4Diagnostic coronary angiography, and the management of non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI) patients, are no longer limited to tertiary cardiac centres with an increased workforce.
The importance of performing coronary angiography to a high standard should not be underestimated. This includes safe vascular access and obtaining appropriate views. Coronary angiography remains the gold-standard test for determining the presence of coronary artery disease. However, to be truly diagnostic it has to be performed well, with acquisition of optimal views in order to fully elucidate the anatomy. There is strong evidence to now suggest that coronary angiography should no longer be performed in isolation. Findings of the R3F (Registre Français de la FFR) and recently published RIPCORD (Does Routine Pressure Wire Assessment Influence Management Strategy at Coronary Angiography for Diagnosis of Chest Pain) and POST-IT (Portuguese Study on the Evaluation of FFR Guided Treatment of Coronary Disease) studies of, collectively, more than 2,000 patients investigated the role of fractional flow reserve (FFR) at the time of diagnostic angiography. 5-7Importantly, in all three studies, the significance of coronary artery disease was reclassified in approximately one-third of patients using FFR compared with coronary angiography alone. In other words, visual assessment of coronary disease was found to be incorrect in one-third of cases. This raises the question of whether or not all coronary angiography should be performed by interventional cardiologists, and, anecdotally, there are cases in which coronary angiography has to be repeated, exposing patients to further radiation and a further procedure. Furthermore, there are certain situations when bail-out PCI is necessary, although rare, these include catheter-induced dissection and NSTEMI with unstable coronary appearances, and it is important in these situations to be able to perform angioplasty promptly and safely. Therefore, the exact role for nurse-led angiography remains unclear, and further work is needed to elucidate which scenarios would be best served by this technique.
Conflicts of interest
None declared.
Editor’s note
There is no question that a nurse can do diagnostic coronary angiography as well as a junior doctor; the problem today is, now we have CT Fractional Flow Reserve (CT FFR), the need for diagnostic angiography is rapidly declining. If, therefore, nurses perform the majority of coronary angiograms, there will not be an opportunity to train doctors so that they can ultimately take on the complex cases or percutaneous coronary intervention (PCI). KF
Thestudy by Yasin et al. to which this editorial refers can be found here.
References
1.Calman K. Hospital doctors: training for the future. BJOG1995; 102:354–6.https://doi.org/10.1111/j.1471-0528.1995.tb11283.x
2.Boulton BD, Bashir Y, Ormerod OJM, Gribbin B, Forfar JC. Cardiac catheterisation performed by a clinical nurse specialist. Heart1997; 78:194–7.https://doi.org/10.1136/hrt.78.2.194
3.DeMots H, Coombs B, Murphy E, Palac R. Coronary arteriography performed by a physician assistant. Am J Cardiol1987; 60:784–7.https://doi.org/10.1016/0002-9149(87)91023-X
4.Ludman P, Bradley A for NICOR, BCIS and HQIP. National audit of percutaneous coronary interventions. Annual public report. 1 January 2015 – 31 December 2015. London: NICOR, 2017. Available from:https://www.hqip.org.uk/wp-content/uploads/2018/02/national-audit-of-percutaneous-coronary-intervention-annual-public-report.pdf
5.Van Belle E, Rioufol G, Pouillot C et al. Outcome impact of coronary revascularization strategy reclassification with fractional flow reserve at time of diagnostic angiography: insights from a large French multicenter fractional flow reserve registry. Circulation2014; 129:173–85.https://doi.org/10.1161/CIRCULATIONAHA.113.006646
6.Curzen N, Rana O, Nicholas Z et al. Does routine pressure wire assessment influence management strategy at coronary angiography for diagnosis of chest pain? The RIPCORD study. Circ Cardiovasc Interv2014; 7:248–55.https://doi.org/10.1161/CIRCINTERVENTIONS.113.000978
7.Baptista SB, Raposo L, Santos L et al. Impact of routine fractional flow reserve evaluation during coronary angiography on management strategy and clinical outcome. Circ Cardiovasc Interv2016; 9:e003288.https://doi.org/10.1161/CIRCINTERVENTIONS.115.003288
Keywords
coronary angiography
nurse specialist
| https://bjcardio.co.uk/2019/04/should-invasive-coronary-angiography-be-performed-by-non-cardiologist-operators/ |
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15/112-05:45:10.250 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF 1508 0.4599 1124 2.7426
15/112-05:45:20.250 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF 1508 0.4599 1125 2.7450
15/112-05:45:23.395 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF 1509 0.4602 1124 2.7426
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15/112-05:45:26.254 ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1509 0.4602 1124 2.7426
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15/112-05:47:05.254 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1510 0.4605 1124 2.7426
15/112-05:47:10.258 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1509 0.4602 1124 2.7426
15/112-05:47:25.254 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1510 0.4605 1124 2.7426
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15/112-05:48:26.262 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1510 0.4605 1124 2.7426
15/112-05:49:15.258 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1511 0.4609 1124 2.7426
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15/112-05:51:00.262 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1512 0.4612 1124 2.7426
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15/112-05:51:10.270 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1512 0.4612 1124 2.7426
15/112-05:51:15.262 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1511 0.4609 1124 2.7426
15/112-05:51:23.406 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1512 0.4612 1124 2.7426
15/112-05:51:26.270 ON ON ON OFF ON ON ON OFF ON OFF ON OFF ON OFF ON OFF ON OFF OFF OFF 1512 0.4612 1124 2.7426
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15/112-05:53:00.270 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1513 0.4615 1123 2.7401
15/112-05:53:05.266 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1512 0.4612 1124 2.7426
15/112-05:53:10.270 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1513 0.4615 1123 2.7401
15/112-05:53:15.266 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1512 0.4612 1124 2.7426
15/112-05:53:20.270 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1513 0.4615 1123 2.7401
15/112-05:53:26.273 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1513 0.4615 1123 2.7401
15/112-05:55:53.418 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1514 0.4618 1122 2.7377
15/112-05:57:23.422 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1515 0.4621 1121 2.7352
15/112-06:00:23.430 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1516 0.4624 1120 2.7328
15/112-06:01:53.434 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1516 0.4624 1119 2.7304
15/112-06:04:53.441 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1515 0.4621 1119 2.7304
15/112-06:05:25.297 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1515 0.4621 1118 2.7279
15/112-06:07:53.449 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1514 0.4618 1118 2.7279
15/112-06:09:23.453 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1514 0.4618 1117 2.7255
15/112-06:10:53.457 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1512 0.4612 1117 2.7255
15/112-06:12:23.461 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1512 0.4612 1116 2.7230
15/112-06:13:53.465 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1493 0.4554 1115 2.7206
15/112-06:15:23.469 ON ON ON OFF ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1273 0.3883 1113 2.7157
15/112-06:15:23.492 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 1273 0.3883 1113 2.7157
15/112-06:16:53.473 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 868 0.2647 1111 2.7108
15/112-06:18:23.477 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 302 0.0921 1098 2.6791
15/112-06:19:53.477 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 6 0.0018 857 2.0911
15/112-06:21:23.484 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 20 0.0061 1022 2.4937
15/112-06:22:53.484 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 27 0.0082 1054 2.5718
15/112-06:24:23.492 ON ON ON ON ON ON ON ON ON OFF ON OFF ON OFF ON OFF OFF OFF OFF OFF 32 0.0098 1071 2.6132
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15/112-06:27:23.496 ON ON ON ON ON ON ON ON ON OFF ON | https://lasp.colorado.edu/maven/sdc/public/data/sites/site-20200331T180943/anc/eng/sasm2/sci_anc_sasm215_111_112.drf |
Changing To Tap Water | Freshwater Aquarium Discussion Forum
A few years ago, when my son started a small tank, there was some reason (I can't remember now, but prob bec our water is hard) we felt we needed to use...
Changing To Tap Water
A few years ago, when my son started a small tank, there was some reason (I can't remember now, but prob bec our water is hard) we felt we needed to use distilled water. Right or wrong, now we have a 20 gal and have been using distilled water. Our parameters have always been 0 ammonia , 0 nitrite, and 5-8 nitrate (tank has been set up and planted for about 2 months). I now realize that most people are using tap, so I should be able to also, unless there's something I'm missing. I understand I must dechlorinate and have Prime for that. I just want to know if I should make the change following a particular method. My lfs suggested taking out 3-4 gal and teplacing it with 3-4 gal of treated tap. TIA
If I were you I'd use spring water. Also tap water would be fine, but make sure you put it in a jug or container and then add the prime and I would also use ph 7 as its great for ammonia and the ph. I know you have zero ammonia, but just in case.
Tap is actually really great since it's usually high in essential minerals, unless you have extremely hard water. Do you know the type of water you have? And what livestock is in the tank?
You are asking a very complicated question there. So good questions create more questions, and here goes: What kind of fish do you have? What is your current pH and hardness? What is the pH and hardness of your tap? The info matters because you aren't just transitioning from water to water, but to different minerals, etc. How the fish will react depends on how large a change you are bringing. It's worth knowing. Unlike Ankers, I always avoid pH altering chemicals unless I know the exact water chemistry I am changing. They can go seriously wrong.
LFS mentioned the water we are using is usually stripped of a lot of minerals, so I think tap is the way to go. Honestly, it's getting too time consuming to run to the store for water refills. I know our water is somewhat hard. The pH in both our tap and the distilled is 7.8.
Stock is 2
platys
, 2
guppies
, 2
otos
, and about 20 fry (of which we plant to rehome most of).
You are asking a very complicated question there. So good questions create more questions, and here goes: What kind of fish do you have? What is your current pH and hardness? What is the pH and hardness of your tap? The info matters because you aren't just transitioning from water to water, but to different minerals, etc. How the fish will react depends on how large a change you are bringing. It's worth knowing. Unlike Ankers, I always avoid pH altering chemicals unless I know the exact water chemistry I am changing. They can go seriously wrong.
Looks like we posted about the same time. The pH of both are the same. However, we don't yet have a hardness test, so I'm not sure. Would finding a report put out by our city's water dept be a good idea?
Also, I do not feel knowledgeable enough, nor do I want to put any chemicals in unless necessary.
7.8 probably reflects moderately hard tapwater, and for the fish you have, that should be okay. It isn't ideal for softwater Otos, but it would be a dream for hardwater evolved guppies. I'd follow the store advice and just do my water changes with tap until the gradual switchover is done. Fish generally react well to an increase in minerals. It's when you go the other way that they suffer.
There might be one online like the store said, gradually do your regular water changes but each time add some tap.
It's always good to know what your water is, so that you can choose fish that thrive in it. There's an often repeated myth that the fish bred in farms happily adapt to any water, and it's only as true as any other myth. Once you know your water (and if you can interpret the info from the city, you'll have great info) you can choose fish that will do really well in your water.
Thank you all so much. I just got the otos yesterday unexpectedly. I was at lfs (45 min away) for something else and asked what fish they had that would be good for taking care of algae, which is beginning to be a moderate issue that my snails aren't taking care of on their own. I feel I need to do a water change now knowing the otos were in harder water at the lfs, plus I tested and nitrates seem to be a little higher than the norm of 5 for me. Would this disturb the otos much? I drip acclimated them for 2 hours and they were eating last night.
Got city water report. Hardness is 16 ppm . What does that mean? Could someone explain what the dH means? Someone at the water dept told me the hardness is 16 ppm, but I lnow our water is hard. Could she be reading it wrong and it really means 16 dH? 0- 4 dH, 0 - 70 ppm : very soft 4 - 8 dH, 70 - 140 ppm : soft 8 - 12 dH, 140 - 210 ppm : medium hard 12 - 18 dH, 210 - 320 ppm : fairly hard 18 - 30 dH, 320 - 530 ppm : hard
Got city water report. Hardness is 16 ppm. What does that mean? Could someone explain what the dH means? Someone at the water dept told me the hardness is 16 ppm, but I lnow our water is hard. Could she be reading it wrong and it really means 16 dH? 0- 4 dH, 0 - 70 ppm : very soft 4 - 8 dH, 70 - 140 ppm : soft 8 - 12 dH, 140 - 210 ppm : medium hard 12 - 18 dH, 210 - 320 ppm : fairly hard 18 - 30 dH, 320 - 530 ppm : hard
As far as I know the only type of hardness measured in ppm is total dissolved solids. dH is degrees hardness I'm pretty sure, 1 dH = 17.9 ppm
When you make the transition do it slowly, 3/4 distilled 1/4 tap for the first couple of water changes, then use 1/2 and 1/2 and so on. You don't want to do it all at once.
KarenW
When you make the transition do it slowly, 3/4 distilled 1/4 tap for the first couple of water changes, then use 1/2 and 1/2 and so on. You don't want to do it all at once.
That's what I was thinking, even though the lfs said to just start replacing with tap 100%.
As far as I know the only type of hardness measured in ppm is total dissolved solids. dH is degrees hardness I'm pretty sure, 1 dH = 17.9 ppm
So, according to the chart I posted, we are in the fairly hard range at 286.4. Now, that makes sense. So, is that
kH
or gH?
-Mak-
So, according to the chart I posted, we are in the fairly hard range at 286.4. Now, that makes sense. So, is that kH or gH?
I believe it's the unit used to measure either. Personally I just use ___ KH or ___ GH without the dH.
KarenW
So, is the 286.4 gH in the aquarium world going to mess with my: Guppies Platys Otos Gourami ??
KarenW
Update I got a kH/gH test kit and have found that our water hardness is 21 gH or @ 400ppm, A LOT harder than I thought. For those of you who have this kind of water, what kind of fish do you keep? I have guppies, platys, otos, and corys and also pond snails and PLAN to switch slowly from bottled to tap. Will they adapt?
| https://www.fishlore.com/aquariumfishforum/threads/changing-to-tap-water.303233/ |
Southwestern Archaeology, Inc. (SWA)
Southwestern Archaeology Special Interest Group (SASIG)
" Got CALICHE ? " Newsletter
Archaeology, Anthropology, and History of the Greater Southwest!
Tuesday April 23, 2002
*****************************************
TEXAS
http://www.bigspringherald.com
70-year-old Katie Cathey, a native of Big Spring, has put together a pictorial history of local landmarks. Using modern technology to help with the centuries-old craft, Cathey scanned in the borrowed photos and printed the images out on material used for the quilt. Each block contains a picture and a caption or story such as the Coahoma school house built in 1910. Other blocks include a confiscated whisky still, two men on horse back observing Webb Air Force Base bomber crews practicing dropping sand bombs and the Birdwell House, the place Cathey first learned to dance.
NEW MEXICO
http://www.lcsun-news.com/Stories/0,1413,115%257E7442%257E562734,00.html
In 1870, the United States asked the Seminole-Negroes to come back. They needed help fighting the Apaches and Commanches, and realized the Seminole-Negroes had been successfully doing that for years. In return, the government agreed to pay them, give them food and guns and a tempting incentive, a plot of land for each soldier who agreed to fight. They became the Seminole-Negro Indian Scouts between 1870 and 1885. Four of them went on to earn the Congressional Medal of Honor. They successfully helped the United States take control of the west.
http://www.abqjournal.com/paperboy/text/news/661070news04-21-02.htm
Once each month, Wilhelmina Phone, 72, and two other fluent Jicarilla speakers meet in Dulce with University of New Mexico linguists to develop the first-ever Jicarilla dictionary. The project is funded by a $226,000 National Science Foundation grant. Researchers plan to complete the project when the grant expires in January 2004.
http://www.oweb.com/newslink/national/MadamMillieP0219.html
Silver City is trying to capitalize on the legacy of Mildred Cusey, even if her "place" was a house of prostitution that operated until 1968 under the watchful, mostly tolerant eye of local authorities. Millie became a Harvey Girl waitress at 14 in Deming, N.M., and part-time prostitute by 16 in El Paso, Texas. In Silver City, Millie tried to be a positive force, following a tradition established by earlier madams, Silver City Museum director Susan Berry said.
http://www.museums.state.nm.us/hpd/news/outreach_cal_prelim.htm
New Mexico Heritage Preservation Week Events Calendar May 10-19, 2002
http://www.swanet.org/zarchives/nmarchyfair/2002_nm_archy_fair_annc.pdf
New Mexico Archaeology Fair (October 4-5, 2002)
COLORADO
http://www.coloradohistory-oahp.org/whatsnew/AHPMbklt.pdf
Colorado Archaeology and Historic Preservation Month statewide calendar of events.
UTAH
http://www.thespectrum.com/news/stories/20020422/localnews/186405.html
Einar Erickson will present a lecture about Healing Ceremonies such as the Squaw Dance, or the more elaborate Nine Day Breathing Way, including the painting, dance, and chant surrounding the sand painting. Erickson lived with the Navajo and Hopi Indian people for more than a year as a teen-ager and became well informed about these unusual, yet sacred ceremonies.
http://history.utah.org/prehist
Utah Prehistory Week May 4-11, 2002
NEVADA
http://www.elynews.com/display/inn_news/news01.txt
Efforts to turn the U.S. Highway 50 corridor from Ely to Delta, Utah into a "national heritage area" passed a hurdle Thursday when supporters outlined their plan to the Senate's natural resources committee. A group, using funds from the Utah Historical Foundation plans, a workshop in Ely on May 3-5, to explain to community and business leaders what designation would accomplish for local tourism efforts.
http://www.austin360.com/statesman/editions/today/news_5.html
A fledgling divorce preservation movement is seeking to protect the state's divorce landmarks. Two of the 11 historic sites listed this month as endangered by the group Preserve Nevada are related to divorce. One is the Virginia Street Bridge. The other is the Silver State Lodge, a vintage log motel. In their prime, hundreds of hotels, motels and boarding houses flourished in the back alleys and sagebrush of Reno, where about 32,000 marriages were dissolved between 1929 and 1939.
http://dmla.clan.lib.nv.us/docs/shpo/hpweek2002.htm
Nevada Archaeology Awareness and Historic Preservation Week May 12-18, 2002
ARIZONA
http://swanet.org/zarchives/misc/opac042202.pdf
Old Pueblo Archaeology Center News
http://groups.yahoo.com/group/AAC-L/message/1254
From: Beth Grindell <grindell@email.arizona.edu> Re: [AAC-L] Commentary on ASM's name change: I would like to suggest that people who are opposed to the name change contact the Az Board of Regents with your opinions. ASM staff are informed that the name change initiative originated there so it is there that the education on the history of the name needs to take place. This is something that is difficult for ASM staff to do without seeming to undermine our director who is in a difficult position on this subject, having been ordered to do it. My private poll of ASM staff shows virtually no support for an ASM name change, but no one wishes to be seen as further undermining an already under-recognized, under-funded institution. Regents' addresses and emails may be found at: http://www.abor.asu.edu/1_the_regents/members/list.html. Since, despite the implications of recent news articles, the name change is not yet approved, you may also wish to call or email UA President Peter Likins [phone 520-621-5511] and express an opinion. Beth Grindell, Ph.D., R.P.A. Assistant Curator, Archaeological Records Arizona State Museum The University of Arizona Tucson, AZ 85721-0026 520-621-1271 FAX 520-621-2976 www.Statemuseum.arizona.edu
http://www.azstarnet.com/star/fri/20419HOHOKAMDIG.html
Archaeologists hired by Southwest Gas Corp. have been working for nearly two months to excavate a site of one of the biggest ancient Hohokam communities, along the Santa Cruz River about 17 miles south of Downtown Tucson. The dig site's exact location is being kept secret to avoid vandalism.
http://www.tucsoncitizen.com/local/4_22_02dig.html
The Zanardalli Site is on both sides of Old Nogales Highway about six miles south of the intersection with Valencia Road.
Editor's Note:
So much for the newspapers keeping confidential site location information!
CALIFORNIA
http://www.dailycal.org/article.asp?id=8438
Just because something is old doesn't mean it's worth saving. It is clear the commission is concerned with little more than making Berkeley inhospitable for all but the old, bored and financially secure. Students searching for next year's housing are well aware of the hassle of finding decent local rooms, and the commission is one of the reasons behind the city's lack of space.
ANTHROPOLOGISTS AND ARCHAEOLOGISTS
http://www.billingsgazette.com/index.php?id=1&display=rednews/2002/04/21/build/local/70-plentycouppark.inc
In 1992, a non-profit group formed to, among other things, develop a protocol for appropriate handling of the extensive artifact collection kept at the site, including sacred medicine bundles.
http://globalarchive.ft.com/globalarchive/article.html?id=020422001563&query=archaeologists
Portable Antiquities, a voluntary scheme to encourage thousands of amateur metal detector users to report all finds, has been a tremendous success. If the Portable Antiquities scheme collapsed, archaeologists in local museums would be left struggling to police detecting on thousands of sites.
http://www.cnn.com/2002/SHOWBIZ/books/04/22/arts.us.jean.auel.ap/index.html
Auel's first four books, beginning with "The Clan of the Cave Bear" in 1980, have sold nearly 35 million copies. Doug Kennett, an archaeology professor at the University of Oregon, said "The Clan of the Cave Bear" was required reading when he was a graduate student. The goal was to help students understand the importance of telling a story based on their research, he said.
http://www.time.com/time/covers/1101020429/qa.html
George Lucas never meant to become a filmmaker. As a teen, he dreamed of becoming an anthropologist...
TOOLS AND TECHNOLOGY
http://www.sirc.org/publik/gossip.shtml
The subject of gossip is increasingly attracting the attention of researchers in social psychology, anthropology, evolutionary psychology, sociolinguistics and social history. Mobiles facilitate gossip. Mobile phones are re-creating the more natural, humane communication patterns of pre-industrial times: we are using space-age technology to return to stone-age gossip. Women use their mobile phones as 'symbolic bodyguards' in the way that they used to use a newspaper as a 'barrier signal' to indicate to predatory males that they were unavailable. Women interviewed about this said that they found the mobile even more effective as a symbolic bodyguard.
http://www.mcguinnessdesigns.com/info_1.htm
http://www.mcguinnessdesigns.com/free_resources_page.htm
Precolumbian Clip Art
CYBERIA
http://www.washingtonpost.com/wp-dyn/articles/A10100-2002Apr18.html
Race (the sine qua non among American transactions) is America's true theme, not freedom, not democracy. North of the US-Mexico border, brown appears as the color of the future. The adjective accelerates into a verb: 'America is browning.' South of the border, brown sinks back into time.
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Southwestern Archaeology, Inc. (SWA) - A 501(c)(3) customer-centric corporation dedicated to electronic potlatch and digital totemic increase rites that focus and multiply historic preservation activities in the Greater Southwest. Our goal is to create and promote the diverse micro-environments and open systems in which archaeologists can develop their talents and take the risks from which innovation and productivity arise.
| http://www.swanet.org/zarchives/gotcaliche/alldailyeditions/02apr/cali042302.txt |
EC:3.4.11.18 - FACTA Search
The receptor for advanced glycation end products (RAGE), a multi-ligand member of the immunoglobulin superfamily of cell surface molecules, interacts with distinct molecules implicated in homeostasis, development and inflammation, and certain diseases such as diabetes and Alzheimer's disease. Engagement of RAGE by a ligand triggers activation of key cell signalling pathways, such as p21ras, MAP kinases, NF-kappaB and cdc42/rac, thereby reprogramming cellular properties. RAGE is a central cell surface receptor for amphoterin, a polypeptide linked to outgrowth of cultured cortical neurons derived from developing brain. Indeed, the co-localization of RAGE and amphoterin at the leading edge of advancing neurites indicated their potential contribution to cellular migration, and in pathologies such as tumour invasion. Here we demonstrate that blockade of RAGE-amphoterin decreased growth and metastases of both implanted tumours and tumours developing spontaneously in susceptible mice. Inhibition of the RAGE-amphoterin interaction suppressed activation of p44/p42, p38 and SAP/ JNK MAP kinases; molecular effector mechanisms importantly linked to tumour proliferation, invasion and expression of matrix metalloproteinases.
...
PMID:Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases. 1083 Sep 43
We report here that immediate early gene pip92 is expressed during anisomycin-induced cell death in fibroblast NIH3T3 cells. To determine the mechanism by which this occurs and to identify downstream signaling pathways, we investigated the induction of the pip92 promoter. The activation of pip92 by anisomycin is mediated by the activation of MAP kinases, such as JNK and p38 kinase, but not ERK. Deletion analysis of the pip92 promoter indicated that pip92 activation occurs primarily within the region containing a serum response element (SRE). Further analysis of the SRE using a heterologous thymidine kinase promoter showed that both an Ets and CArG-like site are required for anisomycin-induced pip92 expression. Elk1, which binds to the Ets site, was phosphorylated by the JNK - and p38-dependent pathways and the phosphorylation of Elk1-GAL4 fusion proteins by these pathways was sufficient for the transactivation. Overall, this study suggested that different MAPK pathways are involved in the expression of immediate early gene pip92 by growth factors and environmental stresses.
...
PMID:Expression of immediate early gene pip92 during anisomycin-induced cell death is mediated by the JNK- and p38-dependent activation of Elk1. 1090
A number of oncogenes alter the regulation of the cell cycle and cell death, contributing to the altered growth of tumours. Expression of the v-Src oncoprotein in Rat-1 fibroblasts prevented cell cycle exit in response to growth factor withdrawal. Here we investigated whether survival of v-Src transformed cells in low serum is dependent on v-Src activity. We used a temperature sensitive v-Src to study the effect inactivating v-Src on transformed cells growing under low serum conditions. We found when we switched off v-Src the cells died by apoptosis characterised by activation of caspases and the stress-activated kinases, JNK (Jun N-terminal kinase) and p38 MAP (mitogen activated protein) kinase. We were able to prevent cell death by addition of serum or overexpression of Bcl-2. Thus v-Src transformed Rat-1 cells can be protected from apoptosis by serum, v-Src, or Bcl-2. We investigated how v-Src protects from apoptosis under these conditions. Amongst other effects, v-Src activates two kinases which have been shown to protect cells from apoptosis, phosphatidylinositol 3-kinase (PI3-K) and extracellular signal-regulated kinase (ERK1/2). We found that switching off v-Src led to a decrease in the activity of both PI3-K and ERK1/2, however, we found that adding a specific inhibitor of PI3-K (LY294002) to v-Src transformed Rat-1 cells grown in low serum induced apoptosis while a specific ERK kinase (MEK1) inhibitor (PD98059) had no effect. This suggests that v-Src protects from apoptosis under low serum conditions by activating PI3-K.
...
PMID:Regulation of both apoptosis and cell survival by the v-Src oncoprotein. 1091 42
Calcitonin gene-related peptide (CGRP) is a neuropeptide with potent cardiovascular effects, which include positive inotropic and chronotropic actions, systemic vasodilation, and hypotension in animal and human studies. Human neuroblastoma cells (SK-N-MC) have been used as a model system to study the CGRP receptors and downstream signaling pathways. This investigation was undertaken to study the role of CGRP in the activation of mitogen-activated protein kinases. While exposure of these cells to CGRP had no significant effect on ERK-1 or p38 MAP kinases, JNK activity was stimulated by CGRP in a time- and concentration-dependent fashion. CGRP-mediated JNK -activation was inhibited by CGRP receptor antagonist, CGRP8-37, confirming that this is a receptor-mediated event. In addition, pretreatment of the cells with H-89, protein kinase A inhibitor or pertussis toxin greatly attenuated CGRP-mediated JNK activation suggesting the requirement of cAMP-dependent protein kinase activation and involvement of pertussis toxin-sensitive G-protein in CGRP-mediated JNK activation.
...
PMID:Involvement of cAMP-dependent protein kinase and pertussis toxin-sensitive G-proteins in CGRP mediated JNK activation in human neuroblastoma cell line. 1102 85
Green tea polyphenols (GTP) have been demonstrated to suppress tumorigenesis in several chemical-induced animal carcinogenesis models, and predicted as promising chemopreventive agents in human. Recent studies of GTP extracts showed the involvement of mitogen-activated protein kinases (MAPKs) in the regulation of Phase II enzymes gene expression and induction of apoptosis. In the current work we compared the biological actions of five green tea catechins: (1) induction of ARE reporter gene, (2) activation of MAP kinases, (3) cytotoxicity in human hepatoma HepG2-C8 cells, and (4) caspase activation in human cervical squamous carcinoma HeLa cells. For the induction of phase II gene assay, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) potently induced antioxidant response element (ARE)-mediated luciferase activity, with induction observed at 25 microM with EGCG. The induction of ARE reporter gene appears to be structurally related to the 3-gallate group. Comparing the activation of MAPK by the five polyphenols, only EGCG showed potent activation of all three MAPKs (ERK, JNK and p38) in a dose- and time-dependent manner, whereas EGC activated ERK and p38. In the concentration range of 25 microM to 1 mM, EGCG and ECG strongly suppressed HepG2-ARE-C8 cell-growth. To elucidate the mechanisms of green tea polyphenol-induced apoptosis, we measured the activation of an important cell death protein, caspase-3 induced by EGCG, and found that caspase-3 was activated in a dose- and time-dependent manner. Interestingly, the activation of caspase-3 was a relatively late event (peaked at 16 h), whereas activation of MAPKs was much earlier (peaked at 2 h). It is possible, that at low concentrations of EGCG, activation of MAPK leads to ARE-mediated gene expression including phase II detoxifying enzymes. Whereas at higher concentrations of EGCG, sustained activation of MAPKs such as JNK leads to apoptosis. These mechanisms are currently under investigation in our laboratory. As the most abundant catechin in GTP extract, we found that EGCG potently induced ARE-mediated gene expression, activated MAP kinase pathway, stimulated caspase-3 activity, and induced apoptosis. These mechanisms together with others, may contribute to the overall chemopreventive function of EGCG itself as well as the GTP
...
PMID:Activation of antioxidant-response element (ARE), mitogen-activated protein kinases (MAPKs) and caspases by major green tea polyphenol components during cell survival and death. 1115 83
Cellular responses to environmental stimuli are controlled by a series of signaling cascades that transduce extracellular signals from ligand-activated cell surface receptors to the nucleus. Although most pathways were initially thought to be linear, it has become apparent that there is a dynamic interplay between signaling pathways that result in the complex pattern of cell-type specific responses required for proliferation, differentiation and survival. One group of nuclear effectors of these signaling pathways are the Ets family of transcription factors, directing cytoplasmic signals to the control of gene expression. This family is defined by a highly conserved DNA binding domain that binds the core consensus sequence GGAA/T. Signaling pathways such as the MAP kinases, Erk1 and 2, p38 and JNK , the PI3 kinases and Ca2+-specific signals activated by growth factors or cellular stresses, converge on the Ets family of factors, controlling their activity, protein partnerships and specification of downstream target genes. Interestingly, Ets family members can act as both upstream and downstream effectors of signaling pathways. As downstream effectors their activities are directly controlled by specific phosphorylations, resulting in their ability to activate or repress specific target genes. As upstream effectors they are responsible for the spacial and temporal expression or numerous growth factor receptors. This review provides a brief survey of what is known to date about how this family of transcription factors is regulated by cellular signaling with a special focus on Ras responsive elements (RREs), the MAP kinases (Erks, p38 and JNK ) and Ca2+-specific pathways and includes a description of the multiple roles of Ets family members in the lymphoid system. Finally, we will discuss other potential mechanisms and pathways involved in the regulation of this important family of transcription factors.
...
Recent etiological study in twins (Tanner et al. 1999) strongly suggests that environmental factors play an important role in typical, non-familial Parkinson's disease (PD), beginning after age 50. Epidemiological risk factor analyses of typical PD cases have identified several neurotoxicants, including MPP(+) (the active metabolite of MPTP), paraquat, dieldrin, manganese and salsolinol. Here, we tested the hypothesis that these neurotoxic agents might induce cell death in our nigral dopaminergic cell line, SN4741 (Son et al. 1999) through a common molecular mechanism. Our initial experiments revealed that treatment with both MPP(+) and the other PD-related neurotoxicants induced apoptotic cell death in SN4741 cells, following initial increases of H(2)O(2)-related ROS activity and subsequent activation of JNK1/2 MAP kinases. Moreover, we have demonstrated that during dopaminergic cell death cascades, MPP(+), the neurotoxicants and an oxidant, H(2)O(2) equally induce the ROS-dependent events. Remarkably, the oxidant treatment alone induced similar sequential molecular events: ROS increase, activation of JNK MAP kinases, activation of the PITSLRE kinase, p110, by both Caspase-1 and Caspase-3-like activities and apoptotic cell death. Pharmacological intervention using the combination of the antioxidant Trolox and a pan-caspase inhibitor Boc-(Asp)-fmk (BAF) exerted significant neuroprotection against ROS-induced dopaminergic cell death. Finally, the high throughput cDNA microarray screening using the current model identified downstream response genes, such as heme oxygenase-1, a constituent of Lewy bodies, that can be the useful biomarkers to monitor the pathological conditions of dopaminergic neurons under neurotoxic insult.
...
PMID:Dopaminergic cell death induced by MPP(+), oxidant and specific neurotoxicants shares the common molecular mechanism. 1118 20
Vascular endothelial growth factor (VEGF), a potent cytokine secreted by virtually all cells plays a key role in tumor angiogenesis. Disruption of one VEGF allele in mice has revealed a dramatic lethal effect in early embryogenesis, suggesting a very tight regulation of this gene. This commentary reviews the mechanisms whereby VEGF mRNA is controlled within the tumor environment by hypoxia and the MAP kinase signaling cascades. Using hamster fibroblasts as a cellular model, we demonstrated that the Ras-mediated activation of p42/p44 MAP kinases exerts a prominent action at the transcriptional level. In normoxic conditions, p42/p44 MAPKs activate the VEGF promoter at the proximal (-88/-66) region where Sp 1/AP-2 transcriptional factor complexes are recruited. At low O2 tension, the stabilized and nuclear hypoxia inducible factor- 1alpha (HIF-1alpha) is directly phosphorylated by p42/p44 MAPKs, an action which enhances HIF-1-dependent transcriptional activition of VEGF. In addition, MAPKs activated under various cellular stresses (p38MAPK and JNK ), contribute to the increased expression of this angiogenic growth and survival factor by stabilizing the VEGF mRNA.
...
PMID:MAP kinases and hypoxia in the control of VEGF expression. 1119 Oct 53
Mechanical force or mechanical stress modulates intracellular signal pathways, including the mitogen-activated protein kinase (MAP kinase) cascades. In our system, cell stretching activated and cell contraction inactivated all three MAP kinase pathways (MKK1/2-extracellular signal-regulated kinase (ERK), MKK4 (SEK1)-cJun N-terminal kinase ( JNK ) and MKK3/6-p38 pathways). However, little is known about the molecular mechanisms that link the mechanical force to the MAP kinase cascades. To test whether Ras and Rap1 are possible components in the stretch-activated MAP kinase pathways, we examined if Ras and Rap1 were activated by cell stretching and if inhibition of their activity decreased the stretch-enhanced MAP kinase activity. Rap1 was activated by cell stretching and inactivated by cell contraction, whereas Ras was inactivated by cell stretching and activated by cell contraction. Rap1GapII and SPA-1, downregulators of Rap1 activity, decreased the stretch-enhanced p38 activity, whereas a dominant-negative mutant of Ras (RasN17) did not inhibit the stretch-initiated activation of MAP kinases. Furthermore, overexpression of Rap1 enhanced p38 activity but not ERK or JNK activity. These results indicate that Rap1 is involved in transducing the stretch-initiated signal to the MKK3/6-p38 pathway, but not to the MEK1/2-ERK or the MKK4 (SEK1)/MKK7- JNK pathway. Thus, Rap1 plays a unique role in force-initiated signal transduction.
...
PMID:Rap1 is involved in cell stretching modulation of p38 but not ERK or JNK MAP kinase. 1122 65
Inhibition of signaling through Ras in BCR-ABL-positive pluripotent K562 cells leads to apoptosis and spontaneous differentiation. However, Ras-induced activation of the mitogen-activated protein kinase ERK has been suggested to play a critical role in either growth or differentiation in different model systems. We studied the role of ERK activation in the growth-promoting and anti-apoptotic effect of Ras and its involvement in hemin-induced nonterminal erythroid differentiation using the BCR-ABL-positive K562 cell line as a model. K562 cells were stably transfected with ERK1 or the dominant inhibitory mutant of ERK1 (ERK1-KR). Overexpression of ERK1-KR inhibited cell growth with an approximately fourfold increase in doubling time and induced apoptosis in K562 cells. Incubation with the MEK1 inhibitor UO126 inhibited cell growth and induced apoptosis in K562 cells in a dose-dependent manner as well. In the presence of exogenously added hemin, K562 cells differentiate into erythroblasts, as indicated by the production of large amounts of fetal hemoglobin. We examined the activation of MAP kinases during hemin-induced differentiation. The ERK1 and 2 activity increased within 2 h post hemin treatment and remained elevated for 24-48 h. During this time, fetal hemoglobin synthesis also increases from 0.8 to 10 pg/cell. There was no activation of JNK or p38 protein kinases. The hemin-induced accumulation of hemoglobin was inhibited in ERK1-KR overexpressing cells and was enhanced in the wild-type ERK1 transfectants. Our results suggest that ERK activation is involved in both growth and hemin-induced erythroid differentiation in the BCR-ABL-positive K562 cell line.
...
PMID:Role of ERK activation in growth and erythroid differentiation of K562 cells. 1126 76
| http://www.nactem.ac.uk/facta/cgi-bin/facta3.cgi?query=EC%3A3.4.11.18%7C111111%7C0%7C0%7C11571%7C50%7C60 |
Agriculture | Free Full-Text | Perceptions of Smallholder Farmers towards Organic Farming in South Africa
In South Africa, smallholder farming is an important aspect of livelihood. More so, organic farming is increasingly becoming popular among farmers. However, many studies undertaken focused on the trade possibilities of the industry leaving the farmers’ perceptions underrepresented. This study, therefore, aims to capture the farmers’ opinions by evaluating the critical factors and policy implications of organic farming in the Limpopo Province of South Africa. A total of 220 semi-structured questionnaires were administered to smallholder farmers in the province. The results revealed that organic farming is gaining recognition according to 82.8% of the participants, and 86.6% believed that organic farming has high-profit returns. However, 88.4% of the respondents agreed that the required standards for organic farming are too restrictive while a further 74.6% indicated that organic farming certification is difficult to obtain. The results also indicated a statistically significant difference in the perceived benefits of organic farming (p ≤ 0.001) and access to markets (p = 0.042). Based on the results, the study suggests more awareness, training and ease of certification as a way forward in changing the perceptions of the farmers in the province.
Perceptions of Smallholder Farmers towards Organic Farming in South Africa
by
Solomon Eghosa Uhunamure 1,* ,
Zongho Kom 2 ,
Karabo Shale 1 ,
Jacobus Steyn 2
1
Faculty of Applied Sciences, Cape Peninsula University of Technology, Cape Town 8000, South Africa
2
Faculty of Science, Engineering and Agriculture, University of Venda, Thohoyandou 0950, South Africa
*
Author to whom correspondence should be addressed.
Agriculture 2021 , 11 (11), 1157; https://doi.org/10.3390/agriculture11111157
Received: 9 October 2021 / Revised: 16 November 2021 / Accepted: 16 November 2021 / Published: 18 November 2021
(This article belongs to the Special Issue Innovative Strategies in Organic Farming Systems )
Abstract
:
In South Africa, smallholder farming is an important aspect of livelihood. More so, organic farming is increasingly becoming popular among farmers. However, many studies undertaken focused on the trade possibilities of the industry leaving the farmers’ perceptions underrepresented. This study, therefore, aims to capture the farmers’ opinions by evaluating the critical factors and policy implications of organic farming in the Limpopo Province of South Africa. A total of 220 semi-structured questionnaires were administered to smallholder farmers in the province. The results revealed that organic farming is gaining recognition according to 82.8% of the participants, and 86.6% believed that organic farming has high-profit returns. However, 88.4% of the respondents agreed that the required standards for organic farming are too restrictive while a further 74.6% indicated that organic farming certification is difficult to obtain. The results also indicated a statistically significant difference in the perceived benefits of organic farming (
p
≤ 0.001) and access to markets (
p
= 0.042). Based on the results, the study suggests more awareness, training and ease of certification as a way forward in changing the perceptions of the farmers in the province.
;
compost
;
farmers’ certification
;
food production
;
organic farming
;
smallholder
1. Introduction
A fundamental challenge facing human existence is meeting the food demands of the teeming population [ 1 ]. According to the United Nations, the present world population of approximately 7.7 billion is predicted to surge to 9.7 billion by 2050 [ 2 ]. The feeding of such a population requires an increase in agricultural production, but there are many limitations in the use of natural resources, energy and farmlands [ 3 ]. Well documented is the role of modern farming practices in the intensification of agricultural production and reduction of resource constraints through a feasible programme such as the Green Revolution and the use of genetic engineering, irrigation systems, machinery, and chemical inputs [ 4 ]. Nonetheless, the application of chemical inputs such as chemical fertilisers, pesticides and heavy metals has generated severe environmental and health concerns [ 5 ]. The adverse effects of the introduction of chemical inputs in farming include surface and groundwater contamination, emission of greenhouse gases, reduced biodiversity and soil degradation [ 6 ].
One input in ensuring sustainable farming and food production systems is the introduction of organic farming which has been regarded as a feasible option to the emanated crisis of modern farming [
7
]. Organic farming is a farming practice that is done without the use or application of synthetic chemicals such as genetically modified seeds, pesticides, fungicides, insecticides or fertilisers. Organic farming involves a wide range of techniques that help in reducing pollution, sustaining the ecosystem, improvement of production and quality nutrition associated with improved economic and social viability. This method has proven to be a suitable method for sustainable agricultural development and practice [
7
]. Organic farming maintains and promotes soil, animal, plant and human health, sustains and enhances biodiversity and ecological systems. More so, it provides a well-balanced nutrient cycling and mineralisation with favourable microclimatic regimes thus affording farmers less risk. Widely acknowledged are the nutritive and health benefits of organic farming [
8
]. Remarkably, among policymakers, consumers, and producers in recent years are the increased popularity of organic farming. Continually rising since the last decade around the world is the growth and significant development of organic farming [
7
].
A survey conducted in 2019 by the Research Institute of Organic Agriculture indicated that the method is still practised in 181 countries, covering 69.8 million hectares of farmland and representing about 1.4% of the world’s farmlands [ 9 ]. In 2017, China and Argentina witnessed 32% and 12% growth in organic farmland respectively, but there was a decrease in Ukraine, Iran, and Kazakhstan. During the same period, there was no growth rate observed in organic farmlands in Japan, Mexico, and the United States of America. Despite the negative or zero growth rate in these countries, consumers’ predisposition to organic produce has increased tremendously [ 9 ]. The benefits of organic produce such as taste, food quality, health and environmental friendliness have increased the demand for these products [ 10 ]. In turn, a potential market for organic produce has been created due to demand [ 11 ]. In effect, since the last two decades, global sales of organic food have increased from US $ 15 billion to US $ 97 billion owing to interest in organic foods. More so, several countries are expanding their global organic market share [ 9 ].
Increasingly, the use of compost manure is considered a more credible option to chemical fertilisers but little is known regarding the factors that could encourage farmers to adopt the practice. Studies conducted on adopting compost as a farming method revealed that socio-economic and technical conditions differ on a country by country basis [ 12 ]. For example, some farmers rely on compost produced by themselves from crop residues and manure [ 12 ], others depend on factors such as availability of raw materials [ 13 ], and training in composting were a significant requisite for its adoption [ 14 ]. In some studies conducted in developed and developing countries, the results revealed that traditional supply-based policies alone may unlikely guarantee an appropriate technological innovation level by farmers [ 15 ]. For instance, in most tropical countries, failures recorded in compositing aroused from the dearth of attention paid in the planning stage to understand the demand, economic and technical aspects involved in organic farming methods [ 16 , 17 ].
Gaps have been identified by a few studies in organic farming development approaches and suggested different implementation strategies such as the application of innovative technologies [ 18 ], local government guidance [ 19 ], scientific research support and implementation [ 4 ], support and subsidies from the government [ 20 ], regulatory standards, modification, management, and constraints of organic farming [ 21 ]. Other identified gaps point to green marketing [ 22 ], creating establishments for organic certification [ 23 ], and trade and financial policies [ 24 ]. Although the development of organic farming has not been all ideal, there are some supportive policies such as financial, legislative, communication, and action plans that have been implemented in developed countries regarding the advancement of organic farming [ 21 ]. Access to markets, appropriate training, access to consulting and extension services, and the presence of strong demand for organic produce [ 25 , 26 ]. Whereas, in developing countries, support from the government regarding organic farming varies from the developed countries. In developing countries, it is almost insignificant and no momentous operational policies and programmes are being implemented. It is thus vital to ascertain and determine strategies that can ease the progress of organic farming based on inclusive factors affecting organic farming.
Nevertheless, other socioeconomic and institutional factors such as farmers’ age, educational level, access to information, access to credit, and land tenure are also relevant in exploring the adoption of organic farming innovations. This study, therefore aimed at examining the perceptions of smallholder farmers regarding organic farming in South Africa, using Limpopo Province as a case study. In fulfilling this aim, the central objective of this study is to explore whether smallholder farmers in the province are willing to convert their farms to organic production and the underlying factors which can positively or negatively influence their perception. The certification system, production challenges, policy, marketing, and feasible interventions for instituting and strengthening organic agro-products supply are also considered. The hypothesis of this study is grounded on the premise that farmers are willing to partake in organic farming is determined by their perceptions, socio-economic, and other institutional factors.
2. Organic Farming in South Africa
In many sub-Saharan countries, most soils are characterised by low organic content matter, physical erosion, acidity, moisture stress, nutrient deficiencies, and crusting [ 27 ]. In some cases, these factors are accelerated by poor land management systems which have reduced agricultural production [ 28 , 29 ]. Although, attempts have been made to maximise agricultural productivity by intensifying the land areas under cultivation but had had similar effects [ 30 ]. It is estimated that about 60% of the arable land in the continent has been affected by land degradation, resulting in a net loss per annum of more than US $ 68 billion in agricultural production [ 31 ]. More so, it is envisaged that if this pattern of land degradation continues in the continent, crop yields could be severely reduced [ 32 ].
There is a long history of organic farming in South Africa. The country was one of the founding members of the International Federation of Organic Movements (IFOAM). As of 2005, the value of organic farming produce in the country was estimated between R200 Million and R400 Million [ 33 ]. According to the World Bank collection of development indicators, in 2018, South Africa was reported to have about 9.9% of arable land [ 34 ]. According to the conservation organisation of the World Wide Fund for Nature (WWF), by 2050, South Africa will have to produce 50% more food to feed a projected population of 73 million people [ 35 ]. Therefore, it is crucial to ensure food security through the implementation of sustainable farming practices such as organic farming. In South Africa, the formal adoption of organic farming practices is low. Nonetheless, informal organic farming by subsistence and smallholder producers in the country may feed as much as two-thirds of the country’s population [ 33 ]. Owing to the complexity of the country’s agricultural sector, the government has envisioned that organic farming will be the mainstream system of agricultural practice in conforming to the agendas such as the proclaimed Green and Clean Economy, Clean Development Mechanism, and Sustainable Agriculture [ 33 ].
However, there is no comprehensive database to collate the actual number of organic farmers countrywide. A report by AgricOrbit [ 35 ], in 2011 indicated that there were around 167 certified producers of organic products, utilising 127,106 hectares of land, approximately 0.04% of all the agricultural land in the country. According to a study by Van Zyl [ 36 ], there are about 350 to 700 hectares of land certified for organic farming in the country with a turnover estimated in the region of R40 million. Parrot et al. [ 37 ], envisaged that 45,000 hectares of land are been utilised for organic farming, representing about 0.54% of the entire farming land in the country. A study by IFOAM indicated that about 500 certified organic farmers who produce crops on approximately 50,012 hectares of land exist in the country [ 9 ]. Organic produce from South Africa is primarily exported and sold at local markets. The crops mainly produced include vegetables, citrus, berries, subtropical fruits, herbs, rooibos tea, and wine [ 38 ].
In South Africa, a high level of fragmentation has characterised the organic farming sector, thus making the sector driven by private and Non-Governmental Organisations (NGOs). There was no particular organisation to represent the interests of the entire organic sector. The fragmentation of the sector originated due to the marginalisation of the agri-business, as only a few practitioners were alienated on the methodologies and means of organic farming. Organic South Africa (OSA), the erstwhile umbrella body for certified farmers became dysfunctional in 2006. This was a result of the culture of silos and the protection of intellectual boundaries developed between the different ethnic organic farming inclinations [
33
]. The course of building a robust national organisation with a comprehensive coherent vision and governance practices is now underway through the Organic Sector Strategy Implementation Committee—South African Organic Sector Organisation (OSSIC—SAOSO). The committee aims to ensure a smooth process, advocating inclusivity and unity, with a clear vision and strong leadership. Numerous organisations which include the Organic Freedom Project (OFP), the Biodynamic Agricultural Association of South Africa (BDAASA) now participate in the process which is driven by the OSSIC—SAOSO forum. The drive of the forum is to ensure that organic substances and surplus producers are integrated, accommodated in the organic sector as full beneficiaries and members of the organic policy. Two distinctive groups have emerged with different agendas: The subsistence smallholder and surplus organic community of farmers primarily supplying the local market and third-party certified organic farmers catering for larger retailers and export markets [
33
].
In South Africa, adherence to private sectors and government institutions regarding organic farming are two international standards. These are the IFOAM and
Codex Alimentarius
(also known as “Codex”). Over the years, several standards regarding organic farming have been developed by the IFOAM. These basic standards are continuously developed to outline how organic products are produced, processed, and handled [
39
]. On their own, these standards however cannot be regarded as a certification but provide a framework for independent certification bodies to develop their own regional or national standards [
39
]. On the other hand, the Codex Alimentarius Commission is a joint venture of the Food and Agricultural Organisation (FAO)/World Health Organisation (WHO) Food Standards Programme which is tasked with developing food standards, guidelines, and code of practice in the food industry [
40
].
There is no official certification system yet in place. Inspection and certification of organic farmers in the country are done by international and domestic certification bodies [
33
]. Hence, not all organic farmers are certified as such, even though thousands of smallholder farmers have been practising the principles for several years where the principles of organic agriculture are followed which are the principles of health, ecology, fairness, and care. Individuals and organisations involved in the certification process oftentimes dismiss the validity of production systems of smallholder farmers as not complying with the principles of organic farming. This is mainly because of the difficulties of smallholder farmers in keeping records to a standard that the certification bodies can confirm there is compliance to organic principles [
33
].
There are two alternative certification pathway models created by IFOAM which is applied in South Africa. The first is the Group certification which is under a third-party certification system and the Participatory Guarantee System (PGS) which is a first-party certification model. The Group certification enables a group of smallholder farmers to collectively manage the production, processing handling, and marketing of their organic products under a co-operative or organisation. Under the scheme, there is a fundamental aspect of an internal control system that is set up to ensure compliance with the ethics of organic farming [
39
]. The Participatory Guarantee System is defined by the IFOAM as a locally focused quality assurance system that certifies producers based on the active participation of stakeholders and is built on social network, knowledge exchange, and foundation of trust [
38
]. The stakeholders involved contribute to developing and implementing the organic standards and procedures [
41
].
3. Materials and Methods
3.1. Study Area
Limpopo Province is the northern-most province of South Africa and covers 125,755 km 2 of the total land area of the country [ 42 ]. The province is divided into five administrative municipal districts namely; Mopani, Vhembe, Capricorn, Sekhukhune, and Waterberg Districts. Due to topographical zones difference in the province, the west is bounded by the northern Drakensburg escarpment, the Soutpansberg with steep peaks and slopes to the east, characterised by a flat undulating Lowveld plain. The Limpopo, Olifants, and Letaba Rivers are the major sources of water and are relied on for irrigation. The climate spatially varies from being arid in the west, semi-arid in the east and temperate areas in the central zones. It offers extremely hot conditions, as it is intersected by the Tropic of Capricorn, with all-year sunshine. The climate type falls within the sub-tropical climate, with an average rainfall of 300–1000 mm per year [ 43 ]. During the summer months, the heat is often interrupted by rainfall and short thunderstorms (October to March). Average temperature can range from 27 °C to as high as 45 °C [ 43 ]. The mountainous areas receive an enormously amount of rainfall yearly, with an average of about 1329 mm [ 43 ]. The seasonal average humidity falls within 80% in the summer and about 38% in the winter [ 43 ]. The soils are characterised as sandy loamy in the west and north, red and black fertile clay in the Springbok flats. However, most parts of the province are dry with occasional drought season.
Agriculture is the mainstay of livelihood, as about 8 million hectares of land are used for agriculture. From which 67% is used for natural grazing, 10% as arable land, 10.4% as nature conservation, and 1.1% for forestry [
42
]. The province is the fourth largest accounting for more than 13% of the total population in the country and of which about 90.8% reside in former homelands or rural areas [
42
]. The agricultural production is diverse with a focus on field crops which is dominated by maize production. Although, citrus and vegetable production are the main farming enterprise in the province, contributing around 64% and 22% to gross income from agriculture [
44
]. The province was specifically selected because of the high concentration of organic farmers [
33
].
3.2. Data Collection
Participation in the study was solely voluntary and an informed consent form was signed by the researchers and the participating farmers before data collection. Primary data were elicited with a semi-structured self-administered questionnaire between October 2020 to June 2021 which is the planting and harvesting season. During the data collection, due to the COVID-19 pandemic, all preventive protocols of wearing a facemask, hand sanitizing, and keeping a social distance were applied. For clarity, repetition, and ambiguity to the ease of the farmers, the questionnaires were pretested with some farmers before the main survey. The pretesting revealed regrouping or rephrasing some questions which were amended to improve clearness. The questionnaire was divided into four sections. Section A entailed demographic and socio-economic characteristics information including gender, age, marital status, educational level, income earned, land ownership. Section B pertains to information relating to certification, changes in farming methods based on certification, market prices for organic produce. Section C includes questions on farmers’ perceptions of organic farming, access to market, and attributes to organic farming. Section D consists of Likert-type questions, using three rating scales to measure the responses of the respondents. The questionnaires were administered in the English language for convenience and simplicity but where indispensable, interpreters were used in local dialects. Engaged research assistants to execute and oversee the administration of the questionnaires were trained to thoroughly monitor the data for quality control and assurance. Approximately, the average duration for administering a questionnaire was 35 min. Secondary data were sourced from unpublished materials, books, research reports, and journals related to organic farming, policies, and certification.
3.3. Sample Size and Procedure
The sampled population comprised of certified, transitional, and non-certified organic farmers in the Limpopo Province. To obtain the sample size, three factors were considered. Firstly, the desired confidence level (95%), secondly, the assumed proportion of the sample, and thirdly, the margin of error. A total of 220 farmers were surveyed using the sample size formula of Yamane [
45
] as:
n
=
N
(
1
+
N
e
2
)
(1)
where:
n = Sample size
N = population size
e
= Margin of Error (MoE),
e
= 0.05 Proportion of estimated sample
n
=
500
(
1
+
500
(
0.05
)
2
(2)
=
500
2.25
(3)
Sample size = 222.2 ≈ 220.
The study adopted a systematic random sampling procedure. The rationale of using the approach was to reduce the potential of human bias in the selection of the farmers with the assurance that the population will be evenly sampled [
46
]. The systematic random sampling method requires using a fixed element in selecting samples based on specific intervals until the desired sample size is achieved [
47
]. Systematically, the questionnaires were administered to every fifth farmer. The farmers could either be male or female. In a case where a farmer declined to participate, another farmer is systematically chosen.
3.4. Data Analysis
The collected data were cleaned, coded and statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 24 developed by International Business Machine (Armonk, NY, USA). Descriptive statistics were applied in evaluating the significance of the variables. The analysis and presentation were quantitative and the results were portrayed in means, percentages, Chi-squares, standard deviations, t-test, Analysis of Variance (ANOVA), and significance intervals. The hypothesized assumption was accepted or rejected using a considered statistical significance level of 0.05 (95% confidence interval).
3.5. Ethical Clearance
This study was approved by the Ethical Committee of the University of Venda (certificate number: SES/16/GGIS/05/1511), to ascertain the avoidance of harm, informed consents of the participants were obtained before the commencement of the study. Necessary permissions were obtained from the local authorities.
4. Results
4.1. Socio-Economic and Demographic Profile of the Respondents
A total of 220 farmers participated in this study as presented in
Table 1
. The breakdown indicated that 36 were certified organic farmers, 86 are transitional and 98 are non-organic farmers. The gender status result indicated a statistical significance (
p
≤ 0.001). Within the certified group, 77.8% were males, 22.2% were females. The transitional group consists of 74.4% males and 25.6% females, while in the non-certified group, the result indicated 79.6% males and 20.4% females. This does not however indicate more males than females in the province but a result of a patriarchal character that remains pervasive in most rural communities. The respondents’ age groups were classified into four categories: 21–30 years, 31–40 years, 41–50 years, and 51 years and above. There were more respondents and active farmers within the 41–50 years category at 69.4% for certified farmers, 53.4%, and 47.9% for transitional and non-certified farmers respectively. The age group category also revealed a statistical significance (
p
= 0.042).
The marital status revealed that most of the participants were married at 69.4% for certified farmers, 59.3% in the transitional group, and 60.2% for non-certified farmers. The result for educational level portrayed that most of the respondents’ in the certified and transitional farmers group had secondary school education at 58.3% and 53.4% respectively, while there were more primary school leavers at 42% in the non-certified category. The years of farming experience indicated that most of the farmers have experience of 11–20 years at 33.2%, 44.2%, and 31.6% for certified, transitional and non-certified farmers respectively. The result for land ownership shows that most of the farmers own their farming plot at 72.2% by the certified farmers, 62.8% transitional, and 63.3% by the non-certified group. The size of farmland in hectares varies among the category of the participants of the survey. Most certified farmers at 50% own 3 hectares of land, and the same for transitional at 28%. The non-certified at 38.8% own between 2 hectares of land.
Vegetables are mostly grown by all three categories of the respondents at 50%, 44.2%, and 47%. The annual farm returns indicated that R21,000 to R30,000 is most earned by the participants of the survey at 44.4% for certified farmers, 30.2% for transitional, and 26.6% for non-certified farmers. Further, there was statistical significance at 0.05 for educational level, land ownership, farm size, and type of farm produce. There was no statistical significance for marital status, farming experience, and annual income earned by the farmers.
4.2. Marketing Channels for Farm Produce
Presented in Figure 1 is the marketing channel used by the farmers. Wholesaling and retailing being used by 64 of the surveyed farmers, and other means in the following order: wholesale 42, wholesale and farmers market 32, retailing and farmers market 28, retailing 22, farmers market 18 and other means at 14 being used by the farmers.
4.3. Perceptual Statement Regarding Organic Farming
The responses of the farmers using a three-rating scale Likert-type questions are presented in Table 2 . The data shows that 82.4% of the farmers agreed that organic farming is environmentally friendly. The majority of the farmers at 92.6% believed that organic produce provides health benefits to the consumers. However, within the responses, 20% of the farmers believed that organic farming returns lower yields, even as 88.4% consider that the required standards in organic farming make it too restrictive to be practical. When practised, 86.6% agreed that organic farming produce has high profits returns even though 74.6% also agreed that certification is difficult to obtain.
4.4. Farmers’ Perceptions towards Organic Farming
From the elicited data from the respondents and to gain an insight about the perceptions of farmers regarding organic farming, the statistically analysed results as presented in
Table 3
indicated that there are no wide deviation in perception regarding the perceived benefits of organic farming at 0.721, 0.332 and 0.651 for certified, transitional and non-certified farmers respectively. The result however shows a statistical significance (
p
≤ 0.001) for the perceived benefits and organic farming. Results for other variables indicates also proximity in deviation for access to market, better farming option, improved farm image, high input costs, and cost of certification. A gap was observed in the transitional group for capital retention and economic benefits. The statistical test however indicated a significance level at 0.05 for access to market, high input cost, cost of certification and capital retention, and economic benefits. While no statistical significance was obtained for better farming options and improved farm image.
4.5. ANOVA Test for Differences in Farmers’ Perceptions of Organic Farming
In evaluating the significance of differences of the variables used in determining farmers’ perceptions regarding organic farming, a one-way ANOVA was performed to examine if the perceptual variables of the respondents could influence their perceptions of organic farming. The results as presented in Table 4 revealed that between and within groups, there was no statistical significance (0.05), for perceived benefits, access to markets, improved farm image, production costs, and capital rendition regarding organic farming. A statistical significance (0.05) was however associated with organic farming as a better farming option and cost of organic certification.
4.6. Survey of Perceived Benefits of Organic Farming by Farmers
The perceived benefits of organic farming differ among the farmers. The result as tabulated and presented in Table 5 shows that there is a statistical significance at 0.05 for premium prices for organic produce, social justice, international market (export), and climate change mitigation while no statistical significance was observed for organic and conventional markets for organic produce and domestic market (local).
4.7. Perceptual Attributes of Organic Farming
The attributes of organic farming are presented in Table 6 . The result indicated that the respondents consider quality, environmental friendliness, chemical-free, and freshness as the utmost attributes. This is followed by health and nutritional benefits, available market/consumers demand, taste, and price/cost as the pushing attributes for organic produce.
5. Discussion
The age of a farmer is one proxy factor used by scholars in determining interest and experience in farming. The majority of the farmers in the study fall within the age group of 41 to 50 years, which indicates a middle and active age group of the farmers. This age group can also be considered to be open-minded, innovative, and have more opportunities to access and adopt the technology of organic farming as a lucrative venture. This result corresponds with a study in India that found a similar age group in their study [ 48 ]. The educational level of the respondents was low with the majority attaining secondary school. This concurs with similar studies conducted in Nepal, Vietnam, and Syria [ 49 , 50 , 51 ]. The educational level of a farmer is positively associated with the adoption of organic farming because education provides key information, awareness, and a favourable attitude for the acceptance of new agricultural practices [ 52 ].
Marital status from the study indicated no statistical significance in line with the study reported by Azam & Banumathi [
53
], and Adesope et al. [
54
], but this does not truly signify that married couples cannot engage or succeed in organic farming. Years of experience in farming is a vital concern in the shift to organic farming. With most of the respondents having between 21 to 30 years of farming experience, this could pave a way for the push and more acceptance of organic farming in the province. A farmer’s experience can swing the adoption of organic farming as a more experienced farmer can cope better with organic farming compared with farmers with lesser years of farming experience [
54
,
55
].
There is a high percentage of land ownership from the study result which can influence the adoption of organic farming in the province. Landholding is an important factor in farming. Land tenure is a very sensitive issue being debated in present-day South Africa. The government is pursuing a land redistribution programme that will promote and ensure equity in land ownership. The issue of land is very fundamental as land ownership is considered a foremost hindrance to agricultural development [
56
]. The study indicated that the average farm size is between 2–3 hectares of land as farm size is proportional to land ownership. There is a positive correlation between converting to organic farming and farm size. A study in India indicated that large farm holding can result in a shift to organic farming [
57
]. More so, the fragmentation of land in the country particularly in the rural settlement has limited the expansion of large-scale farming systems and which could inhibit organic farming [
58
].
The cultivation of fruits and vegetables are the most common farming enterprise among the certified, transitional, and non-certified farmers in the province. The cultivation of organic produce will be a profitable venture in the province and beyond. It will certainly create room for more income generation through international export and domestic consumption as most consumers are now verging for organic produce. There is a steady and increase in demand for organic produce due to their health and nutritional benefits as well as other factors which include the produce being chemical-free [ 59 ]. Income earned by farmers from their products is a critical factor that may persuade farmers in adopting organic farming methods. The result of this study indicated no statistical significance on annual farm income. In literature, some scholars have mentioned a positive association between income and organic farming [ 60 , 61 ], while other studies indicated that income and profit are not favourable factors for farmers to engage in regarding organic farming [ 62 , 63 ].
Most of the farmers believed that organic farming methods cannot control weeds, diseases, and pests as organic pesticides are not readily available. This can however be overcome by the combination of indigenous, cultural practices and skills by growing varieties of crops. The management of pests and insects can be managed in biodiversity alteration through agronomic practices [
64
]. High production costs have been reported as a setback in the adventuring of organic farming. These can be adverted through the assistance of technical and production supports to the farmer. The bureaucratic processes in organic farming certification make it cumbersome for some farmers to handle. The cost of certification, the requirements, and cost to benefit ratio significantly affect farmers’ perceptions [
65
]. The perceived benefits of organic farming differ among the farmers. Some ascribed to the internal benefits such as improved farm image and income through the premium prices attached to organic produce. While for other farmers, the external benefits of market access and social justice are their priority [
66
,
67
].
Access to market and a strong network for marketing channels have a strong influence on adopting organic farming [
68
]. The perception of premium prices reflects the quality of the product and the marketing channel for trading the produce which influences smallholder farmers’ choice to adopt organic farming [
69
]. One factor affecting the perceptions of organic farmers is the perceived premium price for organic produce. This is not uncommon because most organic produce from South Africa is destined for exportation and high-value markets. A study by Harris et al. [
70
], indicated that percentage prices for organic produce are calculated higher than those from conventional produce. Thus, without such opportunity for smallholder farmers, it will be challenging to convince them about organic farming.
6. Conclusions and Policy Implications
Organic farming can play a significant and beneficial role for smallholder farmers once the critical factors are addressed. With the outlook of this study, organic farming offers good potential and opportunities for food security, income, health, and environmental benefits in Limpopo Province and South Africa. This thus accepts the stated hypothesis that farmers’ willingness to partake in organic farming is based on their perceptions, socio-economic, and other institutional factors. However, the identified challenging factors need to be addressed to pave the way for a better-oriented organic sector. Further, the study highlighted the policy options and recommendations that can greatly influence the adoption and success of the sector.
The results from the study suggest that farmers in Limpopo Province are disposed to favourable perceptions towards organic farming and perhaps willing to convert to organic practices and methods. This is likely a good pre-condition for the development of organic farming in the province and possibly the country at large. Regrettably, the conversion to organic farming is still faced with some critical factors that need to be addressed through the development of practical and implementation policies. There is a need for adequate information and knowledge regarding organic farming in the province. One of the obstacles to organic farming is the lack of information.
There is a dearth of information about organic farming production methodologies as well as market and technical information. The introduction of organic farming is inhibited by the absence of knowledge about the concept of organic farming and the management of sustainable organic production schemes. These could be overcome through education and training instruments, as organic production involves high-level skills and efficient training programmes. To shape the future of organic farming in the province, the education of the farmers will play a big role. It is recommended that government and non-governmental organisations as stakeholders can organise an educational approach such as the Famers Field Schools, a group-based approach as advocated by the Food and Agricultural Organisation as a form of adult education in agriculture.
To broaden this, awareness programmes concerning the benefits and principles of organic farming should be continuously highlighted to widen the information available. This could be achieved through print and social media. Organic markets are perceived as niche because certified organic produce fetches premium prices but this lucrative market is not easy to access because of the required standards. Although in South Africa at large, the market is robust but undeveloped because there are limited premiums for organic produce in the local markets. For the product to move in the greater value chain of the market, it is necessary that, in standards, there is no differentiation between export and local organic produce. The marketing channels are essential for long-term growth and can further be expanded whereby the products are easily accessible in supermarkets and specialised stores, even though a reasonable amount of the organic produce is sold to the public by local retailers.
A few certified organic smallholder farmers in the province through their cooperative receive some technical supports to implement the changes needed to convert to organic farming. This is however not enough to persuade other farmers. Technical supports such as best techniques and financial resources and incentive schemes should be made available to emerging farmers. The supports could be in the form of improved seedlings, bio-pesticides, organic fertiliser among others. More so, the fragmented organic sector in the country needs effective leadership that will champion the cause of the sector. A well-resourced credible organisation that is capable to advocate and represent the sector in a wide range of issues is lacking. Presently, structures within the sector advocate for their benefits and responsibilities.
It is recommended that as a sector, there is the need for an organisation that will promote harmony and unity among the stakeholders, facilitate and provide support over the establishment of a strong, credible, and unified body that will represent its interest and develop a regulatory framework to guide its principles. The body can also develop a consultative forum between the organic sector and government departments. The organisation can also help in easing the certification processes and inspections of smallholder organic farmers. The role of the organisation can also extend to ensuring the enforcement of labelling of the product such as “no-spray”. It can also extend to ensuring traceability and record-keeping of the production system as this will guarantee the quality, safety, terroir, origin of provenance, and local content as a way of campaigns and improving the marketing channels for smallholder farmers. Reform policy on land consolidation is recommended as this can push smallholder organic farmers into large-scale farmers.
Importantly, organic farming is a knowledge-intensive sector that depends on a great deal of development through research and technology. Some aspects of organic farming are still major sources of disagreement and contentions which could be laid to rest by putting more emphasis and resource through research development. Holistically, research that deals with organic production systems are needed. The research could be from a short, medium to long term agenda that can sufficiently address the production techniques and practices, soil health and fertility management, pest and disease management, processing techniques, development of appropriate and effective production inputs, nutrition analysis in both macro and micronutrients, life-cycle analysis of all production methods and the integration of indigenous knowledge systems. The study was able to determine the best strategy for the development of organic farming and filled the gap in previous studies by identifying the critical factors affecting organic farming in the country using the Limpopo Province as a case study. South Africa as a country is suffering from a decrease in organic farming, the results however postulate a positive outlook for the Limpopo Province. Also, the article proposed a policy recommendation for decision-makers and the relevant stakeholders that will help upsurge organic farming in the province.
On the study limitations and future research directions, the propositions of this study are the foundational recap of the perceptions of organic farming in South Africa, using the Limpopo Province as a case study. The results, however, cannot be generalised for the entire country as only a province was used in the study because some provinces have shown different levels of commitment in advancing organic farming through their various agricultural departments. The study results, nonetheless, reveal the insightful nature of organic farming in the country. For instance, the issue of land expropriation is synonymous all over the country. To draw a generalised inference, larger sample size may be required in a descriptive study of this nature. Again, the study relied on a systematic sampling procedure which may not denote the perceptions of all the farmers in the province. Depended upon by the study were semi-structured self-administered questionnaires which may recall bias answers from the respondents due to social desirability as some may exaggerate their knowledge and perceptions. Another limitation was due to the COVID-19 pandemic which slowed the entire research. Although, this may also be a pointer for future research as most South Africans have been looking for ways to improve their health, and thus organic food may be one of the better options to do so. Future research could steam from using a larger sample and multi-group to test the stated hypotheses using other areas and methods.
Author Contributions
Conceptualization S.E.U., Z.K. and K.S. Methodology, S.E.U., Z.K., K.S., N.S.N. and J.S. Writing—original draft preparation: S.E.U., Z.K., K.S., N.S.N. and J.S. Writing—review and editing: S.E.U., Z.K., K.S., N.S.N. and J.S. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
This study was approved by the Ethical Committee of the University of Venda (certificate number: SES/16/GGIS/05/1511).
Informed Consent Statement
The authors state that they have obtained an appropriate institutional review board outlined in the Declaration of Helsinki for all human or animal experimental investigations. A signed informed consent document has been obtained from all participants included in the study.
Data Availability Statement
Available on request from the corresponding author.
Acknowledgments
The authors acknowledge with thanks the Centre for Postgraduate Studies and the Postdoctoral Fellowship/Research Committee of the Cape Peninsula University of Technology, and the Directorate of Research and Innovations Committee of the University of Venda.
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1. Farm produce marketing channels.
Figure 1. Farm produce marketing channels.
Table 1. Socio-economic and demographic status of the respondents.
Table 1. Socio-economic and demographic status of the respondents.
Characteristics Responses (Frequency and Percentage) p -Value Certified (36) Transitional (86) Non-Certified (98) Gender <0.001 a * Male 28 (77.8) 64 (74.4) 78 (79.6) Female 08 (22.2) 22 (25.6) 20 (20.4) Age 0.042 b * 21–30 1 (2.8) 4 (4.7) 10 (10.2) 31–40 4 (11.1) 22 (25.7) 28 (28.6) 41–50 25 (69.4) 46 (53.4) 47 (48) 51 and above 6 (16.7) 14 (16.2) 13 (13.2) Marital status 0.252 a Single 4 (11.1) 12 (14) 9 (9.2) Married 25 (69.4) 51 (59.3) 59 (60.2) Divorced 4 (11.1) 11 (12.7) 7 (7.2) Widow/Widower 3 (8.4) 12 (14) 23 (23.4) Educational level 0.004 b * No formal education 0 (0) 0 (0) 18 (18.4) Primary 2 (5.6) 14 (16.2) 42 (42.8) Secondary 21 (58.3) 46 (53.4) 30 (30.6) Basic degree 7 (19.4) 16 (18.7) 5 (5.1) Postgraduate 6 (16.7) 10 (11.7) 3 (3.1) Farming experience 0.233 b Less than 5 year 2 (5.6) 8 (9.4) 16 (16.3) 6 to 10 years 6 (16.7) 14 (16.2) 26 (26.6) 11 to 20 years 12 (33.2) 38 (44.2) 31 (31.6) 21 to 30 years 10 (27.8) 12 (14) 15 (15.3) 31 and above 6 (16.7) 14 (16.2) 10 (10.2) Land ownership 0.028 b * Own land 26 (72.2) 54 (62.8) 62 (63.3) Rented 6 (16.7) 18 (21) 12 (12.2) Own and rented 4 (11.1) 14 (16.2) 24 (24.5) Farm size (Hectare) <0.001 a * ≤1 0 (0) 6 (6.9) 18 (18.4) 2 2 (5.6) 36 (41.7) 38 (38.8) 3 18 (50) 24 (28) 24 (24.5) 4 14 (38.8) 12 (14) 10 (10.2) 5 and above 2 (5.6) 8 (9.4) 8 (8.1) Type of produce 0.003 a * Fruits 10 (27.8) 22 (25.6) 28 (28.5) Vegetables 18 (50) 38 (44.2) 46 (47) Both 8 (22.2) 26 (30.2) 24 (24.5) Annual farm income # 0.582 b Less than R10,000 2 (5.6) 3 (3.4) 8 (8.1) R10,000 to R20,000 4 (11.1) 18 (21) 22 (22.4) R21,000 to R30,000 16 (44.4) 26 (30.2) 26 (26.6) R31,000 to R40,000 8 (22.2) 12 (14) 20 (20.4) R41,000 to R50,000 4 (11.1) 12 (14) 12 (12.2) R51,000 and above 2 (5.6) 15 (17.4) 10 (10.2)
# 1USD equals R15.2 at the time of the study. a Independent t test, b Chi-square test, * statistically significant <0.05.
Table 2. Distribution of perceptual statement of organic farming.
Table 2. Distribution of perceptual statement of organic farming.
Perceptual Statement Responses (%) Agree Disagree Neutral Organic farming is environmentally-friendly 82.4 10 7.6 It cannot control pests, diseases and weeds 83.8 5.6 10.6 It is more profitable than conventional farming systems 74 11.2 14.8 Organic produce has high profits returns 86.6 10.2 3.2 It is gaining popularity among local farmers 82.8 15 2.2 Required standards make it too restrictive to be practical 88.4 8.2 3.4 It is a thrilling new challenge to switch to organic farming 50.8 38.6 10.6 It provides the chance to make good use of farming skills 60.4 37.1 2.5 It requires high production costs 78.4 20.3 1.3 The method is labour intensive 56.8 33.2 10 There is high market competition for organic produce 72 22 6 Organic farming returns lower yields 20 60 20 Certification is difficult to obtain 74.6 15.2 10.2 Organic farming Cooperatives, technical support, and policies 60.5 28.5 11 It can mitigate climate change impacts 84.6 12.2 3.2 Organic produce provide health benefits to the consumers 92.6 5 2.4
Table 3. Descriptive statistics of farmers’ perceptions towards organic farming.
Table 3. Descriptive statistics of farmers’ perceptions towards organic farming.
Variables Producers Mean Standard Deviation Standard Error Mean X 2 p -Value Perceived benefits <0.001 b * Certified 1.46 0.721 0.352 18.4 Transitional 1.94 0.432 0.022 2 Non-certified 1.22 0.651 0.145 4 Access to markets 0.042 a * Certified 1.53 0.663 0.211 22.4 Transitional 1.92 0.482 0.171 3 Non-certified 1.33 0.398 0.120 1 Better farming option 0.072 a Certified 1.29 0.648 0.241 22 Transitional 1.47 0.532 0.276 6 Non-certified 1.32 0.982 0.189 6 Improved farm image 0.942 b Certified 1.78 0.498 0.025 12 Transitional 1.52 0.673 0.199 1 Non-certified 1.21 0.745 0.251 4 High input costs 0.021 b * Certified 1.82 0.341 0.126 14 Transitional 1.43 0.428 0.173 4 Non-certified 1.62 0.584 0.277 2 Cost of certification <0.001 b * Certified 1.37 0.554 0.019 21 Transitional 1.43 0.613 0.211 3 Non-certified 1.27 0.429 0.118 1 Capital retention/economic benefits Certified 1.24 0.342 0.132 16 <0.001 a * Transitional 1.44 0.081 0.182 4 Non-certified 1.18 0.627 0.662 3
a Independent t test, b Chi-square test, * statistically significant < 0.05.
Table 4. ANOVA results on perceptual variables of organic farming in the study.
Table 4. ANOVA results on perceptual variables of organic farming in the study.
Table 5. Descriptive statistics of perceived benefits of organic farming by farmers.
Table 5. Descriptive statistics of perceived benefits of organic farming by farmers.
Benefits Mean Standard Deviation Standard Error Mean X 2 p -Value Premium prices 0.86 0.521 0.024 12.62 0.022 Organic and conventional markets 1.42 0.628 0.064 36.4 0.064 Social justice 1.68 0.332 0.051 28.6 0.044 International market (export) 1.32 0.155 0.032 12.2 0.028 Domestic market (local) 1.28 0.082 0.039 8.63 0.642 Climate change mitigation 1.46 0.122 0.024 12.84 0.034
Table 6. Perceptions of organic produce by farmers (Certified, Transitional and Non-certified).
Table 6. Perceptions of organic produce by farmers (Certified, Transitional and Non-certified).
Attributes Responses High Medium Low Taste 188 28 4 Quality 208 10 2 Price/Cost 178 32 10 Health and nutritional benefits 192 20 8 Chemical-free 200 14 6 Environmental friendliness 206 10 4 Freshness 200 12 8 Available market/Consumers’ demand 190 26 4
Uhunamure SE, Kom Z, Shale K, Nethengwe NS, Steyn J. Perceptions of Smallholder Farmers towards Organic Farming in South Africa. Agriculture. 2021; 11(11):1157.
https://doi.org/10.3390/agriculture11111157
Chicago/Turabian Style
Uhunamure, Solomon Eghosa, Zongho Kom, Karabo Shale, Nthaduleni Samuel Nethengwe, and Jacobus Steyn. 2021. "Perceptions of Smallholder Farmers towards Organic Farming in South Africa" Agriculture11, no. 11: 1157.
https://doi.org/10.3390/agriculture11111157
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here .
Uhunamure SE, Kom Z, Shale K, Nethengwe NS, Steyn J. Perceptions of Smallholder Farmers towards Organic Farming in South Africa. Agriculture. 2021; 11(11):1157.
https://doi.org/10.3390/agriculture11111157
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here .
| https://www.mdpi.com/2077-0472/11/11/1157 |
Marine Drugs | Free Full-Text | Natural Benzo/Acetophenones as Leads for New Synthetic Acetophenone Hybrids Containing a 1,2,3-Triazole Ring as Potential Antifouling Agents
Marine biofouling is a natural process that represents major economic, environmental, and health concerns. Some booster biocides have been used in biofouling control, however, they were found to accumulate in environmental compartments, showing negative effects on marine organisms. Therefore, it is urgent to develop new eco-friendly alternatives. Phenyl ketones, such as benzophenones and acetophenones, have been described as modulators of several biological activities, including antifouling activity (AF). In this work, acetophenones were combined with other chemical substrates through a 1,2,3-triazole ring, a strategy commonly used in Medicinal Chemistry. In our approach, a library of 14 new acetophenone–triazole hybrids was obtained through the copper(I)-catalyzed alkyne-azide cycloaddition “click” reaction. All of the synthesized compounds were evaluated against the settlement of a representative macrofouling species, Mytilus galloprovincialis, as well as on biofilm-forming marine microorganisms, including bacteria and fungi. The growth of the microalgae Navicula sp. was also evaluated after exposure to the most promising compounds. While compounds 6a, 7a, and 9a caused significant inhibition of the settlement of mussel larvae, compounds 3b, 4b, and 7b were able to inhibit Roseobacter litoralis bacterial biofilm growth. Interestingly, acetophenone 7a displayed activity against both mussel larvae and the microalgae Navicula sp., suggesting a complementary action of this compound against macro- and microfouling species. The most potent compounds (6a, 7a, and 9a) also showed to be less toxic to the non-target species Artemia salina than the biocide Econea®. Regarding both AF potency and ecotoxicity activity evaluation, acetophenones 7a and 9a were put forward in this work as promising eco-friendly AF agents.
Natural Benzo/Acetophenones as Leads for New Synthetic Acetophenone Hybrids Containing a 1,2,3-Triazole Ring as Potential Antifouling Agents
Madalena Pinto 1,2 ,
Emília Sousa 1,2 ,
Joana R. Almeida 2,* ,
Honorina Cidade 1,2,* and
Marta Correia-da-Silva 1,2
1
Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
2
CIIMAR—Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida General Norton de Matos, 4450-208 Matosinhos, Portugal
3
Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
4
Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4069-007 Porto, Portugal
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Mar. Drugs 2021 , 19 (12), 682; https://doi.org/10.3390/md19120682
Received: 29 October 2021 / Revised: 23 November 2021 / Accepted: 25 November 2021 / Published: 29 November 2021
(This article belongs to the Special Issue Marine Benzophenones and Xanthones: Isolation and Synthesis )
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Abstract
:
Marine biofouling is a natural process that represents major economic, environmental, and health concerns. Some booster biocides have been used in biofouling control, however, they were found to accumulate in environmental compartments, showing negative effects on marine organisms. Therefore, it is urgent to develop new eco-friendly alternatives. Phenyl ketones, such as benzophenones and acetophenones, have been described as modulators of several biological activities, including antifouling activity (AF). In this work, acetophenones were combined with other chemical substrates through a 1,2,3-triazole ring, a strategy commonly used in Medicinal Chemistry. In our approach, a library of 14 new acetophenone–triazole hybrids was obtained through the copper(I)-catalyzed alkyne-azide cycloaddition “click” reaction. All of the synthesized compounds were evaluated against the settlement of a representative macrofouling species,
Mytilus galloprovincialis
, as well as on biofilm-forming marine microorganisms, including bacteria and fungi. The growth of the microalgae
Navicula
sp. was also evaluated after exposure to the most promising compounds. While compounds
6a, 7a
, and
9a
caused significant inhibition of the settlement of mussel larvae, compounds
3b
,
4b
, and
7b
were able to inhibit
Roseobacter litoralis
bacterial biofilm growth. Interestingly, acetophenone
7a
displayed activity against both mussel larvae and the microalgae
Navicula
sp., suggesting a complementary action of this compound against macro- and microfouling species. The most potent compounds (
6a
,
7a
, and
9a
) also showed to be less toxic to the non-target species
Artemia salina
than the biocide Econea
®
. Regarding both AF potency and ecotoxicity activity evaluation, acetophenones
7a
and
9a
were put forward in this work as promising eco-friendly AF agents.
Keywords:
acetophenones
;
1,2,3-triazole
;
click chemistry
;
antifouling
;
ecotoxicity
;
eco-friendly
Graphical Abstract
1. Introduction
Biofouling is an inevitable natural phenomenon that occurs continually on marine vessels and other submerged structures. Propulsive fuel increase, required to overcome the increased drag created by fouled hulls, constitutes significant costs for the maritime industry, and there is a substantial industrial and commercial interest in controlling the biofouling process, namely by dry-docking, scraping, and re-painting hulls [ 1 ].
The natural process of marine biofouling starts with the deposition of organic material that encourages the attachment of marine bacteria, diatoms, and fungi, and the colonization of macroorganisms, such as macroalgae, sponges, cnidarians, polychaetes, mollusks, barnacles, bryozoans, and tunicates [ 2 ]. Therefore, it is important to target diverse levels of fouling when trying to efficiently combat biofouling.
Antifouling (AF) coatings, used to prevent biofouling, are of great environmental concern. Biocides, after being released from the AF coating, can accumulate in the environment, predominantly in areas where there is intense boating activity. Most biocides are persistent and do not undergo degradation rapidly, bioaccumulating through the food chain and showing negative effects in marine organisms. The deposition in sediments is also a concern, as they will be continually released into the water. Therefore, there is a renewed effort to develop harmless alternatives. In addition to the search of new eco-friendly AF agents, other technologies to prevent marine biofouling have been developed, such as silicone polymer AF coatings, biomimetic AF coatings, or photocatalytic AF coatings; however, these technologies are hard to apply. Therefore, the development of AF compounds with low environmental impact remains one of the most useful strategies in the development of new effective AF coatings [
3
].
In recent years, marine phenyl ketones, such as benzophenones A – D , have been reported in the literature as antibacterial and antifungal agents ( Figure 1 ) [ 4 , 5 , 6 ]. Moreover, the benzophenone scaffold has been used for the preparation of some AF coatings ( E , Figure 1 ) [ 7 ]. Molecular simplification of the benzophenone structure has also been applied in the development of promising AF agents: 2,4-dihydroxyacetophenone ( F , Figure 1 ) was shown to significantly inhibit the spore attachment of a green fouling alga ( Ulva pertusa ) and, after being incorporated in a controlled depletion paint, a significant decrease in fouling biomass was observed [ 8 ]. Therefore, phenyl ketones, such as benzophenones and acetophenones, show potential as new leads to develop eco-friendly and sustainable AF agents for the marine industry.
In this work, several acetophenones were synthesized, and the AF activity was assessed against the settlement of
Mytilus galloprovincialis
, a heavy macrofouler, five strains of biofilm-forming marine bacteria (
Cobetia marina
,
Vibrio harveyi
,
Pseudoalteromonas atlantica
,
Halomonas aquamarina
, and
Roseobacter litoralis
), a marine diatom (
Navicula
sp.), and three fungal strains (
Candida albicans
,
Aspergillus fumigatus
, and
Trichophyton rubrum
). The ecotoxicity and bioaccumulative potential of the most promising compounds was also evaluated in the discovery of eco-friendly compounds.
2. Results and Discussion
2.1. Synthesis and Structure Elucidation
Combining different bioactive ligands/pharmacophores into a single molecule is a strategy currently employed in Medicinal Chemistry even for AF activity [ 9 , 10 ]. Triazole derivatives have undeniable importance in Medicinal Chemistry, displaying several bioactivities, such as antimicrobial, which includes the family of the so-called “azoles” used in the treatment of fungal infections [ 11 ]. The incorporation of a 1,2,3-triazole ring in the benzophenone and acetophenone scaffolds was used to generate compounds with antimicrobial activity [ 12 , 13 ]. Moreover, the presence of triazoles was already associated to AF activity of biocides [ 14 ]. For instance, bromotyramine hybrids containing a 1,2,3-triazole ring were described as inhibitors of biofilm formed by marine bacteria [ 15 ]. Recently, previous research developed by our group has identified a chalcone glycoside with a 1,2,3-triazole moiety with promising AF activity against macro and microfouling species, without ecotoxicity to a non-target marine organism [ 16 ].
Based on these data, and considering the importance of both 1,2,3-triazole and benzo/acetophenone moieties, a series of 14 new 1,2,3-triazole tethered acetophenones ( 3a – 9b ) was synthesized ( Figure 2 ).
The 1,2,3-triazoles are easily obtained through the copper-catalyzed alkyne-azide Huisgen cycloaddition (CuAAC) reaction, a well-known example of a class of chemical reactions called “click reactions” [ 17 , 18 ]. The first step to obtaining triazole-linked acetophenone derivatives 3a – 9b was the propargylation of acetophenones 1a and 1b with propargyl bromide, in the presence of either anhydrous CsCO 3 or K 2 CO 3 , respectively, which gave compounds 2a and 2b in 84% and 76% yield, respectively ( Scheme 1 ).
The incorporation of the triazole was accomplished by the CuAAC reaction ( Table 1 ). To obtain structure–activity relationship (SAR) information, several structure-related acetophenones with diversified substitution patterns were explored: aromatic nitriles ( 3a and 3b ), since isocyanides, their isomers, were extensively studied in AF activity [ 19 ]; aromatic halogens to combine with acetophenones ( 4a – 6b ) and obtain 1,4 disubstituted 1,2,3-triazoles as the literature reports hybrids with these substitutions as having antimicrobial activity [ 20 , 21 , 22 ]; and the other two substituents, namely an aliphatic alcohol ( 7a and 7b ) and a glucose acetamide ( 9a and 9b ) were also included for SAR studies.
Acetophenones 2a and 2b reacted with the selected azides in the presence of catalytically copper (I) ions formed by the reduction of copper (II) from CuSO 4 by sodium ascorbate, to afford derivatives 3a – 9b in 30–84% yields ( Table 1 ).
The newly synthesized compounds 3a – 9b were characterized by infrared spectroscopy (IR), nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS) ( Supplementary material, Figures S1–S28 ). Compounds 2a and 2b were already described in the literature and NMR data are in accordance with the data already published [ 23 , 24 ].
The NMR spectra of compounds
3a
–
9b
showed the characteristic signals of the acetophenone scaffold. The signals corresponding to the triazole ring were also observed (δ
H
-triazole: 7.71–9.00 s, δ
C
-H triazole: 134.7–145.8 and 118.2–121.2). Regarding compounds
3a
–
6b
,
8a
, and
8b
, signals corresponding to the aromatic protons were observed. Additionally, a carbon signal corresponding to C≡N (δ
C
118.2 and 118.6, respectively) was observed for compounds
3a
and
3b
. The NMR spectra of compounds
9a
and
9b
showed several proton and carbon signals corresponding to the acetamide glucose moiety. Aliphatic protons and carbons were observed in the NMR spectra of compounds
7a
and
7b
, and proton and carbons signals assigned to the methoxy group of compounds
8a
and
8b
were observed in the NMR spectra of these compounds.
2.2. Mussel Larvae Anti-Settlement Activity
The presence of macrofouling species has a dominant influence on ship drag [
25
], increasing fuel consumption. The larvae of some species of bryozoans, polychaetes, mollusks, and some other biofoulers may adhere even before biofilm formation. Mussel plantigrade larvae are highly specialized in adhesion to the submerged surfaces and the fixation is made through the production of byssal threads. Therefore, mussel plantigrade larvae were selected to assess the AF activity of the newly synthesized 1,2,3-triazolylacetophenones (
3a
–
9b
). The ability of the synthesized compounds to inhibit the settlement of
Mytilus galloprovincialis
larvae was first screened at 50 μM (
Figure 3
).
Among the 14 tested compounds, 6a , 7a , and 9a presented a percentage of settlement ≤ 40% and were selected as positive hits for dose–response studies to determine the EC 50 and LC 50 /EC 50 values regarding anti-settlement activity ( Table 2 ). In general, when comparing the results of compounds with the same substitution on the 1,2,3-triazole ring, it was found that the presence of two methoxy groups at C-3′ and C-5′ on the phenyl ketone core is more beneficial for the mussel larvae anti-settlement activity than the presence of hydroxyl groups at C-2′.
The three compounds presented an EC 50 < 25 µg·mL −1 , a value recommended by the U.S. Navy program for anti-foulants [ 26 ]. Acetophenone derivative 9a (EC 50 = 9.94 µg·mL −1 ), containing an acetamide glucose moiety was the most effective larval settlement inhibitor, followed by compounds 6a (EC 50 = 11.20 µg·mL −1 ) with an aromatic chlorine, and 7a (EC 50 = 13.46 µg·mL −1 ) with an aliphatic alcohol. Considering toxicity, none of these compounds caused mortality to the target species M. galloprovincialis plantigrades to the highest concentration tested (200 μM).
2.3. Biofilm-Forming Marine Microorganism Growth Inhibitory Activity
The settlement of some macroorganisms might be enhanced by the presence of microbial biofilms present in submerged surfaces [
27
]. Microbial biofilms composed of bacteria, fungi, diatoms, unicellular algae, and protozoa, represent an important component of fouling communities. Therefore, synthesized acetophenones were also evaluated for their ability to inhibit the growth of marine biofilm-forming bacteria (
Vibrio harveyi
,
Cobetia marina
,
Halomonas aquamarina
,
Pseudoalteromonas atlantica,
and
Roseobacter litoralis
), fungi (
Candida albicans
,
Aspergillus fumigatus
, and
Trichophyton rubrum),
and microalgae (
Navicula
sp.). Results showed that compounds
3b
,
4b
, and
7b
were able to significantly inhibit
R. litoralis
biofilm growth (
Figure 4
A). In contrast to the mussel larvae anti-settlement activity, the presence of hydroxyl groups at C-2′ on the phenyl ketone core seems to be more beneficial for the antibacterial activity.
The dose–response activities of 3b and 4b were the most relevant, with an EC 50 of 49.81 µM; 17.35 µg·mL −1 (CI: 39.99–65.63) and 105.02 µM; 34.38 µg·mL −1 (CI: 67.05–235.78), respectively ( Figure 4 B). EC 50 was not possible to estimate for compound 7b , given the low activity at the higher concentrations tested.
Fungi are also important players in the marine biofouling colonization cascade, as they are also able to produce biofilms. Therefore, to evaluate the AF potential of compounds 3a – 9b against microfouling species, their antifungal activity was evaluated against three biofilm-forming fungi species, Candida albicans [ 28 ], Aspergillus fumigatus [ 29 ], and Trichophyton rubrum [ 30 ], by determining minimum inhibitory concentration (MIC). None of the compounds tested showed activity against the fungal strains, with MICs higher than the maximum tested concentration (128 µg·mL −1 ).
Marine diatoms colonize very quickly and effectively submerged surfaces by secreting adhesive extracellular polymer substances, and thus are a good representative of fouling microalgae. The ability to inhibit the growth of the biofilm-forming marine diatom
Navicula
sp. was also evaluated but only for compounds with the most significant AF activity (
6a
,
7a
, and
9a
). From the three tested compounds, acetophenone
7a
showed inhibitory activity against
Navicula
sp. growth (
Figure 5
), with an EC
50
of 26.73 µM; 8.96 µg·mL
−1
(CI: 14.25–111.86). The activity obtained for this compound against
Navicula
sp., as well as the anti-settlement of the macrofouling species
M. galloprovincialis,
suggests a complementary action of
7a
at different levels of the biofouling process, reinforcing its potential as an AF agent.
2.4. Artemia Salina Ecotoxicity Bioassay
The most active compounds ( 6a , 7a , and 9a ,) were further submitted to ecotoxicity assays against non-target organisms. The standard ecotoxicity bioassay using the brine shrimp Artemia salina was used due to its easy culture, short generation time, cosmopolitan distribution, and commercial availability of their eggs in the latent form [ 31 , 32 ]. All tested compounds were found to be less toxic to Artemia salina at both concentrations tested (25 and 50 μM) than the commercial biocide ECONEA ® (100% lethality) [ 33 ], being acetophenones 7a and 9a mortality rates not significantly different from negative control ( Figure 6 ).
2.5. In Silico Evaluation of Bioaccumulation Potential
One of the major concerns on new AF agents is the potential bioaccumulation in marine organisms. Compounds are considered potential bioaccumulative if the LogKow (octanol-water partition coefficient) is higher or equal to 3. Therefore, in silico prediction of LogKow values was calculated for the most promising compounds 7a and 9a . Both compounds presented a LogKow value lower than 3 (0.38 for 7a and −2.32 for 9a ), suggesting their low potential for bioaccumulation [ 34 ].
3. Materials and Methods
3.1. General Methods
Reactions were monitored by analytical thin-layer chromatography (TLC). Purifications of compounds were carried out by flash column chromatography using Macherey-Nagel silica gel 60 (0.04–0.063 mm) and crystallization. Melting points were obtained in a Köfler microscope and are uncorrected.
1
H and
13
C NMR spectra were taken in CDCl
3
or DMSO-d
6
at room temperature, on Bruker Avance 300 instruments (300.13 MHz for
1
H and 75.47 MHz for
13
C). Chemical shifts are expressed in δ (ppm) values relative to tetramethylsilane (TMS) as an internal reference;
13
C NMR assignments were made by 2D (HSQC and HMBC) NMR experiments (long-range
13
C–
1
H coupling constants were optimized to 7 Hz). HRMS mass spectra were performed on an ApexQe FT-ICR MS (Bruker Daltonics, Billerica, MA, USA), equipped with a 7T actively shielded magnet, at C.A.C.T.I. University of Vigo, Spain. Ions were generated using a Combi MALDI-electrospray ionization (ESI) source. Acetosyringone was purchased from TCI. Moreover, 2,4-dihydroxyacetophenone, 80 wt% propargyl bromide in toluene, ~0.5 M solution of 4-(azidomethyl)benzonitrile in
tert
-butyl methyl ether, ~0.5 M solution of 1-azido-4-fluorobenzene in
tert
-butyl methyl ether, ~0.5 M solution of 1-azido-4-bromo benzene in
tert
-butyl methyl ether, ~0.5 M solution of 1-azido-4-chloro benzene in
tert
-butyl methyl ether, 3-azido-1-propanol, and ~0.5 M solution of 4-azidoanisole in
tert
-butyl methyl ether were purchased from Sigma-Aldrich. The 2-azidoethyl 2-acetamido-2-deoxy-
β
-
d
-glucopyranosyl azide was purchased from Synthose.
3.2. Synthesis and Structure Elucidation
3.2.1. Synthesis of Propargyloxy Acetophenone 2a and 2b
Compounds 2a and 2b were synthesized and characterized following previously reported methods and 1 H and 13 C NMR data were in accordance with the previously reported [ 24 ] and [ 16 , 23 ], respectively.
3.2.2. Synthesis of Triazolyl Acetophenones 3 a –9 b
A solution of sodium ascorbate (0.13–1.2 g, 0.64–6.0 mmol) and CuSO
4
·5H
2
O (0.10–0.75 g, 0.64–3.0 mmol) in 5 mL of water was added to a solution of 1-(3,5-dimethoxy-4-(prop-2-yn-1-yloxy)phenyl)ethan-1-one (0.15–0.35 g, 0.64–1.45 mmol) or 1-(2-hydroxy-4-(prop-2-yn-1-yloxy)phenyl)ethan-1-one (0.10–0.30 g, 0.53–1.58 mmol) in 10 mL of THF. After 10 min under stirring, the respective azide was added, and the reaction mixture was left at room temperature for 15 min to 24 h. THF was evaporated and the residue was diluted with water and extracted twice with CH
2
Cl
2
. The organic phase was dried over anhydrous sodium sulfate, filtered, and evaporated until dry.
4-((4-((4-Acetyl-2,6-dimethoxyphenoxy)methyl)-1
H
-1,2,3-triazol-1-yl)methyl)benzonitrile (
3a
). Moreover, ~0.5 M solution of 4-(azidomethyl)benzonitrile in
tert
-butyl methyl ether (1.4 mL, 0.74 mmol). The solid obtained was further purified through crystallization with ethyl acetate (0.16 g, 0.41 mmol, 65% yield). M.p. (ethyl acetate): 149.5–149.8 °C; IR (KBr) υ
max
: 3440, 3124, 3009, 2958, 2842, 2230, 1676, 1586, 1504, 1457, 1414, 1331, 1127, 955, 780 cm
−1
;
1
H NMR (CDCl
3
, 300.13 MHz) δ: 7.71 (1H, brs, H-3″), 7.66 (2H, d,
J
= 8.2 Hz, H-4‴, H-6‴), 7.32 (2H, d,
J
= 8.2 Hz, H-3‴, H-7‴), 7.18 (2H, s, H-2′, H-6′), 5.59 (2H, s, H-1‴), 5.26 (2H, s, H-1″), 3.85 (6H, s, 3′,5′-OCH
3
), 2.58 (3H, s, H-2) ppm;
13
C NMR (CDCl
3
, 75.47 MHz) δ: 197.0 (C1), 153.3 (C3′, C5′), 140.7 (C2″), 139.9 (C4′), 133.1 (C4‴, C6‴), 133.0 (C1′), 128.5 (C3‴, C7‴), 118.2 (C3″, 5‴-CN), 112.9 (C5‴), 105.8 (C2′, C6′), 66.4 (C1″), 56.4 (3′,5′-OCH
3
), 53.6 (C1‴), 26.5 (C2) ppm; HRMS (ESI
+
)
m
/
z
calcd. for C
21
H
21
N
4
O
4
[M + H
+
] 393.1557, found 393.1552.
4-((4-((4-Acetyl-3-hydroxyphenoxy)methyl)-1
H
-1,2,3-triazol-1-yl)methyl)benzonitrile (
3b
). ~0.5 M Solution of 4-(azidomethyl)benzonitrile in
tert
-butyl methyl ether (1.06 mL, 0.53 mmol). The obtained solid was purified through flash column chromatography (
n
-hexane:ethyl acetate, 7:3) (0.154 g, 0.44 mmol, 84% yield). M.p. (
n
-hexane:ethyl acetate): 153.8–155.6 °C; IR (KBr) υ
max
: 3410, 3124, 3084, 2935, 2880, 2232, 1632, 1575, 1506, 1368, 1251, 850, 829 cm
−1
;
1
H NMR (DMSO-d
6
, 300.13 MHz) δ: 12.62 (1H, s, OH-2′), 8.37 (1H, s, H-3″), 7.86 (2H, d,
J
= 8.2 Hz, H-4‴, H-6‴), 7.84 (1H, d,
J
= 8.7 Hz, H-6′), 7.47 (2H, d,
J
= 8.2 Hz, H-3‴, H-7‴), 6.62–6.57 (2H, m, H-3′, H-5′), 5.75 (2H, s, H-1‴), 5.23 (2H, s, H-1″), 2.56 (3H, s, H-2) ppm;
13
C NMR (DMSO-d
6
, 75.47 MHz) δ: 203.3 (C1), 164.4, 164.0 (C2′, C4′), 142.5 (C2″), 141.4 (C2‴), 133.4 (C6′), 132.8 (C4‴, C6‴), 128.8 (C3‴, C7‴), 125.4 (C3″), 118.6 (5‴-CN), 114.0 (C1′), 111.0 (C5‴), 107.7 (C5′), 101.7 (C3′), 61.5 (C1″), 52.3 (C1‴), 26.7 (C2) ppm; HRMS (ESI
+
)
m
/
z
calcd. for C
19
H
17
N
4
O
3
[M + H
+
] 349.1295, found 349.1291.
1-(4-((1-(4-Fluorophenyl)-1
H
-1,2,3-triazol-4-yl)methoxy)-3,5-dimethoxyphenyl)ethan-1-one (
4a
). ~0.5 M Solution of 1-azido-4-fluorobenzene in
tert
-butyl methyl ether (1.8 mL, 0.896 mmol). The solid obtained was further purified through crystallization with acetone (0.128 g, 0.33 mmol, 53% yield). M.p. (acetone): 160.0–160.5 °C; IR (KBr) υ
max
: 3446, 3152, 3075, 2940, 2842, 1669, 1589, 1558, 1521, 1466, 1413, 1359, 1334, 1225, 1130, 964, 846, 612 cm
−1
;
1
H NMR (CDCl
3
, 300.13 MHz) δ: 8.14 (1H, s, H-3″), 7.70 (2H, dd,
J
= 4.5 and 8.8 Hz, H-2‴, H-6‴), 7.25–7.20 (4H, m, H-3‴, H-5‴, H-2′, H-6′), 5.34 (2H, s, H-1″), 3.91 (6H, 3′,5′-OCH
3
), 2.59 (3H, s, H-2) ppm.
13
C NMR (CDCl
3
, 75.47 MHz) δ: 197.1 (C1), 162.6 (d,
J
= 248.9 Hz, C4‴), 153.3 (C3′, C5′), 145.8 (C2″), 140.8 (C4′), 133.5 (C1‴), 133.2 (C1′), 122.7 (d,
J
= 8.7 Hz, C2‴, C6‴), 121.6 (C3″), 116.9 (d,
J
= 23.2 Hz, C3‴, C5‴), 105.8 (C2′, C6′), 66.6 (C1″), 56.5 (3′,5′-OCH
3
), 26.6 (C2) ppm; HRMS (ESI
+
)
m
/
z
calcd. for C
19
H
18
FN
3
NaO
4
[M + Na
+
] 394.1174, found 394.1158.
1-(4-((1-(4-Fluorophenyl)-1
H
-1,2,3-triazol-4-yl)methoxy)-2-hydroxyphenyl)ethan-1-one (
4b
). ~0.5 M Solution of 1-azido-4-fluorobenzene in
tert
-butyl methyl ether (3.19 mL, 1.59 mmol). The obtained solid was purified through flash column chromatography (
n
-hexane:ethyl acetate, 8:2) (0.429 g, 1.31 mmol, 83% yield). M.p. (
n
-hexane:ethyl acetate): 145.9–148.0 °C; IR (KBr) υ
max
: 3129, 3079, 2961, 1923, 1884, 1629, 1518, 1458, 1253, 1231, 1066, 835, 810 cm
−1
;
1
H NMR (CDCl
3
, 300.13 MHz) δ: 12.71 (1H, s, OH-2′), 8.03 (1H, s, H-3″), 7.74–7.65 (3H, m, H-6′, H-2‴, H-6‴), 7.26–7.20 (2H, m, H-3‴, H-5‴), 6.56–6.53 (2H, m, H-3′, H-5′), 5.31 (2H, s, H-1″), 2.56 (3H, s, H-2) ppm.;
13
C NMR (CDCl
3
, 75.47 MHz) δ: 202.9 (C1), 165.2 (C2′), 164.6 (C4′), 162.7 (d,
J
= 249.8 Hz, C4‴), 144.1 (C2″), 133.2 (C1‴), 132.7 (C6′), 122.8 (d,
J
= 8.7 Hz, C2‴, C6‴), 121.4 (C3″), 117.0 (d,
J
= 23.3 Hz, C3‴, C5‴), 114.6 (C1′), 107.8 (C5′), 102.1 (C3′), 62.1 (C1″), 26.4 (C2) ppm; HRMS (ESI
+
)
m
/
z
calcd. for C
17
H
15
FN
3
O
3
[M + H
+
] 328.1092, found 328.1095.
1-(4-((1-(4-Bromophenyl)-1
H
-1,2,3-triazol-4-yl)methoxy)-3,5-dimethoxyphenyl)ethan-1-one (
5a
). ~0.5 M Solution of 1-azido-4-bromo benzene in
tert
-butyl methyl ether (1.4 mL, 0.70 mmol). The solid obtained was further purified through crystallization with acetone (0.179 g, 0.41 mmol, 65% yield). M.p. (acetone): 159.1–160.4 °C; IR (KBr) υ
max
: 3447, 3167, 3098, 3005, 2942, 2838, 1671, 1591, 1498, 1465, 1456, 1416,1357, 1330, 1220, 1204, 1128, 1023, 986, 836, 607 cm
−1
;
1
H NMR (CDCl
3
, 300.13 MHz) δ: 8.18 (1H, s, H-3″), 7.64 (4H, dd,
J
= 12.0, 9.0 Hz, H-2‴, H-3‴, H-5‴, H-6‴), 7.21 (2H, s, H-2′, H-6′), 5.34 (2H, s, H-1″), 3.91 (6H, s, 3′,5′-OCH
3
), 2.59 (3H, s, H-2) ppm;
13
C NMR (CDCl
3
, 75.47 MHz) δ: 197.0 (C1), 153.3 (C3′, C5′), 146.0 (C2″), 140.8 (C4′), 136.2 (C1‴), 133.2 (C1′), 133.1 (C3‴, C5‴), 122.6 (C3″), 122.0 (C2‴, C6‴), 121.3, (C4‴), 105.8 (C2′, C6′), 66.5 (C1″), 56.4 (3′,5′-OCH
3
), 26.6 (C2) ppm; HRMS (ESI
+
)
m
/
z
calcd. for C
19
H
19
BrN
3
O
4
[M + H
+
] 432.0553, found 432.0556.
1-(4-((1-(4-Bromophenyl)-1
H
-1,2,3-triazol-4-yl)methoxy)-2-hydroxyphenyl)ethan-1-one (
5b
). ~0.5 M Solution of 1-azido-4-bromobenzene in
tert
-butyl methyl ether (2.89 mL, 1.45 mmol). The obtained solid was purified through flash column chromatography (
n
-hexane:ethyl acetate, 8:2) (0.21 g, 0.54 mmol, 41% yield). M.p. (
n
-hexane:ethyl acetate): 183.3–184.8 °C; IR (KBr) υ
max
: 3138, 3101, 3068, 2920, 2865, 1647, 1618, 1585, 1267, 1169, 837, 783 cm
−1
;
1
H NMR (DMSO-d
6
, 300.13 MHz) δ: 12.63 (1H, s, OH-2′), 9.00 (1H, s, H-3″), 7.90 (2H, d,
J
= 8.7 Hz, H-2‴, H-6‴), 7.87 (1H, d,
J
= 7.9 Hz, H-6′), 7.81 (2H, d,
J
= 8.9 Hz, H-3‴, H-5‴), 6.67–6.62 (2H, m, H-3′, H-5′), 5.33 (2H, s, H-1″), 2.57 (3H, s, H-2) ppm;
13
C NMR (DMSO-d
6
, 75.47 MHz) δ: 203.3 (C1), 164.3, 164.0 (C2′, C4′), 143.4 (C2″), 135.8 (C1‴), 133.5 (C6′), 132.9 (C3‴, C5‴), 123.2 (C3″), 122.2 (C2‴, C6‴), 121.6 (C4‴), 114.1 (C1′), 107.7 (C5′), 101.7 (C3′), 61.4 (C1″), 26.7 (C2) ppm; HRMS (ESI
+
)
m
/
z
calcd. for C
17
H
15
BrN
3
O
3
[M + H
+
] 388.0291, found 388.0292.
1-(4-((1-(4-Chlorophenyl)-1
H
-1,2,3-triazol-4-yl)methoxy)-3,5-dimethoxyphenyl)ethan-1-one (
6a
). ~0.5 M Solution of 1-azido-4-chloro benzene in
tert
-butyl methyl ether (1.4 mL, 0.70 mmol). The solid obtained was further purified through crystallization with acetone (0.12 g, 0.30 mmol, 47% yield). M.p. (acetone): 152.0–153.7 °C; IR (KBr) υ
max
: 3442, 3140, 2962, 2839, 1678, 1588, 1500, 1457, 1415, 1354, 1330, 1229, 1128, 956, 831, 608 cm
−1
;
1
H NMR (CDCl
3
, 300.13 MHz) δ: 8.22 (1, s, H-3″), 7.69 (2H, d,
J
= 8.8 Hz, H-2‴, H-6‴), 7.51 (2H, d,
J
= 8.7 Hz, H-3‴, H-5‴), 7.22 (2H, s, H-2′, H-6′), 5.34 (2H, s, H-1″), 3.91 (6H, s, 3′,5′-OCH
3
), 2.59 (3H, s, H-2) ppm;
13
C NMR (CDCl
3
, 75.47 MHz) δ: 197.0 (C1), 153.3 (C3′, C5′), 140.8 (C4′), 134.7 (C2″), 133.2 (C1‴), 130.2 (C4‴), 121.9 (C3″, C2‴, C6‴), 105.8 (C2′, C6′), 66.4 (C1″), 56.4 (3′,5′-OCH
3
), 26.6 (C2) ppm; HRMS (ESI
+
)
m
/
z
calcd. for C
19
H
19
ClN
3
O
4
[M + H
+
] 388.1059, found 388.1055.
1-(4-((1-(4-Chlorophenyl)-1
H
-1,2,3-triazol-4-yl)methoxy)-2-hydroxyphenyl)ethan-1-one (
6b
). ~0.5 M Solution of 1-azido-4-chlorobenzene in
tert
-butyl methyl ether (3.19 mL, 1.59 mmol). The obtained solid was purified through flash column chromatography (
n
-hexane:ethyl acetate, 8:2) (0.277 g, 0.81 mmol, 61% yield). M.p. (
n
-hexane:ethyl acetate): 157.0–159.1 °C; IR (KBr) υ
max
: 3445, 3139, 3102, 3070, 1651, 1621, 1504, 1369, 1348, 1266, 840, 783 cm
−1
;
1
H NMR (CDCl
3
, 300.13 MHz) δ: 12.71 (1H, s, OH-2′), 8.05 (1H, s, H-3″), 7.70 (2H, d,
J
= 8.8 Hz, H-2‴, H-6‴), 7.66 (1H, d,
J
= 9.7 Hz, H-6′), 7.51 (2H, d,
J
= 8.7 Hz, H-3‴, H-5‴), 6.57–6.53 (2H, m, H-3′, H-5′), 5.31 (2H, s, H-1″), 2.56 (3H, s, H-2) ppm;
13
C NMR (CDCl
3
, 75.47 MHz) δ: 202.9 (C1), 165.2 (C2′), 164.4 (C4′), 144.3 (C2″), 135.5 (C1‴), 135.0 (C4‴), 132.7 (C6′), 130.2 (C3‴, C5‴), 121.9 (C2‴, C6‴), 121.2 (C3″), 114.6 (C1′), 107.8 (C5′), 102.2 (C3′), 62.1 (C1″), 26.4 (C2) ppm; HRMS (ESI
+
)
m
/
z
calcd. for C
17
H
15
ClN
3
O
3
[M + H
+
] 344.0796, found 344.0797.
1-(4-((1-(3-Hydroxypropyl)-1
H
-1,2,3-triazol-4-yl)methoxy)-3,5-dimethoxyphenyl)ethan-1-one (
7a
). 3-Azido-1-propanol (0.66 mL, 0.768 mmol); The solid obtained was further purified through crystallization with ethyl acetate and flash column chromatography (chloroform:acetone, 8:2) (0.120 g, 0.357 mmol, 56% yield). M.p. (chloroform:acetone): 90.0–93.0 °C; IR (KBr) υ
max
: 3532, 3137, 3008, 2947, 2927, 2869, 2839, 2790, 1680, 1592, 1506, 1466, 1457, 1414, 1362, 1328, 1182, 1128, 1058, 954, 843, 816, 653, 609 cm
1-(2-Hydroxy-4-((1-(3-hydroxypropyl)-1 H -1,2,3-triazol-4-yl)methoxy)phenyl)ethan-1-one ( 7b ). 3-Azido-1-propanol (0.049 mL, 0.53 mmol); The obtained solid was purified through flash column chromatography (chloroform:methanol, 98:2). (0.061 g, 0.21 mmol, 40% yield). M.p. (chloroform:methanol): 69.2–70.5 °C; IR (KBr) υ max : 3311, 3133, 3079, 2922, 2876, 1636, 1615, 1576, 1505, 1270, 1054, 1037, 985, 959, 836, 800 cm −1 ; 1 H NMR (DMSO-d 6 , 300.13 MHz) δ: 8.25 (1H, s, H-3″), 7.85 (1H, d, J = 8.7 Hz, H-6′), 6.62 (1H, d, J = 2.4 Hz, H-3′), 6.59 (1H, dd, J = 8.7, 2.5 Hz, H-5′), 5.21 (2H, s, H-1″), 4.43 (1H, t, J = 7.1 Hz, H-1‴), 3.42–3.38 (signal under water, H-3‴), 2.57 (3H, s, H-2), 2.00–1.92 (2H, m, H-2‴) ppm; 13 C NMR (DMSO-d 6 , 75.47 MHz) δ: 203.2 (C1), 169.2, 164.4 (C4), 164.1 (C2), 141.9 (C2″), 133.4 (C6′), 124.9 (C3″), 114.0 (C1′), 107.7 (C5′), 101.6 (C3′), 61.5 (C1″), 57.9 (C3‴), 46.8 (C1‴), 32.9 (C2‴), 26.7 (C2) ppm; HRMS (ESI + ) m / z calcd. for C 14 H 18 N 3 O 4 [M + H + ] 292.1292, found 292.1298.
1-(3,5-Dimethoxy-4-((1-(4-methoxyphenyl)-1 H -1,2,3-triazol-4-yl)methoxy)phenyl)ethan-1-one ( 8a ). The solid obtained was further purified through flash column chromatography ( n -hexane:ethyl acetate, 8:2 and 7:3) (0.074 g, 0.192 mmol, 30% yield). M.p. ( n -hexane:ethyl acetate): 99.5–102.3 °C; IR (KBr) υ max : 3432, 3153, 3090, 2999, 2934, 2839, 1670, 1585, 1522, 1462, 1412, 1330, 1258, 1216, 1182, 1130, 1033, 982, 839, 827, 811, 652, 609 cm −1 ; 1 H NMR (CDCl 3 , 300.13 MHz) δ: 8.06 (1H, s, H-3″), 7.61 (2H, dd, J = 6.8, 2.1 Hz, H-2‴, H-6‴), 7.21 (2H, s, H-2′, H-6′), 7.02 (2H, dd, J = 6.7, 2.2 Hz, H-3‴, H-5‴), 5.34 (2H, s, H-1″), 3.90 (6H, s, 3′,5′-OCH 3 ), 3.87 (3H, s, 4‴-OCH 3 ), 2.59 (3H, s, H-2) ppm; 13 C NMR (CDCl 3 , 75.47 MHz) δ: 197.1 (C1), 160.0 (C4‴), 153.4 (C3′, C5′), 145.3 (C2″), 140.9 (C4′), 133.1 (C1′), 130.7 (C1‴), 122.3 (C2‴, C6‴), 121.5 (C3″), 114.9 (C-3‴, C5‴), 105.8 (C2′, C6′), 66.6 (C1″), 57.0 (3′,5′-OCH 3 ), 55.8 (4‴-OCH 3 ), 25.6 (C2) ppm; HRMS (ESI + ) m / z calcd. for C 20 H 22 N 3 O 5 [M + H + ] 384.1554, found 384.1551.
1-(2-Hydroxy-4-((1-(4-methoxyphenyl)-1 H -1,2,3-triazol-4-yl)methoxy)phenyl)ethan-1-one ( 8b ). ~0.5 M Solution of 4-azidoanisole in tert -butyl methyl ether (2.66 mL, 1.33 mmol). The obtained solid was purified through flash column chromatography ( n -hexane:ethyl acetate, 9:1) (0.179 g, 0.527 mmol, 40% yield). M.p. ( n -hexane:ethyl acetate): 115.1–117.5 °C; IR (KBr) υ max : 3448, 3134, 3097, 2922, 1645, 1444, 1307, 1187, 861, 837, 812 cm −1 ; 1 H NMR (CDCl 3 , 300.13 MHz) δ: 12.71 (1H, s, OH-2′), 7.99 (1H, s, H-3″), 7.66 (1H, d, J = 10.3 Hz, H-6′), 7.63 (2H, d, J = 9.1 Hz, H-2‴, H-6‴), 7.02 (2H, d, J = 9.0 Hz, H-3‴, H-5‴), 6.57–6.53 (2H, m, H-3′, H-5′), 5.30 (2H, s, H-1″), 3.87 (3H, s, 4‴-OCH 3 ), 2.56 (3H, s, H-2) ppm; 13 C NMR (CDCl 3 , 75.47 MHz) δ: 202.8 (C1), 165.2 (C2′), 164.7 (C4′), 160.1 (C4‴), 143.7 (C2″), 132.7 (C6′), 130.4 (C1‴), 122.4 (C2‴, C6‴), 121.5 (C3″), 115.0 (C3‴, C5‴), 114.5 (C1′), 107.8 (C5′), 102.2 (C3′), 62.2 (C1″), 26.4 (C2) ppm; HRMS (ESI + ) m / z calcd. for C 18 H 18 N 3 O 4 [M + H + ] 340.1292, found 340.1294.
N -((2 S ,3 S ,4 S ,5 R ,6 S )-2-(4-((4-Acetyl-2,6-dimethoxyphenoxy)methyl)-1 H -1,2,3-triazol-1-yl)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2 H -pyran-3-yl)acetamide ( 9a ). 2-Azidoethyl 2-acetamido-2-deoxy- β - d -glucopyranosyl azide (0.73 g, 3.0 mmol). A solid formed in the aqueous phase was filtered and washed with methanol. The solid was further purified by crystallization with methanol. Whitish solid (0.38 g, 0.79 mmol, 54% yield). dec pt: 200 °C; IR (KBr) υ max : 3354, 3126, 2960, 2879, 1680, 1646, 1589, 1551, 1466, 1330, 1202, 1178, 890 cm −1 ; 1 H NMR (DMSO-d 6 , 300.13 MHz) δ : 8.17 (1H, s, H-3″), 7.89 (1H, d, J = 9.2 Hz, 2‴-NH), 7.24 (2H, s, H-2′, H-6′), 5.72 (1H, d, J = 10.0 Hz, H-1‴), 5.29 (1H, d, J = 5.3 Hz, OH-sugar), 5.25 (1H, J = 5.5 Hz, OH-sugar), 5.04 (2H, d, J = 5.2 Hz, H-1″), 4.66 (1H, t, J = 5.7 Hz, OH-sugar), 4.08 (1H, q, J = 9.8 Hz, H-2‴), 3.85 (6H, s, 3′,5′-OCH 3 ), 3.71 (1H, m, H-6‴), 3.59–3.28 (4H, m, H-sugar), 2.58 (3H, s, H-2), 1.62 (3H, s, 2‴-COCH 3 ) ppm; 13 C NMR (DMSO-d 6 , 75.47 MHz) δ : 196.6 (C1), 168.9 (2‴-COCH 3 ), 152.6 (C3′, C5′), 142.8 (C2″), 139.9 (C4′), 132.2 (C1′), 122.8 (C3″), 105.5 (C2′, C6′), 85.7 (C1‴), 79.8 (C-sugar), 73.7 (C-sugar), 69.6 (C-sugar), 65.0 (C1″), 60.5 (C6‴), 55.8 (3′,5′-OCH 3 ), 54.1 (C2‴), 26.4 (C2), 22.5 (2‴-COCH 3 ) ppm; HRMS (ESI-TOF) m / z calcd. for C 21 H 28 N 4 O 4 Na 503.17485, found 503.17612.
N -((2 R ,3 R ,4 R ,5 S ,6 R )-2-(4-((4-Acetyl-3-hydroxyphenoxy)methyl)-1 H -1,2,3-triazol-1-yl)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2 H -pyran-3-yl)acetamide ( 9b ). 2-Azidoethyl 2-acetamido-2-deoxy-β- d -glucopyranosyl azide (0.142 g, 0.578 mmol). A solid formed in the aqueous phase was separated by filtration and washed with water. The solid was further purified by crystallization with ethanol (0.080 g, 0.183 mmol, 35% yield); dec pt: 221 °C; IR (KBr) υ max : 3320, 3089, 2908, 2850, 1655, 1620, 1522, 1375, 1073, 1057, 1047, 1030, 825, 798 cm −1 ; 1 H NMR (DMSO-d 6 , 300.13 MHz) δ: 12.62 (1H, s, OH-2′), 8.30 (1H, s, H-3″), 7.88 (1H, d, J = 9.4 Hz, 2‴-NH), 7.85 (1H, d, J = 9.2 Hz, H-6′), 6.61–6.58 (2H, m, H-3′, H-5′), 5.73 (1H, d, J = 10.0 Hz, H-1‴), 5.21 (2H, s, H-1″), 5.30–5.25 (2H, m, OH-sugar), 4.66 (1H, t, J = 6.5 Hz, OH-sugar), 4.07 (1H, q, J = 9.7 Hz, H-2‴), 3.73–3.68 (1H, m, H-sugar), 3.59–3.28 (m, H-sugar), 2.57 (3H, s, H-2), 1.61 (3H, s, 2‴-COCH 3 ) ppm; 13 C NMR (DMSO-d 6 , 75.47 MHz) δ: 203.3 (C1), 169.2 (2‴-COCH 3 ), 164.4 (C4), 164.0 (C2), 141.8 (C2″), 133.4 (C6′), 123.6 (C3″), 114.0 (C1′), 107.7 (C5′), 101.7 (C3′), 86.1 (C1‴), 80.1 (C-sugar), 74.0 (C-sugar), 69.9 (C-sugar), 61.4 (C1″), 60.7 (C6‴), 54.5 (C2‴), 26.7 (C2), 22.7 (2‴-COCH 3 ) ppm; HRMS (ESI + ) m / z calcd. for C 19 H 25 N 4 O 8 [M + H + ] 437.1667, found 437.1669.
3.3. Mussel (Mytilus galloprovincialis) Larvae Anti-Settlement Activity
Mussel ( Mytilus galloprovincialis ) plantigrades were collected in juvenile aggregates during low neap tides at Memória beach, Matosinhos, Portugal (41°13′59″ N; 8°43′28″ W). In the laboratory, mussel plantigrade larvae (0.5–2 mm) were isolated in a binocular magnifier (Olympus SZX2-ILLT, Tokyo, Japan) to a petri dish with filtered seawater, and those with functional foot and competent exploring behavior were selected to the bioassays. Compounds were screened at 50 µM in 24-well microplates with 4-well replicates per condition and 5 larvae per well, for 15 h, in the darkness at 18 ± 1 °C, according to the previously reported [ 35 , 36 ]. All compounds that caused more than 60% of settlement inhibition (≤40% of settlement) in the screening bioassay were considered active and selected for the determination of the semi-maximum response concentration that inhibited 50% of the larval settlement (EC 50 ), at compounds concentrations of 3.125, 6.25, 12.5, 25, 50, 100, and 200 μM.
3.4. Biofilm-Forming Marine Bacteria Growth Inhibitory Activity
Five strains of marine biofilm-forming bacteria from the Spanish Type Culture Collection (CECT): Cobetia marina CECT 4278, Vibrio harveyi CECT 525, Halomonas aquamarina CECT 5000, Pseudoalteromonas atlantica CECT 570, and Roseobacter litoralis CECT 5395 were selected for antibacterial screening. The experimental procedure was performed according to the previously reported [ 35 , 36 ]. Briefly, bacteria were inoculated and incubated for 24 h at 26 °C in marine broth (Difco) at an initial density of 0.1 (OD600) in 96-well flat-bottom microtiter plates and exposed to the test compounds at 15 μM. Bacterial growth inhibition in the presence of the compounds was determined in quadruplicate at 600 nm using a microplate reader (BioTek Synergy HT, Winooski, VT, USA). Negative and positive controls used were a solution of marine broth with 0.1% DMSO, and a solution of marine broth with penicillin–streptomycin–neomycin, respectively. Bacterial growth inhibition calculations were made based in the formula ((Mc–Mt)/Mc) × 100, where Mc is the mean of the four replicates from negative control, and Mt is the mean of four replicates from each of the tested compounds.
3.5. Antifungal Susceptibility Testing
The antifungal activity was evaluated against Candida albicans ATCC 10231, Aspergillus fumigatus ATCC 204305, and Trichophyton rubrum -FF5. Candida krusei ATCC 6258 was used for quality control. To guarantee the purity and viability, the strains were sub-cultured before each assay on Sabouraud dextrose agar (BioMérieux, Marcy l’Etoile, France). RPMI-1640 broth medium pH 7.0, with L-glutamine and without bicarbonate (Biochrom) and buffered with 0.165 mol·L −1 of 3-( N -morpholino)-propanesulfonic acid (MOPS, Sigma-Aldrich, St. Louis, MO, USA), was used on the evaluation of the antifungal activity. The MICs were evaluated using the broth microdilution method and in accordance with the recommendations of the Clinical and Laboratory Standards Institute (CLSI) reference documents: M27-A3 for yeasts [ 37 ] and M38-A2 [ 38 ] for filamentous fungi. Two-fold serial dilutions of compounds were prepared within the concentration range of 8–128 µg·mL −1 . Yeast cells suspensions were prepared to obtain an inoculum of 1–5 × 10 3 CFU·mL −1 . For filamentous fungi, a spore suspension is prepared, and cell density was adjusted to obtain the adequate inoculum (for dermatophytes 1–3 × 10 3 CFU·mL −1 and 0.4–5 × 10 4 CFU·mL −1 for Aspergillus fumigatus ). Equal volumes of compound dilution in RPMI and cell suspension in RPMI were added in the wells of the microplate. Controls performed were sterility control, growth control, and quality control. Quality control was performed with an ATCC reference strain ( Candida krusei ATCC 6258) with a commercial antifungal compound, voriconazole (Pfizer) ranging between 0.25–1 µg·mL −1 . The plates were incubated aerobically at 35 °C for 48 h for Candida albicans and A spergillus fumigatus and at 25 °C for 5–7 days for dermatophytes. MICs were determined as the lowest concentrations resulting in 100% growth inhibition, in comparison to the compound-free controls. All the compounds were tested independently three times.
3.6. Biofilm-Forming Marine Diatoms Growth Inhibitory Activity
The anti-microalgal activity of the most promising compounds was also evaluated against a benthic marine diatom, Navicula sp., purchased from the Spanish Collection of Algae (BEA), according to the previously reported [ 16 ]. Briefly, diatom cells were inoculated in f/2 medium (Sigma) at an initial concentration of 2–4 × 10 6 cells·mL −1 and grown in 96-well flat-bottom microtiter plates for 14 days in continuous light at 20 °C. Navicula sp. growth inhibition in the presence of each compound at 25 μM was determined in quadruplicate, and cells were counted using a Neubauer counting chamber. Growth inhibition was calculated based in the formula ((Mc–Mt)/Mc) × 100, where Mc is the mean of the cell counts of the four replicates from negative control, and Mt is the mean of the cell counts of the four replicates from each of the tested compounds. Positive control with cycloheximide (3.55 μM) and negative control with f/2 medium 0.1% DMSO were included.
3.7. Artemia Salina Ecotoxicity Bioassay
The brine shrimp ( Artemia salina ) nauplii lethality test was used to determine the ecotoxicity of 6a , 7a , and 9a to non-target organisms [ 35 ]. Briefly, Artemia salina eggs were allowed to hatch in seawater for 48 h at 25 °C. Bioassays were performed in 96-well microplates with 15–20 nauplii per well and 200 μL of the compounds test solution. Test solutions were prepared in filtered seawater at concentrations of 25 and 50 μM. All tests included K 2 Cr 2 O 7 as positive control and DMSO as a negative control. Bioassays run in the dark at 25 °C, and the percentage of mortality was determined after 48 h of exposure.
3.8. In Silico Evaluation of LogKow
Compounds are considered potentially bioaccumulative if the LogKow (octanol–water partition coefficient) is higher than 3. Therefore, the LogKow value is used as an indicator of the bioaccumulation potential of AF compounds. KOWWIN™ v1.68 (a Log octanol–water partition coefficient calculation program), developed by the United States Environmental Protection Agency (EPA) and the Syracuse Research Corporation (SRC) [ 39 ] was used for the in silico calculation of LogKow of the most active compounds in this study.
3.9. Statistical Analysis
Data from anti-settlement, antibacterial, and anti-microalgal bioassay were analyzed by one-way analysis of variance (ANOVA), followed by a multi-comparisons Dunnett’s test against negative control. For all of the bioassays, the half-maximum response concentration (EC 50 ) values for each compound, when applicable, were calculated using probit regression analysis. Significance was considered at p < 0.01, and 95% lower and upper confidence limits (95% LCL; UCL). The software IBM SPSS Statistics 26 (Armonk, New York, NY, USA) was used for statistical analysis.
4. Conclusions
Considering the biological potential of phenyl ketones and 1,2,3-triazole ring, in this work 14 acetophenone-1,2,3-triazole hybrids containing different substitution patterns were synthesized and tested for their AF activity in both macro- and microfouling species. Among them, three compounds ( 6a , 7a , and 9a ), containing methoxy groups in the phenyl ketone core with different substituents linked to the heterocyclic ring, revealed to be the most promising compounds against mussel larvae, with EC 50 values lower than 25 µg·mL −1 , while acetophenones 3b , 4b , and 7b showed some inhibitory effect against the growth of biofilm-forming bacteria Roseobacter litoralis . In addition to the activity on macrofouling species, compound 7a also showed AF activity against the microalgae Navicula sp. (EC 50 = 26.73 µM, 8.96 µg·mL −1 ), suggesting a complementary action of this compound against macro- and microfouling species. The most promising compounds of this study ( 7a and 9a ) were also shown to be non-toxic against the non-target species Artemia salina , as well as low bioaccumulative potential. The overall results highlight 7a and 9a as promising compounds, which could be considered hits for the development of effective and eco-friendly AF compounds.
Supplementary Materials
The following are available online at www.mdpi.com/1660-3397/19/12/682/s1 , Figures S1–S28: 1 H NMR, 13 C NMR and HRMS spectra of compounds 3a – 9b .
Author Contributions
Conceptualization, M.C.-d.-S. and H.C.; methodology, J.R.A., M.C.-d.-S. and H.C.; investigation, A.R.N., D.P., C.G., J.R.A., J.C. and E.P.; formal analysis, A.R.N. and D.P.; data curation, A.R.N., D.P., C.G., J.R.A., J.C. and E.P.; writing—original draft preparation, A.R.N. and D.P.; writing—review and editing, A.R.N., D.P., C.G., E.S., E.P., J.R.A., M.C.-d.-S., H.C., M.P. and V.V.; supervision, J.R.A., E.S., M.C.-d.-S. and H.C.; project administration, E.S. and J.R.A.; funding acquisition, E.S. and J.R.A.; resources, M.P. and V.V. All authors have read and agreed to the published version of the manuscript.
Funding
This research was supported by national funds through the Foundation for Science and Technology (FCT) within the scope of UIDB/04423/2020, UIDP/04423/2020, and under the projects PTDC/SAU-PUB/28736/2017 (reference POCI-01–0145-FEDER-028736) and NASCEM-PTDC/BTA-BTA/31422/2017 (POCI-01-0145-FEDER-031422), co-financed by COMPETE 2020, Portugal 2020 and the European Union through the ERDF, and by FCT through national funds, and a structured program of R&D&I ATLANTIDA (NORTE-01-0145-FEDER-000040), supported by NORTE2020, through ERDF, and CHIRALBIO ACTIVE-PI-3RL-IINFACTS-2019. A.R.N. and D.P. also acknowledge FCT for the Ph.D. scholarships (grant number SFRH/BD/114856/2016 and SFRH/BD/147207/2019, respectively).
Data Availability Statement
Data is contained within the article.
Acknowledgments
The authors thank Sara Cravo for all of the technical support.
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1. Some benzo/acetophenones with promising antimicrobial and AF activities.
Figure 1. Some benzo/acetophenones with promising antimicrobial and AF activities.
Figure 2. Structures of compounds 3a – 9b .
Figure 2. Structures of compounds 3a – 9b .
Scheme 1. Synthesis of propargyl acetophenones 2a and 2b . a ) CsCO 3 , acetone, reflux, 3 h, 84% yield; b ) K 2 CO 3 , acetone, reflux, 3 h, 76% yield.
Scheme 1. Synthesis of propargyl acetophenones 2a and 2b . a ) CsCO 3 , acetone, reflux, 3 h, 84% yield; b ) K 2 CO 3 , acetone, reflux, 3 h, 76% yield.
Figure 3. Anti-settlement activity of compounds 3a – 9b at 50 μM towards plantigrade larvae of the mussel Mytilus galloprovincialis . C-: DMSO control (0.1%); C+: 5 μM CuSO 4 as positive control.
Figure 3. Anti-settlement activity of compounds 3a – 9b at 50 μM towards plantigrade larvae of the mussel Mytilus galloprovincialis . C-: DMSO control (0.1%); C+: 5 μM CuSO 4 as positive control.
Figure 4. Bacterial growth inhibition screening at 15 µM ( A ) and dose–response ( B ) of acetophenone derivatives towards five biofilm-forming marine bacteria: Vibrio harveyi , Cobetia marina , Halomonas aquamarina , Pseudoalteromonas atlantica , and Roseobacter litoralis . C-: negative control with a solution of marine broth with 0.1% DMSO; C+: positive control with penicillin–streptomycin–neomycin stabilized solution. * indicates significant differences against the C- (Dunnett test, p < 0.01).
Figure 4. Bacterial growth inhibition screening at 15 µM ( A ) and dose–response ( B ) of acetophenone derivatives towards five biofilm-forming marine bacteria: Vibrio harveyi , Cobetia marina , Halomonas aquamarina , Pseudoalteromonas atlantica , and Roseobacter litoralis . C-: negative control with a solution of marine broth with 0.1% DMSO; C+: positive control with penicillin–streptomycin–neomycin stabilized solution. * indicates significant differences against the C- (Dunnett test, p < 0.01).
Figure 5. Navicula sp. growth inhibition screening of the most promising compounds 6a , 7a , and 9a at 15 µM ( A ) and dose–response concentration of compound 7a ( B ). C-: negative control with f/2 medium with 0.1% dimethyl sulfoxide (DMSO); C+: positive control with cycloheximide solution (3.55 µM). * Indicates significant differences against the C- (Dunnett test, p < 0.01).
Figure 5. Navicula sp. growth inhibition screening of the most promising compounds 6a , 7a , and 9a at 15 µM ( A ) and dose–response concentration of compound 7a ( B ). C-: negative control with f/2 medium with 0.1% dimethyl sulfoxide (DMSO); C+: positive control with cycloheximide solution (3.55 µM). * Indicates significant differences against the C- (Dunnett test, p < 0.01).
Figure 6. Mortality rate of Artemia salina nauplii after 48 h of exposure to compounds 6a , 7a , and 9a . C-: negative control with 0.1% DMSO in filtered seawater. C+: positive control K 2 Cr 2 O 7 at 13.6 μM. ECONEA ® was added for comparative purposes [ 33 ]. * Indicates significant differences against C- (Dunnett test, p < 0.01).
Figure 6. Mortality rate of Artemia salina nauplii after 48 h of exposure to compounds 6a , 7a , and 9a . C-: negative control with 0.1% DMSO in filtered seawater. C+: positive control K 2 Cr 2 O 7 at 13.6 μM. ECONEA ® was added for comparative purposes [ 33 ]. * Indicates significant differences against C- (Dunnett test, p < 0.01).
Table 1. Synthesis of acetophenone hybrids 3a – 9b .
Table 1. Synthesis of acetophenone hybrids 3a – 9b .
Compound R 1 R 2 R 3 Yield (%) 3a H OCH 3 65 3b OH H 84 4a H OCH 3 53 4b OH H 83 5a H OCH 3 65 5b OH H 41 6a H OCH 3 47 6b OH H 61 7a H OCH 3 56 7b OH H 40 8a H OCH 3 30 8b OH H 40 9a H OCH 3 54 9b OH H 35
Table 2. Anti-settlement effectiveness and toxicity parameters of derivatives 6a , 7a , and 9a towards mussel plantigrade larvae.
Table 2. Anti-settlement effectiveness and toxicity parameters of derivatives 6a , 7a , and 9a towards mussel plantigrade larvae.
Compounds EC 50 (µM) EC 50 (µg·mL −1 ) LC 50 (µM) LC 50 /EC 50 6a 28.87 (95% CI: 18.93–44.39) 11.20 >200 >6.93 7a 40.14 (95% CI: 23.95–69.63) 13.46 >200 >4.98 9a 20.68 (95% CI: 9.70–40.75) 9.94 >200 >9.67
EC 50 : minimum concentration that inhibited 50% of larval settlement; LC 50 : median lethal dose; LC 50 /EC 50 : therapeutic ratio; CI: confidence interval.
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Neves, Ana Rita, Daniela Pereira, Catarina Gonçalves, Joana Cardoso, Eugénia Pinto, Vitor Vasconcelos, Madalena Pinto, Emília Sousa, Joana R. Almeida, Honorina Cidade, and Marta Correia-da-Silva. 2021. "Natural Benzo/Acetophenones as Leads for New Synthetic Acetophenone Hybrids Containing a 1,2,3-Triazole Ring as Potential Antifouling Agents" Marine Drugs19, no. 12: 682.
https://doi.org/10.3390/md19120682
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Supplementary File 1:
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Neves, A.R.; Pereira, D.; Gonçalves, C.; Cardoso, J.; Pinto, E.; Vasconcelos, V.; Pinto, M.; Sousa, E.; Almeida, J.R.; Cidade, H.; Correia-da-Silva, M. Natural Benzo/Acetophenones as Leads for New Synthetic Acetophenone Hybrids Containing a 1,2,3-Triazole Ring as Potential Antifouling Agents. Mar. Drugs 2021, 19, 682.
https://doi.org/10.3390/md19120682
Neves AR, Pereira D, Gonçalves C, Cardoso J, Pinto E, Vasconcelos V, Pinto M, Sousa E, Almeida JR, Cidade H, Correia-da-Silva M. Natural Benzo/Acetophenones as Leads for New Synthetic Acetophenone Hybrids Containing a 1,2,3-Triazole Ring as Potential Antifouling Agents. Marine Drugs. 2021; 19(12):682.
https://doi.org/10.3390/md19120682
Neves, Ana Rita, Daniela Pereira, Catarina Gonçalves, Joana Cardoso, Eugénia Pinto, Vitor Vasconcelos, Madalena Pinto, Emília Sousa, Joana R. Almeida, Honorina Cidade, and Marta Correia-da-Silva. 2021. "Natural Benzo/Acetophenones as Leads for New Synthetic Acetophenone Hybrids Containing a 1,2,3-Triazole Ring as Potential Antifouling Agents" Marine Drugs19, no. 12: 682.
https://doi.org/10.3390/md19120682
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RJPT - CCD based Development and Characterization of Tranexamic acid Loaded Transethosomes for Melasma
This study was intended to develop and optimize Tranexamic acid (TXA) loaded transethosomal (TEL’s) patch for the treatment of melasma. Upon oral administration, TXA is reported to cause gastrointestinal (GI) sideeffects and showed 30-50% bioavailability. Hence an alternative transdermal drug delivery system has been designed in the form of transethosomes (TEL). TXA loaded TELwere prepared by the cold method using Phospholipon 90G as a lipoid, sodium cholate as an edge activator, ethanol, and water. Further size reduction was done using a probe sonicator. For optimization purposes central composite design (CCD) was used. Phospholipon 90G and sodium cholate were selected as independent variables. Particle size (PS) and entrapment efficiency (E.E) were selected as a response. Mathematical equations and 3-D response surface graphs were used to relate dependant and independent variables. The optimized model pre-predicted and experimentally gave the particle size of 72nm, zeta potential of -16mV, encapsulation efficiency of 94%, with an enhanced transdermal flux of 32.85µg/cm2 /h as compared to a conventional topical cream. In vitro and ex-vivo studies were done to check the efficacy of the formulation and the results showed improved release of drug in TEL formulation as compared to conventional marketed formulation.
CCD based Development and Characterization of Tranexamic acid Loaded Transethosomes for Melasma
Author(s): Jessy Shaji , Shamika S. Parab
Email(s): jessy.shaji@gmail.com
DOI: 10.52711/0974-360X.2023.00253
Address: Jessy Shaji*, Shamika S. Parab Department of Pharmaceutics, Prin. K.M. Kundnani College of Pharmacy, Cuffe Parade, Colaba, Mumbai 400005, India. *Corresponding Author
Published In:Volume - 16,
Issue - 4,
Year - 2023
ABSTRACT: This study was intended to develop and optimize Tranexamic acid (TXA) loaded transethosomal (TEL’s) patch for the treatment of melasma. Upon oral administration, TXA is reported to cause gastrointestinal (GI) sideeffects and showed 30-50% bioavailability. Hence an alternative transdermal drug delivery system has been designed in the form of transethosomes (TEL). TXA loaded TELwere prepared by the cold method using Phospholipon 90G as a lipoid, sodium cholate as an edge activator, ethanol, and water. Further size reduction was done using a probe sonicator. For optimization purposes central composite design (CCD) was used. Phospholipon 90G and sodium cholate were selected as independent variables. Particle size (PS) and entrapment efficiency (E.E) were selected as a response. Mathematical equations and 3-D response surface graphs were used to relate dependant and independent variables. The optimized model pre-predicted and experimentally gave the particle size of 72nm, zeta potential of -16mV, encapsulation efficiency of 94%, with an enhanced transdermal flux of 32.85µg/cm2 /h as compared to a conventional topical cream. In vitro and ex-vivo studies were done to check the efficacy of the formulation and the results showed improved release of drug in TEL formulation as compared to conventional marketed formulation.
Cite this article: Jessy Shaji, Shamika S. Parab. CCD based Development and Characterization of Tranexamic acid Loaded Transethosomes for Melasma. Research Journal of Pharmacy and Technology 2023; 16(4):1549-5. doi: 10.52711/0974-360X.2023.00253 Cite(Electronic): Jessy Shaji, Shamika S. Parab. CCD based Development and Characterization of Tranexamic acid Loaded Transethosomes for Melasma. Research Journal of Pharmacy and Technology 2023; 16(4):1549-5. doi: 10.52711/0974-360X.2023.00253 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2023-16-4-1
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Medicine (Baltimore) 2017; 96(19): e6897.doi:10.1097%2FMD.0000000000006897 7. Del Rosario, et al. Randomized, placebo-controlled, double-blind study of oral tranexamic acid in the treatment of moderate-to-severe melasma. Journal of the American Academy of Dermatology 2018; 78(2): 363-369.doi:10.1016/j.jaad.2017.09.053 8. Kaur A, et al. Tranexamic acid in melasma: a review. Pigment Int 2020;7(1):12-25.doi: 10.4103/Pigmentinternational.Pigmentinternational_ 9. Tan AWM, et al. Oral tranexamic acid lightens refractory melasma. Australas J Dermatol 2017;58(3):e105-e108.doi:10.1111/ajd.12474. 10. Zhang L, et al. Tranexamic acid for adults with melasma: a systematic review and meta-analysis. BioMed research international 2018; doi:10.1155/2018/1683414. 11. Grimes PE., et al. New oral and topical approaches for the treatment of melasma. International Journal of Women’s Dermatology 2018; 5(1): 30–36.doi:10.1016/j.ijwd.2018.09.004. 12. Rodrigues M, Pandya A. Melasma: Clinical diagnosis and management options. Australas J Dermatol 2015;56(3):151–63.doi:10.1111/ajd.12290. 13. Sarkar R., et al. Melasma in men: A review of clinical, etiological, and management issues. The Journal of clinical and aesthetic dermatology 2018 11(2), p.53-59. 14. Ikino JK, et al. Melasma and assessment of the quality of life in Brazilian women. An Bras Dermatol 2015;90(2):196–200.doi:10.1590/abd1806-4841.20152771 15. Aishwarya K, et al. Current concepts in melasma - A review article. J Skin Sex Transm Dis 2020;2(1):13-17.doi: 10.25259/JSSTD_34_2019 16. Sandeep Gupta, Dheeraj Ahirwar, Neeraj K Sharma, DeenanathJhade. Proniosomal Gel as a Carrier for Improved Transdermal Delivery of Griseofulvin: Preparation and In vitro Characterization. Research J. Pharma. Dosage Forms and Tech. 2009; 1(1): 33-37. 17. Pawar P et als. Different Techniques for Preparation of Nanosuspension with Reference to its Characterisation and various Applications - A Review. Asian J. Res. Pharm. Sci. 2018; 8(4): 210-216. doi: 10.5958/2231-5659.2018.00035.8 18. Bajaj KJ, et al. Nano-transethosomes: A Novel Tool for Drug Delivery through Skin. Indian J of Pharmaceutical Education and Research 2021;55 Suppl 1:1-10.doi: 10.5530/ijper.55.1s.33. 19. Gondkar SB, et al. Formulation Development and Characterization of Etodolac Loaded Transethosomes for Transdermal Delivery. Research J. Pharm. And Tech. 2017; 10(9):3049-3057. doi:10.5958/0974-360X2017.00541.8. 20. Phatak Atul A., Chaudhari Praveen D. Development and Evaluation of Nanogel as a Carrier for Transdermal Delivery of Aceclofenac. Asian J. Pharm. Tech, 2012; 2(4): 125-132. 21. Kumara Swamy S, Ramesh Alli. Preparation, Characterization and Optimization of Irbesartan Loaded Solid Lipid Nanoparticles for Oral Delivery. Asian Journal of Pharmacy and Technology. 2021; 11(2):97-4. doi: 10.52711/2231-5713.2021.00016 22. Honary S, Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems-a review (Part 1). Trop J Pharm Res. 2013;12(2):255-64.doi:10.4314/tjpr.v12i2.19. 23. Jessy Shaji, Monika Kumbhar. Linezolid Loaded Biodegradable Polymeric Nanoparticles Formulation and Characterization. Res. J. Pharm. Dosage Form. & Tech. 2018; 10(4): 272-278. doi: 10.5958/0975-4377.2018.00040.X 24. Varshosaz, J, et al. Lipid Nanocapsule-Based Gels for Enhancement of transdermal Delivery of Ketorolac Tromethamine. J. Drug Deliv. 2011,2011, 1-7.doi: 10.1155/2011/571272. 25. Wu IY, et al. Interpreting non-linear drug diffusion data: Utilizing Korsmeyer-Peppas model to study drug release from liposomes. Eur J Pharm Sci. 2019 October 1;138: 105026.doi: 10.1016/j.ejps.2019.105026. 26. D.R. Paul. Elaborations on the Higuchi model for drug delivery. Int J Pharm. 2011;418:13-17. doi:10.1016/j.ijpharm.2010.10.037. 27. Rehman Q, et al. Role of Kinetic Models in Drug Stability. In: Akash M.S.H., Rehman K. (eds).Drug Stability and Chemical Kinetics. Springer, Singapore.2020 Nov 02;155-165.doi:10.1007/978-981-15-6426-0_11. 28. Singhvi G, Singh M. In vitro drug release characterization models. Int J Pharm Stud Res. 2011;2:77-84. 29. Yang Z, et al. Design of a zero-order sustained release PLGA microspheres for palonosetron hydrochloride with high encapsulation efficiency. Int. J. Pharm. 2020:119006. doi:10.1016/j.ijpharm.2019.119006. 30. Shaji J, Garude S. Transethosomes and Ethosomes for Enhanced Transdermal Delivery of Ketorolac Tromethamine : A Comparative Assessment. International Journal of Current Pharmaceutical Research. 2014;6(4):88 - 93. 31. Vinod K.R., Sandhya S. Factorial Designing for Pharmaceutical Product and Process Development. Research J. Pharma. Dosage Forms and Tech. 2011; 3(5): 199-202. 32. Tipre DN, Vavia PR. Formulation optimization and stability study of transdermal therapeutic system of nicorandil. Pharm. Dev. Technol. 2002;7:325–32.doi:10.1081/PDT-120005729. 33. Sinico, C, et al. Liposomes as carriers for dermal delivery of tretinoin: in vitro evaluation of drug permeation and vesicle–skin interaction. Journal of Controlled Release 2005;103(1):123–136.doi:10.1016/j.jconrel.2004.11.020. 34. K.Vijaya S et al. Formulation and Evaluation of Rutin Loaded Nanosponges. Asian J. Res. Pharm. Sci. 2018; 8(1):21-24. doi: 10.5958/2231-5659.2018.00005.X 35. Shaji, J., and S. Garude. “Transethosomes and Ethosomes FOR enhanced Transdermal Delivery of Ketorolac Tromethamine: A Comparative Assessment”. International Journal of Current Pharmaceutical Research 2014;6(4):88-93. 36. Talib S, et al. Chitosan-chondroitin based artemether loaded nanoparticles for transdermal drug delivery system. Journal of Drug Delivery Science and Technology 2021; 61: p.102281.doi:10.1016/j.jddst.2020.102281. 37. Saraswathi B et al. Formulation and Characterization of Tramadol HCl Transdermal Patch. Asian J. Pharm. Tech. 2018; 8 (1):23-28 . doi: 10.5958/2231-5713.2018.00004.1 38. Salve P et al. Formulation and Evaluation of Solid Lipid Nanoparticle Based Transdermal Drug Delivery System for Alzheimer’s Disease. Res. J. Pharm. Dosage Form. and Tech. 2016; 8(2):73-80. doi: 10.5958/0975-4377.2016.00011.2
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Insects | Free Full-Text | Evaluation of Phytoseiid and Iolinid Mites for Biological Control of the Tomato Russet Mite Aculops lycopersici (Acari: Eriophyidae)
Our search for a suitable biological agent to control the tomato russet mite (TRM), Aculops lycopersici, was initiated in 2013. Neoseiulus californicus, Amblyseius andersoni, and Neoseiulus fallacis showed a promising pest reduction potential in a curative control strategy. Although these beneficials had a low survival on tomato and were not able to eradicate the pest, plants did not present typical TRM damage. However, their inability to establish in the tomato crop means that their commercial use would require repeated introductions, making their use too expensive for growers. Other predatory mites in the survey, such as the iolinids Homeopronematus anconai and Pronematus ubiquitus, showed the potential for a preventative strategy as they can establish and reach high densities on tomato with weekly or biweekly provision of Typha angustifolia pollen as a food source. When the tomato crop was adequately colonized by either iolinid, the development of TRM and any damage symptoms could be successfully prevented. The potential of iolinid predatory mites for biological control of eriophyids is discussed.
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Evaluation of Phytoseiid and Iolinid Mites for Biological Control of the Tomato Russet Mite Aculops lycopersici (Acari: Eriophyidae)
by
Juliette Pijnakker 1,* ,
Asli Hürriyet 1 ,
Clément Petit 1 ,
Dominiek Vangansbeke 1 ,
Marcus V. A. Duarte 1 ,
Yves Arijs 1 ,
Rob Moerkens 1 ,
Louis Sutter 2 ,
Dylan Maret 2 and
Felix Wäckers 1
1
R&D Department, Biobest Group N.V., 2260 Westerlo, Belgium
2
Agroscope, Plant-Production Systems, 1964 Conthey, Switzerland
*
Author to whom correspondence should be addressed.
Insects 2022 , 13 (12), 1146; https://doi.org/10.3390/insects13121146
Received: 31 October 2022 / Revised: 25 November 2022 / Accepted: 1 December 2022 / Published: 12 December 2022
(This article belongs to the Special Issue Management of the Tomato Russet Mite, Aculops lycopersici )
Simple Summary
The tomato russet mite (TRM), Aculops lycopersici (Eriophyidae), causes severe damage to tomato plants Lycopersicon esculentum, which results in a wilted, russetted appearance with desiccated leaves. This study focused on the search for a suitable biological control agent against TRM, as an alternative to commonly used sulfur or chemicals. The efficacy of several potential predatory mite species was assessed. Pronematus ubiquitus proved successful in preventing the development of TRM and damage symptoms. The potential of iolinid predatory mites for the biological control of eriophyids is discussed.
Abstract
Our search for a suitable biological agent to control the tomato russet mite (TRM),
Aculops lycopersici
, was initiated in 2013.
Neoseiulus californicus
,
Amblyseius andersoni,
and
Neoseiulus fallacis
showed a promising pest reduction potential in a curative control strategy. Although these beneficials had a low survival on tomato and were not able to eradicate the pest, plants did not present typical TRM damage. However, their inability to establish in the tomato crop means that their commercial use would require repeated introductions, making their use too expensive for growers. Other predatory mites in the survey, such as the iolinids
Homeopronematus anconai
and
Pronematus ubiquitus
, showed the potential for a preventative strategy as they can establish and reach high densities on tomato with weekly or biweekly provision of
Typha angustifolia
pollen as a food source. When the tomato crop was adequately colonized by either iolinid, the development of TRM and any damage symptoms could be successfully prevented. The potential of iolinid predatory mites for biological control of eriophyids is discussed.
Keywords:
Acari
;
Iolinidae
;
Homeopronematus
;
Pronematus
;
tomato
;
greenhouse
;
biological control
;
small iolinid mites
;
big impact on TRM
1. Introduction
The tomato russet mite (TRM), Aculops lycopersici Massee (Eriophyidae), is a cosmopolitan pest of unknown geographical origin and original host [ 1 ]. The species is found in almost all agricultural regions where solanaceous crops are cultivated [ 1 , 2 , 3 ]. Due to the fact that TRM infestations usually remain undetected at the base of the tomato plant, the mite is able to progress towards the canopy [ 4 ]. The pest causes serious damage to the head of the tomato plants, resulting in a wilted, russetted appearance with desiccated leaves [ 5 , 6 ]. The abaxial side of the lower leaves is often silvered, and the stems lose trichomes and develop a brown color, often with small fissures. Fruits can become bronzed on highly infested plants. To avoid serious crop damage, tomato growers in northwestern Europe increasingly use preventative sulfur sprays (or evaporation) and chemical control measures with compounds such as abamectin and/or spiromesifen upon the first signs of plant damage (Juliette Pijnakker, personal experience). Since TRM is difficult to detect early-on and has a high reproduction capacity, with populations doubling in less than three days at 25 °C [ 7 ], the eradication of the pest is difficult.
Studies investigating the use of predatory phytoseiid mites against TRM (Duso et al., 2010) [ 6 ] are mostly limited to relatively small-scale laboratory experiments. Several phytoseiid predators have been observed feeding on TRM, including the phytoseiid mites Amblyseius andersoni (Chant) [ 8 ], Amblydromalus limonicus (Garman and McGregor) [ 9 , 10 , 11 ], Amblyseius swirskii (Athias-Henriot) [ 12 , 13 , 14 ], Neoseiulus californicus (McGregor) [ 8 , 15 ], Neoseiulus cucumeris Oudemans [ 8 , 16 , 17 ], Neoseiulus fallacis (Garman) [ 16 ], and Typhlodromus ( Anthoseius ) recki Wainstein [ 18 ]. Even though TRM is a suitable prey for some phytoseiids [ 16 ], their impact in terms of biological control is often insufficient [ 8 , 11 , 16 ]; therefore, phytoseiid mites are rarely used in commercial tomato crops against TRM. The capacity of phytoseiid mites to survive, move, and reproduce—and thus establish—on the tomato plants is hampered by glandular trichomes [ 11 , 14 , 19 , 20 , 21 , 22 , 23 , 24 ]. Furthermore, toxic secondary metabolites (in plants and prey) are thought to be lethal to the phytoseiids [ 24 , 25 ]. The poor performance of phytoseiids on tomato was confirmed in a few greenhouse trials on tomato plants in Europe. In France, N. cucumeris and N. californicus only reduced TRM populations when high numbers of predators were released: 3000 N. californicus and over 12,000 N. cucumeris per plant [ 17 ]. Although a single preventative release rate of 100 A. andersoni mites per plant) resulted in in a low TRM density on stems after eight weeks in comparison with a curative or simultaneous release of the predator, it could not fully eradicate the pest [ 8 ]. Curative releases of 140 and 420 A. swirskii individuals per tomato plant did not reduce the pest [ 11 ], and A. limonicus was also hampered by tomato trichomes [ 15 ].
Alternative options to promote the biological control of TRM include adapting predatory mites to the tomato plant [ 26 ] or developing tomato cultivars with fewer harmful trichomes [ 27 , 28 ]. Some mite species of the Tydeoidae, including the families Tydeidae and Iolinidae, are about five times smaller than most phytoseiid predators [ 29 ]. They are not hindered by the tomato trichomes, allowing them to move under and between the trichomes [ 30 ]. This applies to the mite species Homeopronematus anconai (Baker) [ 31 ], Pronematus ubiquitus (McGregor), and Tydeus kochi Oudemans [ 32 , 33 , 34 , 35 ]. Some of these species have been reported to occur naturally on tomato. The feeding habits of tydeids and iolinids range from predators, phytophages, mycophages, and parasitism on insects to scavengers [ 36 , 37 ]. Some species are reported to be pollen-feeders [ 31 , 38 , 39 , 40 , 41 ] and predators of small arthropods [ 16 , 31 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ]. Many Tydeoidea species have been reported to be associated with eriophyoids, such as H. anconai , P. ubiquitus , Pronematus staerki Schruft [ 51 ], T. kochi , Tydeus californicus (Banks), Tydeus caudatus Dugès [ 52 ], Tydeus caryae Kanjani and Ueckermann, and Tydeus goetzi Schruft [ 53 ]. Homeopronematus anconai and P. ubiquitus are common species that have been well-studied in relatively small-scale laboratory experiments [ 30 ]. In 1961, Rice reported predation of TRM by P. ubiquitus [ 32 ]. Carmona found remnants of TRM in the gut of P. ubiquitus [ 33 ]. Hessein and Perring [ 31 ] found H. anconai in their TRM rearing and collected the predator from tomato plants. Homeopronematus anconai was able to develop and reproduce on TRM and succeeded in reducing TRM populations on tomato plants. Adults and nymphs of H. anconai and P. ubiquitus have been reported to kill all stages of TRM [ 30 ]. Homeopronematus anconai adults showed daily predation of about 70 A. lycopersici deutonymphs in the laboratory [ 54 , 55 ] or 3 to 4 adults of TRM adults per day [ 16 ]. Haque and Kawai [ 54 , 55 ] observed more than 2000 individuals of a naturally occurring population of H. anconai per leaf on tomato plants infested by A. lycopersici .
In this study, we investigated the efficacy of different predatory mites against TRM. The search for suitable biological agents for TRM started in 2013, when we compared the efficacy on individual plants of diverse phytoseiid predatory mites, either commercially available or from experimental rearing. Subsequently, following an important survey on Solanaceae, our focus shifted to iolinids, including a demonstration trial in a semi-commercial setting.
2. Materials and Methods
2.1. Pest, Beneficials, and Additional Food Source
A population of Aculops lycopersici was maintained on potted tomato plants in a greenhouse of Biobest Group N.V. (Westerlo, Belgium) at 25 °C. Narrow-leaved cattail pollen ( Typha angustifolia L., Nutrimite ™ ), predatory mites, pest material, predatory bugs, and parasitic wasps to control whitefly populations during the trials were obtained from Biobest Group N.V.
2.2. Curative Releases with Nine Species of Phytoseiids on Individual Tomato Plants
To assess the efficacy of predatory mites in controlling TRM, a trial was conducted on individual tomato plants in a greenhouse of 150 m
2
at the Greenlab facilities of Biobest Group N.V. The trial was performed from March to May 2013 at 70 ± 20% RH and an average temperature of 22 ± 8 °C with natural light. The plants were sown in the same facilities and grown in potted soil (Greenyard Horticulture, Ghent, Belgium) in 5 L pots. The pots were placed in containers on tables and watered by hand. A single head was kept per plant and all lateral shoots were removed weekly. No sulfur was used.
Encarsia formosa
Gahan was released preventatively against whiteflies.
Tomato plants cv. Marmande (Somers, Mechelen, Belgium) (1.5 month old, 6 leaves) grown in pots were placed on growing tables. Ten treatments (nine predator species tested alone and a control with only TRM) were assigned with three or six replicates using a randomized block design. For all treatments, one replicate was represented by one plant. Due to a shortage of breeding material,
Euseius ovalis
(Evans) and
Phytoseiulus macropilis
(Banks) were tested in three replicates only, whereas all other predatory mites treatments consisted of six replicates.
On 25 March, a piece of tomato stem infested with approximately 500
A. lycopersici
was attached with a thread between the 2nd and 3rd leaf. One day later, 500 mites of the species
A. limonicus
,
A. andersoni
,
A. swirskii
,
E. ovalis
,
Galendromus occidentalis
(Nesbitt),
N. californicus
,
N. fallacis
, and
P. macropilis
were released evenly over each plant. The predators were released each week for four consecutive weeks. All marketed predators were released in their commercial carrier,
E. ovalis
and
P. macropilis
were introduced in a sawdust carrier.
Amblyseius swirskii
was released either with or without cattail pollen as a supplemental food, while
E. ovalis
was always tested with pollen as Nutrimite
™
is known to be particularly effective in boosting these two species [
56
]. The pollen (0.5 g/plant/week) was supplied weekly with a brush for four consecutive weeks after the predators’ introductions. Six weeks after the introduction of the pest and two weeks after the last release of the predatory mites, the number of healthy and damaged leaves and the percentage of stem russetted were assessed per plant to evaluate the efficacy of the predators. Eight leaves were removed per plant and examined under a stereomicroscope (Optika SZM-LED2, Ponteranica, Italy). The number of predators was counted per collected leaf to estimate the establishment of the predators. All predatory mites were collected at the end of the trials, to confirm species identity. The identification was done using a microscope (Zeiss Axio Scope.A1, Carl Zeiss, Jena, Germany) after mites had been mounted and cleared in a Marc André solution (Upton) [
57
] for three days on a warm plate.
All statistical analyses were performed using the statistical software R version 3.6.1 [ 58 ]. Differences in mite densities and the damage level on stem and leaf at the sampling period were analyzed with a general linear model using the function glht of the package lsmeans [ 59 ]. A pairwise post-hoc Tukey test was used to check for differences between objects.
2.3. Preventative Releases of Two Iolinids Species with One Application of Pollen/Week on Individual Tomato Plants
In 2018, a trial was performed on individual tomato plants cv. Merlice (De Ruiter, Bergschenhoek, The Netherlands) to evaluate the impact of
H. anconai
and
P. ubiquitus
(supplied with cattail pollen) on TRM. Thirty-six plants were sown on 29 April and grown as described in the previous trial, except that the pots were placed in containers on the concrete floor, with sticky cardboard under each plant to avoid TRM contamination and movement of iolinids between treatments.
Treatments were arranged in a randomized block design with eleven replicates for the treatments with predatory mites supplied with pollen, and fourteen for the untreated control. For all treatments, one plant represented one replicate. The treatments were evaluated for 17 weeks from June until October in a greenhouse with natural light at 70 ± 20% RH and an average temperature of 21 ± 3 °C (setting: 19 °C night/20 °C day). Leaves, well-colonized by predators, were collected from a rearing on blackberry plants provided with the pollen of
T. angustifolia
. Leaves containing 50 predatory mites and about 10 eggs were introduced once preventatively on each tomato plant (of one stem) on 19 June. The berry leaves colonized with the predatory mites were placed on a tomato leaf against the stem at 90 cm from the growing substrate. The pollen (Nutrimite, Biobest Group N.V., 0.15 g per plant) was applied weekly with a pollen-blowing device (Nutrigun, Biobest Group N.V.). The control treatment received neither pollen nor predators. Plants were infested with the pest on 10 July, three weeks after the introduction of the predators. One infested tomato stem piece with ca. 300 TRM (mixed stages) was fixed with a wire to the tomato stem next to the release point of the predatory mites.
To follow the population dynamics of TRM and predatory mites, nine (3 and 5 weeks after predator release) and twenty-seven leaflets (9, 13, and 17 weeks after predator release) were collected from each plant in three strata (top, middle, bottom) of the plant. The number of tydeoids and eriophyoids was counted per leaflet using a stereomicroscope (Optika SZM-LED2). Microscopic slides of 60 predatory mites were made per plant to confirm the predators’ identity. The first damage was only visible 5 weeks after the release of the pest. The number of green, yellow, and bronzed leaves was first counted weekly from 14 August to 28 August and then biweekly until 19 October (16 weeks after the release of the predator and 13 weeks after the release of the pest).
The number of predatory and pest mites and green leaves was analyzed among treatments with a linear mixed-effects model (LME) with treatment and time as fixed factors and plant identity as a random factor to correct for repeated measures [ 58 ].
2.4. Demonstration Trial in Semi-Commercial Conditions
In 2021, a demonstration trial was organized in an experimental crop with tomato plants cv. Marinice (De Ruiter, The Netherlands) to demonstrate the control of TRM by P. ubiquitus supplied with cattail pollen, compared with untreated plants without iolinids. P. ubiquitus was selected as it reproduces faster on pollen than H. anconai [ 30 ].
In total, 240 plants were sown on 28 April in a nursery and grown in rockwool slabs in a greenhouse of 180 m
2
from 16 June to 6 October. Temperatures averaged 20 °C with a range of 16.5–21.5 °C. The relative humidity was 75 ± 10% RH. Two heads were kept per plant and all auxiliary shoots were removed weekly. The lowest leaves were cut off once the plants reached a total number of 18 leaf branches. This procedure was continued during the trial in order to assure that the total number of leaf branches did not exceed 18. The predatory bug
Macrolophus pygmaeus
Rambur (2 × 1/m
2
on 20 and 27 July) and
Encarsia formosa
Gahan (12.5/m
2
/week) were released to control whiteflies.
Phytoseiulus persimilis
Athias-Henriot (25/m
2
/week + 250/m
2
on 28 July, 4, 11 and 18 August),
Feltiella acarisuga
(Vallot) (10/m
2
/week on 28 July, 4, 11 and 18 August), and
Diglyphus isaea
Walker (2 × 5/m
2
on 1 and 8 September) were introduced to control spider mites and leaf miners.
Half of the greenhouse was inoculated with
P. ubiquitus
. Two rows of gutters were kept empty to separate the two sections of the greenhouse. There was no extra physical barrier to prevent the spread of mites between the treatments. Per plant (two stems), 100 mixed stages of the mites were introduced in a sawdust carrier on the top of the plants on 16 June and once more on 1 July. Four weeks after the last introduction of the predators, eight plants per treatment were infested with TRM on 28 July, and later two more infestations on 26 August and 2 September to speed up infection. An infested tomato stem piece with respectively ca. 50, 50, and 500 mixed stages of TRM was therefore fixed to the tomato stems below the bottom leaf of each plant.
Initially, pollen (500 g/ha) was blown weekly until 7 August (7 weeks after the first release of the predatory mites) over the plants and then biweekly with the Nutrigun until the end of the demonstration. The control treatment received neither pollen nor predators.
The development of the predator and the pest was followed until 6 October. From 7 July (third week after the first release of
P. ubiquitus
), twenty-five leaflets were collected weekly randomly in three strata (top, middle, down) of the plant in each treatment. To assess TRM, six leaflets were collected from three leaves of each infested plant. The TRM infestation level on stems was evaluated with two stickers placed around the stem (9.5 cm long) nearby the release point of the pest, with the sticky part towards the plant. All leaflets and stickers were examined under a stereomicroscope to count the number of predatory mites and eriophyoids. At the end of the demonstration, the number of plants presenting TRM damage was counted and the stems of the infested plants were examined for brown symptoms. The number of pest mites was analyzed with a linear mixed-effects model (LME).
3. Results
3.1. Curative Releases with Nine Species of Phytoseiids (Individual Plants)
Neoseiulus californicus , A. andersoni, and N. fallacis showed the most pronounced TRM damage reduction. There was a significant interaction between the treatments and the damage level of the leaves and the stems ( Figure 1 A,B). Although these species had a low survival ( Figure 2 ) and the curative strategy did not eliminate the pest, plants remained healthy ( Figure 1 ). Only A. swirskii and A. limonicus developed and reproduced well ( Figure 2 ).
Figure 1.
Percentage of damaged leaves (
A
) and brown stem (
B
) (mean ± SE) caused by TRM on the tomato plants of the different treatments six weeks after TRM inoculation and following four weekly curative releases of 500 predators per plant. Different letters above the data points denote significant differences among treatments after the generalized linear model (
p
< 0.05).
Figure 2. Number of established predatory mites (mean ± SE) on tomato plants infested with TRM six weeks after TRM inoculation and following four weekly curative releases of 500 predators per plant ( A. limonicus and A. swirskii found on untreated plants). Different letters above the data points denote significant differences among treatments after the generalized linear model ( p < 0.05).
3.2. Preventative Releases of Homeopronematus Anconai and Pronematus Ubiquitus with One Application of Pollen/Week (Individual Plants)
Both iolinids reached a density of about five mites per leaflet five weeks after their first introduction ( Figure 3 ). Their populations increased to 15–20 predatory mites per leaflet nine weeks after their release. Both iolinids species were also found in week nine on the control plants, which were highly infested by the pest ( Figure 4 ).
Figure 3. Population dynamics of predatory mites (Pu Pronematus ubiquitus and Ha Homeopronematus anconai ) on tomato plants for 17 weeks. Different letters indicate a significant difference in the number of iolinids between the inoculated tomato plants and the control plants (linear mixed-effects models, p < 0.05).
Figure 4. Population dynamics of TRM on tomato plants for 14 weeks. Different letters indicate a significant difference in the number of Aculops lycopersici between the inoculated tomato plants and the control plants (linear mixed-effects models, p < 0.05).
Plants where the predators established at an early stage presented drastically fewer TRMs and less damage ( Figure 4 and Figure 5 ). Damage was limited to the area of the inoculation point of the pest.
Figure 5. Remaining healthy (green) leaves per treatment. Different letters indicate a significant difference in the number of green leaves between the inoculated tomato plants and the control plants (linear mixed-effects models, p < 0.05).
3.3. Demonstration Trial in Semi-Commercial Conditions
Six weeks after the first release, the predator reached a density of five predators per leaflet (
Figure 6
). Only the top leaves showed a low predatory mite density (
Figure 6
). Two weeks after the inoculation of 500 TRM per stem, the pest population on the control plants increased drastically, both on the leaves (
Figure 7
A) and the stems (
Figure 7
B). At the end of the demonstration, 38.7 ± 4.9% (mean ± SE) of the artificially infested stems became rusty brown in the untreated plot, and the pest spread beyond the inoculation plants. Sixty-six stems out of the 240 stems without
P. ubiquitus
presented leaves with TRM damage. Plants which had been colonized by
P. ubiquitus
remained damage-free throughout the trial (green stem and no damaged leaves). Only a few living pest mites were recorded in the
Pronematus
plots (average of 10.2 ± 8.4 TRM per leaflet on 10.4% of the examined leaflets).
Figure 6. Population dynamics of Pronematus ubiquitus (mean number of mobile mites per leaflet ± SE) in an experimental greenhouse tomato crop.
Figure 7. Population dynamics of TRM (mean number of mobile mites ± SE) found on the leaflets ( A ) and on the stem ( B ) nearby the point of the artificial infestation in an experimental greenhouse tomato crop.
4. Discussion
Many phytoseiid species feed on TRM as prey in laboratory studies [ 16 ]. However, most of these predators are not effective biocontrol agents of TRM in greenhouse tomatoes as their establishment is hampered by the plant trichomes [ 10 , 24 ]. In our trial, only A. swirskii and A. limonicus became established, and only on damaged leaves with collapsed trichomes. Our studies confirmed that N. californicus [ 17 ], A. andersoni [ 8 ], and N. fallacis [ 16 ] could be used in an inundative strategy against TRM. However, as these phytoseiid mites do not establish on tomato plants, the high numbers and repeated introductions required are not economically viable for growers or could only be applied locally where TRM infestations are first expected (along the paths, the façades, and heating pipes).
Unlike the tested phytoseiid species, the iolinid species H. anconai and P. ubiquitus showed a strong affinity for tomato crops, as already reported by Van Houten et al. [ 60 ] and Pijnakker et al. [ 61 ]. These tiny mites (225–280 µm) can survive on healthy tomato plants and circulate under and between the plant trichomes. In commercial tomato crops, these tydeoids are sometimes observed to occur spontaneously, probably feeding on tomato pollen, fungi in the phyllosphere, tarsonemids, and/or spider mites [ 62 , 63 , 64 ]. In our trials, both predatory mites reached high densities when released preventatively and supplied weekly with cattail pollen. A five or six week period was often needed to observe a density of about five predators per leaflet on tomato plant when only pollen was available. Most predatory mites were found in the bottom and middle strata, and less often in the top. Average densities of 20 predatory mites per tomato leaflet (top, middle, low leaves) were common in our controlled experimental designs, with numbers higher than 100 mites per leaflet at best. In contrast, most phytoseiid predators failed to establish or had populations 25 times smaller than the iolinid predators. Previously, Hessein and Perring [ 40 ] found a 4-fold increase in the survival of H. anconai (10–39%) when they added pollen to a TRM diet. Duarte et al. [ 62 ] showed that P. ubiquitus was able to reproduce on tomato pollen as a sole food source, but that T. angustifolia pollen yielded a higher reproduction than tomato pollen. As for reproduction on TRM alone, Vervaet et al. [ 30 ] found an oviposition rate over five days of 14.5 ± 1.7 and 14.4 ± 1.4 eggs for P. ubiquitus and H. anconai , respectively. Both species could reproduce and survive on diet of solely TRM. However, the predators’ fecundity reported by Vervaet et al. [ 30 ] was increased 1.7-fold when cattail pollen was added to the diet of TRM, with P. ubiquitus reproducing faster than H. anconai .
Brodeur et al. [ 16 ] considered H. anconai unsuitable for biological control of TRM in tomato crops, questioning the requirement of the predator for relatively high temperatures (28–30 °C optimal) and pollen for the oogenesis [ 65 ]. Our study demonstrated the preventative biological control potential of both iolinids with the addition of pollen on tomato plants at field realistic temperatures. Vervaet et al. [ 30 ] found that the presence of pollen lowers the predation of TRM by both iolinid species in laboratory trials. However, this does not need to compromise biocontrol at the plant level, as increased reproduction more than compensates for the reduced predation of individual mites [ 66 ]. Our study showed that both species could reduce TRM population densities on tomato plants when established prior to the inoculation of the pest. For H. anconai, these results are consistent with those of Hessein and Perring [ 31 ], where the predator reduced the pest infestation by 94.7% and 98.31%, respectively, one and two weeks after the first predatory mites were noticed. In our demonstration trial, the tomato plants showing a high colonization by P. ubiquitus were protected from A. lycopersici and outbreaks of the pest were avoided. This confirms the results obtained in a trial on individual tomato plants [ 63 ]. In our second trial, the decrease in TRM numbers found on the control plants in week 17 are also likely explained by the contamination of the control plants with a high number of iolinids.
Although the direct predation effect of both iolinid species on TRM has been well-studied [ 30 ], the elicitation of plant defensive secondary metabolites by the iolinids can be a further mechanism underlying the effects, as both predators complement their diets with plant feeding. These indirect effects are already widely discussed for other plant-feeding organisms [ 67 , 68 , 69 ]. Importantly, we have never observed any visible damage nor negative impacts on plant growth, even at the high densities obtained in our trials.
Iolinids have not been used as biological control agents until now as pollen or TRM are needed to obtain effective high densities of predators [ 38 , 39 ]. Furthermore, the mass-rearing of the predators is complicated by the fact that plant tissue seems required for their survival [ 31 , 40 , 64 ]. However, since cattail pollen and other food supplements have been made available as commercial products, supplementing food has now become common practice in biocontrol programs in several greenhouse crops [ 70 , 71 , 72 ]. The new commercial availability of cattail pollen also allows the implementation of iolinids as predators of TRM. Pollen has to be supplied at least biweekly for a proper establishment of the iolinids [ 62 ]. A suitable release strategy will have to be elaborated, taking into account many aspects such as the moment and method of introduction, the dose, frequency and application method of pollen, the moment and importance of deleafing of the tomato plants, the presence of initial chemical residues, and compatibility with the use of fertilizers, (bio)pesticides [ 73 ], and other beneficials. The use of sulfur, as it is currently used against TRM as well as against powdery mildew, impedes the use of iolinids in greenhouse crops. The establishment of P. ubiquitus was considered to be impossible, due to the central role of sulfur [ 60 ]. However, recent studies have shown that the iolinids not only control TRM, but also effectively suppress powdery mildew [ 63 ], opening up opportunities for sulfur-free tomato production.
5. Conclusions
In summary, we showed that N. californicus , A. andersoni, and N. fallacis are effective predators of TRM when released repeatedly in high numbers. Still, they cannot maintain populations on healthy or lightly infested plants as they are impeded by tomato trichomes.
We confirmed that H. anconai and P. ubiquitus are extremely suitable predators of TRM in tomato. The predatory mites can survive and reproduce on tomato plants when they are provided with pollen. Through preventative introductions and (bi)weekly pollen applications, the iolinid predators can reach high population densities. The high predator densities keep TRM populations low. Our study reinforces the importance of preventative establishment and ‘power by numbers’ in biocontrol.
Author Contributions
Conceptualization, J.P., D.V. and F.W.; methodology, J.P., D.V., L.S., D.M. and F.W.; data curation, J.P., A.H., C.P., L.S. and D.M. formal analysis, J.P., D.V. and R.M.; writing—original draft preparation, J.P.; writing—review and editing, J.P., D.V., M.V.A.D., R.M., Y.A., L.S., D.M., A.H., C.P. and F.W.; supervision, F.W. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Data Availability Statement
Not applicable.
Acknowledgments
The authors are grateful to the following colleagues for providing technical assistance: Alfredo Benavente, Diana Overgaag, Amandine De Souza, Izabela Toczko, Nancy Lenaerts, Peggy Bogaerts, and Ilse Jacobs. This work was partly undertaken alongside and in interaction with the Flanders Agency for Innovation and Entrepreneurship VLAIO project ‘BALTO’.
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1. Percentage of damaged leaves ( A ) and brown stem ( B ) (mean ± SE) caused by TRM on the tomato plants of the different treatments six weeks after TRM inoculation and following four weekly curative releases of 500 predators per plant. Different letters above the data points denote significant differences among treatments after the generalized linear model ( p < 0.05).
Figure 2. Number of established predatory mites (mean ± SE) on tomato plants infested with TRM six weeks after TRM inoculation and following four weekly curative releases of 500 predators per plant ( A. limonicus and A. swirskii found on untreated plants). Different letters above the data points denote significant differences among treatments after the generalized linear model ( p < 0.05).
Figure 3. Population dynamics of predatory mites (Pu Pronematus ubiquitus and Ha Homeopronematus anconai ) on tomato plants for 17 weeks. Different letters indicate a significant difference in the number of iolinids between the inoculated tomato plants and the control plants (linear mixed-effects models, p < 0.05).
Figure 4. Population dynamics of TRM on tomato plants for 14 weeks. Different letters indicate a significant difference in the number of Aculops lycopersici between the inoculated tomato plants and the control plants (linear mixed-effects models, p < 0.05).
Figure 5. Remaining healthy (green) leaves per treatment. Different letters indicate a significant difference in the number of green leaves between the inoculated tomato plants and the control plants (linear mixed-effects models, p < 0.05).
Figure 6. Population dynamics of Pronematus ubiquitus (mean number of mobile mites per leaflet ± SE) in an experimental greenhouse tomato crop.
Figure 7. Population dynamics of TRM (mean number of mobile mites ± SE) found on the leaflets ( A ) and on the stem ( B ) nearby the point of the artificial infestation in an experimental greenhouse tomato crop.
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MDPI and ACS Style
Pijnakker, J.; Hürriyet, A.; Petit, C.; Vangansbeke, D.; Duarte, M.V.A.; Arijs, Y.; Moerkens, R.; Sutter, L.; Maret, D.; Wäckers, F. Evaluation of Phytoseiid and Iolinid Mites for Biological Control of the Tomato Russet Mite Aculops lycopersici(Acari: Eriophyidae). Insects 2022, 13, 1146.
https://doi.org/10.3390/insects13121146
AMA Style
Pijnakker J, Hürriyet A, Petit C, Vangansbeke D, Duarte MVA, Arijs Y, Moerkens R, Sutter L, Maret D, Wäckers F. Evaluation of Phytoseiid and Iolinid Mites for Biological Control of the Tomato Russet Mite Aculops lycopersici(Acari: Eriophyidae). Insects. 2022; 13(12):1146.
https://doi.org/10.3390/insects13121146
Chicago/Turabian Style
Pijnakker, Juliette, Asli Hürriyet, Clément Petit, Dominiek Vangansbeke, Marcus V. A. Duarte, Yves Arijs, Rob Moerkens, Louis Sutter, Dylan Maret, and Felix Wäckers. 2022. "Evaluation of Phytoseiid and Iolinid Mites for Biological Control of the Tomato Russet Mite Aculops lycopersici(Acari: Eriophyidae)" Insects13, no. 12: 1146.
https://doi.org/10.3390/insects13121146
| https://www.mdpi.com/2075-4450/13/12/1146/htm |
Graphical circular genome map of Paraburkholderia tropica strain... | Download Scientific Diagram
Download scientific diagram | Graphical circular genome map of Paraburkholderia tropica strain IAC/BECa 135. The rings indicate coding sequences, Clusters of Orthologous Groups of proteins (COGs) categories, GC content, and GC skew. from publication: Sorghum Growth Promotion by Paraburkholderia tropica and Herbaspirillum frisingense: Putative Mechanisms Revealed by Genomics and Metagenomics | Bacteria from the genera Paraburkholderia and Herbaspirillum can promote the growth of Sorghum bicolor, but the underlying mechanisms are not yet known. In a pot experiment, sorghum plants grown on sterilized substrate were inoculated with Paraburkholderia tropica strain... | Sorghum, Metagenomics and Comparative Genomics | ResearchGate, the professional network for scientists.
Graphical circular genome map of Paraburkholderia tropica strain IAC/BECa 135. The rings indicate coding sequences, Clusters of Orthologous Groups of proteins (COGs) categories, GC content, and GC skew.
Source publication
Sorghum Growth Promotion by Paraburkholderia tropica and Herbaspirillum frisingense: Putative Mechanisms Revealed by Genomics and Metagenomics
Bacteria from the genera Paraburkholderia and Herbaspirillum can promote the growth of Sorghum bicolor, but the underlying mechanisms are not yet known. In a pot experiment, sorghum plants grown on sterilized substrate were inoculated with Paraburkholderia tropica strain IAC/BECa 135 and Herbaspirillum frisingense strain IAC/BECa 152 under phosphat...
Contexts in source publication
Context 1
... subsystem category distribution of each genome showed that 22% and 26% of proteins P. tropica strain IAC/BECa 135 ( Figure 1B) and H. frisingense strain IAC/BECa 152 ( Figure 2B), respectively, could be annotated by the Rapid Annotation using Subsystem Technology (RAST) server. P. tropica strain IAC/BECa 135 assembly resulted in one chromosome and four chromids with lengths between 455.01 kb and 3280.34 kb (
Figure 3
), whereas H. frisingense strain IAC/BECa 152 assembly resulted in a single chromosome of 5548.49 kb (Figure 4). ...
Context 2
... functional profiles of the metagenomes were highly similar at a high level of abstraction. The distribution of COG terms among the metagenomes did not differ by more than 1% between treatments (Supplementary Figure S3). Additionally, the abundances of KO pathways in the metagenomes did not differ significantly. ...
Context 3
... Species contribution to PCA2. Analysis was performed using the standard prcomp() function in R; Supplementary Figure S3: Abundance of COG terms per sample inoculated with Pt: P. tropica IAC/BECa 135 strain and Hf: H. frisingense IAC/BECa 152 strain and Ccontrol. 1, 2, 3 are replicates. ...
Management of drought stress through application of plant growth promoting rhizobacteria (PGPR) is now considered as an effective strategy in the present scenario of altered environmental conditions of the world. The aims and objectives of the present investigation was isolation, characterization and identification of some potential microbial resou...
Citations
... RG36 T . Quorum-sensing autoinducers, such as N-acyl-homoserine lactones (AHL), cause a pronounced interkingdom signaling effect on plants, provoking priming processes of pathogen defense and insect pest control (Issa et al., 2018;
Kuramae et al., 2020)
. In addition, some PGP bacteria only harbor genes for AHL receptors, so-called LuxR-solo genes, which can contribute to plant growth promotion and biological control (Kuramae et al., 2020). ...
... Quorum-sensing autoinducers, such as N-acyl-homoserine lactones (AHL), cause a pronounced interkingdom signaling effect on plants, provoking priming processes of pathogen defense and insect pest control (Issa et al., 2018;Kuramae et al., 2020). In addition, some PGP bacteria only harbor genes for AHL receptors, so-called LuxR-solo genes, which can contribute to plant growth promotion and biological control
(Kuramae et al., 2020)
. In our study, we also found only LuxR genes in the genome of strain RG36 T . ...
... Type I system is responsible for the export of small molecules, transfer of molecules to recipient cells, and secretion of unfolded proteins, type II which is responsible for the secretion of folded proteins. Strain RG36 T harbors only four genes for the type III secretion system, which are known to be large nanomachines, utilized by both pathogenic and symbiotic bacteria to inject effector proteins directly into the cytoplasm of host cells and facilitate host cell colonization
(Kuramae et al., 2020;
Tapia-García et al., 2020). Type IV, responsible for the secretion of large molecules into the cytoplasm of recipient cells. ...
[51]
The increase in microbial sequenced genomes from pure cultures and metagenomic samples reflects the current attainability of whole-genome and shotgun sequencing methods. However, software for genome visualization still lacks automation, integration of different analyses, and customizable options for non-experienced users. In this study, we introduce GenoVi, a Python command-line tool able to create custom circular genome representations for the analysis and visualization of microbial genomes and sequence elements. It is designed to work with complete or draft genomes, featuring customizable options including 25 different built-in color palettes (including 5 color-blind safe palettes), text formatting options, and automatic scaling for complete genomes or sequence elements with more than one replicon/sequence. Using a Genbank format file as the input file or multiple files within a directory, GenoVi (i) visualizes genomic features from the GenBank annotation file, (ii) integrates a Cluster of Orthologs Group (COG) categories analysis using DeepNOG, (iii) automatically scales the visualization of each replicon of complete genomes or multiple sequence elements, (iv) and generates COG histograms, COG frequency heatmaps and output tables including general stats of each replicon or contig processed. GenoVi's potential was assessed by analyzing single and multiple genomes of Bacteria and Archaea. Paraburkholderia genomes were analyzed to obtain a fast classification of replicons in large multipartite genomes. GenoVi works as an easy-to-use command-line tool and provides customizable options to automatically generate genomic maps for scientific publications, educational resources, and outreach activities. GenoVi is freely available and can be downloaded from https://github.com/robotoD/GenoVi.
... The main active bacteria are Chitinophaga, which can synthesize active substances (Huq and Akter, 2021), but there is very little research in sauce-flavor Baijiu. Bacteria from the genera Herbaspirillum can promote the growth of Sorghum
(Kuramae et al., 2020)
, have also been detected during solid-state fermentation of Chinese baijiu, but have not attracted the attention of researchers due to low levels and lack of in-depth studies. ...
Exploration of microbiome diversity of stacked fermented grains by flow cytometry and cell sorting
Sauce-flavor baijiu is one of the twelve flavor types of Chinese distilled fermented product. Microbial composition plays a key role in the stacked fermentation of Baijiu, which uses grains as raw materials and produces flavor compounds, however, the active microbial community and its relationship remain unclear. Here, we investigated the total and active microbial communities of stacked fermented grains of sauce-flavored Baijiu using flow cytometry and high-throughput sequencing technology, respectively. By using traditional high-throughput sequencing technology, a total of 24 bacterial and 14 fungal genera were identified as the core microbiota, the core bacteria were Lactobacillus (0.08–39.05%), Acetobacter (0.25–81.92%), Weissella (0.03–29.61%), etc. The core fungi were Issatchenkia (23.11–98.21%), Monascus (0.02–26.36%), Pichia (0.33–37.56%), etc. In contrast, using flow cytometry combined with high-throughput sequencing, the active dominant bacterial genera after cell sorting were found to be Herbaspirillum , Chitinophaga , Ralstonia , Phenylobacterium , Mucilaginibacter , and Bradyrhizobium , etc., whereas the active dominant fungal genera detected were Aspergillus , Pichia , Exophiala , Candelabrochaete , Italiomyces , and Papiliotrema , etc. These results indicate that although the abundance of Acetobacter , Monascus , and Issatchenkia was high after stacked fermentation, they may have little biological activity. Flow cytometry and cell sorting techniques have been used in the study of beer and wine, but exploring the microbiome in such a complex environment as Chinese baijiu has not been reported. The results also reveal that flow cytometry and cell sorting are convenient methods for rapidly monitoring complex microbial flora and can assist in exploring complex environmental samples.
... Paraburkholderia tropica strain IAC/BECa 135 and Herbaspirillum frisingense strain IAC/BECa 152 stimulated PGP traits in sorghum and its putative mechanisms were deciphered by genomics and metagenomics analysis
(Kuramae et al. 2020)
. Similarly, seeds treatment of sorghum (Sorhum bicolor L.) with chitosan synergizes the PGP activity of Pseudomonas aeruginosa-P17 (Kumar et al. 2019). ...
PGPR: the treasure of multifarious beneficial microorganisms for nutrient mobilization, pest biocontrol and plant growth promotion in field crops
Plant growth-promoting rhizobacteria (PGPR) have multifarious beneficial activities for plant growth promotion; act as source of metabolites, enzymes, nutrient mobilization, biological control of pests, induction of disease resistance vis-a-vis bioremediation potentials by phytoextraction and detoxification of heavy metals, pollutants and pesticides. Agrochemicals and synthetic pesticides are currently being utilized widely in all major field crops, thereby adversely affecting human and animal health, and posing serious threats to the environments. Beneficial microorganisms like PGPR could potentially substitute and supplement the toxic chemicals and pesticides with promising application in organic farming leading to sustainable agriculture practices and bioremediation of heavy metal contaminated sites. Among field crops limited bio-formulations have been prepared till now by utilization of PGPR strains having plant growth promotion, metabolites, enzymes, nutrient mobilization and biocontrol activities. The present review contributes comprehensive description of PGPR applications in field crops including commercial, oilseeds, leguminous and cereal crops to further extend the utilization of these potent groups of beneficial microorganisms so that even higher level of crop productivity and quality produce of field crops could be achieved. PGPR and bacteria based commercialized bio-formulations available worldwide for its application in the field crops have been compiled in this review which can be a substitute for the harmful synthetic chemicals. The current knowledge gap and potential target areas for future research have also been projected.
... Burkholderia-Caballeronia-Paraburkholderia N 2 -fixation, P solubilization, IAA production, siderophore production, cellulolytic enzyme production. Rangjaroen et al. (2015) and
Kuramae et al. (2020)
Enterobacteriaceae N 2 -fixation, P solubilization, IAA production, siderophore production, antimicrobial activity. ...
Replacement of water yam (Dioscorea alata L.) indigenous root endophytes and rhizosphere bacterial communities via inoculation with a synthetic bacterial community of dominant nitrogen-fixing bacteria
Biofertilizers containing high-density plant growth-promoting bacteria are gaining interest as a sustainable solution to environmental problems caused by eutrophication. However, owing to the limitations of current investigative techniques, the selected microorganisms are not always preferred by the host plant, preventing recruitment into the native microbiota or failing to induce plant growth-promoting effects. To address this, five nitrogen-fixing bacteria previously isolated from water yam (Dioscorea alata L.) plants and showing dominant abundance of 1% or more in the water yam microbiota were selected for analysis of their plant growth-promoting activities when used as a synthetic bacterial inoculant. Water yam cv. A-19 plants were inoculated twice at 10 and 12 weeks after planting under greenhouse conditions. Bacterial communities in root, rhizosphere, and bulk soil samples were characterized using high-throughput 16S rRNA amplicon sequencing. Compared with non-inoculated plants, all bacterial communities were significantly altered by inoculation, mainly at the genus level. The inoculation effects were apparently found in the root communities at 16 weeks after planting, with all inoculated genera showing dominance (in the top 35 genera) compared with the control samples. However, no significant differences in any of the growth parameters or nitrogen contents were observed between treatments. At 20 weeks after planting, the dominance of Stenotrophomonas in the inoculated roots decreased, indicating a decline in the inoculation effects. Interestingly, only the Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium clade was dominant (>1% relative abundance) across all samples, suggesting that bacteria related to this clade are essential core bacteria for water yam growth. This is the first report on addition of a synthetic nitrogen-fixing bacterial community in water yam plants showing that native bacterial communities can be replaced by a synthetic bacterial community, with declining in the effects of Stenotrophomonas on the modified communities several weeks after inoculation.
... Genome and metagenome profiling endophytic bacteria in sorghum Future exploration of sorghum associated bacteria in a similar experiment for optimal use in agricultural productivity
[196]
Tomatoes Understanding the population and functions of endophytic bacteria in the pathogen-infected and non-infected tomato roots Strategic measures for future exploration of endophytic bacteria in the control of plant-parasitic nematodes for improved yield [197] Rice Insights into functional attributes of rice endophytic microbiome using shotgun metagenome approach ...
Bioprospecting and Challenges of Plant Microbiome Research for Sustainable Agriculture, a Review on Soybean Endophytic Bacteria
This review evaluates oilseed crop soybean endophytic bacteria, their prospects, and challenges for sustainable agriculture. Soybean is one of the most important oilseed crops with about 20–25% protein content and 20% edible oil production. The ability of soybean root-associated microbes to restore soil nutrients enhances crop yield. Naturally, the soybean root endosphere harbors root nodule bacteria, and endophytic bacteria, which help increase the nitrogen pool and reclamation of another nutrient loss in the soil for plant nutrition. Endophytic bacteria can sustain plant growth and health by exhibiting antibiosis against phytopathogens, production of enzymes, phytohormone biosynthesis, organic acids, and secondary metabolite secretions. Considerable effort in the agricultural industry is focused on multifunctional concepts and bioprospecting on the use of bioinput from endophytic microbes to ensure a stable ecosystem. Bioprospecting in the case of this review is a systemic overview of the biorational approach to harness beneficial plant-associated microbes to ensure food security in the future. Progress in this endeavor is limited by available techniques. The use of molecular techniques in unraveling the functions of soybean endophytic bacteria can explore their use in integrated organic farming. Our review brings to light the endophytic microbial dynamics of soybeans and current status of plant microbiome research for sustainable agriculture.
... isolate, associated previously with the solubilization of Bayóvar phosphate and antibiosis to Fusarium sp., was efficient in promoting the growth of the A. vera plants, inducing leaf production and a greater accumulation of fresh biomass in the leaves and biomass in the roots. Paraburkholderia species have already been shown to promote growth in a number of other plants (Bolívar-Anillo et al., 2016;Huo et al., 2018;Zhou et al., 2018;
Kuramae et al., 2020;
García et al., 2020;Souza et al., 2020;Herpell et al., 2020). These bacteria are known to fix nitrogen (De Meyer et al., 2018;Tapia-García et al., 2020;Paulitsch et al., 2020), solubilize phosphate, and have antifungal activity (Bernabeu et al., 2018;Gao et al., 2018b;Hye-Jin & Min-Ho, 2019). ...
Endophytic bacteria promote growth and increase the aloin content of Aloe vera [Las bacterias endofíticas promueven el crecimiento y aumentan el contenido de aloína del Aloe vera]
Thales Caetano De Oliveira
Aloe vera is among the world's economically most important medicinal plants, but as the growth of this plant and, consequently, the accumulation of metabolites is slow, we tested the hypothesis that root endophytic bacteria isolated from A. vera plants can promote growth and increase the accumulation of aloin in the gel and latex. For this, we inoculate seedlings with four endophytic bacteria and a combination of them. We confirmed the hypothesis and identified two strains with potential for the formulation of inoculants to improve the cultivation of A. vera. The bacterium 149H Paraburkholderia sp. increases the number of leaves and the accumulation of biomass, but on the other hand, 35V Enterobacter ludwigii inoculation increased the content of aloin in the gel and in the latex. Further research should focus on the association of these two strains in a single inoculant, to both promote growth and increase the synthesis of metabolites. Resumen: Aloe vera se encuentra entre las plantas medicinales económicamente más importantes del mundo, pero como el crecimiento de esta planta y, en consecuencia, la acumulación de metabolitos es lento, probamos la hipótesis de que las bacterias endofíticas de raíces aisladas de las plantas de A. vera pueden promover el crecimiento y aumentar la acumulación de aloína en el gel y látex. Para ello, inoculamos plántulas con cuatro bacterias endofíticas y una combinación de ellas. Confirmamos la hipótesis e identificamos dos cepas con potencial para la formulación de inoculantes para mejorar el cultivo de A. vera. La bacteria 149H Paraburkholderia sp. aumenta el número de hojas y la acumulación de biomasa, pero, por otro lado, la inoculación con Enterobacter ludwigii 35V aumentó el contenido de aloína en el gel y en el látex. La investigación adicional debe centrarse en la asociación de estas dos cepas en un solo inoculante, tanto para promover el crecimiento como para aumentar la síntesis de metabolitos.
... Inoculation of Pseudomonas conferred plant with growth promotion and bacterial phytopathogen biocontrol (Rodríguez et al., 2020). Bacteria from the genera Paraburkholderia can promote plant growth
(Kuramae et al., 2020)
. It is reported that plant growth-promoting rhizobacteria Paraburkholderia phytofirmans (strain PsJN:gfp2x) were beneficial against the grapevine trunk pathogen Neofusicoccum parvum . ...
Cadmium phytoextraction through Brassica juncea L. under different consortia of plant growth-promoting bacteria from different ecological niches
Combined bioaugmentation inoculants composed of two or more plant growth-promoting bacteria (PGPB) were more effective than single inoculants for plant growth and cadmium (Cd) removal in contaminated soils. However, the principles of consortia construction still need to be discovered. Here, a pot experiment with Cd natural polluted soil was conducted and PGPB consortia with different ecological niches from hyperaccumulator Sedum alfredii Hance were used to compare their effects and mechanisms on plant growth condition, Cd phytoextraction efficiency, soil enzymatic activities, and rhizospheric bacterial community of Brassica juncea L. The results showed that both rhizospheric and endophytic PGPB consortia inoculants promoted plant growth (6.9%–22.1%), facilitated Cd uptake (230.0%−350.0%) of oilseed rape, increased Cd phytoextraction efficiency (343.0%−441.0%), and enhanced soil Cd removal rates (92.0%−144.0%). PGPB consortia inoculants also enhanced soil microbial carbon by 22.2%−50.5%, activated the activities of soil urease and sucrase by 74.7%−158.4% and 8.4%−61.3%, respectively. Simultaneously, PGPB consortia inoculants increased the relative abundance of Flavobacterium, Rhodanobacter, Kosakonia, Pseudomonas and Paraburkholderia at the genus level, which may be beneficial to plant growth promotion and bacterial phytopathogen biocontrol. Although the four PGPB consortia inoculants promoted oilseed growth, amplified Cd phytoextraction, and changed bacterial community structure in rhizosphere soil, their original ecological niches were not a decisive factor for the efficiency of PGPB consortia. therefore, the results enriched the present knowledge regarding the significant roles of PGPB consortia as bioaugmentation agents and preliminarily explored construction principles of effective bioaugmentation inoculants, which will provide insights into the microbial responses to combined inoculation in the Cd-contaminated soils.
... P. tropica has relevant in vitro and in vivo features as a plant growth-promoting bacterium and as an efficient rhizoplane and internal root and/or stem tissue colonizer of different host plants [18,
32]
. Effective P. tropica plant colonization is the first prerequisite for successful plant-microbe interaction and plant growth promotion, as reported for other PGPB [3]. ...
Tracking and plant growth‐promoting effect of Paraburkholderia tropica MTo‐293 applied to Solanum lycopersicum
May 2022
J BASIC MICROB
Santiago A. Vio
Pamela R. Bernabeu
Sabrina S. García
María L. Galar
María F. Luna
Paraburkholderia tropica MTo‐293 was applied as an experimental bio‐input to Solanum lycopersicum (tomato) cv. Platense. Different plant growth systems and inoculation strategies were tested to evaluate P. tropica plant colonization at the seedling stage (growth chamber) using culture‐dependent and ‐independent techniques. The effect of P. tropica on plant growth was evaluated in the growth chamber and greenhouse (productive stage) by biomass accumulation and fruit production, respectively. P. tropica was able to colonize the surface and inner root and stem of tomato seedlings regardless of the inoculation strategy—at sowing and/or before transplanting—showing the competitive nature of P. tropica in nonsterile substrate systems. A nested polymerase chain reaction was validated to track P. tropica in tomato plants even in the inner stem with endophytic P. tropica populations of less than 102 CFU g–1 of fresh weight. Efficient colonization of P. tropica correlated with a positive effect on tomato growth when applied at sowing and/or before transplanting: plant growth promotion was observed not only at the seedling stage but also at productive stages improving crop yield in two different seasons. To our knowledge, this report is the first to track and evaluate the plant growth‐promoting effect of P. tropica MTo‐293 in tomato plants grown in nonsterile substrate systems.
... Moreover, the abundance of 2AEP transporters and degradation pathways in bacterial meta-omics datasets suggests 2AEP production is ubiquitous (Murphy et al., 2021). We speculate that 2AEP acquisition provides a clear advantage during nutrient limiting growth conditions which are frequently observed in plant rhizospheres (Bell et al., 2014;Cui et al., 2018), by expanding the metabolic repertoire of BIRD-1 to utilize substrates associated with the plant microbiome
(Kuramae et al., 2020;
Akinola et al., 2021). Indeed, 2AEP catabolism may present a key nutrient driving plant-Pseudomonas interactions and partially explain why this genus forms abundant components of rhizosphere, rhizoplane and root endophyte communities (Robinson et al., 2016;Rathore et al., 2017). ...
2‐Aminoethylphosphonate utilization in Pseudomonas putida BIRD ‐1 is controlled by multiple master regulators
Article
Full-text available
Mar 2022
ENVIRON MICROBIOL
Andrew R. J. Murphy
David J. Scanlan
Yin Chen
Gary D. Bending
Ian D.E.A. Lidbury
| https://www.researchgate.net/figure/Graphical-circular-genome-map-of-Paraburkholderia-tropica-strain-IAC-BECa-135-The-rings_fig3_341375886 |
Phillips-Medisize LLC | Medical Product Outsourcing
Phillips-Medisize, LLC, a Molex company, is a leading global outsource provider of design and manufacturing services to the drug delivery, consumable diagnostics, medical device, and specialty commercial markets
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Phillips-Medisize, LLC, a Molex company, is a leading global outsource provider of design and manufacturing services to the drug delivery, consumable diagnostics, medical device, and specialty commercial markets. Backed by the combined global resources of Molex and its parent company Koch Industries, Phillips-Medisize’s core advantage to customers is the knowledge of its people to integrate design, molding, and automation, providing innovative, high-quality manufacturing solutions.
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Patient Monitoring
An FAQ on Continuous Glucose Monitors and Other Wearables—A Medtech Makers Q&A
Since CGMs are gaining acceptance, stakeholders need to be familiar with their details on usage and development.
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Purely pork | Meatpoultry.com | November 01, 2016 15:48 | MEAT+POULTRY
Beeler’s has refined its pork production and processing business by looking up and down the supply chain for opportunities.
Purely pork
Beeler's has refined its pork production and processing business by looking up and down the supply chain for opportunities.
Fifth-generation pig farmers, Tim Beeler and his brothers bought the family farm from their father in the early 1980s. At that time the farm used the conventional method for marketing its products; it loaded meat into a truck and shipped it to a larger packing company. But the conventional approach wasn’t delivering the results the brothers wanted, so they made a decision to go in a different direction.“We decided to try to market our own product,” says Tim Beeler, president, Beeler’s Pure Pork, Le Mars, Iowa. “At that time the natural and antibiotic-free industries were just starting to evolve, so that’s what we decided was going to make us different.”The move to natural and antibiotic-free pork worked out well for Beeler’s. Now, the company is evolving again with the introduction of Beeler’s Heluka line. The Heluka branded pork will remain natural and antibiotic free, but it will also be marketed as non-GMO.The transition beginsAfter the decision to go natural, Beeler’s pulled growth promotants and antibiotics from its feed rations and opened a retail store for its products in West Des Moines, Iowa. The store eventually took the form of a meat market and bakery, but Beeler wondered if the natural and antibiotic-free products provided significant value to the customers that shopped there.“I think the thing that was more important was the fact that we were a family operation,” he says. “My brothers and I worked in the shop with our wives and our kids and people got to know us. I think that was more important, the fact that people knew where their meat was coming from and that it was a family operation.”After eight years, Beeler decided the market had developed and grown enough to get into the wholesale side of the natural business. The family sold the retail shop and began looking for a plant. The Beeler family found a natural plant in the northwest corner of Iowa that was going out of business.“We didn’t buy them or anything, we just kind of picked up the pieces and started evolving from there,” Beeler says.The original Beeler’s farm in southern Iowa still produced pork in the conventional method as the company began its natural operations in northwest Iowa by working with other independent livestock producers to raise pigs to Beeler’s standards.A look toward welfare friendlyBeeler’s early customer base included Wild Oats and some independent retailers like the Wedge cooperative in Minneapolis and Cid’s Food Market in Taos, New Mexico. Eventually, as the market evolved, Beeler’s became the exclusive pork supplier to Wild Oats along with supplying the co-ops and began to do some business with Whole Foods as well. Ultimately, Whole Foods acquired Wild Oats.Beeler’s began doing significant business with Whole Foods and supplied large portions of the western half of the United States. When Whole Foods started to write its Global Animal Partnership (GAP) standards, animal welfare standards and humane raising standards, Tim Beeler sat on the committee and helped.Helping Whole Foods write its standards for animal well-being resulted in Beeler taking a trip to Europe in the fall of 2004 to look at different farms there. By 2005 there were plans in the works for Beeler’s to start building a new facility.“After seeing the welfare-friendly farms in Europe, we came home and tore down the factory farm and built our own welfare-friendly farrowing farm in northwest Iowa,” Beeler says. “On that particular farm, we don’t use gestation crates and we don’t use farrowing crates. The gestating sows are housed in large social groups, deep bedded and they can even go outdoors.” The farm was completed in the fall of 2005.Up to the challengeOnce Beeler’s made the decision to do things differently, challenges on the production side presented themselves, but the company was dedicated to relearning how to raise pigs the way they were produced 50 years ago. However, there were some differences that Beeler’s needed to account for.“We were trying to do this on a larger scale basis,” Beeler says. “So it’s not like we just had 30 to 50 sows to contend with, we had 2,000. So we were trying to see if we could build a larger welfare-friendly farm and make it work, and there were a lot of challenges.”Once in production mode, those challenges began to pop up. The first thing Beeler learned pertained to the genetics of the sows. The previous operation relied on gestation crates and without them the sows had difficulty adapting to large social groups, Beeler says. “There was a lot of fighting and they got too big, so we had to select a different genetic strain.”Beeler’s decided on Duroc boars from Europe crossed with European-based females to get the temperament they needed for the welfare friendly environment. Beeler says they found the sows to be more docile and friendlier in the open gestation system. “Their mothering characteristics were better in a box where they were not confined to crates,” he explains.Along with a new strain of animal and the elimination of gestation crates, Beeler’s stopped using farrowing crates. At the start, Beeler’s saw a pre-weaning mortality rate of 50 to 55 percent. Beeler knew that a mortality rate that high would not only put the farm out of business, but was also inhumane. After six months of observation and study, Beeler’s came up with a redesign.“The goal was, the sow is supposed to be able to stand up, turn around, be able to move, and lay down in full recumbency,” Beeler says. “So how were we going to accomplish that and yet save pigs?”The newly designed box gave sows the ability to physically behave in accordance with the goals set forth. Protective bars were fitted to what Beeler refers to as a maternity box. The box gives the sow the room to exhibit the necessary behaviors, but the bars protect the pigs due to the sow’s ability to easily step over them.“Those bars are placed in there in such a way that there is only one way for her to lie down and that is between the bars. And that gives the pigs a chance to get out of her way,” Beeler says.The maternity/farrowing boxes were raised on wire, like the conventional style, allowing for nesting and keeping the sow and her pigs dry. Once the boxes were designed, remodeled and constructed to the spec necessary, the farrowing performance improved dramatically, Beeler says.
| https://www.meatpoultry.com/articles/19246-purely-pork |
Sézary syndrome | Encyclopedia MDPI
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Sézary syndrome
History
Subjects: Genetics & Heredity
Sézary syndrome is an aggressive form of a type of blood cancer called cutaneous T-cell lymphoma. Cutaneous T-cell lymphomas occur when certain white blood cells, called T cells, become cancerous; these cancers characteristically affect the skin, causing different types of skin lesions. In Sézary syndrome, the cancerous T cells, called Sézary cells, are present in the blood, skin, and lymph nodes. A characteristic of Sézary cells is an abnormally shaped nucleus, described as cerebriform.
genetic conditions
1. Introduction
The cancerous T cells can spread to other organs in the body, including the lymph nodes, liver, spleen, and bone marrow. In addition, affected individuals have an increased risk of developing another lymphoma or other type of cancer.
Sézary syndrome most often occurs in adults over age 60 and usually progresses rapidly; historically, affected individuals survived an average of 2 to 4 years after development of the condition, although survival has improved with newer treatments.
Although Sézary syndrome is sometimes referred to as a variant of another cutaneous T-cell lymphoma called mycosis fungoides, these two cancers are generally considered separate conditions.
2. Frequency
Sézary syndrome is a rare condition, although its prevalence is unknown. It is the second most common form of cutaneous T-cell lymphoma after mycosis fungoides, accounting for approximately 3 to 5 percent of cases of cutaneous T-cell lymphoma.
3. Causes
The cause of Sézary syndrome is unknown. Most affected individuals have one or more chromosomal abnormalities, such as the loss or gain of genetic material. These abnormalities occur during a person's lifetime and are found only in the DNA of cancerous cells. Abnormalities have been found on most chromosomes, but some regions are more commonly affected than others. People with this condition tend to have losses of DNA from regions of chromosomes 10 and 17 or additions of DNA to regions of chromosomes 8 and 17. It is unclear whether these alterations play a role in Sézary syndrome, although the tendency to acquire chromosomal abnormalities (chromosomal instability) is a feature of many cancers. It can lead to genetic changes that allow cells to grow and divide uncontrollably.
4. Inheritance
The inheritance pattern of Sézary syndrome has not been determined. This condition occurs in people with no history of the disorder in their family and is not thought to be inherited in most cases.
5. Other Names for This Condition
Sezary erythroderma
Sezary syndrome
Sezary's lymphoma
This entry is adapted fromhttps://medlineplus.gov/genetics/condition/sezary-syndrome
References
Campbell JJ, Clark RA, Watanabe R, Kupper TS. Sezary syndrome and mycosisfungoides arise from distinct T-cell subsets: a biologic rationale for theirdistinct clinical behaviors. Blood. 2010 Aug 5;116(5):767-71. doi:10.1182/blood-2009-11-251926.
Caprini E, Cristofoletti C, Arcelli D, Fadda P, Citterich MH, Sampogna F,Magrelli A, Censi F, Torreri P, Frontani M, Scala E, Picchio MC, Temperani P,Monopoli A, Lombardo GA, Taruscio D, Narducci MG, Russo G. Identification of key regions and genes important in the pathogenesis of sezary syndrome by combininggenomic and expression microarrays. Cancer Res. 2009 Nov 1;69(21):8438-46. doi:10.1158/0008-5472.CAN-09-2367.
Hwang ST, Janik JE, Jaffe ES, Wilson WH. Mycosis fungoides and Sézarysyndrome. Lancet. 2008 Mar 15;371(9616):945-57. doi:10.1016/S0140-6736(08)60420-1. Review.
Iżykowska K, Przybylski GK, Gand C, Braun FC, Grabarczyk P, Kuss AW, Olek-HrabK, Bastidas Torres AN, Vermeer MH, Zoutman WH, Tensen CP, Schmidt CA. Geneticrearrangements result in altered gene expression and novel fusion transcripts in Sézary syndrome. Oncotarget. 2017 Jun 13;8(24):39627-39639. doi:10.18632/oncotarget.17383.
Iżykowska K, Przybylski GK. Genetic alterations in Sezary syndrome. LeukLymphoma. 2011 May;52(5):745-53. doi: 10.3109/10428194.2010.551159.
Laharanne E, Oumouhou N, Bonnet F, Carlotti M, Gentil C, Chevret E, Jouary T, Longy M, Vergier B, Beylot-Barry M, Merlio JP. Genome-wide analysis of cutaneous T-cell lymphomas identifies three clinically relevant classes. J Invest Dermatol.2010 Jun;130(6):1707-18. doi: 10.1038/jid.2010.8.
Prasad A, Rabionet R, Espinet B, Zapata L, Puiggros A, Melero C, Puig A,Sarria-Trujillo Y, Ossowski S, Garcia-Muret MP, Estrach T, Servitje O,Lopez-Lerma I, Gallardo F, Pujol RM, Estivill X. Identification of Gene Mutationsand Fusion Genes in Patients with Sézary Syndrome. J Invest Dermatol. 2016Jul;136(7):1490-1499. doi: 10.1016/j.jid.2016.03.024.
Vural S, Akay BN, Botsalı A, Atilla E, Parlak N, Okçu Heper A, Şanlı H.Transformation of Mycosis Fungoides/Sezary Syndrome: Clinical Characteristics andPrognosis. Turk J Haematol. 2018 Mar 1;35(1):35-41. doi: 10.4274/tjh.2016.0502.
Wong HK, Mishra A, Hake T, Porcu P. Evolving insights in the pathogenesis and therapy of cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome). Br J Haematol. 2011 Oct;155(2):150-66. doi: 10.1111/j.1365-2141.2011.08852.x.
Woollard WJ, Pullabhatla V, Lorenc A, Patel VM, Butler RM, Bayega A, Begum N, Bakr F, Dedhia K, Fisher J, Aguilar-Duran S, Flanagan C, Ghasemi AA, Hoffmann RM,Castillo-Mosquera N, Nuttall EA, Paul A, Roberts CA, Solomonidis EG, Tarrant R,Yoxall A, Beyers CZ, Ferreira S, Tosi I, Simpson MA, de Rinaldis E, Mitchell TJ, Whittaker SJ. Candidate driver genes involved in genome maintenance and DNArepair in Sézary syndrome. Blood. 2016 Jun 30;127(26):3387-97. doi:10.1182/blood-2016-02-699843.
Yamashita T, Abbade LP, Marques ME, Marques SA. Mycosis fungoides and Sézarysyndrome: clinical, histopathological and immunohistochemical review and update. An Bras Dermatol. 2012 Nov-Dec;87(6):817-28; quiz 829-30. Review.
| https://encyclopedia.pub/entry/history/show/13622 |
IJGI | Free Full-Text | Indexing Mixed Aperture Icosahedral Hexagonal Discrete Global Grid Systems
Discrete global grid systems (DGGSs) are an emerging multiresolution 3D model used to integrate and analyze big earth data. The characteristic of multiresolution is usually realized by hierarchically subdividing cells on the sphere using certain refinement. This paper introduces mixed aperture three- and four- icosahedral hexagonal DGGSs using two types of refinement, the various combinations of which can provide more resolutions compared with pure aperture hexagonal DGGSs and can flexibly design the aperture sequence according to the target resolutions. A general hierarchy-based indexing method is first designed, and related indexing arithmetics and algorithm are developed based on the indexing method. Then, the grid structure on the surface of the icosahedron is described and by projection spherical grids are obtained. Experiments show that the proposed scheme is superior to pure aperture schemes in choosing grid resolutions and can reduce the data volume by 38.5% in representing 1-km resolution raster dataset; using the proposed indexing arithmetics to replace spherical geometry operations in generating discrete spherical vector lines based on hexagonal cells can improve the generation efficiency.
Indexing Mixed Aperture Icosahedral Hexagonal Discrete Global Grid Systems
by Rui Wang , Jin Ben * , Jianbin Zhou and Mingyang Zheng
Abstract
:
Keywords:
discrete global grid system
hexagon
mixed aperture
indexing method
indexing arithmetics
1. Introduction
In recent years, the explosive growth of geospatial data volume and the increasingly complicated and multiple data structures have posed a great challenge to their integration and analysis [ 1 ]. Traditional two-dimensional (2D) maps based on map projections usually represent local areas of the earth and only provide a flat view of the globe [ 2 ]. In addition, location representation using geographical coordinates may cause truncation errors in computers due to the use of floating-point numbers and thus add calculation complexity [ 3 ]. The longitude and latitude framework can represent the three-dimensional (3D) globe. However, cells in this framework are usually irregular [ 2 ], where the cells will change from the equator to poles with increasing of latitude and at the poles the quadrilateral cells degenerate into triangles [ 4 ].
Discrete global grid system (DGGS) is a spatial reference framework being developed to solve the above problems. Under this framework, the earth is discretized into a set of cells. Each cell represents an area on the surface of the earth and all data related to the area can be assigned to the cell, which helps integration of multi-source datasets. DGGS can provide more regular cells to partition the Earth into a multiresolution hierarchy, and the earth is approximated by a regular polyhedron as the initial tessellation [ 4 ]. The integer index is assigned to each cell for location representation. Based on these characteristics, DGGSs have aroused widespread academic attention and been developed in various fields, such as global gazetteer [ 5 ], ocean tidal simulation [ 6 ], and handling big Earth data with cloud computing technology [ 7 ]. The Open Geospatial Consortium (OGC) has released an abstract specification for DGGS [ 8 ], which highlights equal-area cells desirable in the integrated analysis of very large, multisource, and multiresolution geospatial data. DGGSs differ in basic elements such as the base polyhedron, the type of cells, the type of refinement and the indexing method.
Regular cells used in DGGSs are triangles, quadrilaterals, and hexagons. Among the three shapes, hexagons have a uniform neighboring relationship that can help spatial analysis [ 4 , 9 ]. They also have the highest packing density and best approximate the circular regions [ 10 ]. ARCGIS has developed a tool of creating the hexagon tessellation on the 2D plane for statistical analysis due to its good geometric properties [ 11 ]. However, unlike triangles and quadrilaterals, hexagons have no congruence that means a big hexagon cannot be composed of several small hexagons, which complicates the multi-resolution application of hexagons.
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DGGSs should be able to visualize, integrate, and analyze various geospatial datasets [ 2 , 14 ]. To assign the data into associated cells, an indexing method is necessary for data querying. Indexing arithmetics also need to be defined for geospatial analysis such as neighboring finding and distance measurement. Hierarchy-based indexing methods have extremely high efficiency in hierarchical traversal. A hierarchical index can not only embody location information but also reflect the cell resolution, thus there is no need for metadata [ 13 ]. Since hexagons have no congruence, the hierarchical relationship for hexagonal cells is not as simple and clear as that for triangular and quads; therefore researchers have studied and proposed different hierarchy-based indexing methods for hexagonal DGGSs [ 10 , 15 , 16 , 17 ]. Current hierarchy-based indexing methods and related indexing algorithms are mainly focused on pure aperture hexagonal DGGSs and cannot be applied to mixed aperture ones. CPI defines a general indexing method for different mixed aperture sequences, but it involves less about specific indexing arithmetics and algorithms.
This paper focuses on mixed aperture 3 and 4 hexagonal DGGSs and proposes a hierarchy-based indexing method based on cell directions. The general arithmetic rule and algorithm are also given for all mixed aperture 3 and 4 sequences. To verify the availability and efficiency of our scheme, this paper represents the current global raster dataset, uses current vector data to generate discrete spherical vector lines, and respectively compares the data volume used and number of cells in vector lines generated in unit time between the proposed scheme and other existing schemes.
We organize the paper as follows: related work is presented in Section 2 . Section 3 describes the proposed scheme for the mixed aperture 3 and 4 hexagonal DGGS. The proposed indexing method for the mixed aperture 3 and 4 hexagonal grid and related indexing arithmetics and algorithm are first described. Then, the grid on the surface of the icosahedron and projection into the sphere is discussed. In Section 4 , global raster datasets and vector data are applied in our scheme, and comparisons with other schemes are given. Conclusions and future work are presented in Section 5 .
2. Related Work
Base polyhedron: There are five regular polyhedrons used in DGGSs, which are tetrahedrons, cubes, octahedrons, dodecahedrons, and icosahedrons ( Figure 1 ).
The tetrahedron is simple and it was ever used to construct the virtual globe [ 18 ]. DGGSs based on cubes are popular [ 12 , 19 , 20 ]. Cubes can fit the Cartesian coordinate system well, which facilitates calculation. The octahedron has a relatively simple location relation with the earth [ 4 , 21 ]. Bai et al. and Ben et al. have studied the hexagonal DGGSs based on an octahedron about hierarchical partitioning, indexing, and grid generation [ 21 , 22 ]. The dodecahedron is used less often due to its pentagonal faces. The distortion of grid cells in DGGSs based on an icosahedron is the smallest because faces of the icosahedron are the most [ 23 ]. All faces of the icosahedron are triangles and can be covered by hexagons without overlap and gap (except 12 pentagons centered at 12 vertices of the icosahedron). Currently, most hexagonal DGGSs use an icosahedron as the base polyhedron. The general idea used to construct the icosahedral hexagonal DGGS is illustrated in Figure 2 . The idea is to first study the properties of hexagonal grid systems on the infinite plane, then build the hexagonal grid system on the closed surface of the icosahedron, and finally project the icosahedral hexagonal grid system to the sphere. In this paper, an icosahedron is used as the base polyhedron for our proposed scheme.
Types of cells: Triangles, hexagons and quadrilaterals are commonly used in DGGSs. Since the faces of most regular polyhedrons are triangles, it is natural to use triangular cells to partition these faces. However, the neighboring relationship for triangles is complicated, as Figure 3 a illustrates. It is the same as quads ( Figure 3 b), but quads can be compatible with most of the current datasets, hardware, and algorithms [ 12 ]. The six distances from one hexagonal cell to its six neighbors are identical ( Figure 3 c), thus hexagons have uniform adjacency which is desirable for spatial analysis in GIS [ 4 ]. In addition, relevant research has proven that hexagons have the highest sampling efficiency and angular resolution [ 9 ]. In this paper, our scheme chooses hexagons as the base cell.
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Section 1
Types of index: In a DGGS, each cell is assigned a unique index as a representation of locations, and operations of cells are usually performed through indexing arithmetics. Therefore, the characteristics and arithmetic rules of indices impact the efficiency and reliability of data processing in a DGGS and are the core factors for a DGGS. For aperture 3 hexagonal DGGSs, Vince proposed the barycentric indexing method using an octahedron [ 27 ]. Vince also proposed the radix indexing based on an icosahedron. PYXIS is an aperture 3 icosahedral hexagonal DGGS and has been successfully applied in an online-service system for geospatial data called Global Grid Systems by the PYXIS inonovation inc [ 28 ]. The indexing arithmetics of this method are complicated because of its fractal coverage hierarchy [ 24 ]. Sahr proposed two indexing methods in [ 15 ], pyramid indexing and path indexing. The pyramid indexing method is mainly applicable to single resolution. Path indexing is a hierarchy-based indexing method and is similar to that of PYXIS. For aperture 4 hexagonal DGGSs, Tong et al. proposed the hexagonal quad balanced structure (HQBS) [ 16 ], but this method indexes centers and vertices of hexagonal cells at the same time, which leads to complicated indexing arithmetic rule and possible failure of operation [ 29 ]. Wang et al. proposed the hexagonal lattice quad tree (HLQT) based on a symmetric assignment of aperture 4 child cells [ 17 ]. The above are all designed for the pure aperture based on one specific type of polyhedron. Amiri used a coordinate system and designs a general indexing method that is independent of the base polyhedron and aperture [ 24 ].
The existing indexing method for mixed aperture hexagonal DGGSs that can be found in the literature is CPI [ 3 , 13 ]. CPI uses the base digits {0,1,2,3,4,5,6} to index hierarchical cells and the assignment of digits is the same as generalized balanced ternary (GBT). CPI also gives the realization of unique index. As discussed earlier, CPI focuses on the general concepts and construction of the mixed aperture hexagonal DGGSs. In this paper, our indexing method is partly developed from CPI because of the use of unique index, but considers cell directions on the 2D plane to define basic digits to simplify operations. We also discuss the indexing arithmetics and algorithms of our scheme in detail.
3. Framework
The characteristics of the mixed aperture 3 and 4 grid are first described. Then, the indexing method is proposed, and the indexing arithmetic rules and related algorithm are given. Finally, the mixed aperture 3 and 4 grid on the surface of the icosahedron and projection onto the sphere is introduced.
3.1. Mixed Aperture 3 and 4
Figure 5
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Figure 5
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3.2.1. Indexing Method
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As shown in Figure 5 , the hexagons at level 1 can have at most seven child cells at level 2 and may result in multiple indices for a cell at level 2. In a DGGS, each cell has one unique index. To realize the uniqueness of index, each parent cell in one level can generate three child cells for aperture 3 and four child cells for aperture 4 to ensure that the area sum of their children cells is the same as that of the parent cell, and the generated finer cells do not overlap and do not have gaps [ 13 ]. Figure 6 illustrates the possible types of child cells chosen from the seven related finer cells for a parent cell, in which the gray cells are the chosen child cells and the white finer cells are the child cells of other parent cells. It can be seen that all types must contain the child cell that shares the center with the parent cell.
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3.2.2. Indexing Arithmetics and Algorithms
As discussed earlier, indices are just the one-dimensional (1D) integer representations of the 2D floating-point coordinates of cells on the plane; therefore, indexing arithmetics correspond to 2D vector arithmetics [ 30 ], which can improve the calculation efficiency because integers are more suitable for computers to process. The most important and essential indexing arithmetic is index addition for most spatial analyses are realized based on it, such as neighborhood queries and buffering analyses. Index subtraction is just the inverse operation of addition [ 30 ]. In this section, we introduce indexing addition of our proposed indexing method.
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Appendix A gives an example of addition tables obtained by the above proposed method and an example of index addition.
3.3. Grid on the Surface of the Icosahedron and Projection
As Figure 2 shows, hexagonal grid systems are usually built on the surface of an icosahedron first and then projected onto the sphere to obtain the hexagonal DGGS as the planar grids cannot be placed directly on the sphere, which will cause the grids to break. The faces of the polyhedron can be seen as planes so that we can easily partition the grids on them; then, the polyhedral hexagonal grids can be projected onto the sphere by projections. The topological relationship between cells also remains unchanged; thus, the result of indexing addition remains the same.
10
Figure 10
To simplify the operations, the 20 hexagons and 12 pentagons are used as the initial cell. In the subsequent partition, we restrict the generated grid inside the boundaries of each tile, which are the edges of the hexagon and pentagon respectively. Therefore, the number and assignment of the generated cells in each tile are not related with the specific aperture sequence.
32
Figure 11
(
4. Experiments and Discussion
Two experiments are presented to verify the advantages of our proposed scheme. A DGGS should support both raster datasets such as images or elevation datasets, and vector data. In the first experiment, we compare the data volume different schemes use to represent the raster dataset. In the second experiment, the discrete vector line using hexagonal grids is generated based on the index arithmetics we propose in Section 3 and we compare the generation efficiency, which is measured by number of cells generated in unit time, with that of the traditional algorithm.
4.1. Mixed Aperture Hexagonal Representation of a Global Raster Dataset
Figure 12
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8
The specific steps for representing GTOPO30 in the proposed scheme are as follows:
(1) Comparison with existing pure aperture hexagonal DGGS to specify the grid level and the aperture sequence;
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| https://www.mdpi.com/2220-9964/9/3/171/htm#ijgi-09-00171-f013 |
Animals | Free Full-Text | Integrated Transcriptome and Microbiota Reveal the Regulatory Effect of 25-Hydroxyvitamin D Supplementation in Antler Growth of Sika Deer
The level of plasma 25-hydroxyvitamin D (25(OH)D) is associated with the growth of the antler, a fast-growing bone organ of Cervidae. However, the benefits of 25(OH)D supplementation on antler growth and the underlying mechanisms remain unclear. Here, the antler growth profile and transcriptome, plasma parameters, rumen bacteria, and metabolites (volatile fatty acids and amino acids) were determined in sika deer in a 25(OH)D supplementation group (25(OH)D, n = 8) and a control group (Ctrl, n = 8). 25(OH)D supplementation significantly increased the antler weight and growth rate. The levels of IGF-1,25(OH)D and 1,25-dihydroxyvitamin D were significantly higher in the 25(OH)D group than in the Ctrl group, while the levels of LDL-C were lower. The levels of valerate and branched-chain amino acids in the rumen fluid were significantly different between the 25(OH)D and Ctrl groups. The bacterial diversity indices were not significantly different between the two groups. However, the relative abundances of the butyrate-producing bacteria (families Lachnospiraceae and Succinivibrionaceae) and the pyruvate metabolism pathway were higher in the 25(OH)D group. The transcriptomic profile of the antler was significantly different between the 25(OH)D and Ctrl groups, with 356 up- and 668 down-regulated differentially expressed genes (DEGs) in the 25(OH)D group. The up-regulated DEGs were enriched in the proteinaceous extracellular matrix and collagen, while the down-regulated DEGs were enriched in the immune system and lipid metabolism pathways. Overall, these results provide novel insights into the effects of 25(OH)D supplementation on the host metabolism, rumen microbiota, and antler transcriptome of sika deer.
Integrated Transcriptome and Microbiota Reveal the Regulatory Effect of 25-Hydroxyvitamin D Supplementation in Antler Growth of Sika Deer
by Huazhe Si 1,† , Songze Li 1,† , Weixiao Nan 1 , Jianan Sang 1 , Chao Xu 2,* and Zhipeng Li 1,3,4,*
1
2
Department of Special Animal Nutrition and Feed Science, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China
3
Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer, Jilin Agricultural University, Changchun 130118, China
4
Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Animals 2022 , 12 (24), 3497; https://doi.org/10.3390/ani12243497
Received: 29 October 2022 / Revised: 21 November 2022 / Accepted: 7 December 2022 / Published: 11 December 2022
(This article belongs to the Section Animal Nutrition )
Versions Notes
Abstract
:
Simple Summary
The antler is an important product of deer, which involves in the fast growth of bone. Previous study demonstrated that the production efficiency of 1,25(OH)
2
2
D precursor that is closely associated with bone development in mammals. However, the direct effects on antler growth and transcription, and the responses of the gut microbiota and metabolism of 25(OH)D supplementation in deer remain unclear. In this study, we demonstrated that 25(OH)D supplementation directly increased the growth and affected the gene expression profiles of sika deer antler. The bacteria community composition and metabolites in rumen were also changed following 25(OH)D supplementation, suggesting the enhanced metabolism of branch-amino acids. Our results confirmed the positive effect of 25(OH)D on antler growth and revealed the regulation of 25(OH)D supplementation on the host and microbes in sika deer.
Abstract
The level of plasma 25-hydroxyvitamin D (25(OH)D) is associated with the growth of the antler, a fast-growing bone organ of Cervidae. However, the benefits of 25(OH)D supplementation on antler growth and the underlying mechanisms remain unclear. Here, the antler growth profile and transcriptome, plasma parameters, rumen bacteria, and metabolites (volatile fatty acids and amino acids) were determined in sika deer in a 25(OH)D supplementation group (25(OH)D,
n
= 8) and a control group (Ctrl,
n
= 8). 25(OH)D supplementation significantly increased the antler weight and growth rate. The levels of IGF-1,25(OH)D and 1,25-dihydroxyvitamin D were significantly higher in the 25(OH)D group than in the Ctrl group, while the levels of LDL-C were lower. The levels of valerate and branched-chain amino acids in the rumen fluid were significantly different between the 25(OH)D and Ctrl groups. The bacterial diversity indices were not significantly different between the two groups. However, the relative abundances of the butyrate-producing bacteria (families Lachnospiraceae and Succinivibrionaceae) and the pyruvate metabolism pathway were higher in the 25(OH)D group. The transcriptomic profile of the antler was significantly different between the 25(OH)D and Ctrl groups, with 356 up- and 668 down-regulated differentially expressed genes (DEGs) in the 25(OH)D group. The up-regulated DEGs were enriched in the proteinaceous extracellular matrix and collagen, while the down-regulated DEGs were enriched in the immune system and lipid metabolism pathways. Overall, these results provide novel insights into the effects of 25(OH)D supplementation on the host metabolism, rumen microbiota, and antler transcriptome of sika deer.
Keywords:
25-hydroxyvitamin D
;
sika deer
;
antler transcriptome
;
immune response
;
lipid metabolism
1. Introduction
Sika deer ( Cervus nippon ) is an important ruminant species that periodically grows velvet antlers, which is a completely regenerated organ with a fast growth rate in mammals [ 1 ]. Antlers start to grow from bony pedicles located on the head of male sika deer in the spring of each year, and antler bone growth occurs through a combination of modified endochondral ossification within each antler distal tip after cartilage formation during the growth period [ 2 ]. Furthermore, the antler is a typical example of rapid bone growth, with rates reaching 0.67 cm/day in red deer [ 3 ], 1.25 cm/day in sika deer [ 4 ], to 2.75 cm/day in elk [ 5 ]. The morphological and histological evidence demonstrates that antler growth is a manifestation of cartilage ossification, including endochondral ossification and intramembranous ossification [ 6 ]. Transcriptomic analysis has further indicated that the genes mainly involved in mesenchymal progenitor cell proliferation, chondrogenesis, and osteogenesis are responsible for the rapid growth of antlers in sika deer [ 7 , 8 ]. These results suggest that bone metabolism likely affects antler growth in sika deer.
Growing evidence has demonstrated that the active forms of vitamin D, 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH) 2 D), are essential for bone metabolism [ 9 ]. 25(OH)D directly promotes osteoclast differentiation to regulate bone resorption, while 1,25(OH) 2 D indirectly stimulates the differentiation of precursor cells into osteoclasts by inducing the production of the receptor activator nuclear factor-κB ligand [ 10 ]. The results of studies in dairy cows have also suggested that calcium absorption and bone resorption are affected by the plasma concentration of 1,25(OH) 2 D [ 11 ]. For Cervidae, it has been observed that the serum level of 1,25(OH) 2 D in white-tailed deer is associated with the antler growth rate [ 12 ]. Sempere et al. (1989) suggested that the local production of 1,25(OH) 2 D in antlers likely contributes to their bone growth in roe deer [ 13 ]. Importantly, we previously demonstrated that the efficiency of 1,25(OH) 2 D production is also associated with the growth of reindeer antlers [ 14 ]. We thus hypothesized that 25(OH)D supplementation could accelerate the antler growth profile of sika deer. However, Rodney et al. (2018) found a positive correlation in Holstein cows between 25(OH)D and insulin-like growth factor 1 (IGF-1) [ 15 ], an endocrine factor involved in regulating antler growth [ 16 ]. Vitamin D treatment increases both 25(OH)D and IGF-1 concentrations in humans [ 17 ]. Moreover, a previous study demonstrated that reserve mesenchymal stem cells (MSCs) within the antler growth center (AGC) [ 18 ] were mediated by IGF-1 [ 19 ]. Thus, there is a possibility that 25(OH)D supplementation affects the production of IGF-1 and the transcriptome of AGC to promote antler growth in sika deer.
It has also been reported that supplementation with 25(OH)D affects energy metabolism [ 15 ], promotes colostrum yield in Holstein dairy cows [ 20 ], and linearly increases the average daily gain and feed efficiency of preweaning calves [ 21 ]. It is well known that the rumen is the key location affecting feed digestion, energy metabolism, and host performance [ 22 ]. These results suggest that 25(OH)D supplementation affects rumen metabolism. Importantly, several studies have suggested an interaction between the gut microbiota and circulating vitamin D levels. Singh et al. (2020) suggested that vitamin D supplementation significantly increased gut microbial diversity and the Bacteroidetes-to-Firmicutes ratio of women [ 23 ]. Thomas et al. (2020) found that higher levels of 1,25(OH) 2 D were associated with the abundances of specific butyrate producers from the Clostridiales order [ 24 ]. Therefore, we hypothesized that 25(OH)D supplementation is related to the composition and function of the rumen microbiota in sika deer.
In this study, we aimed to investigate (i) whether antler growth and plasma parameters are associated with 25(OH)D supplementation; (ii) whether rumen microbiota features and metabolites are affected by 25(OH)D supplementation using 16S rRNA gene sequencing and gas chromatography; and (iii) how the transcriptome in the AGC responds to 25(OH)D supplementation in sika deer.
2. Materials and Methods
2.1. Animals, Experimental Design, and Diets
A total of 16 four-year-old male sika deer (mean body weight = 109.5 ± 2.1 kg) with a similar casting time of the hard antler button (around 25 April 2020) were used in this study at the research farm of Jilin Agricultural University. The sika deer were randomly assigned to two groups, were fed a total mixed ration (TMR) based on roughage and concentrate (45:55, dry matter basis,
Table S1
), and were randomly assigned to one of two experimental diets: a basal diet (Ctrl group,
n
= 8) or 3 mg/d 25(OH)D supplementation diet (120,000 IU per sika deer per day, 25(OH)D group,
n
= 8). The sika deer in each group were raised in an individual pen, were fed twice daily at 07:00 a.m. and 16:00 p.m., and had free access to drinking water. The experiments were conducted for 8 weeks after the removal of the hard antler button, with 1 week for adaptation followed by 7 weeks of dietary treatment. All of the animal-specific procedures were approved and authorized by the Animal Ethics Committee of Jilin Agricultural University.
2.2. Sample Collection and Measurement
The antlers were harvested and weighed at the end of the experiment before morning feeding. The blood samples were collected by puncture of the jugular vein of each sika deer into heparinized evacuated tubes. The AGC tissues were collected and cut into small pieces approximately 0.5 cm × 0.5 cm, and then immediately frozen in liquid nitrogen. About 200 mL rumen liquid was obtained via the stomach tube, and the first 50 mL of rumen fluid was discarded to avoid saliva contamination, and then stored in liquid nitrogen for further analysis.
The blood samples were centrifuged at 3500×
g
for 10 min at 4 °C to obtain the plasma from the heparinized evacuated tubes, and then were used to determine the concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), total protein (TP), triglyceride (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glucose, and urea nitrogen using commercial kits (Jiancheng Bioengineering Institute, Nanjing, China). The levels of plasma IGF-1, 1,25(OH)
2
D, and 25(OH)D were determined using Enzyme-linked immunosorbent assay (ELISA) kits (Jianglai Biocompany, Shanghai, China). The rumen liquid was centrifuged at 12,000×
g
for 5 min at 4 °C, the molar concentrations of volatile fatty acids (VFAs) were determined according to a previous study by gas chromatography (6890GC, Agilent Technologies, Santa Clara, CA, USA) with a flame ionization detector and a DB-FFAP column [
25
], and the concentrations of amino acid were measured by using ion-exchange chromatography (L8900, Hitachi Technology, Tokyo, Japan).
2.3. DNA and RNA Extraction and Sequencing
Microbial genomic DNA was extracted from the rumen liquid samples (five samples in each group) using a QIAamp
®
Fast DNA Stool Mini Kit (QIAGEN, Valencia, CA, USA), according to the manufacturer’s instructions. The primers 341F (5′-CCTACGGGAGGCAGCAG-3′) and 806R (5′-GGACTACHVGGGTWTCTAAT-3′) were used to amplify the bacterial 16S rRNA gene in the V3-V4 region. Each primer pair contained the appropriate Illumina adapter sequence and an 8-bp barcode. The resulting amplicons were purified using the QIAquick PCR Purification Kit (QIAGEN, Valencia, CA, USA) and sequenced on the Illumina Novaseq 6000 to generate paired-end reads. The total RNA of the AGC tissue (five samples in each group) were isolated using Qiagen RNeasy Mini Kit (QIAGEN, Valencia, CA, USA), and checked for the RNA concentration and quality using a NanoDrop 2000 (NanoDrop, Wilmington, DE, USA). RNA samples with an integrity number (RIN) greater than 7.0 were used for the library construction. A total of 1.5 μg RNA from each sample was used to construct the RNA-Seq library using NEBNext
®
UltraTM RNA Library Prep Kit (Illumina, San Diego, CA, USA). Each library was quantified using a Qubit 2.0 Fluorometer (Invitrogen, Carlsbad, CA, USA), and then sequenced on an Illumina HiSeq 4000 platform (150 bp paired-end sequencing).
2.4. Bioinformatics Analysis
For the 16S rRNA sequences, the paired-end sequences were first assembled into contigs using FLASH [ 26 ]. The obtained contigs were then processed using QIIME 1.9.1 [ 27 ]. The sequences were clustered into operational taxonomic units (OTUs) with 97% sequence identity using UPARSE [ 28 ], and the potential chimeras were identified and removed using UCHIME [ 29 ]. The representative sequences of each OTU were assigned against the SILVA database (v138) [ 30 ]. Singletons were removed and each sample was sub-sampled with a minimum number (37,535) to reduce the effects of the sequencing depth. Alpha-diversity indices were also calculated using QIIME 1.9.1. Principal coordinates analysis (PCoA) based on Bray–Curtis dissimilarity matrices were performed to reveal the differences in rumen bacterial communities between the two groups. PERMANOVA was performed to indicate group difference, and the p values were determined based on 999 permutations. The phylogenetic investigation of communities by reconstruction of the unobserved states (PICRUSt) was applied to predict the functional profiles of the rumen microbiota resulting from reference-based OTU picking against the Greengenes database [ 31 ]. The predicted genes were then summarized according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.
For the transcriptome analysis, Trimmomatic was used to remove the low quality and adapter sequence [ 32 ]. After that, HISAT2 was used to align the remaining clean reads to the reference genome of the sika deer [ 33 ]. StringTie was applied to estimate the expression of each gene transcript by fragments per kilobase of transcript per million fragments mapped (FPKM) [ 34 ]. The differentially expressed genes (DEGs) were determined using the edgeR package [ 35 ] by |log 2 (FC)| > 0.5 and with a false discovery rate (FDR < 0.05) based on the Benjamini and Hochberg correction. The principal component analysis (PCA) was applied to reveal the gene expression of AGC tissues between the two groups. The significantly enriched gene ontology (GO) term and KEGG pathways of DEGs were performed by KOBAS using a false discovery rate (FDR < 0.05) based on Benjamini and Hochberg correction [ 36 ]. The gene-concept networks for DEGs were performed using clusterProfiler [ 37 ].
2.5. Statistical Analysis
The Wilcoxon rank sum (WRS) test was used to determine the statistical significance of the antler weight, antler growth, plasma parameter levels, volatile fatty acids (VFAs) and amino acid concentrations in the rumen fluid, alpha diversity indices, the relative abundance of bacteria according to taxonomy, and the enrichment of the KEGG pathways between the Ctrl and 25(OH)D groups. The p values of the WRS tests were corrected using the false discovery rate of the Benjamini-Hochberg method. Linear regression analysis was used to estimate the association between the plasma 25(OH)D and IGF-1 concentrations. All p values ≤ 0.05 were considered to indicate statistical significance.
3. Results
3.1. Increased Antler Production and Altered Plasma Parameters
We first evaluated the production performance of the antlers and found that the final weight ( p = 0.03, Figure 1 A) and daily growth weight of the antlers ( p = 0.01, Figure 1 B) in the 25(OH)D group were significantly greater than those in the Ctrl group. Further examination of the plasma parameters showed that the levels of IGF-1 ( p = 0.04), 25(OH)D ( p < 0.01), and 1,25(OH) 2 D ( p = 0.04) were significantly higher in the 25(OH)D group than in the Ctrl group. The level of LDL-C in the 25(OH)D group ( p = 0.05) was lower than that in the Ctrl group ( Figure 1 C). Then, we found an apparently positive association between the plasma 25(OH)D and IGF-1 concentrations ( p < 0.001, R 2 = 0.92) based on linear regression analysis ( Figure 1 D).
3.2. Variations in VFA and Amino Acid Profiles in the Rumen
The results showed that the concentration of total VFAs (
p
= 0.82) and the molar proportions of acetate (
p
= 0.77), propionate (
p
= 0.53), butyrate (
p
= 0.74), and isovalerate (
p
= 0.91) were not significantly different between the Ctrl and 25(OH)D groups (
Figure 2
A). However, the molar proportion of valerate in the 25(OH)D group was significantly greater than that in the Ctrl group (
p
= 0.01), indicating the alteration of the metabolism of branched-chain amino acids (BCAAs) in the rumen. Thus, we further compared the amino acid concentrations between the two groups. The results showed that a total of 11 amino acids, including aspartate, glutamate, glycine, alanine, valine, cysteine, methionine, leucine, tyrosine, lysine, and proline, as well as their related metabolites (cystathionine, ammonia, and hydroxyproline), were significantly enriched in the Ctrl group compared with those in the 25(OH)D group (
p
< 0.05); however, the concentrations of citrulline, phenylalanine, β-alanine, histidine, β-aminoisobutyric acid, and EOHNH
2
were lower (
p
< 0.05,
Figure 2
B).
3.3. 25(OH)D Supplementation Alters the Rumen Bacterial Composition
Then, we examined the rumen bacterial community based on the 16S rRNA sequences. A total of 440,260 high-quality reads were obtained, with an average of 44,026 sequences for each sample (37,535 to 51,506). After rarefication to the minimum number, we obtained a total of 3464 OTUs based on 97% sequence identity. Based on these OTUs, we identified a total of 48 phyla in the rumen liquid from the two groups (
Figure S1A
), dominated by the phyla Bacteroidota, Firmicutes, and Proteobacteria (
Figure S1B
). At the genus level, the identified OTUs were further classified into 283 genera (
Figure 3
A). In the Ctrl group,
Prevotella
(20.12%) was the most dominant bacteria, followed by bacteria belonging to Rikenellaceae RC9 (9.88%), Christensenellaceae R7 (5.35%), Prevotellaceae UCG 003 (3.20%), and
Fibrobacter
(3.04%), accounting for ~45.0% of the overall bacterial composition. In the 25(OH)D group, the genus
Prevotella
(22.76%) was predominant, followed by bacteria belonging to Succinivibrionaceae UCG 002 (7.80%), Rikenellaceae RC9 (7.56%), Christensenellaceae R7 (4.76%), and
Ruminobacter
(3.11%), accounting for 46.0% of the bacterial composition.
We further revealed the difference in bacterial community composition between the Ctrl and the 25(OH)D groups. The PCoA results showed that the bacterial community composition in the rumen of the 25(OH)D group was distinct from that in the Ctrl group, based on Bray-Curtis dissimilarity matrices ( Figure 3 B), explaining at least 47.0% of the variation. The results of PERMANOVA also indicated a significant difference between the Ctrl and the 25(OH)D groups. However, the Shannon and Chao1 indices were not significantly different between the Ctrl and the 25(OH)D groups ( Figure 3 C).
Moreover, the relative abundances of
Anaerosporobacter
,
Bauldia
,
Coprococcus
,
Iamia
,
Kribbella
,
Oribacterium
,
Ruminobacter
,
Succinimonas
,
Vibrio
, and
Virgisporangium
, bacteria belonging to Lachnospiraceae NC2004, Lachnospiraceae NK4B4, and Succinivibrionaceae UCG 002, were significantly higher in the 25(OH)D group than in the Ctrl group (
p
< 0.05,
Figure 3
D). In contrast, the relative abundances of
Acinetobacter
,
Enterococcus
,
Pyramidobacter
,
Ruminiclostridium
,
Saccharospirillum
,
Sphaerochaeta
,
Sphingobacterium
, and bacteria, belonging to Prevotellaceae NK3B31 were significantly higher in the Ctrl group than in the 25(OH)D group (
p
< 0.05,
Figure 3
D).
We then applied PICRUSt to predict the potential functions of the rumen bacteria and compared the difference between the two groups. The PCA results showed that the bacterial metabolic pathways at the KEGG level 3 in the 25(OH)D group separated from that in the Ctrl group (
Figure 3
E). Moreover, the relative abundances of the pyruvate metabolism, the bacterial secretion system, electron transfer carriers, ion channels, and bacterial invasion of the epithelial cell were increased in the 25(OH)D group compared with those in the Ctrl group (
p
< 0.05,
Figure 3
F). However, the pathways of nitrogen metabolism, N-Glycan biosynthesis, and novobiocin biosynthesis were significantly decreased in the 25(OH)D group (
p
< 0.05,
Figure 3
F).
3.4. 25(OH)D Supplementation Leads to Extensive Transcriptome Changes in AGC Tissue
We next examined whether the genes were differentially expressed in the AGC tissue after 25(OH)D supplementation. RNA sequencing was performed, and we confirmed that dietary 25(OH)D supplementation affected the gene expression of the AGC, as indicated by the PCA results, explaining approximately 46% of the total variation ( Figure 4 A). We identified 1024 DEGs in the AGC of sika deer in the 25(OH)D group compared with the Ctrl group (356 up-regulated and 668 down-regulated, Table S2 ), indicating that many genes within AGC are responsive to 25(OH)D supplementation. The up-regulated DEGs included MAMDC2 , PTN , FN1 , TNC , TNN , TGFBI , CDH2 , TNFRSF11B , TCF7 , and WINT10B , while the down-regulated DEGs included AFAP1L2 , LCP1 , IFI16 , BCR , CYTIP , ALDH1A1 , IL18 , GPAT2 , PTPRU , IF16 , NPR3 , IFITM1 , SFMBT2 , CXCR4 , APCDD1L , and ARHGAP30 ( Figure 4 B). These up-regulated DEGs were enriched in 13 Gene Ontology (GO) cell component categories, including actin cytoskeleton, cell-cell junction, peroxisome, axon, proteinaceous extracellular matrix, and collagen. They were also enriched in two GO molecular function categories, namely, mRNA binding and integrin binding ( Figure 4 C). For the 668 down-regulated DEGs, according to the GO analysis of the cellular components, these DEGs were significantly enriched for microtubule cytoskeleton, spindle microtubule, extracellular space, extracellular region, and intermediate filament. They were also enriched for the biological function GO terms involved in the heme biosynthetic process, inflammatory response, lipid catabolic process, and membrane lipid metabolic process ( Figure 4 C).
According to the KEGG analysis, the up-regulated DEGs were enriched in only a few pathways, including protein processing in the endoplasmic reticulum, focal adhesion, adherens junction, and ECM–receptor interaction (
Figure 4
D). In contrast, the down-regulated DEGs were significantly enriched in the pathways of the immune response (cytokine-cytokine receptor interaction, leukocyte transendothelial migration, B cell receptor signaling, and natural killer cell mediated cytotoxicity), lipid metabolism (fatty acid elongation, biosynthesis of unsaturated fatty acids, fatty acid metabolism, and adipocytokine signaling), and signaling pathways (PI3K−Akt signaling, Rap1 signaling, Ras signaling, TNF signaling, and peroxisome proliferator-activated receptor (PPAR) signaling pathways,
Figure 4
D).
To further interpret the enrichment of the KEGG pathways, we conducted an interactive enrichment network analysis based on the up- and down-regulated DEGs. The results showed that the pathways of the biosynthesis of unsaturated fatty acids, adipocytokine signaling pathway, and PPAR signaling pathway were closely associated, and were connected by genes such as
ELOVL5
,
ELOVL6
,
ELOVL7
,
PPARA
,
PPARG
,
ACSL1
,
ACSL3
,
ACSL5
,
ACADL
, and
FADS2
. Moreover, the cytokine-cytokine receptor interaction, osteoclast differentiation, B cell receptor signaling pathway, PI3K-Akt signaling pathway, natural killer cell mediated cytotoxicity, and Rap1 signaling pathway, were also closely connected, involving genes such as
NGF
,
NGFR
,
IL6R
,
EPOR
,
PRLR
,
IL3RA
,
IFNAR2
,
TNFRSF11B
,
IFNAR2
,
TGFBR2
,
CSF1
,
LCP2
,
SYK
, and
BLNK
(
Figure 5
). Moreover, the enrichment network analysis also showed that the GO biological process categories, including RNA splicing via transesterification reactions, inorganic anion transport, the apoptotic signaling pathway, regulation of binding, and inflammatory response, were closely associated, while the GO molecular function categories, including integrin binding and mRNA binding, were also identified (
Figure S2
).
4. Discussion
The results of this study indicate that 25(OH)D supplementation significantly increased the antler final weight and growth rate and 25(OH)D and 1,25(OH) 2 D levels in the plasma. Consistent with our observation, 25(OH)D supplementation can promote 1,25(OH) 2 D synthesis in weaning calves [ 38 ]. Previous studies have also demonstrated that the 1,25(OH) 2 D concentration was significantly increased during antler growth in white-tailed deer [ 12 ] and fallow deer [ 39 ]. These results thus confirmed the regulatory role of 25(OH)D and 1,25(OH) 2 D on antler growth. We also found a positive correlation between the plasma concentrations of 25(OH)D and IGF-1, an important antler-stimulating hormone [ 16 ]. Consistently, Bogazzi et al. (2011) also observed that IGF-1 concentrations were significantly correlated with 25(OH)D levels in humans [ 40 ]. Moreover, a significant decrease was observed in the plasma levels of LDL-C upon 25(OH)D supplementation. It has been reported that a reduced IGF-1 concentration impairs the expression of the genes encoding the low-density lipoprotein receptors that are involved in lipid catabolism [ 41 ]. These findings suggest a possible interaction among 25(OH)D, IGF-1 and lipid metabolism during antler growth.
We further examined whether 25(OH)D supplementation affected rumen metabolism. The results showed that the molar proportion of valerate was significantly increased, and the concentrations of amino acids significantly differed in the 25(OH)D group. Valerate is an end-product of proline, lysine, and methionine degradation [
42
]. Accordingly, the proline, lysine, and methionine concentrations were significantly decreased in the rumen of the 25(OH)D group. Moreover, the concentration of leucine decreased, whereas that of isovalerate increased. Isovalerate is a product of BCAAs, such as leucine [
43
]. It has been observed that vitamin D
3
supplementation significantly lowers the circulating levels of BCAAs in type two diabetes mellitus [
44
]. These results suggest that 25(OH)D supplementation may affect BCAAs metabolism in the rumen of sika deer.
We further investigated how the rumen bacterial community was affected by 25(OH)D supplementation, due to its key role in rumen metabolism, and confirmed the dominance of Prevotella in the rumen of sika deer [ 45 ]. However, the rumen bacterial composition was significantly different between the 25(OH)D group and the Ctrl group, consistent with the observations in healthy humans, which indicated that the Bacteroidetes-to-Firmicutes ratio increased with vitamin D supplementation [ 23 ], and that the abundances of specific taxonomies (Clostridia order) were associated with the level of 1,25(OH) 2 D [ 24 ]. The relative abundance of members belonging to the Succinivibrionaceae family (Succinivibrionaceae UCG 002 and Ruminobacter ) and Lachnospiraceae family ( Coprococcus , Oribacterium , Lachnospiraceae NC2004, Anaerosporobacter, and Lachnospiraceae NK4B4) significantly increased in the 25(OH)D group. Members of the Succinivibrionaceae family mainly capture hydrogen to produce succinate, thereby promoting the production of VFAs [ 46 ], and are associated with rumen energy metabolism in sika deer [ 25 ]. Our findings support previous observations of a dynamic interplay between active vitamin D metabolites and the Lachnospiraceae family [ 24 ]. Members within the Lachnospiraceae family are important butyrate-producing bacteria [ 47 ]. We also found that the relative abundance of pyruvate metabolism was increased in the 25(OH)D group. These results suggest that butyrate producers were affected by 25(OH)D supplementation in the rumen of sika deer.
We then examined whether and how the gene expression profiles in AGC responded to 25(OH)D supplementation. We identified 356 up-regulated DEGs in the 25(OH)D group in comparison with those in the Ctrl group, including FN1 , TNC , TNN , TGFBI , CDH2 , TNFRSF11B , TCF7 , WINT10B, and PTN . FN1 encodes the extracellular matrix (ECM) protein and is a vitamin D target [ 48 ], whose expression linearly increased during the antler growth period [ 49 ], indicating a direct role of 25(OH)D in antler growth. The overexpression of TNFRSF11B , encoding an osteoclastogenesis inhibitory factor, resulted in a strong upregulation of cartilage extracellular matrix components [ 50 ]. CDH2 , WNT10B, and PTN are highly expressed genes in the antler. The former mediates cell-cell interactions and enhances MSC aggregation, resulting in chondrogenic differentiation [ 51 ], while the latter two genes regulate the differentiation of antler chondrocytes [ 7 ]. TCF7 is considered a regulator of early osteoblast differentiation of MSCs [ 52 ]; TGFBI is a core gene regulating antler growth and ossification [ 53 ]; and PTN has been identified as a critical factor promoting cartilage regeneration, angiogenesis, and chondrogenesis [ 54 ]. In addition, previous findings revealed that 1,25(OH) 2 D regulated cell-to-cell communication by post-transcriptionally altering the expression of the genes involved in ECM organization and receptor interactions [ 55 ]. Interestingly, these up-regulated DEGs were enriched in the pathways of the ECM−receptor interaction and protein processing in the endoplasmic reticulum. The statistically enriched biological cellular component terms were proteinaceous extracellular matrix and collagen. In this context, it is relevant that the chondrocyte differentiation and osteoblast ossification pathways were up-regulated by 25(OH)D supplementation, leading to increased antler growth.
Notably, following 25(OH)D supplementation, the majority of changes (65.2%) in the gene expression reflected downregulation, and down-regulated genes were enriched in different pathways of the immune system, such as the B cell receptor signaling pathway, complement and coagulation cascades, and cytokine−cytokine receptor interaction. The immunomodulatory effects of vitamin D on both innate and adaptive immunity are well documented [
56
], indicating that the immune response in antlers was affected by 25(OH)D supplementation. It has been reported that 1,25(OH)
2
D stimulates IL-10 release in dendritic cells, towards a less mature and more tolerogenic phenotype, resulting in a reduction in the anti-inflammatory activity of macrophages (i.e., IL-6 and TNF-α) [
56
]. In our study, 25(OH)D supplementation selectively down-regulated the expression of TNF superfamily members 1B, 13, 15, and 21 and up-regulated the IL-10 receptor in AGC. Thus, our observation indicated that a physiological role of 25(OH)D supplementation is to potentially shift the immune system to a more tolerogenic status. Moreover, the
IL18
and
IFI16
expression levels were significantly down-regulated in the 25(OH)D group. This finding is consistent with previous observations in mice, that 1,25(OH)
2
D markedly suppressed the expression of
IL18
in primary keratinocytes and modulated the cutaneous inflammatory reactions [
57
]. The DNA sensor IFI16 is essential for DNA-driven innate immune responses in keratinocytes, is up-regulated in psoriatic skin lesions, and is localized to the cytoplasm in a subpopulation of cells [
58
]. Keratinocytes are involved in protecting the body from infections and environmental challenges. These results further indicate the downregulation of the immune response in the AGC by 25(OH)D supplementation and a possible balance between the immune response and antler growth.
Another major finding of the transcriptome analysis was the enrichment of down-regulated DEGs in lipid metabolism pathways (i.e., ELOVL5 , ELOVL6 , ELOVL7 , PPARA, and PPARG ), including fatty acid elongation, biosynthesis of unsaturated fatty acids, the adipocytokine signaling pathway, and the PPAR signaling pathway. Moreover, the enriched biological process terms were the membrane lipid metabolic process and lipid catabolic process. This result suggests that 25(OH)D supplementation might result in the regulation of lipid metabolic regulatory pathways via target genes. Seven distinct elongation of very-long-chain fatty acid (FA) enzymes (ELOVL1–ELOVL7) play important roles in the elongation of medium to long-chain FAs into very-long-chain FAs [ 59 ]. In addition, the loss of function of the vitamin D–vitamin D receptor (VD-VDR) system in mice resulted in increased levels of very-long-chain FAs (C18–C24) in the white adipose tissue [ 60 ]. The decreased expression level of ELOVL s indicates a potential inhibitory effect of 25(OH)D supplementation on the synthesis of long-chain FAs in antlers. PPARα and PPARγ are key regulators of lipid homeostasis and are activated by a structurally diverse group of compounds, including long-chain arachidonic acid [ 61 ], which is mediated by the enzyme ELOVL5 [ 62 ]. However, the VD-VDR system has also shown an anti-PPARG activity, as inhibiting its expression leads to adipogenesis in the adipocyte cells [ 63 ], suggesting that long-chain FAs might be involved in the PPAR signaling pathway. This hypothesis is also supported by the connection of the metabolic pathway by acyl-CoA synthetases long-chain (ACSLs), the key enzymes converting nonpolar hydrophobic FA substrates into acyl-CoAs. Regarding increased levels of 25(OH)D and 1,25(OH) 2 D, the results of the present study reveal the possibility of the interaction of vitamin D, long-chain FAs, and the PPAR signaling pathway in the regulation of metabolic homeostasis and antler growth.
5. Conclusions
Our results suggest that 25(OH)D supplementation (i) increases the antler weight and growth rate of sika deer; (ii) alters the rumen bacterial community composition and metabolic profiles, particularly regarding butyrate producers and the amino acid concentrations; and (iii) affects the genes expression of the immune response and lipid metabolism in antlers. Future studies are needed to elucidate the relationship between FA composition and antler growth. Taken together, these observations provide a better understanding of the effects of 25(OH)D supplementation on sika deer.
Supplementary Materials
The following supporting information can be downloaded at:
https://www.mdpi.com/article/10.3390/ani12243497/s1
. Table S1. Dietary composition and nutrient levels. Table S2. The DEGs based on |Log
2
(FC)| > 0.5 and adjust
p
< 0.05. Figure S1. Rumen bacterial composition and core microbiome profilers. (A) Bacterial composition in the rumen fluid of sika deer between Ctrl and 25(OH)D groups at the phylum level. (B) Identification of core microbiome in the rumen fluid of sika deer during antler growth period. Figure S2. Gene-concept networks based on enrichment GO terms between Ctrl and 25(OH)D groups. The enrichment biology process (A) and molecular function (B) were calculated using the gene set enrichment analysis. Each significantly enriched GO term is represented as a circle. Circle colors indicate the significance of the enriched terms from minimum (red) to maximum (yellow). Circle size indicates the number of DEGs. Gene sets with overlapping genes are connected with an edge. Red and green nodes indicate up- and down-regulated DEGs in 25(OH)D group compared with the Ctrl group. The network is displayed as the Bipartite layout.
Author Contributions
Conceptualization, C.X. and Z.L.; methodology, H.S. and Z.L.; software, H.S., Z.L. and J.S.; formal analysis, H.S., S.L. and W.N.; writing—original draft preparation, H.S; writing—review and editing, Z.L.; funding acquisition, Z.L. All authors have read and agreed to the published version of the manuscript.
Funding
This work was supported by the National Natural Science Foundation of China (32122083), the Science and Technology Research Project from Jilin Province (20220304003YY) to Z.L., and the Science and Technology Research Project of the Jilin Provincial Department of Education (JJKH20220363KJ) to H.S.
Institutional Review Board Statement
The animal study protocol was approved by the Animal Care and Use Committee of Jilin Agricultural University in China (Approval ID: 20210314001).
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study.
Data Availability Statement
Sequence files associated with each sample have been submitted to the NCBI Sequence Read Archive. This data can be found here: https://www.ncbi.nlm.nih.gov/sra . (accessed on 8 October 2022. PRJNA888231 and PRJNA888245)
Conflicts of Interest
The 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.
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Figure 1.
Changes in antler production performances and host metabolism with 25(OH)D supplementation. Comparison of the (
A
) antler weight, (
B
) growth rate of the antler, and (
C
) plasma metabolites between the Ctrl and 25(OH)D groups. ns means no significant differences.
p
value indicates the statistical significance of the differences, which were determined using WRS test based on the Benjamini–Hochberg correction. (
D
) The correlation between plasma 25(OH)D and IGF-1 concentrations.
p
value indicates the statistical significance of the differences, which were determined using liner regression analysis. The R
2
value indicates the coefficient of determination. IGF-1: Insulin Growth Factor-1, AST: Aminotransferase, ALT: Alanine Aminotransferase, LDH: Lactate Dehydrogenase, TP: Total Protein, TG: Triglyceride, HDL-C: High-Density Lipoprotein Cholesterol, LDL-C: Low-Density Lipoprotein Cholesterol, 1,25(OH)D: 1,25-Dihydroxyvitamin D, 25(OH)D: 25-Hydroxyvitamin D.
Figure 1. Changes in antler production performances and host metabolism with 25(OH)D supplementation. Comparison of the ( A ) antler weight, ( B ) growth rate of the antler, and ( C ) plasma metabolites between the Ctrl and 25(OH)D groups. ns means no significant differences. p value indicates the statistical significance of the differences, which were determined using WRS test based on the Benjamini–Hochberg correction. ( D ) The correlation between plasma 25(OH)D and IGF-1 concentrations. p value indicates the statistical significance of the differences, which were determined using liner regression analysis. The R 2 value indicates the coefficient of determination. IGF-1: Insulin Growth Factor-1, AST: Aminotransferase, ALT: Alanine Aminotransferase, LDH: Lactate Dehydrogenase, TP: Total Protein, TG: Triglyceride, HDL-C: High-Density Lipoprotein Cholesterol, LDL-C: Low-Density Lipoprotein Cholesterol, 1,25(OH)D: 1,25-Dihydroxyvitamin D, 25(OH)D: 25-Hydroxyvitamin D.
Figure 2. The changed production of VFAs and amino acids in rumen liquid between the Ctrl and 25(OH)D groups. ( A ) Comparison of VFAs in the rumen liquid between the Ctrl and 25(OH)D groups. ns means no significant differences. ( B ) Heatmap showing the concentrations of amino acids in rumen liquid between the Ctrl and 25(OH)D groups. Square colors indicate the amino acids concentration from low (blue) to high (red). Samples from the Ctrl group and 25(OH)D group were indicated by grey and red bars at bottom of heatmap. p value indicates the statistical significance of the differences, and were determined using WRS test based on the Benjamini–Hochberg correction. ** and * indicate p < 0.01 and p < 0.05, respectively. TVFAs: Total Volatile Fatty Acids.
Figure 2. The changed production of VFAs and amino acids in rumen liquid between the Ctrl and 25(OH)D groups. ( A ) Comparison of VFAs in the rumen liquid between the Ctrl and 25(OH)D groups. ns means no significant differences. ( B ) Heatmap showing the concentrations of amino acids in rumen liquid between the Ctrl and 25(OH)D groups. Square colors indicate the amino acids concentration from low (blue) to high (red). Samples from the Ctrl group and 25(OH)D group were indicated by grey and red bars at bottom of heatmap. p value indicates the statistical significance of the differences, and were determined using WRS test based on the Benjamini–Hochberg correction. ** and * indicate p < 0.01 and p < 0.05, respectively. TVFAs: Total Volatile Fatty Acids.
Figure 3.
Rumen bacterial community and the predicted functional profiles. (
A
) Bacterial composition in the rumen fluid of sika deer between the Ctrl and 25(OH)D groups at the genus level. (
B
) Comparison of the alpha diversity indices in the rumen fluid of sika deer between the Ctrl and 25(OH)D groups. ns means no significant differences. (
C
) PCoA results showing the separation of the rumen bacteria between Ctrl and 25(OH)D groups at the OTU level based on the Bray–Curits dissimilarity matrix. (
D
) Heatmap showing the significantly changed bacteria genera in the rumen liquid between the Ctrl and 25(OH)D groups. Square colors indicate the normalized relative abundance of each genera from the minimum (blue) to maximum (orange). Rumen liquid samples from the Ctrl group and 25(OH)D group were indicated by grey and red bars on the right side of the heatmap, respectively. (
E
) PCA revealing the difference in the bacterial functional profiles at KEGG level 3 (relative abundance) based on the Euclidean metric. (
F
) Histograms showing the significantly changed pathways at KEGG level 3.
Figure 3. Rumen bacterial community and the predicted functional profiles. ( A ) Bacterial composition in the rumen fluid of sika deer between the Ctrl and 25(OH)D groups at the genus level. ( B ) Comparison of the alpha diversity indices in the rumen fluid of sika deer between the Ctrl and 25(OH)D groups. ns means no significant differences. ( C ) PCoA results showing the separation of the rumen bacteria between Ctrl and 25(OH)D groups at the OTU level based on the Bray–Curits dissimilarity matrix. ( D ) Heatmap showing the significantly changed bacteria genera in the rumen liquid between the Ctrl and 25(OH)D groups. Square colors indicate the normalized relative abundance of each genera from the minimum (blue) to maximum (orange). Rumen liquid samples from the Ctrl group and 25(OH)D group were indicated by grey and red bars on the right side of the heatmap, respectively. ( E ) PCA revealing the difference in the bacterial functional profiles at KEGG level 3 (relative abundance) based on the Euclidean metric. ( F ) Histograms showing the significantly changed pathways at KEGG level 3.
Figure 4. 25(OH)D supplementation affects the gene expression of the AGC tissue. ( A ) PCA analysis of the gene expression in the AGC tissue of sika deer between the Ctrl and 25(OH)D groups. ( B ) Volcano plots show up- and down-DEGs in the AGC tissue between two groups. Red and blue dots indicate up- and down-regulated DEGs ( p < 0.05 and |log 2 (FC)| > 1) in the 25(OH)D group compared to Ctrl group. FC = fold change. The enriched GO terms ( C ) and KEGG pathways ( D ) of the up- and down-regulated DEGs in the 25(OH)D group in comparison with the Ctrl group. Numbers in circles indicate the number of DEGs.
Figure 4. 25(OH)D supplementation affects the gene expression of the AGC tissue. ( A ) PCA analysis of the gene expression in the AGC tissue of sika deer between the Ctrl and 25(OH)D groups. ( B ) Volcano plots show up- and down-DEGs in the AGC tissue between two groups. Red and blue dots indicate up- and down-regulated DEGs ( p < 0.05 and |log 2 (FC)| > 1) in the 25(OH)D group compared to Ctrl group. FC = fold change. The enriched GO terms ( C ) and KEGG pathways ( D ) of the up- and down-regulated DEGs in the 25(OH)D group in comparison with the Ctrl group. Numbers in circles indicate the number of DEGs.
Figure 5. Identification of the transcriptional enrichment networks. The enrichment pathway was calculated using the gene set enrichment analysis. Each significantly enriched KEGG pathway is represented as a circle. Circle colors indicate the significance of the enriched KEGG pathways from minimum (red) to maximum (yellow). The circle size indicates the number of DEGs. Gene sets with overlapping genes are connected with an edge. Red and green nodes indicate up- and down-regulated DEGs in the 25(OH)D group compared with the Ctrl group. The network is displayed as the Bipartite layout.
Figure 5. Identification of the transcriptional enrichment networks. The enrichment pathway was calculated using the gene set enrichment analysis. Each significantly enriched KEGG pathway is represented as a circle. Circle colors indicate the significance of the enriched KEGG pathways from minimum (red) to maximum (yellow). The circle size indicates the number of DEGs. Gene sets with overlapping genes are connected with an edge. Red and green nodes indicate up- and down-regulated DEGs in the 25(OH)D group compared with the Ctrl group. The network is displayed as the Bipartite layout.
AMA Style
Si H, Li S, Nan W, Sang J, Xu C, Li Z. Integrated Transcriptome and Microbiota Reveal the Regulatory Effect of 25-Hydroxyvitamin D Supplementation in Antler Growth of Sika Deer. Animals. 2022; 12(24):3497.
https://doi.org/10.3390/ani12243497
Chicago/Turabian Style
Si, Huazhe, Songze Li, Weixiao Nan, Jianan Sang, Chao Xu, and Zhipeng Li. 2022. "Integrated Transcriptome and Microbiota Reveal the Regulatory Effect of 25-Hydroxyvitamin D Supplementation in Antler Growth of Sika Deer" Animals12, no. 24: 3497.
https://doi.org/10.3390/ani12243497
| https://www.mdpi.com/2076-2615/12/24/3497/html |
Chinese medical herbs for hyperthyroidism - Han, S - 2005 | Cochrane Library
*Phytotherapy [adverse effects]; Drugs, Chinese Herbal [adverse effects, *therapeutic use]; Hyperthyroidism [complications, *drug therapy]; Randomized Controlled Trials as Topic; Thyroid Hormones [blood]
Chinese medical herbs for hyperthyroidism
S Han
Taixiang Wu
Guanjian Liu
Han Su
Version published: 20 July 2005Version history
https://doi.org/10.1002/14651858.CD005450
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To assess the effects of Chinese medicinal herbs for treating hyperthyroidism. We are also interested in comparing the effects of various medicinal herbs with integrated Western medicine and medicinal herbs, and in adverse events in the treatment of hyperthyroidism.
Visual summary
Background
Both hyperthyroidism and thyrotoxicosis are used to described a pathological syndrome in which there is an excessive amount of thyroid hormones circulating in the blood because of an overactive thyroid gland, or caused by an excess of thyroid hormones from any cause, the patients thus characterized by tachycardia, warm moist skin, and raised body temperature.
The most frequent cause of hyperthyroidism is Graves' disease; followed by non‐cancerous growths of the thyroid gland or pituitary gland; tumours of the testes or ovaries; inflammation (irritation and swelling with presence of extra immune cells) of the thyroid due to viral infections or other causes; ingestion of excessive amounts of thyroid hormone; and ingestion of excessive iodine. Graves' disease accounts for 85% of all cases of hyperthyroidism (Brown 2002).
Hyperthyroidism is common. Unsuspected and undiagnosed hyperthyroidism was found in roughly 0.5% of women in a large population‐based British survey, done in the 1970s (Cooper 2003). Approximately 2% of women and 0.2% of men in the general population are affected by hyperthyroidism (Farling 2000). Hyperthyroidism can occur at all ages, but is less common before 15. At the other extreme, hyperthyroidism is one of the major causes of morbidity in the elderly. Graves' disease can occur at any age, whereas toxic multinodular goitre is more common in patients older than 60 (John 1997).
The actual diagnosis of hyperthyroidism is easy to make once its possibility is entertained. Accurate and widely available blood tests can confirm or rule out the diagnosis. In most patients, free tri‐iodothyronine and thyroxine concentrations in serum are raised, and serum thyrotropin is undetectable. The 24‐hour radioactive iodine uptake is a measure of the iodine avidity of the thyroid gland. In most hyperthyroid diseases, including Graves' disease, toxic multinodular goitre and toxic adenoma, the results are at the higher end of normal or raised. But this test is generally not needed to make the diagnosis. However, it can be very useful in distinguishing mild Graves' disease from silent or postpartum thyroiditis in which the 24‐h uptake of radioactive iodine will be low (Cooper 2003).
TreatmentThe treatment of hyperthyroidism includes symptom relief and therapy with antithyroid medications, therapy with radioactive iodine 131 (I‐131), and thyroidectomy. The extrathyroidal manifestations are not improved by treatment directed at hyperthyroidism and specific treatment is needed (McKenna 2001).
Symptom reliefMany of the neurological and cardiovascular symptoms such as tremor, palpitation and anxiety of thyrotoxicosis are relieved by beta‐blocker therapy because these medicines can block the peripheral effects of the excess thyroid hormones (Cheetham 1998). Those with a longer duration of action such as propranolol,metoprolol, atenolol, and nadolol are usually preferred. But as they can not return oxygen consumption or the negative nitrogen balance seen in hyperthyroidism to normal, they are not primary treatments. Beta‐antagonists are generally well tolerated, but can cause depression, nausea, headache, and fatigue. Furthermore, these drugs should be used cautiously in patients with asthma, congestive heart failure, or Raynaud's phenomenon (Cooper 2003). Calcium channel blockers can be used for the same purposes when beta‐blockers are contraindicated or poorly tolerated.
Antithyroid medicationsAntithyroid drugs (thioamides: carbimazole, methimazole, or propylthiouracil) are used for almost all patients with thyrotoxicosis in European countries. Carbimazole 0.5 to 1.0 mg/kg/day or propylthiouracil 5 to 10 mg/kg/day in divided doses can usually bring the hyperthyroidism under control in about four to eight weeks. In practice, antithyroid drugs are usually given for 12 to 24 months when used alone. When the circulating thyroid hormone levels are restored to normal, treatment can be reduced to a single daily dose and titrated against regular thyroid function tests to maintain euthyroidism (McKenna 2001). As with any long term treatment, patients' appliance is not good because many patients and their families find it remarkably difficult to remember to take the drugs regularly. Some 2‐5% of patients will develop minor side effects with an antithyroid drug, such as rash, nausea, headache, or arthralgia. Usually such symptoms are transient but if they persist the patient can be changed to the other major agent, as cross sensitivity is unusual. Serious side effects are rare, but include neutropenia, agranulocytosis (which is nearly always reversible), and hepatotoxicity,all of which need to be dealt with immediately once it is discovered (Cheetham 1998).
Radioactive Iodine 131Radioactive iodine therapy is the most common treatment of hyperthyroidism in adults in the United States. It is easy to administrate, lack of significant adverse effects, and the cost is relatively low. Those who relapse after a course of antithyroid drugs are usually prescribed radioactive iodine or partial thyroidectomy. About 20% of patients will require a second dose of radioactive iodine. Whereas 50% become hypothyroidal within 5 years irrespective of the dose (McKenna 2001).
ThyroidectomySurgery for hyperthyroidism is used infrequently all over the world (Cooper 1998). Thyroidectomy is only used in specific situations include patient preference, poor response to antithyroid drugs, especially in pregnancy; the presence of a very large goitre, and the presence of a co‐existing potentially malignant thyroid nodule (Cooper 2003). The amount of thyroid tissue to be removed is not easy to decide and too conservative an operation will result in a high rate of recurrent hyperthyroidism and too radical a thyroidectomy in hypothyroidism. Either of these two problems could occur unpredictably many years later. Besides, a short hospital stay is needed and potential problems of the operation include the discomfort of the operation, the scar (which may form keloid), the risk of general anaesthesia and surgical complications, the risk of damage to the recurrent laryngeal nerves, and transient or permanent hypoparathyroidism (Cheetham 1998).
All currently available therapies are effective, but all the three have problems as well. Antithyroid drugs usually do not cure the patient, need to be used for long time, and have rare but potentially life‐threatening adverse effects. Surgery is expensive, may cause permanent hypothyroidism, and can be a source of significant morbidity from complications. Radioiodine necessitates radiation exposure, may cause almost inevitable hypothyroidism, and may be associated with exacerbation of Graves ophthalmopathy in certain patient subsets (Cooper 1998).
Chinese herbs for hyperthyroidismMedicinal herbs are widely used to treat many diseases including hyperthyroidism in China and many other countries. Chinese herbs including membranous milk vetch root, begonia, tangshen, common anemarrhena rhizome, dwarf lilyturf tuber, Chinese magnoliavine fruitfigwort, rehmannia dride rhizome, common selfheal fruit‐spike, etc. have been used to treat hyperthyroidism. These herbs are able to decrease the raised affinity of α‐adrenergic receptor in hyperthyroidism, weaken the bio‐effect of thyroxine, and inhibit the transformation of T4 to T3 (Yao 1998). Some are said to be able to modulate the function of sympathetic nerves or immune system (Li 1998). The contents of traditional Chinese herbs preparations are variable depends on traditional Chinese medicine syndromes of patients. They are used to treat hyperthyroidism along or integrated with other anti hyperthyroidism drugs. The advantage of herbs usually considered relatively cheap and their adverse effects seem to be rare. But their effectiveness and definite adverse effects are uncertain as their chemical components are not clearly identified.
Objectives
To assess the effects of Chinese medicinal herbs for treating hyperthyroidism. We are also interested in comparing the effects of various medicinal herbs with integrated Western medicine and medicinal herbs, and in adverse events in the treatment of hyperthyroidism.
Methods
Criteria for considering studies for this review
Types of studies
We will consider randomised clinical trials and quasi‐RCTs, irrespective of blinding, publication status, or language for inclusion in the review. If cross‐over studies were performed, their effect will also be assessed in a sensitivity analysis. The minimum duration of the intervention needed to be six months and the minimum duration of follow‐up needed to be one year from completion of therapy to assess the outcomes of relapse (recurrence of hyperthyroidism) and hypothyroidism.
Types of participants
Participants will be male or female of any age or ethnic origin with hyperthyroidism. Participants will be excluded if they have acute myocardial infarction, heart failure, hepatic failure or renal failure.
Diagnostic criteria :1. Clinical manifestations, such as weight loss, heat intolerance, irritability, anxiety, palpitations and tremors;2. Laboratory abnormalities, such as increase of FT3, FT4 and decrease of TSH in the serum;3. Complications, such as ophthalmopathy and pretibial myxoedema.
Types of interventions
Interventions will be Chinese medicinal herbs alone or Chinese medicinal herbs integrated with antithyroid drugs including carbimazole, propylthiouracil, methimazole. The comparisons will be placebo, antithyroid drugs including carbimazole, propylthiouracil, methimazole.
Types of outcome measures
Main outcome measures1. Mortality;2. Relapse rates (recurrence of hyperthyroidism) at least one year after completion of drug treatment;3. Incidence of hypothyroidism.
Additional outcome measures1. Course of ophthalmopathy (need for corticosteroids, radiotherapy, visual compromise);2. Adverse effects (agranulocytosis, drug rash, hepatitis, vasculitis);3. Symptoms of hyperthyroidism (anxiety, tachycardia, heat intolerance, diarrhoea, oligomenorrhoea);4. Thyroid antibody status;5. Weight change;6. Thyroid function tests;7. Health related quality of life;8. Economic outcomes;9. Compliance rates (for example by pharmacy prescription calculations, pill counts);10. Restoration of serum FT3, FT4 and TSH. Adverse events outcome measuresWe have defined serious adverse events according to the ICH Guidelines (CFR & ICH 1997) as any event that leads to death, is life‐threatening, requires in‐patient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability, and any important medical event which may have jeopardised the patient or requires intervention to prevent it. All other adverse events will be considered non‐serious.
We will formulate a comprehensive and exhaustive search strategy in an attempt to identify all relevant studies regardless of language or publication status (published, unpublished, in press, and in progress).
Electronic searchesWe will search(1) The Cochrane Central Register of controlled trials (CENTRAL);(2) MEDLINE (1967 to present);(3) EMBASE (to present);(4) CBM (Chinese biomedical database(to present);(5) Chinese Cochrane Centre Controlled Trials Register (to present).
We will use this search strategy to search CENTRAL and adapt this search for use on other databases.
Ongoing trialsWe will also search databases of ongoing trials:(1) Current Controlled Trials (www.controlled‐trials.com);(2) The National Research Register (www.update‐software.com/National/nrr‐frame.html). HandsearchesWe will handsearch the following Chinese medical journals:Journal of clinical endocrinology;Chinese endocrine journal;Chinese journal of endocrinology;National medical journal of China.
We will try to identify additional studies by searching the reference lists of relevant trials and reviews identified. We will send a list of identified studies to the study authors and ask them to notify us of any other published or unpublished work. Other search strategiesWe will contact organisations (including the World Health Organization), individual researchers working in the field, and drug manufacturers to obtain additional references, unpublished trials, or ongoing trials, confidential reports and raw data of published trials. There will be no language restriction.
Data collection and analysis
Trial selectionHS and WT will scan the results of the search strategy for potentially relevant trials, and retrieve the full articles for all potentially relevant trials. We will scrutinise each trial report for multiple publications from the same data set. HS and WT will independently assess each of these trials for inclusion in the review using an eligibility form based on the contents of the section 'Criteria for Inclusion'. We will resolve any disagreements through discussion or by a consulting the Co‐ordinating Editor of the Cochrane Metabolic and Endocrine Disorders Group. We will exclude studies that do not meet the inclusion criteria and state the reason in the 'Characteristics of excluded studies' table. Interrater agreement for study selection will be measured using the kappa statistic (Cohen 1960).
Assessment of methodological qualityAccording to the empirical evidence (Jadad 1996;Juni 2001;Kjaergard 2001;Moher 1998;Schulz 1995), we will assess the methodological quality as described in Cochrane Reviewer's Handbook 4.2.2:
(1) generation of the allocation sequence: adequate (computer generated random numbers, table of random numbers, or similar) or inadequate (other methods or not described);(2) allocation concealment: adequate (central independent unit, sealed envelopes, or similar) or inadequate (not described or open table of random numbers or similar);(3) double blinding: adequate (identical placebo tablets or similar) or inadequate (not performed or tablets versus injections or similar);(4) follow up: adequate (number and reasons for dropouts and withdrawals described) or inadequate (number or reasons for dropouts and withdrawals not described).
Based on these criteria, we will assign studies to one of the following three categories:A ‐ all quality criteria met: low risk of bias;B ‐ one or more of the quality criteria only partly met: moderate risk of bias;C ‐ one or more criteria not met: high risk of bias.
This classification will be used as the basis of a sensitivity analysis. Additionally, we will assess individual quality criteria.
Each trial will be assessed independently by two reviewers (HS, WT). Interrater agreement will be calculated using the kappa statistic. In cases of disagreement, the rest of the group will be consulted and a judgement will be made based on consensus.
Data extractionHS and WT will independently enter data onto a data extraction form. We will extract data on study characteristics including methods, participants, interventions, and outcomes. We will resolve any disagreements by referring to the trial report and through discussion, or by consulting LJ. If data from the trial reports are insufficient or missing, we will contact the authors for additional information. Where possible we will extract data to allow an intention to treat analysis (the analysis should include all the participants in the groups to which they were originally randomly assigned). If the number randomised and the number analysed are inconsistent, we will calculate the percentage loss to follow up and report this information in an additional table. For binary outcomes, we will record the number of participants experiencing the event in each group of the trial. For continuous outcomes, we will extract the arithmetic means and standard deviations for each group. If the data are reported using geometric means, we will extract standard deviations on the log scale. Medians and ranges will be extracted and reported in tables.
Data analysisWe will perform a meta‐analysis if the data are available, of sufficient quality and sufficiently similar. A meta‐analysis will include only randomised controlled trials. We expect both event (dichotomous) data and continuous data. We will express dichotomous data as relative risks. They may be converted to absolute measures like the number needed to treat if doses and follow‐up times are similar. Continuous data will be expressed as weighted mean differences. We will test for heterogeneity using the Z score and the chi square statistic with significance being set at P < 0.1. Quantification of the effect of heterogeneity will be assessed by means of I squared, ranging from 0‐100% including its 95% confidence interval (Higgins 2002). I squared demonstrates the percentage of total variation across studies due to heterogeneity and will be used to judge the consistency of evidence. We will use a random effects model when heterogeneity is detected, otherwise we will use a fixed effect model. We will assess possible sources of heterogeneity by sensitivity and subgroup analyses as described below. We will test for small study bias using the funnel plot or other corrective analytical methods depending on the number of clinical trials included in the systematic review.
We will aim to perform subgroup analyses in order to explore effect size differences as follows:(1) Duration of follow up;(2) Dose (low, medium, high ‐ based on data).
We will explore possible reasons for heterogeneity in studies and examine the effects of excluding study subgroups if necessary, for example studies with lower methodological quality. We will list non‐randomised controlled studies, but will not discuss them further. We will provide a qualitative description of studies relating to adverse effects.
Sensitivity analysisWe will perform sensitivity analyses in order to explore the influence of the following factors on effect size:1. Repeating the analysis excluding unpublished studies.2. Repeating the analysis taking account of study quality, as specified above.3. Repeating the analysis excluding any very long or large studies to establish how much they dominate the results.4. Repeating the analysis excluding studies using the following filters: diagnostic criteria, language of publication, source of funding (industry versus other), country.
The robustness of the results will also be tested by repeating the analysis using different measures of effects size (risk difference, odds ratio etc.) and different statistic models (fixed and random effects models).
| https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005450/full |
Mechanisms of Tropical Atlantic SST Influence on North American Precipitation Variability in: Journal of Climate Volume 23 Issue 21 (2010)
Abstract The dynamical mechanisms associated with the impact of year-to-year variability in tropical North Atlantic (TNA) sea surface temperatures (SSTs) on North American precipitation, during the cold and warm halves of the hydrological year (October–September) are examined. Observations indicate that during both seasons warmer-than-normal TNA SSTs are associated with a reduction of precipitation over North America, mainly west of ∼90°W, and that the effect can be up to 30% of the year-to-year seasonal precipitation RMS variability. This finding confirms earlier studies with observations and models. During the cold season (October–March) the North American precipitation variability associated with TNA fluctuations is considerably weaker than its association with ENSO. During the warm season (April–September), however, the Atlantic influence, per one standard deviation of SST anomalies, is larger than that of ENSO. The observed association between TNA SST anomalies and global and North American precipitation and sea level pressure variability is compared with that found in the output of an atmospheric general circulation model (AGCM) forced with observed SST variability, both globally and in the tropical Atlantic alone. The similarity between model output and observations suggests that TNA SST variability is causal. The mechanisms of the “upstream” influence of the Atlantic on North American precipitation are seasonally dependent. In the warm season, warmer-than-normal TNA SSTs induce a local increase in atmospheric convection. This leads to a weakening of the North Atlantic subtropical anticyclone and a reduction in precipitation over the United States and northern Mexico, associated with the anomalous southward flow there. In the cold season, a response similar to the warm season over the subtropical Atlantic is identified, but there is also a concomitant suppression of convection over the equatorial Pacific, which leads to a weakening of the Aleutian low and subsidence over western North America, similar to the impact of La Niña although weaker in amplitude. The impact of TNA SST on tropical convection and the extratropical circulation is examined by a set of idealized experiments with a linear general circulation model forced with the tropical heating field derived from the full AGCM.
3. Observed association between tropical Atlantic SST and North American droughts
a. North American precipitation
b. Global patterns
4. AGCM results
5. Linear model results
6. Summary and discussion
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Bacmeister
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On the cause of the 1930s Dust Bowl.
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Figures
Fig . 1.
Seasonal precipitation anomaly associated with concomitant variations of (a),(b) ENSO and (c),(d) tropical Atlantic SST variability, calculated using a multiple regression on the Niño-3.4 and TNA SST indices for the (a),(c) cold season (October–March) and (b),(d) warm season (April–September). Contours are drawn every 2 mm day −1with positive (solid) [negative (dashed)] values and the zero contour (bold) shown. Shading is added to indicate regions where the anomalies are significant at the two-sided 10% level. Data are from NOAA/NCEP/PREC-L analysis (Chen et al. 2002) for the years from 1948 to 2007.
Fig . 2.
Patterns of SLP (contours, every 0.2 hPa) and precipitation (colors, mm day −1) anomalies associated with tropical Atlantic SST variability between 1979 and 2007 as determined by a using multiple regression analysis on standardized Niño-3.4 and TNA SST indices. Only the TNA regression coefficients are shown. (a) The cold season (October–March) and (b) the warm season (April–September) are shown. SLP is from the NCEP–NCAR reanalysis (Kalnay et al. 1996;Kistler et al. 2001) and precipitation is from GPCP (Huffman et al. 1997). The results of the analysis were smoothed in space with two passes of a binomial (1–2–1) filter to remove small-scale features, which are most likely associated with noise.
Fig . 3.
As in
Fig. 2
, but for the (left) GOGA and (right)
TAGA
model ensemble means. Data were not smoothed in space because the ensemble averaging leads to substantial reduction in the “noise” level (i.e., variability between one ensemble member and another). Also,
TAGA
results are derived by a simple linear regression.
Fig . 4.
Precipitation anomalies associated with one standard deviation of TNA SST in observations for (a) October–March and (b) April–September; data are from GPCP (
Huffman et al. 1997
) and, in the model simulations, from (c),(d) GOGA (winter and summer, respectively) and (e),(f)
TAGA
(winter and summer, respectively). Winter is defined as October–March and summer as April–September. Contours are in mm day
−1
, with positive (solid) and negative (dashed) values indicated. Shading indicates regions where the anomalies are significant at the two-sided 10% level. All calculations were done for the years 1979–2007.
Fig . 5.
The vertically structure of the
TAGA
tropical (20°S–20°N) heating anomaly, as determined by linearly regressing the three-dimensional diabatic heating field, by season, on the TNA SST index for (a) October–March and (b) April–September. Contours are every 0.04 K day
−1
. Negative contours (dashed) and the zero contours (heavy black lines) are shown. Gray shades are added to emphasize the main features.
Fig . 6.
(left) The
TAGA
warm-season streamfunction regression on the TNA SST index at the sigma level of (a) 0.866 and (b) 0.17. (right) The linear model streamfunction response to tropical heating at (c),(d) the same model levels, respectively. Contour interval is (a),(c) 2 and (b),(d) 10. Units are 10
5
m
2
s
−1
. Negative contours (dashed) and the zero contours (heavy black lines) are shown. Shading is added to emphasize the main features.
View in gallery
Fig . 7.
Cold-season streamfunction response in midtroposphere (sigma level of 0.46). (a) The regression of the
TAGA
streamfunction field on the TNA SST index. Linear model response to (b) full tropical heating, (c) Atlantic-only heating, and (d) Pacific-only heating. Units are 10
5
m
2
s
−1
. Contour interval is 2, and negative contours (dashed) and the zero contours (heavy black lines) are shown.
Fig . 8.
Vertical cross section of the linear model cold-season (October–March) response to tropical Atlantic heating derived from the
TAGA
ensemble regression on the TNA SST index. (a) Vertical cross section of the vertical motion; contours every 0.3 10
3
day
−1
. (b) As in (a), but for temperature, with contours every 0.05°C. Both fields are averaged between 20°S and 20°N and are plotted as a function of longitude and sigma level. The negative contours (dashed) and the zero contours (heavy black lines) are shown.
Fig . 9.
Tropical region (20°S–20°N) vertical cross section of the
TAGA
ensemble-mean temperature regressed on the TNA SST index for the (a) cold season (October–March) and (b) warm season (April–September). Contours are every 0.05°C. The negative contours (dashed) and the zero contours (heavy black lines) are shown.
Fig . 10.
Annual PDSI (from NADA;Cook et al. 2004) for the American West (25°–50°N, 125°–90°W; thick black solid line), the index of tropical North Atlantic SST (thin dashed line), and the Niño-3.4 index (thin solid line). All time series are based on annual means, low-pass-filtered to emphasize fluctuations with periods of a decade and longer. All time series were linearly detrended in time to crudely remove the effect of global warming. The ordinate is in standardized values for Niño-3.4 and the TNA index and in PDSI units for PDSI.
Fig . 11.
The multimodel-averaged SLP (contours) and precipitation (colors) response to a North Atlantic SST anomaly, calculated using the AGCMs participating in the CLIVAR Drought Working Group. All models were integrated for several decades with an SST anomaly resembling the change associated with the AMO added to and subtracted from the climatological state (for the SST pattern, seeSchubert et al. 2009). The figure displays the difference between integrations forced with the positive and the negative phases of the anomaly, divided by 2 [in the CLIVAR DWG notation: (PnAw − PnAc)/2]. (a) Cold-season (October–March) and (b) warm-season (April–September) responses are shown. Contours every 0.2 hPa, with positive (solid) and negative (dashed) contours and a thick zero contour (solid) shown.
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GENERAL CONDITIONS
Author:
A. J. HENRY
No. III
BAROMETRIC PRESSURE
VERIFICATIONS
Editorial Type:
Article
Article Type:
Research Article
Mechanisms of Tropical Atlantic SST Influence on North American Precipitation Variability
Yochanan Kushnir
Yochanan Kushnir Lamont-Doherty Earth Observatory, Columbia University Earth Institute, Palisades, New York Search for other papers by Yochanan Kushnir in Current site Google Scholar PubMed Close
,
Richard Seager
Richard Seager Lamont-Doherty Earth Observatory, Columbia University Earth Institute, Palisades, New York Search for other papers by Richard Seager in Current site Google Scholar PubMed Close
,
Mingfang Ting
Mingfang Ting Lamont-Doherty Earth Observatory, Columbia University Earth Institute, Palisades, New York Search for other papers by Mingfang Ting in Current site Google Scholar PubMed Close
,
Naomi Naik
Naomi Naik Lamont-Doherty Earth Observatory, Columbia University Earth Institute, Palisades, New York Search for other papers by Naomi Naik in Current site Google Scholar PubMed Close
, and
Jennifer Nakamura
Jennifer Nakamura Lamont-Doherty Earth Observatory, Columbia University Earth Institute, Palisades, New York Search for other papers by Jennifer Nakamura in Current site Google Scholar PubMed Close
Print Publication:
01 Nov 2010
Collections:
U.S. CLIVAR Drought
DOI:
https://doi.org/10.1175/2010JCLI3172.1
Page(s):
5610–5628
Article History
Abstract
The dynamical mechanisms associated with the impact of year-to-year variability in tropical North Atlantic (TNA) sea surface temperatures (SSTs) on North American precipitation, during the cold and warm halves of the hydrological year (October–September) are examined. Observations indicate that during both seasons warmer-than-normal TNA SSTs are associated with a reduction of precipitation over North America, mainly west of ∼90°W, and that the effect can be up to 30% of the year-to-year seasonal precipitation RMS variability. This finding confirms earlier studies with observations and models. During the cold season (October–March) the North American precipitation variability associated with TNA fluctuations is considerably weaker than its association with ENSO. During the warm season (April–September), however, the Atlantic influence, per one standard deviation of SST anomalies, is larger than that of ENSO.
The observed association between TNA SST anomalies and global and North American precipitation and sea level pressure variability is compared with that found in the output of an atmospheric general circulation model (AGCM) forced with observed SST variability, both globally and in the tropical Atlantic alone. The similarity between model output and observations suggests that TNA SST variability is causal. The mechanisms of the “upstream” influence of the Atlantic on North American precipitation are seasonally dependent. In the warm season, warmer-than-normal TNA SSTs induce a local increase in atmospheric convection. This leads to a weakening of the North Atlantic subtropical anticyclone and a reduction in precipitation over the United States and northern Mexico, associated with the anomalous southward flow there. In the cold season, a response similar to the warm season over the subtropical Atlantic is identified, but there is also a concomitant suppression of convection over the equatorial Pacific, which leads to a weakening of the Aleutian low and subsidence over western North America, similar to the impact of La Niña although weaker in amplitude. The impact of TNA SST on tropical convection and the extratropical circulation is examined by a set of idealized experiments with a linear general circulation model forced with the tropical heating field derived from the full AGCM.
Corresponding author address:Yochanan Kushnir, 61 Route 9W, Lamont-Doherty Earth Observatory, Palisades, NY 10964. Email:kushnir@ldeo.columbia.edu
This article included in the U.S. CLIVAR Drought special collection.
Abstract
The dynamical mechanisms associated with the impact of year-to-year variability in tropical North Atlantic (TNA) sea surface temperatures (SSTs) on North American precipitation, during the cold and warm halves of the hydrological year (October–September) are examined. Observations indicate that during both seasons warmer-than-normal TNA SSTs are associated with a reduction of precipitation over North America, mainly west of ∼90°W, and that the effect can be up to 30% of the year-to-year seasonal precipitation RMS variability. This finding confirms earlier studies with observations and models. During the cold season (October–March) the North American precipitation variability associated with TNA fluctuations is considerably weaker than its association with ENSO. During the warm season (April–September), however, the Atlantic influence, per one standard deviation of SST anomalies, is larger than that of ENSO.
The observed association between TNA SST anomalies and global and North American precipitation and sea level pressure variability is compared with that found in the output of an atmospheric general circulation model (AGCM) forced with observed SST variability, both globally and in the tropical Atlantic alone. The similarity between model output and observations suggests that TNA SST variability is causal. The mechanisms of the “upstream” influence of the Atlantic on North American precipitation are seasonally dependent. In the warm season, warmer-than-normal TNA SSTs induce a local increase in atmospheric convection. This leads to a weakening of the North Atlantic subtropical anticyclone and a reduction in precipitation over the United States and northern Mexico, associated with the anomalous southward flow there. In the cold season, a response similar to the warm season over the subtropical Atlantic is identified, but there is also a concomitant suppression of convection over the equatorial Pacific, which leads to a weakening of the Aleutian low and subsidence over western North America, similar to the impact of La Niña although weaker in amplitude. The impact of TNA SST on tropical convection and the extratropical circulation is examined by a set of idealized experiments with a linear general circulation model forced with the tropical heating field derived from the full AGCM.
Corresponding author address:Yochanan Kushnir, 61 Route 9W, Lamont-Doherty Earth Observatory, Palisades, NY 10964. Email:kushnir@ldeo.columbia.edu
This article included in the U.S. CLIVAR Drought special collection.
Keywords: Precipitation ; Sea surface temperature ; ENSO ; North America ; Climate variability ; Climate models ; Dynamics
1. Introduction
The nature and cause of North American hydroclimate variability is a subject of heightened concern because of the recent droughts 1in the American West 2and in northern Mexico (Seager 2007,2009) and because projections of anthropogenic influence on the climate of the twenty-first century indicate a turn toward increasing aridity there (Seager et al. 2007). The latter finding, based on output from climate models that participated in the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4) suggests that droughts such as the present one may become a permanent feature of the region.
Many recent studies examine the interannual and multiyear variability of precipitation and other indicators of drought in North America (e.g.,Hoerling and Kumar 2003;Cook et al. 2004;McCabe et al. 2004;Schubert et al. 2004a,b;Acuna-Soto et al. 2005;Seager et al. 2005b). The North American region west of the Mississippi (∼90°W) is relatively dry outside of a narrow band along the U.S. West Coast and in the high mountain areas of the northern Rockies. Its hydrological state is thus vulnerable to climatic fluctuations on interannual and longer time scales. The climatic history of the region is dotted with long dry periods that have affected the natural environment and human settlement and activities and have had an impact on interstate water-right agreements and policies. Better understanding of the physical–dynamical setting for such events is important for future planning and predictions. The present work is concerned with these aspects as they affect interannual-to-decadal time-scale variability.
Recent modeling studies indicate that the main regulating mechanism of interannual and multiyear variability of precipitation in the American West and northern Mexico, are low-frequency fluctuations in tropical Pacific sea surface temperatures (SSTs). It is well known that tropical Pacific SSTs exhibit large fluctuations with a period of 2–7 yr, which are related to the El Niño–Southern Oscillation (ENSO) phenomenon. These fluctuations neither are symmetric around the mean nor are they regular. Thus, when averaged over a time interval equal to or longer than the ENSO period, they leave a small but dynamically significant residual, either positive or negative, on eastern equatorial Pacific (EEP) SSTs. Evidence that these small anomalies are important to North American climate comes from the work ofSchubert et al. (2004a,b)andSeager et al. (2005b).Seager et al. (2005b), in particular, integrated two ensembles of the National Center for Atmospheric Research (NCAR) Community Climate Model 3 (CCM3), both of which were forced with a century and a half (1856–2006) of observed monthly mean SSTs. One ensemble was forced with observed global SST variability, and the other with SSTs prescribed only in the tropical Pacific. 3The two ensembles yielded extremely similar results regarding the variability of rainfall in the American West. Both were in good agreement with the observed record, showing that multiyear droughts in the American West occur when SSTs in the EEP are colder than normal, on average, for several years in a row. The reverse is also true, that is, protracted warming in the EEP leads to a wet interval in the American West (see alsoHuang et al. 2005). The studies ofSchubert et al. (2004a,b)yielded similar results using a different climate model [National Aeronautics and Space Administration’s (NASA’s) Seasonal-to-Interannual Prediction Project model 1 (NSIPP1)]. They demonstrated the importance of the tropical Pacific forcing by comparing the results of ensembles forced with observed global SSTs and several idealized integrations with SSTs prescribed in different ocean basins.
The explanation to the EEP SST impact lies in the response of the atmosphere to ENSO (seeSeager et al. 2003,2005a). In particular, warmer (colder)-than-normal EEP SSTs lead to an overall warming (cooling) of the tropical atmosphere; this causes the maximum in the westerlies to move equatorward (poleward) of its mean position and change the pattern of baroclinic eddy momentum flux convergence in the upper troposphere, thus affecting the mean meridional circulation (MMC). The result is a zonally and hemispherically symmetric anomalous ascent (decent) in the midlatitudes, which in the Northern Hemisphere enhances (suppresses) precipitation in the latitude band of 25°–45°N. In winter, the midlatitude response over North America is enhanced by a stationary wave anomaly caused by the changes in the location of the convective heating centers in the tropics, which forces low (high) pressure in the Gulf of Alaska and ascent (descent) over the American West [a phenomenon known as the Pacific–North American (PNA) pattern; see, e.g.,Horel and Wallace (1981),Wallace and Gutzler (1981), andTrenberth et al. (1998)]. Both the zonally symmetric and wavelike response to ENSO thus lead to anomalously wet (dry) winters over North America during El Niño (La Niña) conditions, particularly in the western and southern parts of the country. In the summer, the atmospheric circulation anomalies are weaker, yet similar in phase, and precipitation is probably also affected by changes in the local soil moisture availability, which is carried over from the preceding winter.
As indicated above, the results ofSchubert et al. (2004a)andSeager et al. (2005b)suggest that the reason for multiyear drought conditions (and also for persistent wet conditions) lies in cold (warm) SST anomalies that, while smaller in amplitude than their annual counterparts, can affect the state of the climate on decadal time scales (Zhang et al. 1997;Seager et al. 2004;Huang et al. 2005). During the decade-long “Dust Bowl” drought of the 1930s, for example, EEP SSTs were colder than normal, on average, by about 0.2°C, and there was no major El Niño. While there were interannual variations in the strength of this anomaly, the almost-decade-long weak, negative SST anomaly was the leading cause, according to the models, for the drought event. 4However,Schubert et al. (2004b)andSeager et al. (2008)pointed out that during these years North Atlantic SSTs were considerably warmer than normal north of the equator, and they showed that the tropical North Atlantic (TNA) warmth was important for the persistence of the drought.
That Atlantic SST variability is associated with, and possibly causes, North American hydroclimate variations, was suggested earlier in the observational studies ofEnfield et al. (2001)andMcCabe et al. (2004). In the North Atlantic, a multidecadal time-scale “oscillation” of SSTs stands out clearly, even in the temporally unfiltered instrumental record. The phenomenon was referred to as the Atlantic multidecadal oscillation (AMO) byKerr (2000)and was described earlier byKushnir (1994)andSchlesinger and Ramankutty (1994).Enfield et al. (2001)argued for the existence of a causal link between the warm phase of the AMO and the relatively warm and dry climate of North America throughout the 30-yr interval of 1931–60, during which the Dust Bowl and the 1950s droughts occurred. After 1960 the Atlantic began to cool and for almost three decades the North American climate turned wetter and colder.McCabe et al. (2004)looked at the association of bidecadal North American drought frequency with both the AMO and its Pacific counterpart, the Pacific decadal oscillation (PDO;Zhang et al. 1997) in twentieth-century observations. Their results supported the conclusions of prior observational studies and are consistent with the recent modeling studies, described in previous paragraphs.
A more recent model study looking at the Atlantic influence on North America hydroclimate was reported bySutton and Hodson (2005,2007). These articles provide a detailed analysis of the role of the AMO in precipitation variability around the Atlantic basin. The study consisted of a set of controlled atmospheric general circulation model (AGCM) experiments, using the third climate configuration of the Met Office Unified Model (HadCM3) forced in the North Atlantic with a fixed SST anomaly pattern corresponding to the positive and negative phases of the AMO. The AMO SST anomaly was enhanced by a factor of 4, and each of the two model integrations was carried out for 40 yr, thus providing a robust signal of the atmospheric response. The results show a persistent year-round tropical response that consists of an increase in rainfall in the tropical North Atlantic during a warm AMO phase, combined with reduced rainfall in the eastern tropical Pacific and Indian Oceans. In the American West, significant negative rainfall anomalies occur during the boreal spring and summer when the North Atlantic is warm. Repeating the model integrations, with only the north tropical Atlantic portion of the AMO SST anomaly, yielded similar results in these regions, and differences were found only over the high-latitude North Atlantic.Sutton and Hodson (2005,2007)concluded that as far as the impact on North American hydroclimate is concerned, it is tropical Atlantic SSTs that are the primary driver.
Most recently, the U.S. Climate Variability and Predictability (CLIVAR) Drought Working Group (DWG) initiated a series of global climate model simulations forced with idealized, fixed (in time) SST anomaly patterns that were prescribed in a different ocean basin. The purpose of this activity was to conduct a comprehensive multimodel study of the mechanisms and impact of global and regional SST forcing on droughts, particularly in the United States, and to investigate the role of land–atmosphere feedbacks. The research methodology was akin to that used bySutton and Hodson (2005,2007). However, three different SST patterns were used to force five different AGCMs so that impacts of different ocean basins could be compared and model similarities and discrepancies could be identified. The experimental setting and major results are described in a paper bySchubert et al. (2009, see also more details insection 2). We will later refer to these experiments as they relate to this study.
The goal of the present paper is to add to the existing body of work on the climate processes governing North American hydroclimate by further studying the role of Atlantic SST variability in North American precipitation variability and, in particular, the underlying dynamical mechanisms. Here we use the NCAR CCM3, forcing it with observed time-varying global SSTs (as inSeager et al. 2005b) and with SSTs varying only in the tropical Atlantic basin. In this way we test the sensitivity of prior results (e.g.,Sutton and Hodson 2007) to the model and its forcing methodology while maintaining a realistic relation between the SST anomalies (timing and amplitude) and the seasonal cycle. The present experimental methodology also helps to address the role of the Atlantic relative to the Pacific in forcing North American hydroclimate variability. In addition we employ a linear, primitive-equation model to study the underlying dynamical mechanisms.
The plan of the paper is as follows: Insection 2we describe the observational datasets and the modeling methodology used in the study. The results of the analyses of the observations and AGCM output are described insections 3and4, and the linear model results are described insection 5. A summary and discussion are presented in the concluding section.
2. Observations and models
a. Observations
For observations we use a range of available gridded climate analyses. For global precipitation variability, covering both ocean and land regions, we analyze the satellite–gauge blend of the Global Precipitation Climatology Project (GPCP;Huffman et al. 1997). The rather short GPCP record, which extends from 1979 to the present, is supplanted by the National Oceanic and Atmospheric Administration (NOAA) precipitation reconstruction over land (PREC/L) data (Chen et al. 2002), available since 1948, when examining the observed variations of precipitation over North America in detail. Atmospheric data (specifically, sea level pressure data) are taken from the National Centers for Environmental Prediction (NCEP)–NCAR reanalysis (Kalnay et al. 1996;Kistler et al. 2001).
For indices of tropical Pacific and tropical Atlantic SST variability we use the Niño-3.4 index, defined as the SST average in the region lying between 5°S and 5°N and between 170° and 120°W, and the SST average over the tropical North Atlantic between the equator and 30°N (hereafter the TNA SST index). These indices were averaged over the cold and warm months of the hydrological year (October–March and April–September, respectively) and normalized (divided by their RMS value during the relevant period of analysis) when used in the multiple regression analysis calculations described below.
b. Model experiments
This study follows the methodology applied in our previous works, where a relatively large ensemble of AGCM integrations, all forced with the same prescribed SST history but each starting at different initial atmospheric states, is analyzed to determine the response common to all ensemble members. InSeager et al. (2005b)we pursued the hypothesis that decadal equatorial Pacific SST variability is a primary forcing of multiyear droughts in the American West. Three ensembles of the NCAR CCM3 (Kiehl et al. 1998) were integrated for that purpose, each with different SST forcing. Here we use one of these ensembles, consisting of 16 members and forced with observed global SST variability prescribed month by month, from 1856 to the present. This is the Global Ocean (forcing) Global Atmosphere (response; GOGA) experiment. For SST forcing we used a combination of the Lamont optimally smoothed SST dataset (Kaplan et al. 1998) in the tropics and before 1870, and Hadley Centre Global Sea Ice and Sea Surface Temperature (HadISST;Rayner et al. 2003) elsewhere.
Along with the GOGA ensemble, and to clearly identifying the Atlantic influence, a new ensemble consisting of 16 members was integrated, using the same climate model but with observed SST variability prescribed only in the tropical Atlantic region, between 30°S and 30°N, leaving climatological conditions elsewhere. Eight such integrations were performed, each starting from different initial conditions. We dubbed this the Tropical Atlantic (forcing) Global Atmosphere (response;
TAGA
) experiment. In this way the experiment builds on the conclusions of
Sutton and Hodson (2005
,
2007)
, who showed that it is tropical Atlantic SST variability that forces North American precipitation changes. Note, however, that Sutton and Hodson focused on the AMO, using a fixed SST pattern, corresponding to the difference between the warm Atlantic years (1930–60) and the cold years (1960–90), enhanced by a factor of 4, while here we prescribe the actual (unenhanced) entire ∼150-yr SST history. These two experiments allow the model to vary internally as well as to respond to the prescribed patterns of SST variability globally and in the tropical Atlantic alone. This makes it possible to apply the same analysis methodologies as those applied to the observations, and to compare Pacific and Atlantic impacts.
To support the results obtained in our SST-forced NCAR CCM3 integrations, we present a figure of a multimodel average derived from the output of the Atlantic SST-forced experiments of the U.S. CLIVAR DWG. As indicated above, NCAR’s CCM3 used by our Lamont group was one of the AGCMs participating in the CLIVAR study, as was the NSIPP1 model, the NCEP Global Forecast System (GFS) model, the NCAR Community Atmosphere Model, version 3 (CAM3.5), and the Geophysical Fluid Dynamics Laboratory (GFDL) Atmosphere Model version 2.1 (AM2.1). These models were forced with fixed, idealized SST anomalies in the equatorial Pacific (associated with ENSO), the North Atlantic (resembling the AMO pattern), and globally (associated with the twentieth-century warming trend). The models were integrated for several decades, with the anomalies held fixed at their positive and negative phases as well as with a series of combinations of these idealized anomalies. The difference between the multiyear average of these integrations serves as a measure of the model’s response to a single or combined anomaly forcing [for more information, seeSchubert et al. (2009)andhttp://www.usclivar.org/Organization/drought-wg.html]. Here we briefly compare our present results to the idealized AMO SST-forced DWG results (seesection 6).
In addition to the use of a complex, full AGCM, with realistic atmospheric variability, we employ in this study a linear, dry primitive-equation model, to test hypotheses emerging from the analysis of the former. The linear model is an exact linearization of the NOAA/GFDL spectral model with R30 resolution and 14 vertical layers, inearized around a realistic three-dimensional basic state, as in
Ting and Yu (1998)
. In this particular application the model was forced with a three-dimensional heating field between 30°N and 30°S, corresponding to TNA forcing. The heating field was derived from the
TAGA
ensemble mean by regressing on SST averaged in the tropical North Atlantic Ocean (0°–30°N) region. To suppress high-frequency transients, the model was highly damped. The model was integrated for 50 days, and an average of the last 20 days of the integration is used to represent the stationary response.
3. Observed association between tropical Atlantic SST and North American droughts
a. North American precipitation
Seager et al. (2009)recently studied the relationship between the TNA and Niño-3.4 time series and North American precipitation, by season. They used gridded gauge data from the Universidad Nacional Autónoma de México (UNAM), which covers the United States, Mexico, Central America, and northern South America. Using multiple regression analysis Seager et al. showed that the major effect of both TNA and EEP SST is much more coherent in the cold season (which that study defined as November–April) than in the warm season (defined as May–October). InFig. 1, we present results of a similar multiple regression analysis applied to the NOAA PREC/L dataset for the years from 1948 to 2007. The precipitation data are averaged by the two halves of the hydrological year and are regressed on the same season Niño-3.4 and TNA indices (seesection 2a). The results are consistent with those ofSeager et al. (2009, see their Figs. 1 and 2) and with a similar calculation using the shorter GPCP record (Fig. 4below), indicating the robustness of the main features. Note that a multiple regression on one of the indices amounts to testing its association with the variability in precipitation assuming the other index is held fixed in time.
In the cold season, ENSO’s “influence” (Fig. 1a) is roughly twice as large as that of TNA SST (Fig. 1c). As expected, a cold-season warm equatorial Pacific event (El Niño) is associated with larger-than-normal precipitation over the American West and the U.S. Southeast and over northern Mexico. The anomalies inFig. 1aamount to up to 60% of the total seasonal RMS variability (not shown). During the same season, warmer-than-normal TNA SSTs are associated with drier-than-normal conditions in most of the same locations, but prominently so over the southwestern U.S. and northwestern Mexico and in the Mississippi River basin and the Great Lakes region. In these regions, anomalies associated with TNA SST variability reach up to 30% of the seasonal precipitation RMS value (not shown). If this association is forced byTNA SST variability, it indicates a competition between the Pacific and the Atlantic influences on North American precipitation. That is because during the cold season, ENSO forces the same-sign SST anomaly in the tropical Atlantic (e.g.,Enfield and Mayer 1997). Thus, a Pacific warm (cold) event forces an increase (decrease) in North American precipitation, and at the same time induces a warming (cooling) of the TNA region, which affects precipitation in the opposite manner [i.e., a weakening (strengthening) of precipitation] in much of the same regions. This competition is obviously won by the Pacific, but the overall effect is a weaker ENSO influence. Notably, however, TNA SSTs display variability independent of ENSO (e.g.,Czaja et al. 2002), which could, at times, work in consort with ENSO to increase the overall impact on North American precipitation, and vice versa.
The association of the Mississippi River basin and the Great Lakes region precipitation variability with Atlantic SST fluctuations is consistent with the studies that looked at the long-term impact of the Atlantic Ocean on North American precipitation (e.g.,Enfield et al. 2001;McCabe et al. 2004).
The warm-season anomalies associated with TNA SSTs (Fig. 1d) are similar to their cold-season counterparts but are somewhat less extensive (Fig. 1c). Drying associated with warm TNA SST anomalies is found in the American Southwest and in northern Mexico, with a secondary maximum in the Great Lakes region. Note also that the impact of the Atlantic during the summer is stronger than that of ENSO (Fig. 1b). (Confirmation of these observational results from a different dataset, covering a shorter period, can be found inFig. 4below.)
b. Global patterns
The global SLP and precipitation patterns associated with tropical Pacific and tropical Atlantic SST variability were derived in a similar manner, using multiple regressions on the Niño-3.4 and TNA SST normalized indices. The analysis is confined to the years from 1979 to 2007 to match the satellite record, which provides precipitation estimates over the oceans.Figure 2presents only the TNA-related multiple regression patterns. The Niño-3.4 regression patterns (not shown) display the well-known, extensive tropical Pacific precipitation anomalies and the weaker ones forced over other parts of the world. In SLP, there is a negative cold-season anomaly over the North Pacific and the eastern tropical Pacific, which is related to the response to anomalous tropical convective activity associated with ENSO (e.g.,Trenberth et al. 1998;Seager et al. 2005a). A similar but weaker pattern is seen in the warm-season months.
The cold-season SLP regression on TNA SST (Fig. 2a) displays a dipole pattern over the North Atlantic, which resembles the North Atlantic Oscillation (NAO). The sense of the relationship is such that warmer-than-normal TNA SSTs are associated with a negative NAO state. This is consistent with the notion that a negative NAO forces warm SSTs over the subpolar and TNA regions (Seager et al. 2000;Hurrell et al. 2003) and is therefore, most likely, the cause of (and not the response to) the TNA SST change. However, as we shall see below, the model results indicate that the subtropical low pressure anomaly may also include a forced response to the warm TNA SST.
Over the North Pacific and North America, the cold-season SLP pattern associated with a warm TNA SST anomaly (Fig. 2a) displays a pattern that resembles the negative phase of the PNA teleconnection pattern, associated with (and forced by) cold EEP SST anomalies (Horel and Wallace 1981). Note that the association seen inFig. 2ais in opposite polarity to that which would be expected if the TNA SST anomaly were forced by ENSO. If that were the case, we would expect to find, associated with a negative PNA, coldSST anomalies in the TNA region (Enfield and Mayer 1997), while the pattern inFig. 2acorresponds to warmTNA SSTs. Thus, the multiple regression analysis points at a Pacific response that is most likely forced from the TNA or that both the TNA and the North Pacific are forced by a third “party” not associated with ENSO (see further discussion below). Together, the North Atlantic and North Pacific SLP anomalies ofFig. 2aindicate a southward flow over the American West, which should be associated with dynamically driven subsidence and hence with a negative precipitation anomaly in the region [see discussion of the stationary response to El Niño inSeager et al. (2005a)].
The Pacific sector SLP anomalies inFig. 2aare symmetric about the equator, with the high pressure anomalies over the eastern North Pacific paralleled by an anomaly of the same sign in the South Pacific. This hemispheric symmetry is consistent with tropical forcing. An examination of the precipitation anomaly field indicates that the midlatitude anticyclone pair in the middle of the Pacific basin straddles a negative precipitation anomaly situated in the central tropical Pacific and is flanked by positive anomalies to the west and east. As we shall argue below, based on results from a hierarchy of global models, this weak “La Niña-like” arrangement in the Pacific basin is forced remotely by increased convection over the warm TNA SST.
The warm-season SLP pattern associated with TNA SST (Fig. 2b) is, to some extent, a weaker expression of that of the cold season. Here too we find enhanced precipitation over the western TNA and a low pressure anomaly over the subtropical North Atlantic. Over North America, precipitation is reduced. In the Pacific, precipitation increases west of 150°W but mainly over the Maritime Continent and the Indian Ocean. This is associated with a subtropical anticyclonic pair straddling the equator in the western Pacific and negative subtropical precipitation anomalies.
We note that because of the short record of satellite-based precipitation estimates, these results should be viewed with caution. However, we did confirm that the main SLP features inFig. 2are reproducible by repeating the multiple regression analysis with a longer reanalysis record and with the century-long Hadley Centre Sea Level Pressure (HadSLP) dataset (not shown). Also important to note is that regression analysis does not indicate that TNA SST variability is forcing the observed changes. It is possible that the changes in the global SLP pattern, in particular, are forced from other ocean regions that tend to vary in phase with TNA SST. During 1979–2007, TNA SST exhibited a warming trend that explains ∼6.25% of its seasonal variance. This trend is consistent with the warming trend in other tropical ocean regions, particularly the Indian Ocean and the South Atlantic. We chose not to remove the trend from the observed TNA SST time series because it could be, in part, attributable to the AMO (seeTing et al. 2009). Moreover, we are interested here in the impact of TNA SST warming regardless of its cause. The disadvantage of this approach is that it is possible that the changes in the Pacific circulation, in particular, are partially linked to the SST trend in other ocean regions. In the next sections we compare the observed patterns with the AGCM results, forced only with TNA SST variability, which by their similarity to their observed counterparts add further credence to the role of the TNA in forcing the changes in circulation described above.
4. AGCM results
Figure 3
displays the results of a multiple regression analysis applied to the GOGA and
TAGA
ensemble-mean output (note that with
TAGA
the multiple regression reduces to a simple linear regression with the TNA index). Both the global SLP and precipitation fields are analyzed following the same procedure applied to the observations in
Fig. 2
. Here too, only the regression patterns corresponding to TNA SSTs are shown. The analysis is performed over the same time interval used for the observations (1979–2007) for better comparison. The resemblance to observations (
Fig. 2
) is striking, considering that
Fig. 2
is derived based on the (single) observed realization, while the model results are based on an ensemble average of 16 GOGA and
TAGA
independent realizations, forced with the same SST conditions. Ensemble averaging strongly reduces the variability that is not related to the prescribed SSTs, and thus the fields should be less “noisy.” In addition, we should consider the fact that the observed relationship includes atmospheric variability that could have caused the TNA SST anomalies (such as the NAO), and not only the response to the latter. In the AGCM, the atmospheric variability that is unrelated to the prescribed SSTs has no influence on the state of the ocean and thus has been averaged out. The model results, however, may include spurious features that are unphysical, such as the tendency to precipitate excessively (compared to observations) over areas with prescribed warmer-than-normal SSTs. In areas where the anomalous SSTs are related to increased insolation because of reduced clouds and precipitation, the model precipitation response is unrealistic. We will return to this issue below in discussing the model precipitation response to TNA SSTs.
The model SLP regression patterns confirm that over the TNA, the circulation responds to SST variability in both cold and warm seasons by increased convection activity and a weak, albeit significant, low pressure anomaly. In the cold season (
Figs. 3a,c
) the model displays a low pressure anomaly over the entire North Atlantic basin, in contrast with the observations, where a large, positive anomaly is centered just east of Greenland (
Fig. 2a
). As discussed above, the observed pattern mainly reflects the NAO forcing of TNA SST variability (e.g.,
Seager et al. 2000
). The model results indicate, however, that TNA SST anomalies can force a weakening of the Atlantic subtropical anticyclone with consequences to North American precipitation. This positive feedback response from TNA SSTs (in the case of NAO forcing) was mentioned in earlier studies (e.g.,
Terray and Cassou 2002
;
Peng et al. 2005
). The simulated high pressure anomaly over the Gulf of Alaska and the North Pacific is more robust than in observations and is much stronger (and more so in GOGA than in
TAGA
; see more below). Circulation features over the South Pacific are weaker than those in the observations but are consistent in phase (missing is the noisy pattern over Antarctica, which in observations can be attributed to the short record and to deficiencies in the reanalysis output over this data-sparse region). In the warm season (
Figs. 2b
and
3b,d
), the agreement is in the low pressure anomaly over the TNA region as well as the anomaly centers over the Pacific, both north and south of the equator, although here the North Pacific anticyclonic anomaly is weak.
The layout of tropical precipitation anomalies in the GOGA (
Figs. 3a,b
) and
TAGA
(
Figs. 3c,d
) is similar to the observed features discussed in
section 2
. A more detailed comparison of the TNA-related observed and modeled precipitation anomalies over the tropical Atlantic and the Americas is shown in
Fig. 4
. GOGA (
Figs. 4b,c
) and
TAGA
(
Figs. 4e,f
) exhibit significant positive precipitation anomalies over the TNA region, extending from the West African seaboard to the Caribbean and Central America. The pattern resembles the layout of the summertime ITCZ and corresponds to its intensification resulting from warmer TNA SSTs. We are not the first to note that there is a positive correlation between TNA SSTs and precipitation in that region. Refer, for example, to
Ruiz-Barradas et al. (2000)
or
Chiang and Vimont (2004)
for analyses based on the estimated satellite precipitation and to
Seager et al. (2009)
and
Giannini et al. (2001)
for analyses based on a longer regional station record. However, in the model experiments, particularly the
TAGA
runs, these positive precipitation anomalies are much stronger than those in the observations (cf.
Figs. 4a,b
). This could be due to the ensemble averaging (which removes features that are not related to the prescribed SSTs) and/or to the fact that AGCMs with prescribed SSTs are known to display an excessive convective response to prescribed warm anomalies (e.g.,
Biasutti et al. 2006
).
Figure 4implies that the model response, while exaggerated, is not unrealistic, and that convection in the TNA region is positively correlated with underlying SSTs. Particularly noteworthy is the similarity in the wintertime pattern of the positive precipitation response over the Caribbean Sea and into the eastern Pacific, where the focal point of the SST-forced response is located. Note also the general similarity in the impact over North America to which we refer again below. The model precipitation anomalies in the central equatorial Pacific (Fig. 3) are generally negative, reaching ∼1 mm day −1in the center of the basin during the cold season (Fig. 3a).
There are some notable differences between the
TAGA
and GOGA responses to TNA SST anomalies (
Fig. 3
). In
TAGA
(
Figs. 3c,d
), the precipitation anomalies over the tropical Pacific are weaker and less coherent compared to GOGA (
Figs. 3a,b
) and the SLP anomaly in the Gulf of Alaska during winter is also weaker. In the Atlantic, however, the low pressure anomaly over the northern ocean basin is stronger. Also noticeable in
TAGA
is a large negative precipitation response over the tropical Indian Ocean, particularly during the warm season, when the anomaly over the Bay of Bengal reaches −1 mm day
−1
. In the observations (
Fig. 2
) and in GOGA there are positive precipitation anomalies there. We attribute the difference to the specification of climatological SST conditions in the Indian Ocean in
TAGA
, while in GOGA SST they vary realistically. Observed SST variability in the tropical Indian Ocean exhibits considerable coherence with TNA SST variability, mainly due to the gradual warming of most of the tropics, excluding the EEP, during the twentieth century. This warming trend could have lead to the increased convection over the Indian Ocean (as seen in GOGA). Furthermore, increased Indian Ocean convection could also lead to a remote effect in the North Pacific, specifically the Gulf of Alaska (see
Hoerling and Kumar 2003
;
Hoerling et al. 2004
), and thus explain the stronger wintertime North Pacific response in GOGA compared to
TAGA
(
Figs. 3a,c
).
Figure 4
provides a comparison between the simulated and observed seasonal change in North American precipitation associated with TNA SST. Concerning these continental patterns, we note first that the observed anomalies during 1979–2007 (
Figs. 4a,b
) compare quite well with their counterparts during the 60-yr period used in
Fig. 1
. We also find that the model ensembles (
Figs. 4c–f
) display a rather successful simulation during both winter and summer months. Notably, the
TAGA
response (
Figs. 4e,f
) is stronger than that of GOGA (
Figs. 4c,d
). This seems consistent with the stronger convection response in
TAGA
over the TNA region.
5. Linear model results
As described in
section 2
, the linear model was forced with the tropical-band, three-dimensional diabatic heating field, which was derived by regressing the
TAGA
ensemble-mean field on the TNA SST index, by season. We chose the
TAGA
output to demonstrate most clearly the role that tropical Atlantic SST variability can play in North American precipitation variability. Our intention is to isolate the role of TNA SST-driven diabatic heating alone, and not to create the best simulation of the observations or the AGCMs by using a linear model. We wanted to study the response to the heating confined to the region of specified SSTs but also to explore the hypothesis put forward above that during winter, TNA SSTs exert a remote impact on the tropical Pacific convection with implications for North America. When forcing the linear model, the imposed heating was limited to the latitude belt of 30°S–30°N. The linear model was integrated with full tropical heating, the TNA part of the heating (specified between 100°W and 0°), and the Pacific part of the heating (specified as 110°E–100°W) separately. The results shown below are not very sensitive to the exact choice of these latitude–longitude boundaries.
The horizontal pattern of the vertically averaged TNA-regressed
TAGA
heating (not shown) mimics, as expected, the pattern of the precipitation anomaly shown in
Figs. 3c,d
. The anomaly varies somewhat by season, with a year-round enhancement of diabatic heating in the TNA region and a suppression of tropical Pacific heating around the date line.
Figure 5
shows the vertical structure of the
TAGA
heating regressed on the TNA index and averaged between 20°S and 20°N, where the largest precipitation anomalies are located. The figure displays a positive heating anomaly over the tropical Atlantic basin, associated with increased convection there and elevated anomalous cooling almost everywhere else. The cooling is associated with the suppressed convection over the Pacific and Indian Ocean basins. There is weak warming in a shallow layer in the lower troposphere in the tropical Pacific. However, the elevated cooling is the most likely feature to affect the extratropical regions, as evident from the forced linear model results discussed below. The seasonal differences are small and are mainly associated with a stronger tropical Atlantic signal in the warm season. A multiple regression of the GOGA heating field on the TNA SST index (not shown) yields qualitatively similar results except for the Indian Ocean region, where the signal is weakly positive, consistent with the precipitation field in
Fig. 3
.
Figure 6
displays the lower- and upper-tropospheric warm-season streamfunction response of the linear model to the all-tropics heating. The full
TAGA
AGCM streamfunction regressions on TNA SST are shown for comparison in the top two panels. Over the Atlantic and the Americas, the
TAGA
warm-season response to SST imposed in the tropical Atlantic (
Figs. 6a,b
) is consistent with the “Gill response” to tropical heating (
Gill 1980
;
Jin and Hoskins 1995
;
Ting and Yu 1998
). With TNA heating only (not shown) the response over the Atlantic and the Americas is similar, confirming that the “chain of events” in summer is that warm SST anomalies in the TNA region lead to increased convection, mainly in the core of the Atlantic ITCZ region, which forces a pair of low-level cyclonic circulation anomalies straddling the heating center. Aloft, there is a pair of anticyclones. The linear model response confirms that effect of the Caribbean-centered low-level anomalous cyclone over the American West and northern Mexico is to induce an anomalous subsiding southward flow and a negative precipitation anomaly (not shown). What seems to be unrelated to Atlantic heating is the large lower-tropospheric response over the Indian Ocean, which is simulated by the linear models only when the entire tropical heating pattern is enforced and is thus related to local SST forcing. The impact of Pacific heating alone on the summer circulation is negligible (not shown).
In the observations and the AGCM used here, the tropical Atlantic is also responsible for reduced precipitation over North America in winter. We suggested earlier that the winter drying is associated with a more complex dynamical response to TNA SSTs than that found in summer. This cold-season response is studied further inFig. 7. Outside of the immediate vicinity of the heating maximum, in the TNA region the response is equivalent barotropic (not shown), which is consistent with theory (seeHoskins and Karoly 1981). Thus, the midtropospheric streamfunction response inFig. 7is chosen to represents a troposphere-deep pattern in both the North Pacific and the North Atlantic. Only within the TNA region is the response baroclinic (as anticipated from a heating-forced response), with a high pressure anomaly in the upper troposphere overlying a local low-level low pressure anomaly (not shown).
To reproduce close to the full strength and detailed response of the cold-season atmosphere to TNA SST, the linear model had to be forced by the full tropical heating field (cf.Figs. 7a,b; the small discrepancies in the strength of the response pattern can be attributed to the absence of transients and/or extratropical heating in the linear model). With the Atlantic portion of the heating alone, the model responds most strongly (but with a lower amplitude than the full heating field) over the North Atlantic (Fig. 7c), and with Pacific heating alone the model responds mainly over the North Pacific (Fig. 7d). The tropical Pacific suppressed convection response to the warm Atlantic SST (Fig. 5) is thus important for explaining the high pressure (and La Niña like) response over the North Pacific. The linear model shows that broad, continental-scale subsidence over the United States is associated with the TNA-only forcing and that the Pacific heating response is enhancing this subsidence over the American Southwest and northern Mexico (not shown).
We argued above that warm TNA SST anomalies force the diabatic cooling response in the rest of the tropics, as seen in
Fig. 5
. Indeed, an examination of the
TAGA
tropical vertical motion field reveals broad areas of subsidence consistent with the regions of diabatic cooling in
Fig. 5
(not shown). However, in the full GCM this pattern of vertical motion cannot be viewed separately from the suppressed convection, and thus it may not be causal. To explore the forced vertical motion response to tropical Atlantic SST alone we turn to the linear model experiment with the heating imposed only over the TNA region.
Figure 8a
displays the average linear model vertical motion response to TNA heating. Over the tropical Atlantic we find the expected upward motion associated with the heating; elsewhere the model displays weak subsidence.
The subsidence seen in
Fig. 8a
is tied to the horizontal spreading of high-level warming by equatorial waves (Kelvin and Rossby waves) and the associated stabilization of the tropical atmosphere outside of the immediate region of increased convection.
Yulaeva and Wallace (1994)
demonstrated the existence of such a mechanism accompanying ENSO. Recently,
Chiang and Sobel (2002)
invoked this mechanism to explain the tropical convection and SST response to ENSO variability outside of the tropical Pacific. As seen in
Fig. 8b
, the tropospheric high-level tropics-wide warming is a linear stationary response to the heating prescribed over the tropical Atlantic. The combined effect of the stabilization of the atmosphere and the associated subsidence over the equatorial Pacific are therefore the result of the increase convection over the TNA region. The tropical temperature response in the full
TAGA
ensemble (
Fig. 9
) displays a strong warming signal over the TNA but a weak cooling over the tropical Pacific that is deep in winter (
Fig. 9a
) and shallow in summer (
Fig. 9b
). This pattern obviously reflects the equilibrated response to the remote influence of the Atlantic, which includes the effect of the forced reduction in convective heating over the Pacific.
6. Summary and discussion
Observations and model studies indicate that changes in SST on interannual and longer time scales in the tropical North Atlantic affect the precipitation in North and Central America. Positive SST anomalies in the TNA region are associated with negative precipitation anomalies (and droughts) over most of the contiguous United States, particularly in the West (Figs. 1and2) and over Mexico. This is the case in both halves of the hydrological year—October through March and April through September—with a somewhat larger effect in the cold half of the year. In experiments with an AGCM forced with the observed history of SST variability, the association between TNA SST variability and North American precipitation is reasonably well simulated (Fig. 4). Overall, the model results indicate that TNA SST variability is forcing North American precipitation.
During the cold season, the change in precipitation associated with one standard deviation of TNA SSTs is considerably smaller than the change associated with the normalized Niño-3.4 index, but in summer the Atlantic influence is larger (Fig. 1). On interannual time scales, the standard deviation of EEP SSTs is considerably larger than that of TNA SSTs. Thus, tropical Pacific SST fluctuations should dominate the variability of precipitation in North and Central America when year-to-year changes are concerned. However, on decadal and multidecadal time scales, SST variability in both ocean regions is comparable and the Atlantic influence should become more important, particularly so in the warm season. Moreover, the Atlantic influence is realized year-round, thus reducing the likelihood for soil moisture recharge during multiyear droughts.
The interplay between the Pacific and Atlantic effects on North American hydroclimate can be discerned inFig. 10. The figure displays a long time series of an indicator of North American hydroclimate, along with the low-frequency variations of Niño-3.4 and the TNA SST indices. The hydroclimate indicator is the tree-ring-based estimate of the annual Palmer Drought Severity Index (PDSI) taken from the North American Drought Atlas( NADA;Cook et al. 2004). NADAprovides a temporally stable fit to the observations in the recent past and a regression-based extrapolation to the preinstrumental era (which, in some location, covers the last two millennia). Here we use the NADAfrom 1856 to the present and display the average over the American West (25°–50°N, 125°–90°W).Figure 10exhibits a systematic relationship between North American hydroclimate variability and EEP SST fluctuations. In particular, we note that on decadal time scales, the PDSI time series follows the Niño-3.4 fluctuation. However,Fig. 10also indicates that the American West is subjected to more severe droughts when the TNA is warmer than normal, compared to when it is colder than normal. In particular, the Dust Bowl, the 1950s drought, and the recent turn-of-the-century drought (Seager et al. 2007) occurred during cold equatorial Pacific events and an extended interval of warm TNA SSTs. In contrast, cold events in the Pacific did not affect the American West as severely when the TNA was in a cold state (e.g., around 1910 or in the mid-1970s).
During the short interval corresponding to the era of satellite observations, the Atlantic-related precipitation variability in North America is associated with dynamically consistent features surrounding North America over the Atlantic and Pacific Ocean basins. Positive TNA SST anomalies in both halves of the hydrological year are associated with a local increase in precipitation and a weakening of the Atlantic subtropical anticyclone (Fig. 2). A comparison with the output of the SST-forced AGCMs (Fig. 3) indicates that these features are robust and that the change in subtropical Atlantic precipitation can be attributed to the change in SST (Fig. 4). In the cold half of the hydrological year a consistent string of changes over the Pacific, in both the observations and model simulations, are found accompanying the TNA SST variability. The tropical rainfall field displays a negative anomaly in the central equatorial Pacific, which is straddled by positive SLP anomalies in the extratropics of both hemispheres (Figs. 2and3).
Considering the similarity between the model simulations and the observations, we argue that warmer-than-normal SST anomalies in the tropical Atlantic during the warm season lead to increased convection there, and that this forces a “Gill type” response that weakens the subtropical North Atlantic anticyclone. The resulting influence over North America is an anomalous southward flow and cold advection in the low troposphere. This leads to anomalous subsidence, via the heat and vorticity balances, over the American West, as well as reduced moisture flux convergence, and hence a suppression of rainfall. This hypothesis is confirmed with a linear AGCM forced with the tropical heating field associated with TNA SST anomalies in the full AGCM. The linear model results show that the TNA portion of the tropical heating field alone can explain the circulation response in both seasons.
In the cold season the TNA heating anomalies alone cannot explain the complex circulation features, which include an upstream impact on the North Pacific. Here we argue that increased convection in the TNA region, related to warm SSTs, leads to the suppression of convection over the central tropical Pacific. This is due to subsidence and increased tropical static stability forced from the tropical Atlantic through the tropical waveguide. The suppression of normal convective activity in the tropical Pacific forces a positive North Pacific pressure anomaly (a weakening of the seasonal Aleutian low), which is an atmospheric response that exacerbates the suppression of precipitation over the American West resulting from the Atlantic impact alone. It is worth noting that the influence of a TNA SST warming during the cold season on the North Pacific atmospheric circulation and American West precipitation yields a pattern that is similar to that of a typical La Niña event, though it is much weaker in magnitude. This is why a combination of a cold tropical Pacific (La Niña) and a warm tropical North Atlantic (cf., the negative phase of the AMO) cause the most severe dry conditions over the western North America. Interestingly, a recent article by
Okumura et al. (2009)
reaches similar conclusions regarding the tropical Atlantic impact on Pacific climate in a study of the global atmospheric response to a shutdown of the Atlantic meridional overturning circulation (AMOC) in four coupled GCMs. The AMOC shutdown leads to widespread cooling of the Atlantic, including the TNA region and a southward shift of the ITCZ in both the Atlantic and Pacific basins. In addition, there is a substantial low pressure response in the North Pacific, which is quite similar to that seen in the
TAGA
and GOGA integrations. The Okumura et al. study shows that the change in North Pacific SLP (and geopotential height) is due to the cooling of the TNA region and the related impact on the tropical Pacific.
It is interesting to compare the results of our study to those obtained in the idealized set of experiments taken up by the U.S. CLIVAR DWG (seesection 2b). The “consensus” AGCM precipitation and precipitation and SLP response to a typical AMO SST change (positive–negative experiments), shown inFig. 11, is entirely consistent with the findings in this study (cf.Figs. 3c,d), despite the different methodology (prescribed fixed versus time-varying SSTs and the domain covered by the prescribed anomalies) and the additional models used in these composites. It confirms the existence of a local Atlantic basin response to a warming of Atlantic SST, as well as a remote Pacific response associated with the suppression of tropical Pacific convection.
The present study thus confirms previous work that proposed, based on observations and models, that Atlantic SST variability, particularly in the TNA region, influences seasonal and annual precipitation variability in parts of North and Central America (e.g.,Enfield et al. 2001;McCabe et al. 2004;Schubert et al. 2004b;Sutton and Hodson 2005,2007;Seager et al. 2008,2009). Our paper emphasizes that the Atlantic impact is felt on interannual time scales and not necessarily just on multidecadal scales, as emphasized by some on the previous studies. While the impact of the Atlantic is relatively weak compared to that of ENSO during winter, it is felt year-round [and not only in summer as suggested, e.g., byEnfield et al. (2001)orSutton and Hodson (2005,2007)]. This is important particularly in the Southwest United States and northern Mexico where winter precipitation is as much or even more important than in the summer. In addition, the present study provides more information regarding the dynamical mechanisms underlying the Atlantic influence. The experiments with the linear stationary wave model place on firm dynamical ground the association between U.S. precipitation anomalies and TNA SSTs, seen previously in observations and models. In addition to confirming the Gill-type response to SST-induced heating in the TNA region, these experiments also suggest that the influence of the Atlantic extends into the Pacific through the equatorial waveguide, a mechanisms that may have broader relevance to global climate variability.
Acknowledgments
The authors acknowledge the support from NOAA awards NA03OAR4320179, NA08OAR4320754, and NA06OAR4310143. We would also like to acknowledge the U.S. CLIVAR drought working group activity supported by NASA, NOAA, and NSF to coordinate and compare climate model simulations forced with a common set of idealized SST patterns. The authors thank NASA’s Global Modeling and Assimilation Office (GMAO) for making the NSIPP1 runs available, the Lamont-Doherty Earth Observatory of Columbia University for making their CCM3 runs available, NOAA’s Climate Prediction Center (CPC)/Climate Test Bed (CTB) for making the GFS runs available, NOAA’s Geophysical Fluid Dynamics Laboratory (GFDL) for making the AM2.1 runs available, the National Center for Atmospheric Research (NCAR) for making the CAM3.5 runs available, and the Center for Ocean Land Atmosphere (COLA) and the University of Miami Rosenstiel School of Marine and Atmospheric Science for making the CCSM3.0 coupled model runs available.
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Fig . 1.
Seasonal precipitation anomaly associated with concomitant variations of (a),(b) ENSO and (c),(d) tropical Atlantic SST variability, calculated using a multiple regression on the Niño-3.4 and TNA SST indices for the (a),(c) cold season (October–March) and (b),(d) warm season (April–September). Contours are drawn every 2 mm day −1with positive (solid) [negative (dashed)] values and the zero contour (bold) shown. Shading is added to indicate regions where the anomalies are significant at the two-sided 10% level. Data are from NOAA/NCEP/PREC-L analysis (Chen et al. 2002) for the years from 1948 to 2007.
Citation: Journal of Climate 23, 21;10.1175/2010JCLI3172.1
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Fig . 1.
Seasonal precipitation anomaly associated with concomitant variations of (a),(b) ENSO and (c),(d) tropical Atlantic SST variability, calculated using a multiple regression on the Niño-3.4 and TNA SST indices for the (a),(c) cold season (October–March) and (b),(d) warm season (April–September). Contours are drawn every 2 mm day −1with positive (solid) [negative (dashed)] values and the zero contour (bold) shown. Shading is added to indicate regions where the anomalies are significant at the two-sided 10% level. Data are from NOAA/NCEP/PREC-L analysis (Chen et al. 2002) for the years from 1948 to 2007.
Citation: Journal of Climate 23, 21;10.1175/2010JCLI3172.1
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Fig . 2.
Patterns of SLP (contours, every 0.2 hPa) and precipitation (colors, mm day −1) anomalies associated with tropical Atlantic SST variability between 1979 and 2007 as determined by a using multiple regression analysis on standardized Niño-3.4 and TNA SST indices. Only the TNA regression coefficients are shown. (a) The cold season (October–March) and (b) the warm season (April–September) are shown. SLP is from the NCEP–NCAR reanalysis (Kalnay et al. 1996;Kistler et al. 2001) and precipitation is from GPCP (Huffman et al. 1997). The results of the analysis were smoothed in space with two passes of a binomial (1–2–1) filter to remove small-scale features, which are most likely associated with noise.
Citation: Journal of Climate 23, 21;10.1175/2010JCLI3172.1
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Fig . 2.
Patterns of SLP (contours, every 0.2 hPa) and precipitation (colors, mm day −1) anomalies associated with tropical Atlantic SST variability between 1979 and 2007 as determined by a using multiple regression analysis on standardized Niño-3.4 and TNA SST indices. Only the TNA regression coefficients are shown. (a) The cold season (October–March) and (b) the warm season (April–September) are shown. SLP is from the NCEP–NCAR reanalysis (Kalnay et al. 1996;Kistler et al. 2001) and precipitation is from GPCP (Huffman et al. 1997). The results of the analysis were smoothed in space with two passes of a binomial (1–2–1) filter to remove small-scale features, which are most likely associated with noise.
Citation: Journal of Climate 23, 21;10.1175/2010JCLI3172.1
Fig . 3.
As in
Fig. 2
, but for the (left) GOGA and (right)
TAGA
model ensemble means. Data were not smoothed in space because the ensemble averaging leads to substantial reduction in the “noise” level (i.e., variability between one ensemble member and another). Also,
TAGA
results are derived by a simple linear regression.
Citation: Journal of Climate 23, 21;10.1175/2010JCLI3172.1
Download figure as PowerPoint slide
Fig . 3.
As in
Fig. 2
, but for the (left) GOGA and (right)
TAGA
model ensemble means. Data were not smoothed in space because the ensemble averaging leads to substantial reduction in the “noise” level (i.e., variability between one ensemble member and another). Also,
TAGA
results are derived by a simple linear regression.
Citation: Journal of Climate 23, 21;10.1175/2010JCLI3172.1
Fig . 4.
Precipitation anomalies associated with one standard deviation of TNA SST in observations for (a) October–March and (b) April–September; data are from GPCP (
Huffman et al. 1997
) and, in the model simulations, from (c),(d) GOGA (winter and summer, respectively) and (e),(f)
TAGA
(winter and summer, respectively). Winter is defined as October–March and summer as April–September. Contours are in mm day
−1
, with positive (solid) and negative (dashed) values indicated. Shading indicates regions where the anomalies are significant at the two-sided 10% level. All calculations were done for the years 1979–2007.
Citation: Journal of Climate 23, 21;10.1175/2010JCLI3172.1
Download figure as PowerPoint slide
Fig . 4.
Precipitation anomalies associated with one standard deviation of TNA SST in observations for (a) October–March and (b) April–September; data are from GPCP (
Huffman et al. 1997
) and, in the model simulations, from (c),(d) GOGA (winter and summer, respectively) and (e),(f)
TAGA
(winter and summer, respectively). Winter is defined as October–March and summer as April–September. Contours are in mm day
, with positive (solid) and negative (dashed) values indicated. Shading indicates regions where the anomalies are significant at the two-sided 10% level. All calculations were done for the years 1979–2007.
Citation: Journal of Climate 23, 21;10.1175/2010JCLI3172.1
Fig . 5.
The vertically structure of the
TAGA
tropical (20°S–20°N) heating anomaly, as determined by linearly regressing the three-dimensional diabatic heating field, by season, on the TNA SST index for (a) October–March and (b) April–September. Contours are every 0.04 K day
−1
. Negative contours (dashed) and the zero contours (heavy black lines) are shown. Gray shades are added to emphasize the main features.
Citation: Journal of Climate 23, 21;10.1175/2010JCLI3172.1
Download figure as PowerPoint slide
Fig . 5.
The vertically structure of the
TAGA
tropical (20°S–20°N) heating anomaly, as determined by linearly regressing the three-dimensional diabatic heating field, by season, on the TNA SST index for (a) October–March and (b) April–September. Contours are every 0.04 K day
−1
. Negative contours (dashed) and the zero contours (heavy black lines) are shown. Gray shades are added to emphasize the main features.
Citation: Journal of Climate 23, 21;10.1175/2010JCLI3172.1
Download figure as PowerPoint slide
| https://journals.ametsoc.org/view/journals/clim/23/21/2010jcli3172.1.xml?result=3&rskey=aheUSa |
Diversity | Free Full-Text | Phylogenomic Reconstruction of the Neotropical Poison Frogs (Dendrobatidae) and Their Conservation
The evolutionary history of the Dendrobatidae, the charismatic Neotropical poison frog family, remains in flux, even after a half-century of intensive research. Understanding the evolutionary relationships between dendrobatid genera and the larger-order groups within Dendrobatidae is critical for making accurate assessments of all aspects of their biology and evolution. In this study, we provide the first phylogenomic reconstruction of Dendrobatidae with genome-wide nuclear markers known as ultraconserved elements. We performed sequence capture on 61 samples representing 33 species across 13 of the 16 dendrobatid genera, aiming for a broadly representative taxon sample. We compare topologies generated using maximum likelihood and coalescent methods and estimate divergence times using Bayesian methods. We find most of our dendrobatid tree to be consistent with previously published results based on mitochondrial and low-count nuclear data, with notable exceptions regarding the placement of Hyloxalinae and certain genera within Dendrobatinae. We also characterize how the evolutionary history and geographic distributions of the 285 poison frog species impact their conservation status. We hope that our phylogeny will serve as a backbone for future evolutionary studies and that our characterizations of conservation status inform conservation practices while highlighting taxa in need of further study.
Phylogenomic Reconstruction of the Neotropical Poison Frogs (Dendrobatidae) and Their Conservation
by Wilson X. Guillory 1,* , Morgan R. Muell 1 , Kyle Summers 2 and Jason L. Brown 1
Department of Zoology, Southern Illinois University, Carbondale, IL 62901, USA
Department of Biology, East Carolina University, Greenville, NC 27858, USA
Diversity 2019 , 11 (8), 126; https://doi.org/10.3390/d11080126
Received: 10 June 2019 / Revised: 21 July 2019 / Accepted: 26 July 2019 / Published: 29 July 2019
Abstract
:
Keywords:
UCE
phylogenetics
amphibians
Dendrobatidae
Aromobatidae
frogs
systematics
Graphical Abstract
1. Introduction
Neotropical poison frogs, represented by the family Dendrobatidae within Anura, are one of the most charismatic and well-studied groups of amphibians. Popularly known for their powerful skin toxins and extravagant aposematism, dendrobatids have featured in scientific studies for decades in fields as diverse as reproductive behavior [ 1 , 2 ], pharmacology [ 3 , 4 , 5 ], color evolution [ 6 , 7 , 8 ], and biogeography [ 9 , 10 , 11 ], as well as recently fueling important studies in the evolution of monogamy [ 12 ] and toxin autoresistance [ 13 , 14 ]. In the context of Anura, Dendrobatidae is moderately diverse, inhabiting a range of habitats and ecological niches throughout Central and South America. Many dendrobatids are unfortunately threatened by a variety of factors including habitat destruction [ 15 , 16 ] and smuggling for the pet trade [ 17 , 18 ], making their conservation an important priority for biologists. Despite heavy popular and scientific interest in dendrobatids, in-depth studies of dendrobatid phylogenetic systematics have become scarce despite the rapid progress of phylogenomics. In this paper, we aim to provide the first evolutionary hypothesis of Dendrobatidae derived from genomic-scale data, to put to rest many of the outstanding questions concerning dendrobatid phylogeny.
The first dendrobatid described was Rana tinctoria by Cuvier in 1797 [ 19 ], later transferred to Dendrobates by Wagler in 1830 [ 20 ], where it remains to this day. Since then, described dendrobatid diversity has grown significantly, with roughly 198 species in 16 genera as of 2019 ( Table 1 ). Until the 2006 revision of Dendrobatidae by Grant et al. [ 21 ], most dendrobatid species were confined to the genera Dendrobates, Phyllobates, Colostethus, Epipedobates, and Minyobates. Phylogenetic estimates constructed during this time from molecular data [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ] generally recovered two main clades of dendrobatids: one composed of mostly aposematic frogs in Phyllobates and Dendrobates , and the other composed of more cryptic frogs in Colostethus and Epipedobates . A third group, which would later be established as the subfamily Hyloxalinae, was generally placed as sister to the Dendrobates clade ([ 22 , 23 , 27 ], though see [ 28 ] for an exception). During this time, the systematics and taxonomy of Dendrobatidae and its sister family Aromobatidae (then regarded as part of Dendrobatidae; this is still the taxonomy used by AmphibiaWeb) were confused and inconsistent. Phylogenies produced during this period were mostly constructed from alignments of a few mitochondrial loci, making them vulnerable to incomplete lineage sorting [ 31 , 32 ].
In 2006, Grant et al. comprehensively revised Dendrobatidae [ 21 ], splitting many of the previously paraphyletic genera into a multitude of new, monophyletic ones: Ranitomeya, Adelphobates , and Oophaga from Dendrobates; Ameerega from Epipedobates; and Silverstoneia and Hyloxalus from Colostethus . Most species within Minyobates were absorbed into Ranitomeya, leaving M. steyermarki as the sole member of the now-monotypic genus. The dendrobatid tree was becoming clearer now, with the genera previously in Dendrobates, along with Phyllobates and Minyobates, forming the subfamily Dendrobatinae, Epipedobates, Ameerega, Colostethus, and Silverstoneia forming Colostethinae, and Hyloxalus forming its own subfamily Hyloxalinae, which Grant et al. recovered as sister to Dendrobatinae rather than Colostethinae, conflicting with most previous phylogenies [ 21 ]. After this seminal study, dendrobatid taxonomy continued to fragment, with Twomey and Brown erecting the genus Excidobates in 2008 [ 35 ], Brown et al. (2011) splitting Andinobates from Ranitomeya [ 43 ], and Grant et al. (2017) establishing Leucostethus , a sister genus to Ameerega, as well as Paruwrobates and Ectopoglossus, both members of Hyloxalinae, in another broad systematic review [ 41 ].
Since Grant et al.’s 2006 revision, relatively few large-scale phylogenetic studies of dendrobatids have been undertaken [ 41 , 44 , 45 ]. Santos et al. published a time-calibrated phylogeny of Dendrobatidae in 2009 constructed from ~2400 bp of mitochondrial data [ 44 ], and Pyron and Wiens (2011) published an Amphibia supertree constructed via maximum likelihood containing many representatives of Dendrobatidae [ 45 ]. Most recently, Grant et al. (2017) published the most comprehensive dendrobatid tree to date [ 41 ], constructed using parsimony, and containing representatives of all genera. They provided evidence for the paraphyly of Colostethus, as C. ruthveni is nested within Dendrobatinae. The latter two studies were based on approximately a dozen mitochondrial and nuclear loci, with the addition of morphological data in the case of Grant et al. (2017). All of these studies recover Hyloxalinae as the sister group to Dendrobatinae, not Colostethinae, consistent with many pre-2006 studies [ 22 , 23 , 24 , 25 , 26 , 27 , 29 ]. Previous estimates differ with respect to the sister genus of Dendrobates, which is either Oophaga [ 44 ] or Adelphobates [ 41 , 45 ]. Finally, the problematic taxon Minyobates steyermarki is recovered in various places throughout the dendrobatine phylogeny, either as sister to Adelphobates [ 45 ] or to all other dendrobatines aside from Phyllobates and C. ruthveni [ 41 ].
Many dendrobatid frogs are of conservation concern. The International Union for Conservation of Nature Red List of Threatened Species (also known as the IUCN Red List), is one of the world’s most comprehensive inventories of the global conservation status of biological species and has evaluated the status of many dendrobatids. It uses a set of criteria to evaluate the extinction risk of thousands of species globally and is recognized as an authority in the status of biological diversity. Here we present a novel approach for visualizing the relationships between IUCN Red List status, phylogenetic relationships, and spatial distributions. This is a tractable approach for visualizing complex patterns and large quantities of data in relatively simple infographics. These infographics are aimed at summarizing broad patterns, facilitating additional assessment, and complementing more detailed quantitative analyses.
2. Materials and Methods
2.1. Data Collection
We gathered 63 dendrobatoid tissue samples from a combination of museum collections, our own field work, and the collections of collaborators ( Table S1 ). Our sample represents 36 species in 13 dendrobatid genera (the newly erected genera Paruwrobates, Ectopoglossus, and Leucostethus were not included) and includes the aromobatid Allobates femoralis as an outgroup taxon. In many cases, we include multiple representatives of a given species to account for geographic variation.
For each sample, we performed sequence capture of UCEs in the manner of Faircloth et al. [ 46 ]. We extracted genomic DNA from each tissue sample with the Qiagen DNeasy Blood and Tissue Kit (Valencia, CA, USA) and performed quality and yield assessment with a Qubit 3 fluorometer (ThermoFisher Scientific). Extracted DNA was sent to RAPiD Genomics (Gainesville, FL, USA), who performed Illumina sequencing of UCEs, enriching the samples with the Tetrapods-UCE-5Kv1 probe set, which contains 5472 probes that target 5060 UCE loci. Raw reads for each sample are available at the NCBI Sequence Read Archive under project number PRJNA547821.
2.2. Bioinformatics Pipeline
We used the software package PHYLUCE v1.5.0 [ 61 ] and associated tools to trim, assemble, and align our sequenced reads. We performed quality trimming on raw reads using Illumiprocessor v2.0.6 [ 62 ], a Python wrapper for Trimmomatic v0.36 [ 63 ]. We then assembled the trimmed reads with Trinity v1.6 [ 64 ] as implemented in PHYLUCE. After assembly, we created two separate taxon sets for later analyses: one containing all samples ( n = 63, “large dataset”), the other with one sample per species ( n = 37, “small dataset”). The purpose of the small dataset was to increase computational efficiency for divergence time estimation. After mapping assembled contigs to UCE loci using PHYLUCE, we retained 2733 loci for the large dataset and 2639 for the small one. We performed individual alignments on each locus using MUSCLE v3.8.31 [ 65 ] as implemented in PHYLUCE. We filtered for matrix incompleteness by only retaining loci present in 60% or more of taxa and performed additional filtering by calculating the number of parsimony-informative sites (PIS) with PHYLOCH v1.5-5 [ 66 ], implemented in a custom R script, and retaining only loci with 10 < PIS < 120. Our upper limit on PIS was to filter out outlier loci, while our lower limit was to filter out relatively uninformative loci. After both filtering steps, for the large dataset we retained 1719 of the original 2733 loci, and for the small dataset we retained 1706 of the original 2639 loci. This study was conducted in accordance with the Institutional Animal Care and Use Committee of Southern Illinois University (Protocol number: 18-009, Animal Assurance number: D16-00044).
2.3. Phylogenetic Analyses
For both large and small datasets, we performed both maximum likelihood (ML) and multispecies coalescent-consistent phylogenetic analyses. We used IQ-TREE v1.5.5 [ 67 ] to perform our ML analyses, using a general time-reversible (GTR) model and assessing support with 10,000 ultrafast bootstrap replicates [ 68 ]. ML analyses were performed on an unpartitioned concatenated matrix (large matrix: 787,199 characters; small matrix: 786,510 characters) to increase computational efficiency. As UCEs are usually not protein-coding, it is unclear which partition schemes should be used for them, or whether they should be used at all [ 55 ].
69
-czb
70
-a
2.4. Divergence Time Estimation
We performed divergence time estimation of our dendrobatid phylogeny using BEAST 2 v2.5.0 [ 71 ]. Because Bayesian methods are computationally intensive, we reduced our small dataset, consisting of 1706 loci for 37 samples, to four subsets of 50 random loci each for analysis in BEAST, amounting to a total matrix size of 92,742 characters. We analyzed each subset twice in order to ensure that convergence occurred. We concatenated the loci in each subset and did not partition the alignment in order to avoid the intractably long periods of time a partitioned Bayesian analysis can take to converge [ 72 ].
We used the utility BEAUti to specify our BEAST settings. We used an HKY model with 4 gamma rate categories, with base frequencies set to “empirical,” avoiding the GTR model because it can lead to overparameterization and subsequently low ESS values [ 73 ]. We used a relaxed log-normal clock model with a clock rate prior of 1e-10, the same order of magnitude as an estimate of avian UCE substitution rates from Winker et al. [ 74 ]. To further reduce computational demands, we fixed the analysis to our small ASTRAL topology by setting the subtreeSlide , narrowExchange , wideExchange , and wilsonBalding operators to zero, an approach used by Hsiang et al. [ 75 ]. We used a Yule tree prior with other priors set to their default values.
44
Allobates femoralis
σ
We ran each analysis with an MCMC chain length of 100,000,000 generations, with a log sampling frequency of 100,000 generations and a tree sampling frequency of 10,000 generations. We assessed convergence between runs of each subset and ESS values for each run with Tracer v1.7.1 [ 76 ]. We found that all parameters had ESS values over the popular threshold of 200, and that convergence was reached for each subset. We used LogCombiner v2.5.0 [ 71 ] to combine the posterior distributions of trees from each of the eight runs, accounting for a burn-in of 10%. We then used TreeAnnotator v2.5.0 [ 71 ] to summarize the combined tree files, targeting the maximum clade credibility tree with mean node heights.
2.5. Visualizing Evolutionary History, Conservation Risk, and Spatial Distributions
To better understand how the evolutionary history and the geographic distribution of poison frogs impacts their conservation status and extinction risk, we downloaded IUCN Red List classifications for all surveyed species of Dendrobatidae and its sister family Aromobatidae ( n = 285) [ 77 ]. For each species, we recorded its population status, Red List status, and its countries of occurrence. The relationships between these factors were visualized in two circular plots created in the R package circlize [ 78 ]. The phylogenetic results of this study and those of Grant et al. (2017) [ 41 ] characterized the genus-level relationships among all input species.
3. Results
We obtained two maximum likelihood trees from IQ-TREE and two species trees from ASTRAL-III. A summarized genus-level phylogeny with divergence times is shown in Figure 1 . The large IQ-TREE phylogeny ( Figure S1 ) and small IQ-TREE phylogeny ( Figure S2a ) had identical topologies in terms of relationships between species. The large ASTRAL-III phylogeny (where 63 samples were coalesced into 38 species; Figure S2b ) was nearly identical to the small ASTRAL-III phylogeny ( Figure S2c ) and the small IQ-TREE phylogeny ( Figure S2a ), with the exceptions of the additional unidentified Allobates sp. sample and the rearrangement of several Ameerega species ( Figure S2b , gray labels). Topologies for the small IQ-TREE and small ASTRAL-III analyses were also identical ( Figure S2 ), pointing to an overall concordance between methods. In terms of species relationships, the large ASTRAL-III topology differed from the large IQ-TREE topology only in the rearrangement of the three Ameerega species mentioned above. Topologies and support values were extremely similar across trees. Each genus was always monophyletic with high support, as well as the three dendrobatid subfamilies. We found Hyloxalinae sister to Colostethinae rather than Dendrobatinae. In all trees, Oophaga was recovered as sister to Dendrobates , and Minyobates was recovered as sister to Adelphobates ( Figure 1 ). Regarding other generic relationships, we found that the clade containing Oophaga and Dendrobates is sister to the clade containing Adelphobates and Minyobates. Ranitomeya and Andinobates are recovered as sister genera, with Excidobates sister to this clade. Phyllobates is recovered as the sister genus to all other dendrobatines. In Colostethinae, we recovered Epipedobates and Silverstoneia as sister genera, with this clade itself sister to the clade containing Ameerega and Colostethus .
Node age estimates and associated error bars (representing uncertainty in node age estimates) are summarized in Table S2 and visualized in a time-calibrated phylogeny in Figure S3 . Uncertainty in node age generally increases with deeper time. Our analyses indicate the subfamilies Colostethinae and Hyloxalinae diverged around 30 ± 10 mya. Dendrobatinae diverged from the common ancestor of Hyloxalinae and Colostethinae around 32 ± 10 mya. Dendrobatidae diverged from its sister family Aromobatidae 36 ± 10 mya.
4. Discussion
Establishing a robust understanding of phylogenetic relationships in Dendrobatidae is crucial for addressing questions about dendrobatid evolution and directing conservation efforts towards areas of diversity in maximum need. While a handful of studies have generated phylogenies of the family in recent years, none has used genomic data in their analyses. We used maximum likelihood and coalescent methods in conjunction with a large matrix of genomic markers to construct the first phylogenomic tree of Dendrobatidae. The usage of ML and coalescent methods in conjunction with genome-scale UCE data is intended to bring the status of dendrobatid phylogenetics more in line with current studies in herpetological phylogenetics, which frequently make use of these techniques [ 53 , 54 , 55 , 56 , 57 ]. Concerns with parsimony, which was used to construct the most recent large-scale phylogenetic analysis of dendrobatids [ 41 ], as a statistically-consistent phylogenetic method [ 79 , 80 , 81 ], and the presence of potential incomplete lineage sorting among large numbers of genes [ 32 , 58 ], also compelled us to use these techniques. Additionally, we estimated divergence times using a Bayesian method, which is currently the most widely-used and accepted type for divergence time estimation [ 82 ]. We found that most relationships among dendrobatid genera are largely congruous with the results of past studies, with some exceptions (see below). Our estimated divergence times are very similar to those estimated by Santos et al. (2009), which is to be expected since we used secondary calibrations taken from their study ( Figure S3 ) [ 44 ]. However, our divergence time estimation involves different methods (BEAST 2 [ 71 ] rather than MULTIDIVTIME [ 83 ]) and considerably more genetic data (92,742 characters vs 2380 characters in Santos et al. [ 44 ]). Additionally, we recognize that since we used a secondary calibration taken from Santos et al.’s study due to the lack of poison frog fossils, our divergence time estimates may be biased towards younger node dates [ 84 ].
Much of our phylogeny is consistent with past phylogenies from mitochondrial and nuclear datasets, but with some key differences. Our analyses place Hyloxalinae sister to Colostethinae rather than Dendrobatinae [ 22 , 23 ], contrary to more recent studies on the family [ 21 , 41 , 44 , 45 ]. We also find support for placing the genus Dendrobates sister to Oophaga [ 21 , 22 , 23 , 35 , 44 ], in contrast to previous placements of Dendrobates as sister to Adelphobates [ 29 , 41 , 45 ], or even the rest of Dendrobatinae [ 43 ]. Lastly, we find strong support for placing Minyobates sister to Adelphobates . This problematic taxon has previously been placed anywhere from sister to Excidobates [ 29 ], to the rest of Dendrobatinae (excluding Phyllobates ) [ 21 , 41 ]. Our conclusion for the placement of Minyobates corroborates placements recovered by more recent analyses that utilized maximum likelihood and Bayesian methods [ 35 , 44 , 45 ] rather than parsimony [ 21 , 41 ].
Maximizing efforts to conserve poison frogs (and other species) requires identifying both vulnerable lineages and geographical areas. A crucial step in this process is clarifying the evolutionary relationships of the taxa of interest, followed by the collection of basic population, distributional, and life history data for each taxon. Like many tropical amphibians, poison frogs face threats including habitat destruction [ 15 , 16 ] and smuggling for the pet trade [ 17 , 18 , 43 ]. Despite being one of the better-studied groups of frogs, a surprising number of poison frog species evaluated by the IUCN were classified as “data deficient” (37.5%, 107 of 285 species), hampering basic aspects of their conservation. Many of these data-deficient taxa belong to understudied genera with mostly cryptic coloration. In particular, the four genera Hyloxalus, Colostethus, Allobates, and Anomaloglossus contain a majority (70.1%, 75 of 107) of the “data deficient” taxa ( Figure 2 ). In addition, though comprised of only a few species, little is known of the genera Paruwrobates and Ectopoglossus , where 3 (of 3) and 7 (of 8) of the contained species are classified as “data deficient”, respectively ( Table S3 ). Further, in Ectopoglossus , the only species not classified as “data deficient” is classified as “endangered,” increasing the urgency for collecting basic life-history data in this group.
Roughly a quarter (22.1%, 63 of 285) of poison frog species were classified as “critically endangered” or “endangered” (18 and 45 species, respectively). Many of these at-risk taxa are concentrated in a few genera, most notably the clade that contains the two Aromobatid genera endemic to the northern Andes, Aromobates and Mannophryne (containing six “critically endangered” and 14 “endangered” species). The genera Allobates , Hyloxalus , and Ameerega contain a majority of the remaining at-risk species, though the proportions of at-risk species are similar to those of other genera. Additional unique evolutionary lineages of concern, though represented by only a few species, are the genera Phyllobates , Excidobates and Minyobates , where most surveyed taxa are at-risk ( Table S3 ).
Furthermore, some geographic zones possess much higher at-risk diversity than others (“critically endangered” and ”endangered” in Figure 3 ). The northern Andean countries possess both the highest species diversity and the highest diversity of at-risk species, especially Colombia, Peru, and Venezuela. ( Figure 3 ). However, only Venezuela’s proportions of ‘at-risk’ species are much greater than the country average, with 25.5% “endangered” and 16.4% “critically endangered” (average of 11.3% and 5.1%, respectively; Table S4 ). In contrast, countries with mostly lower elevation species (e.g., Brazil or Bolivia) seem to be well below the average of at-risk species ( Table S4 ).
85
86
Leucostethus, Paruwrobates
Ectopoglossus
41
41
Colostethus
C. ruthveni
Supplementary Materials
https://www.mdpi.com/1424-2818/11/8/126/s1
Author Contributions
Conceptualization: W.X.G. and J.L.B. Methodology: W.X.G. and J.L.B. Validation: W.X.G., M.R.M., and J.L.B. Formal Analysis: W.X.G. and M.R.M. Investigation: J.L.B. Resources: J.L.B., K.S. Data Curation: W.X.G. and M.R.M. Writing—Original Draft Preparation: W.X.G., M.R.M., and J.L.B. Writing – Review and Editing: W.X.G., M.R.M., J.L.B., and K.S. Author Contribution List-Maker: M.R.M. Food Stylist: W.X.G. Visualization: W.X.G. and J.L.B. Supervision: J.L.B. Project Administration: J.L.B. Funding Acquisition: J.L.B.
Funding
This research was funded by start-up funding to J.L.B. from Southern Illinois University Carbondale.
Acknowledgments
We are grateful for the continued support of Southern Illinois University, East Carolina University, Servicio Nacional Forestal y de Fauna Silvestre (Peru), and Centro de Ornitología y Biodiversidad (CORBIDI). We thank Ivan Prates and Miguel T. Rodrigues for generously providing several tissue samples. We are thankful to Peter Larson, Ryan Campbell and Anne Yoder for providing inspiration for Figure 2 and Figure 3 . M.R.M. and W.X.G. are grateful for support from the Students United in Preserving, Exploring, and Researching Biodiversity (SUPERB) fellowship, funded by the US National Science Foundation (NSF).
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1. Time-calibrated genus-level phylogeny of Dendrobatidae produced using BEAST. Node labels indicate divergence times (mya). This figure is reduced to one tip per genus from the species-level chronogram in Figure S3 . Art by WXG.
Figure 1. Time-calibrated genus-level phylogeny of Dendrobatidae produced using BEAST. Node labels indicate divergence times (mya). This figure is reduced to one tip per genus from the species-level chronogram in Figure S3 . Art by WXG.
Figure 2.
An evolutionary perspective of the Red List status of Aromobatidae and Dendrobatidae. Each species is characterized by a ribbon that is connected to its current Red List status (bottom). The numerical values below each genus depict the number of species with the associated Red List status. Bars on the outer ring depict the current population status of the corresponding genus, either: decreasing, stable or unknown (black, dark grey, or light grey respectively). A tree representing the evolutionary relationships of the genera surrounds the main diagram. Relationships for taxa not included in our study (Dendrobatidae:
Paruwrobates, Ectopoglossus, Leucostethus;
Aromobatidae:
Aromobates, Anomaloglossus, Mannophryne, Rheobates
) are reproduced from Grant et al. 2017 [
41
].
Figure 2. An evolutionary perspective of the Red List status of Aromobatidae and Dendrobatidae. Each species is characterized by a ribbon that is connected to its current Red List status (bottom). The numerical values below each genus depict the number of species with the associated Red List status. Bars on the outer ring depict the current population status of the corresponding genus, either: decreasing, stable or unknown (black, dark grey, or light grey respectively). A tree representing the evolutionary relationships of the genera surrounds the main diagram. Relationships for taxa not included in our study (Dendrobatidae: Paruwrobates, Ectopoglossus, Leucostethus; Aromobatidae: Aromobates, Anomaloglossus, Mannophryne, Rheobates ) are reproduced from Grant et al. 2017 [ 41 ].
Figure 3. A geographic perspective of the Red List status of Aromobatidae and Dendrobatidae. The species composition of each country is characterized by ribbons connected to the current Red List status for each species (bottom). The numerical values below each country name depict the number of species with the associated Red List status. Bars on the outer ring depict the corresponding color of that country on the main map (top right). Maps to the left display Red List groups, where the intensity of color depicts larger number of species. If a species exists in more than one country, it was represented in each country of occurrence in the plot.
Figure 3. A geographic perspective of the Red List status of Aromobatidae and Dendrobatidae. The species composition of each country is characterized by ribbons connected to the current Red List status for each species (bottom). The numerical values below each country name depict the number of species with the associated Red List status. Bars on the outer ring depict the corresponding color of that country on the main map (top right). Maps to the left display Red List groups, where the intensity of color depicts larger number of species. If a species exists in more than one country, it was represented in each country of occurrence in the plot.
Table 1. Dendrobatid genera and relevant information. The authority and type species for each genus is given, as well as the number of described species and a very basic description of each genus’ geographic range. Species counts and authorities retrieved from Amphibian Species of the World [ 33 ].
Table 1. Dendrobatid genera and relevant information. The authority and type species for each genus is given, as well as the number of described species and a very basic description of each genus’ geographic range. Species counts and authorities retrieved from Amphibian Species of the World [ 33 ].
Subfamily Genus Authority Type Species No. Species Range Dendrobatinae Adelphobates Grant et al. 2006 [ 21 ] castaneoticus 3 Amazonia Andinobates Twomey et al. 2011 [ 34 ] bombetes 15 N Amazonia Dendrobates Wagler 1830 [ 20 ] tinctorius 5 C America, N Amazonia, Hawaii (introduced) Excidobates Twomey and Brown 2008 [ 35 ] mysteriosus 3 NW Peru Minyobates Myers 1987 [ 36 ] steyermarki 1 Venezuela Oophaga Bauer 1994 [ 37 ] pumilio 12 C America, W Andean versant Phyllobates Bibron 1840 [ 38 ] bicolor 5 C America, Colombia Ranitomeya Bauer 1986 [ 39 ] reticulata 16 Amazonia Colostethinae Ameerega Bauer 1986 [ 39 ] trivittata 30 Amazonia, Bolivia Colostethus Cope 1866 [ 40 ] latinasus 15 Panama, NW S America Epipedobates Myers 1987 [ 36 ] tricolor 8 W Andean versant Leucostethus Grant et al. 2017 [ 41 ] argyrogaster 6 W Amazonia Silverstoneia Grant et al. 2006 [ 21 ] nubicola 8 C America, Colombia Hyloxalinae Ectopoglossus Grant et al. 2017 [ 41 ] saxatilis 7 C America, W Andean versant Hyloxalus Jiménez de la Espada 1870 [ 42 ] fuliginosus 60 Panama, W Andean versant, NW Amazonia Paruwrobates Bauer 1994 [ 37 ] andinus 3 W Andean versant
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Guillory, W.X.; Muell, M.R.; Summers, K.; Brown, J.L. Phylogenomic Reconstruction of the Neotropical Poison Frogs (Dendrobatidae) and Their Conservation. Diversity 2019, 11, 126.
https://doi.org/10.3390/d11080126
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Guillory WX, Muell MR, Summers K, Brown JL. Phylogenomic Reconstruction of the Neotropical Poison Frogs (Dendrobatidae) and Their Conservation. Diversity. 2019; 11(8):126.
https://doi.org/10.3390/d11080126
Chicago/Turabian Style
Guillory, Wilson X., Morgan R. Muell, Kyle Summers, and Jason L. Brown. 2019. "Phylogenomic Reconstruction of the Neotropical Poison Frogs (Dendrobatidae) and Their Conservation" Diversity11, no. 8: 126.
https://doi.org/10.3390/d11080126
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set forth in subsection (b). The written notice of the hearing shall state the
reason for the proposed withdrawal.
(i) It shall be unlawful for the insurer to
issue or use forms or premium rates after the effective date of their
withdrawal.
(j) If a group policy of credit life insurance
or credit disability insurance has been delivered in this State before July 1,
1969, or has been or is delivered in another state before or after July 1,
1969, the insurer shall be required to file only the group certificate and
notice of proposed insurance delivered or issued for delivery in this State as
specified in section 431:10B-107(b) and (e). The forms shall be approved by
the commissioner if:
(1) They conform with the requirements specified in
those subsections;
(2) They are accompanied by a certification in a form
satisfactory to the commissioner that the substance of the forms are in
substantial conformity with the master policy; and
(3) The schedules of premium rates applicable to the
insurance evidenced by the certificate or notice are not in excess of the
insurer's schedules of premium rates filed with and approved by the
commissioner;
provided that the premium rate in effect on existing
group policies may be continued until the first policy anniversary date
following July 1, 1969.
(k) Any order or final determination of the
commissioner under this section shall be subject to chapter 91. [L 1987, c 347,
pt of §2 as superseded by c 348, §16; am L 1988, c 363, §3; am L 1989, c 207,
§12; am L 2000, c 182, §10; am L 2004, c 122, §38; am L 2020, c 70, §56]
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Small Heat Shock Proteins Induce a Cerebral Inflammatory Reaction | Journal of Neuroscience
Articles, Neurobiology of Disease
Small Heat Shock Proteins Induce a Cerebral Inflammatory Reaction
Journal of Neuroscience 17 August 2011, 31 (33) 11992-12000; DOI: https://doi.org/10.1523/JNEUROSCI.0945-11.2011
Ilona B. Bruinsma
Mieke de Jager
Anna Carrano
Alexandra A. M. Versleijen
Robert Veerhuis
Wilbert Boelens
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Abstract
More than 80% of Alzheimer's disease (AD) patients have some degree of cerebral amyloid angiopathy (CAA). In addition to arteries and veins, capillaries can also be affected. Capillary CAA (capCAA), rather than CAA in larger vessels, is associated with flame-like amyloid-beta (Aβ) deposits that may extend beyond the vessel wall and radiate into the neuropil, a phenomenon also known as “dyshoric angiopathy.” Aβ deposits in AD, parenchymal as well as (cap)CAA and dyshoric angiopathy, are associated with a local inflammatory reaction, including activation of microglial cells and astrocytes that, among others, produce cytokines and reactive oxygen species. This neuroinflammatory reaction may account for at least part of the cognitive decline. In previous studies we observed that small heat shock proteins (sHsps) are associated with Aβ deposits in AD. In this study the molecular chaperones Hsp20, HspB8 and HspB2B3 were found to colocalize with CAA and capCAA in AD brains. In addition, Hsp20, HspB8 and HspB2B3 colocalized with intercellular adhesion molecule 1 (ICAM-1) in capCAA-associated dyshoric angiopathy. Furthermore, we demonstrated that Hsp20, HspB8 and HspB2B3 induced production of interleukin 8, soluble ICAM-1 and monocyte chemoattractant protein 1 by human leptomeningeal smooth muscle cells and human brain astrocytes in vitroand that Hsp27 inhibited production of transforming growth factor beta 1 and CD40 ligand. Our results suggest a central role for sHsps in the neuroinflammatory reaction in AD and CAA and thus in contributing to cognitive decline.
Introduction
In Alzheimer's disease (AD) amyloid-β (Aβ) is deposited as plaques in the parenchyma, but also as cerebral amyloid angiopathy (CAA) (Selkoe, 1991). Capillary Aβ deposits (capCAA) correlates with severity of AD pathology and clinical deterioration, whereas larger vessel CAA does not (Attems and Jellinger, 2004;Eurelings et al., 2010). Furthermore, in capCAA, flame-like Aβ deposits may extend beyond the vessel wall and radiate into the neuropil, a phenomenon known as “dyshoric angiopathy” (Attems et al., 2011). Neuropathological examination of (cap)CAA reveals activated microglia and astrocytes surrounding these lesions (McGeer and McGeer, 1995;Yamada et al., 1996;Akiyama et al., 2000;Rozemuller et al., 2005;Richard et al., 2010;Attems et al., 2011) and colocalization of inflammatory factors such as intercellular adhesion molecule 1 (ICAM-1) (Verbeek et al., 1996).
In AD brains, an inflammatory reaction may occur in conjunction with Aβ deposits, characterized by the increased expression of, among others, transforming growth factor β1 (TGF-β 1) (Wyss-Coray et al., 1997), interleukin (IL) 1β, IL-8, monocyte chemoattractant protein 1 (MCP-1), ICAM-1 and CD40 ligand (Akiyama et al., 2000;Calingasan et al., 2002;Sokolova et al., 2009;Heneka et al., 2010). This inflammatory reaction may occur in response to the presence of extracellular Aβ or phagocytosis of Aβ deposits by microglia (Malm et al., 2010). Inflammation, both directly via interaction of activated glial cells and indirectly via secreted neurotoxic mediators may compromise neuronal function. Indeed, transgenic mice with extensive CAA showed cognitive decline as a result of increased microglial activation and neuroinflammation (Xu et al., 2007), which could be reduced by treatment with the anti-inflammatory drug minocycline, and thereby improved cognition (Fan et al., 2007). Epidemiological studies demonstrated that most patients with CAA-related inflammation show at least a partial clinical improvement to high dose corticosteroids or other immunosuppressive agents (Chung et al., 2011). Thus both human and mouse studies provide evidence for a contribution of Aβ to CAA-related neuroinflammation and subsequent cognitive decline. However, the neuroinflammatory reaction in AD patients may be more complex.
In AD, several macromolecules colocalize with plaques and CAA, including small heat shock proteins (sHsps) (Wilhelmus et al., 2006b,c). Previous research showed that expression of αB-crystallin and Hsp27 is increased in reactive astrocytes of AD brains (Renkawek et al., 1993,1994;Wilhelmus et al., 2006c). Hsp20 codeposited with Aβ in diffuse and classic plaques and HspB2 with classic plaques and CAA (Wilhelmus et al., 2006c). Moreover, HspB8 colocalized with classic plaques in AD and with CAA in hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D) (Wilhelmus et al., 2006b). Furthermore, we observed that these sHsps, but not Aβ, induced IL-6 production in various cerebral cell cultures (Wilhelmus et al., 2009), suggesting that sHsps may play a pivotal role in inducing neuroinflammation. Therefore, we investigated the association of sHsps with (cap)CAA and CAA-associated inflammation in postmortem brain and investigated the effect of selected sHsps on the production of inflammatory factors by cultured human leptomeningeal smooth muscle cells and astrocytes in vitro.
Materials and Methods
Reagents.
Lyophilized Aβ 1–42(95% pure) and Aβ 1–40(98% pure) were purchased from Quality Controlled Biochemicals. Aβ with the “Dutch” mutation (22 Glu→Gln, d-Aβ 1–40, 96% pure) was purchased from 21 stCentury Biochemicals. d-Aβ 1–40was used as a model peptide, because it causes CAA in hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D) (Davis and Van Nostrand, 1996;Verbeek et al., 1997;Wilhelmus et al., 2007). Aβ 1–42, Aβ 1–40, and d-Aβ 1–40were dissolved in 1,1,1,3,3,3-hexafluoro-2 propanol (HFIP) (Sigma-Aldrich), air-dried, and dissolved in DMSO at a concentration of 5 m m. Aliquots of the solutions were stored at −80°C.
Autopsy material.
Patient selection was based on neuropathological findings at autopsy. Tissue samples were selected for the presence of capCAA (Richard et al., 2010). For immunohistochemistry, tissue samples from the occipital neocortex from 3 AD patients with capCAA (age 76 ± 12 years; postmortem delay 5:53 ± 2:09 h) were obtained after rapid autopsy and immediately frozen in liquid nitrogen. Informed consent was obtained according to European guidelines.Table 1provides an overview of the diagnosis, Braak stage, CERAD score, CAA grade, age, postmortem interval (PMI) and gender. Neuropathological evaluation was performed on frozen tissue from occipital pole cortex. CAA score was defined as follows: severe (+++), moderate (++), mild (+) as previously described (Richard et al., 2010). Staging of AD was evaluated according to the criteria established by Braak and Braak and CERAD (Braak and Braak, 1991;Mirra et al., 1991).
Table 1.
Overview of the origin of astrocyte and HBP cell cultures and tissue sections
Immunohistochemistry.
InTable 2. the primary antibodies used in this study are listed. Unless mentioned otherwise, we used biotin-labeled horse anti-mouse antibodies (Vector Laboratories) as the detection antibody for mouse monoclonal antibodies, or biotin-labeled goat-anti-rabbit antibodies (Vector Laboratories) in the case of rabbit polyclonal antibodies.
Table 2.
Primary antibodies used in this study
Serial cryosections (4 μm) were air-dried and fixed in acetone for 5 min. Endogenous peroxidase activity was blocked using acetone containing 0.15% H 2O 2for 5 min. Sections were preincubated for 30 min with 20% animal serum, the type of which was determined by the specific biotin-labeled antibody used. Subsequently, sections were incubated overnight at 4°C with primary antibody (Table 2), with secondary antibodies for 60 min at room temperature, and with the avidin-biotin complex according to the manufacturer's description. Between incubation steps, sections were extensively washed using PBS. 3-Amino-9-ethyl carbazole (AEC) was used as a chromogen. After a short rinse in tap water the preparations were incubated with hematoxylin for 1 min and thoroughly washed with tap water for 10 min. Finally, sections were mounted with Imsol mount (Klinipath). All antibodies were diluted in PBS containing 1% bovine serum albumin (BSA), which also served as a negative control. At regular intervals, sections were stained with anti-Aβ to allow for topographical alignment of CAA with the stains for sHps and inflammatory factors.
For double immunostaining of Aβ and/or astrocytes/microglia, sections were stained using the EnVision method as previously described (Richard et al., 2010). Briefly, sections were incubated overnight at 4°C with primary antibodies (Table 2), followed by incubation with EnVision HRP. EnVision 3,3-diaminobenzidine (DAB) was used as chromogen. Antibodies were diluted in PBS/1% BSA, which also served as a negative control. After each incubation, slides were extensively washed with PBS. For the detection of fibrillar Aβ in plaques and CAA, sections were stained with Congo Red (0.5% in Ethanol 80%, 3% NaCl) for 20 min at room temperature. Finally, sections were mounted with DePeX mounting medium Gurr.
Expression and purification of recombinant proteins.
Recombinant human αB-crystallin and HspB2B3 were expressed and purified as described previously (Wilhelmus et al., 2006a). Since it was demonstrated that HspB2 and HspB3 form functional heterogeneous complexes of 150 kDa (Sugiyama et al., 2000), both proteins were expressed together in one vector. Coding sequences for the following sHsps were ligated into the pET-46 Ek/LIC vector which also introduces a N-terminal His-tag sequence (Novagen, Merck Chemicals Ltd): human Hsp27, human Hsp20, and human HspB8. Hsp20 and HspB8 were expressed in Rosetta(DE3)pLysS competent cells (Novagen). Hsp27 was expressed in its BL21(DE3)pLysS competent cells (Novagen). A culture inoculated from a single colony was induced by addition of 0.25 m misopropyl-thio-β- d-galactopyranoside (IPTG) for 4 h at 37°C, with the exception of Hsp20, which was induced for 16 h at 25°C. After incubation with IPTG, cells were harvested and lysed by sonication in native lysis buffer (NLB; 50 m mNaH 2PO 4, 300 m mNaCl, pH 8.0) supplemented with EDTA-free protease inhibitor (Roche Applied Science). Insoluble proteins were removed by centrifugation. All sHsps were purified over a Ni-NTA agarose column (Qiagen) using NLB supplemented with increasing concentrations of imidazole (Sigma-Aldrich Chemie BV) ranging from 20 up to 250 m m. After desalting, sHsps were concentrated in 10 m mTris, 50 m mNaCl, pH 7.4 buffer by using an iCON concentrator spin column (Thermo Fisher Scientific Inc.). Protein concentration was determined using a BCA Protein Assay kit according to the manufacturer's description (Thermo Fisher Scientific). Purified sHsps were aliquoted and stored at − 80°C. Purity of the preparations was ≥95%.
Cell culture.
Smooth muscle cells (SMCs) and astrocytes were both isolated from human brain tissue obtained after rapid autopsy, as described previously (De Groot et al., 1997;Verbeek et al., 1994b;Veerhuis et al., 1998) (Table 1). Diagnosis and grading of patients was performed according to the criteria mentioned previously. SMCs were maintained in Eagle's modification of essential medium (EMEM; PAA Laboratories GmbH), supplemented with 10% human serum (Lonza BioWhittaker Benelux BV), 20% fetal bovine serum (PAA Laboratories GmbH), recombinant basic fibroblast growth factor (1 ng/ml) and gentamycin (2.5 μg/ml). Astrocytes were maintained in a mixture (1:1 v/v) of DMEM and Ham's F10 supplemented with 10% fetal bovine serum, 2 m m l-glutamine (Cambrex) and gentamycin (2.5 μg/ml). All primary cell cultures were cultured at 37°C, 5% CO 2and 90% relative humidity. Although the cultured astrocytes and SMCs were derived from different clinical backgrounds (i.e., either AD or control patients), we did not observe differences with respect to their responses in the various types of experiments.
Cell passages 3–9 were used for the experiments. Control cells incubated with EMEM or DMEM/Ham's F10 and 0.1% BSA (serum-free medium) demonstrated normal morphology. Experiments were performed at least twice.
ELISA.
Duplicate wells (12-well plate; Corning Inc) with cultured cells were preincubated with serum-free medium for a minimum of 4 h. Subsequently, cells were incubated with 12.5 μ msynthetic Aβ 1–40, Aβ 1–42, d-Aβ 1–40or 12.5 μ mpurified sHsps (αB-crystallin, Hsp27, Hsp20, HspB8 and HspB2B3) at 37°C and 5% CO 2. This concentration was the lowest concentration to induce a significant effect across all sHsps tested. In addition, the same concentration of Aβ induced biological effects in cultured SMCs and astrocytes (Verbeek et al., 1997;Bruinsma et al., 2010) and was therefore chosen in the experiments. Lipopolysaccharide (LPS; 055:B5; Sigma-Aldrich) stimulation (1 μg/ml) was used as a positive control for inducing cytokine production. After 48 h of incubation, supernatants and cell lysates (solubilized in RIPA; 50 m mTris HCl, pH7.4, 150 m mNaCl, 1% Nonidet P-40, 0.5% sodium deoxycholate, and 0.1% SDS in Milli-Q) were collected, centrifuged at 13.200 rpm for 10 min at 4°C and stored at −80°C until further use. To exclude endotoxin contamination, potentially present in the purified sHsp samples, coincubation with polymixin B (PMB; Sigma-Aldrich; 10 μg/ml) was used to inhibit LPS-mediated inflammation. In these experiments, PMB was preincubated with both the LPS and the sHsps for 1 h at 37°C before addition to the cells.
Il-8, ICAM-1, MCP-1, CD40 ligand, and TGF-β 1levels in cell culture supernatant were measured using commercial enzyme immunoassay kits according to the manufacturer's instructions (DuoSet ELISA, R&D Systems). To correct for differences in cell density, inflammatory factor production was normalized to protein content of the cell lysate which was determined by using a BCA Protein Assay kit according to the manufacturer's description (Thermo Fisher Scientific Inc.). Concentrations of the various inflammatory factors were expressed as pg/mg protein.
Statistical analysis.
Statistical analyses were performed using an independent sample ttest in SPSS 14.0 for Windows software. Statistical significance was set at p< 0.05.
Results
Inflammatory cells in AD brains with severe CAA pathology, capCAA, and dyshoric angiopathy
Double staining for GFAP and Congo red demonstrated the presence of astrocytes around Aβ-laden vessels, with a more prominent GFAP staining around the larger vessels (Fig. 1 A, C). Clusters of HLA-DR-positive microglia were also observed around larger vessels and capillaries laden with Aβ and were particularly prominent around the capillaries (Fig. 1 B, D).
Figure 1.
Immunohistochemical staining of GFAP ( A, C) and microglial cell marker (LN3; B, D) in CAA ( A, B) and capCAA ( C, D). All sections are double stained with Congo Red. GFAP-positive reactive astrocytes are present around both larger vessels and capillaries ( A, C). Microglial activation is associated with both large vessels and capillaries, however more prominent around the latter ( B, D).
Expression of sHsps in AD brains with severe CAA pathology, capCAA, and dyshoric angiopathy
In control brains, αB-crystallin staining was observed in glial cells (Fig. 2 B). Furthermore, leptomeningeal vessels as well as a few astrocytes in the white matter were also stained (data not shown). Hsp27 staining in control brains was limited to leptomeningeal vessels (data not shown), but not observed in parenchymal vessels (Fig. 2 D). Hsp20 staining in control brains was occasionally observed in astrocytes in white and gray matter (data not shown). Weak immunoreactivity of Hsp20 was also observed in large parenchymal (Fig. 2 F, open arrow) and leptomeningeal vessels (data not shown). HspB8 staining in control brains was observed in astrocytes in both gray and white matter (Fig. 2 H, arrow) and in cerebrovascular cells of large parenchymal vessels (Fig. 2 H, open arrow). Furthermore, weak staining for HspB2 was observed in cerebrovascular cells in large parenchymal vessels (Fig. 2 J, open arrow) and in an occasional astrocyte or microglial cell in the brain parenchyma (data not shown). IL-8 (Fig. 2 L) and MCP-1 (Fig. 2 P) staining was not observed in normal parenchymal or leptomeningeal vessels in control brains, whereas ICAM-1 staining was observed in endothelial cells in control brains (Fig. 2 N, arrow).
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Figure 2.
Immunohistochemical staining of Aβ ( A, C, E, G, I, K, M, O), sHsps ( B, D, F, H, J; open arrow), and inflammatory factors ( L, N, P; open arrow) in or near normal vessels in the occipital cortex of control patients. Serial sections: A, B; C, D; E, F; G, H; I, J; K, L; M, N; O, P. Anti-αB-crystallin antibodies stained glial cells throughout the cortex ( B, arrow). Anti-Hsp27 antibodies were only occasionally immunoreactive with leptomeningeal vessels (data not shown), but not with parenchymal vessels ( D). Hsp20 was occasionally demonstrated in astrocytes in normal brains (data not shown). Weak immunoreactivity of Hsp20 was also observed in large parenchymal ( F, open arrow) and leptomeningeal vessels. HspB8 staining was observed in astrocytes in both gray and white matter ( H, arrow) and in cerebrovascular cells of large parenchymal vessels ( H, open arrow). Weak staining for HspB2 was observed in cerebrovascular cells in large parenchymal vessels ( J, open arrow) and in an occasional astrocyte or microglial cell in the brain parenchyma (data not shown). Furthermore, anti-IL-8 ( L) and anti-MCP-1 ( P) staining was absent from normal parenchymal or leptomeningeal vessels. The anti-ICAM antibodies stained endothelial cells ( N, arrow). Original magnification 200×.
In AD brains with severe (cap)CAA pathology, the anti-Aβ antibody (6C6) stained Aβ-affected vessels and capillaries (Fig. 3 A, B). In addition, dyshoric angiopathy (Fig. 3 A) was often observed. The antibodies directed against αB-crystallin, Hsp27, Hsp20, HspB8 and HspB2 showed different staining patterns for these sHsps in CAA, capCAA and dyshoric angiopathy. Representative staining results are shown inFigure 3and a summary of the immunohistochemical results is shown inTable 3. Anti-αB-crystallin antibody stained reactive astrocytes and activated microglia associated with CAA (Fig. 3 C) and capCAA (Fig. 3 D). Hsp27 staining was not observed in gray matter (Fig. 3 E, F), but was occasionally observed in reactive astrocytes and microglia in the white matter (data not shown). In addition, reactive astrocytes surrounding CAA were immunopositive for Hsp20 (Fig. 3 G) and occasionally Hsp-20-positive reactive astrocytes were observed surrounding capCAA (data not shown). Anti-HspB8 stained reactive astrocytes and microglia in both white and gray matter and occasionally immunoreactivity of HspB2 was observed with reactive astrocytes and microglia. Whereas HspB2 (Fig. 3 L) colocalized with Aβ in capCAA and CAA, no immunostaining for αB-crystallin (Fig. 3 C, D), Hsp27 (Fig. 3 E, F), Hsp20 (Fig. 3 G, H) and HspB8 (Fig. 3 I, J) was observed. Furthermore, colocalization of Hsp20 (Fig. 3 G), HspB8 (Fig. 3 I) and HspB2 (Fig. 3 K), but not of αB-crystallin (Fig. 3 C) and Hsp27 (Fig. 3 E), with Aβ surrounding CAA and capCAA (dyshoric angiopathy) was observed.
Figure 3.
Immunohistochemical staining of sHsps and inflammatory factors in or near CAA vessels ( A, C, E, G, I, K, M, O, Q; serial sections) and capCAA ( B, D, F, H, J, L, N, P, R; serial sections; arrows indicate the same capillary in each panel to serve as a reference to allow optimal comparison with other panels) in the occipital cortex of AD brains. The anti-Aβ antibody 6C6 stained CAA, capCAA, and dyshoric angiopathy in AD brains ( A, B; to allow optimal comparison with other stains, these panels are shown twice). Both anti-αB-crystallin ( C, D) and anti-Hsp27 ( E, F) antibody staining was absent in Aβ deposits. No anti-Hsp20 and anti-HspB8 staining was observed in CAA and capCAA; however, colocalization of Hsp20 and HspB8 ( G, H; I, J) with dyshoric angiopathy (Aβ surrounding CAA) was observed. The presence of HspB2 in CAA ( K) and capCAA ( L) of AD brains with severe CAA was observed, but also colocalization of HspB2 with dyshoric angiopathy ( K) was observed. The anti-αB-crystallin ( C), anti-Hsp20 ( G), and anti-HspB8 antibodies ( I) stained reactive astrocytes and microglia associated with CAA. Occasionally, immunoreactivity of HspB2 with reactive astrocytes and microglia was observed. Furthermore, anti-IL-8 ( M, N, arrow) and anti-MCP-1 ( Q, R, arrow) staining was absent from CAA and capCAA vessels. In addition, ICAM-1 was associated with dyshoric angiopathy, but not with the Aβ deposits in the vessel wall ( O, P, arrow; inset, ICAM-1 staining (left) and Aβ staining (right) of another capCAA vessel). Original magnification 200×.
Table 3.
Summary of the immunohistochemical results
Expression of inflammatory factors in AD brains with severe CAA pathology, capCAA, and dyshoric angiopathy
ICAM-1 was associated with dyshoric Aβ deposits surrounding CAA and capCAA, but not with the Aβ deposits within the vessel wall (Fig. 3 O, P), suggesting colocalization of Hsp20, HspB8 and HspB2 with ICAM-1 in dyshoric angiopathy near (cap)CAA. Although ICAM-1 has also been detected in a soluble form (Harning et al., 1991;Rothlein et al., 1991), it is mainly described as a membrane-bound cell adhesion molecule. Therefore, the ICAM-1 staining we observed is very likely due to membrane-bound ICAM-1. In earlier studies an increase in IL-8 and MCP-1 in AD brains was observed after soluble protein extraction of human brain lysates or in paraffin-embedded formalin-fixed tissue (Akiyama et al., 2000;Calingasan et al., 2002;Sokolova et al., 2009). In the present study, no IL-8 and MCP-1 was detectable in tissue from AD patients with severe CAA pathology (Fig. 3 M, N, Q, R). In cryosections, these soluble factors might escape detection due to mild fixation of the tissue.
sHsps induce the production of inflammatory factors by human leptomeningeal smooth muscle cells and human brain astrocytes
Our immunohistochemical studies suggest that both Aβ and sHsps accumulate in or near (cap)CAA, where an inflammatory reaction is observed as well. Since human leptomeningeal SMCs are already early affected by Aβ in CAA (Vinters et al., 1996), we studied whether Aβ or sHsps were able to induce production of cytokines and other inflammatory factors by cultured SMCs. In addition, since reactive astrocytes colocalize near (cap)CAA (Fig. 1), we also studied the potential of Aβ and sHsps to induce an inflammatory reaction in human brain astrocytes.
Neither Aβ 1–40, Aβ 1–42, nor d-Aβ 1–40(12.5 μ m) induced production of IL-8, ICAM-1, MCP-1, TGF-β 1or CD40 ligand by SMCs or astrocytes, above control levels (Figs. 4,5). Incubation of 1 μg/ml LPS induced IL-8 production (Fig. 4 A; p< 0.05) by SMCs, but not production of soluble ICAM-1 (sICAM-1;Fig. 4 B), MCP-1 (Fig. 4 C) and TGF-β 1(Fig. 4 D). Furthermore, incubation of 1 μg/ml LPS induced IL-8 (Fig. 5 A; p< 0.01), sICAM-1 (Fig. 5 B; p< 0.01) and MCP-1 (Fig. 5 C; p< 0.05) production by astrocytes, but not production of TGF-β 1(Fig. 5 D) and CD40 ligand (Fig. 5 E). After preincubation and coincubation of LPS with PMB, production of inflammatory factors by SMCs and astrocytes returned to control levels (Fig. 5; p< 0.05), indicating that PMB efficiently inhibited the LPS-induced inflammatory reaction.
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Figure 4.
Production of inflammatory factors by human brain leptomeningeal SMCs. Cultured SMCs were incubated with 12.5 μ m d-Aβ 40, Aβ 42, Aβ 40, Hsp27, Hsp20, HspB8, HspB2B3, or 1 μg/ml LPS for 2 d at 37°C. Supernatant was collected and IL-8 ( A), sICAM-1 ( B), MCP-1 ( C), and TGF-β 1( D) concentrations were measured using ELISA. Statistical analysis was performed using an independent sample ttest. The level of significance of the difference compared with control is indicated as follows: * p< 0.05; ** p< 0.01; *** p< 0.001; p> 0.05 is not indicated. Means ± SEM are shown.
Figure 5.
Production of inflammatory factors by human brain astrocytes. Cultured astrocytes were incubated with 12.5 μ m d-Aβ 40, Aβ 42, Aβ 40, Hsp27, Hsp20, HspB8, HspB2B3, or 1 μg/ml LPS for 2 d at 37°C. Supernatant was collected and IL-8 ( A), sICAM-1 ( B), MCP-1 ( C), TGF-β 1( D), and CD40 ligand ( E) concentrations were measured using ELISA. Statistical analysis was performed using an independent sample ttest. The level of significance of the difference compared with control is indicated as follows: * p< 0.05; ** p< 0.01; *** p< 0.001; p> 0.05 is not indicated. Means ± SEM are shown.
Incubation of SMCs with 12.5 μ mHsp20, HspB8 or HspB2B3 resulted in a strong induction of IL-8 (Fig. 4 A; p< 0.01), sICAM-1 (Fig. 4 B; Hsp20, HspB2B3, p< 0.001; HspB8, p< 0.01) and MCP-1 (Fig. 4 C; Hsp20, HspB2B3, p< 0.001; HspB8, p< 0.01) secretion, but not of TGF-β 1(Fig. 4 D). In contrast to the increased levels of IL-8 production after incubation with 12.5 μ mHsp27 (Fig. 4 A; p< 0.001), decreased ( p< 0.01) TGF-β 1production was observed after Hsp27 treatment compared with control (Fig. 4 D). In addition, incubation with Hsp27 did not induce levels of sICAM-1 (Fig. 4 B) and MCP-1 (Fig. 4 C) above control levels in SMCs. Furthermore, SMCs did not seem to secrete CD40 ligand, since after incubation of these cells with either Aβ 1–40, Aβ 1–42, and d-Aβ 1–40or sHsps, the concentrations of CD40 ligand remained below the detection level (data not shown).
Incubation of astrocytes with 12.5 μ mHsp20, HspB8 or HspB2B3 also resulted in a strong induction of IL-8 (Fig. 5 A; p< 0.001), sICAM-1 (Fig. 5 B; p< 0.001) and MCP-1 (Fig. 5 C; p< 0.001) secretion, but not of TGF-β 1(Fig. 5 D). In addition, only 12.5 μ mHspB8 and HspB2B3 induced CD40 ligand production by astrocytes (Fig. 5 E; p< 0.05 and p< 0.01 respectively). Comparable to the effects of Hsp27 in SMCs, IL-8 production by astrocytes was also increased after incubation with 12.5 μ mHsp27 (Fig. 5 A; p< 0.01), however, Hsp27 induced a decrease in the production of TGF-β 1(Fig. 5 D; p< 0.001) and CD40 ligand (Fig. 5 E; p< 0.01) compared with control. Furthermore, incubation with Hsp27 did not result in levels of sICAM-1 (Fig. 5 B) and MCP-1 (Fig. 5 C) above control levels in astrocytes.
To exclude LPS contamination, potentially present in the purified sHsp samples, we coincubated cell samples with PMB and sHsps to inhibit potential LPS-mediated inflammation. After preincubation and coincubation of LPS with PMB, production of inflammatory factors by SMCs and astrocytes returned to control levels (Fig. 6 A, B; p< 0.05), indicating that PMB efficiently inhibited the LPS-induced inflammatory reaction. Whereas 12.5 μ mαB-crystallin seemed to induce IL-8 secretion by SMCs and astrocytes, this effect was completely abolished by preincubation and coincubation with PMB (Fig. 6 A, B; p< 0.05), indicating that traces of LPS in the αB-crystallin preparations are responsible for the observed effects. In contrast, PMB had no, or only a minimal effect, on the production levels of IL-8 by SMCs and astrocytes induced by the other sHsps samples (Fig. 6 A, B), suggesting a strong inducing effect of these sHsps on cytokine production.
Figure 6.
Production of IL-8 by human brain leptomeningeal SMCs ( A) and human brain astrocytes ( B) after coincubation with PMB. Cultured cells were coincubated with 1 μg/ml LPS or a 12.5 μ mconcentration of the indicated sHsp with or without 10 μg/ml PMB for 2 d at 37°C. In these experiments, PMB was preincubated with both the LPS and the sHsps for 1 h at 37°C before addition to the cells. Supernatant was collected and IL-8 concentrations were measured using ELISA. PMB efficiently abolished the effects of LPS and αB-crystallin on IL-8 production, but not of the other sHsps. Statistical analysis was performed using an independent sample ttest. The level of significance of the difference compared with control is indicated as follows: * p< 0.05; p> 0.05 is not indicated. Means ± SEM are shown.
Discussion
The main findings of this study are as follows: 1) Hsp20, HspB8 and HspB2 are associated with (cap)CAA and dyshoric angiopathy in AD brains with severe CAA pathology; 2) these sHsps colocalize with ICAM-1 in dyshoric angiopathy near (cap)CAA; 3) sHsps (especially Hsp20, HspB8 and HspB2B3), but not Aβ, increased secretion of IL-8, sICAM-1 and MCP-1 by cultured human leptomeningeal SMCs and human brain astrocytes; 4) Hsp27 reduced secretion of TGF-β 1by SMCs and astrocytes and CD40 ligand secretion by astrocytes.
The observed astrocytic and microglial activation, indicative of an inflammatory reaction, around (cap)CAA in this report is in line with earlier studies (Richard et al., 2010;Attems et al., 2011). In addition, colocalization of Hsp20, HspB8 and HspB2, but not αB-crystallin and Hsp27, with (cap)CAA and dyshoric angiopathy near (cap)CAA is also in line with our previous studies in which colocalization of these sHsps was found with CAA and/or parenchymal deposits of Aβ (Wilhelmus et al., 2006b,c,2009). It has been suggested that Hsp20, HspB8 and HspB2 are predominantly associated with fibrillar Aβ in vivo(Wilhelmus et al., 2006b,c,2009) and our results suggest a similar association of these sHsps with fibrillar Aβ in (cap)CAA and with dyshoric angiopathy near (cap)CAA. Thus, Hsp20, HspB8 and HspB2 are clearly associated with various types of Aβ deposits in AD brains and may participate in the local inflammatory reaction.
CAA-related inflammation is of clinical importance since patients with this type of pathology present with cognitive decline, seizures and headaches, that improve upon anti-inflammatory treatment (Eng et al., 2004;Kinnecom et al., 2007;Chung et al., 2011). In addition, it has been suggested that especially capCAA with spreading of the Aβ deposits into the neuropil could contribute to a rapid clinical deterioration (Eurelings et al., 2010), suggesting an important role of capCAA and dyshoric angiopathy, rather than plaques and CAA, in cognitive decline. In AD, Aβ has been shown to trigger neuroinflammation by e.g., activation of the complement system (Heneka et al., 2010), and activation of microglia and astrocytes (Tan et al., 1999;Heneka et al., 2010). In addition, the proinflammatory factors IL-8, MCP-1 and CD40 ligand are increased in AD (Akiyama et al., 2000;Calingasan et al., 2002;Sokolova et al., 2009) and ICAM-1 and TGF-β 1colocalize with Aβ deposits (Verbeek et al., 1996;Wyss-Coray et al., 1997), suggesting that Aβ may induce the expression of these inflammatory factors. In contrast, however, the results of the present study suggest that sHsps may be much more potent inducers of an inflammatory reaction in AD brains than Aβ. Interestingly, the proinflammatory effect of these sHsps does not seem to be limited to a single parameter such as IL-6 (Wilhelmus et al., 2009), but includes multiple inflammatory factors that are observed in vivo. We obtained in vivoevidence for the colocalization of sHsps near sites of Aβ-associated inflammation in the cerebral vasculature and demonstrated in vitrothat Hsp20, HspB8 and HspB2B3 induced production and secretion of IL-8, MCP-1 and sICAM-1 in SMCs and astrocytes, with little or no effect of Hsp27 and no effect of αB-crystallin on these factors. These results are in line with, and extend, our previous findings that sHsps may be among the key mediators of the inflammatory reactions associated with (cap)CAA, since they also induced IL-6 production in cultured SMCs, astrocytes and microglia (Wilhelmus et al., 2009). Interestingly, our results suggest that those sHsps that occur extracellularly in plaques or dyshoric angiopathy and (cap)CAA (i.e., Hsp20, HspB8 and HspB2B3) have a potent proinflammatory effect, indicating that especially these sHsps are important in the inflammatory reaction in CAA. Interestingly, HspB8 and HspB2B3 induced CD40 ligand expression in astrocytes, but not in SMCs, suggesting that the reported upregulation of CD40 ligand in AD (van der Wal et al., 1993;Calingasan et al., 2002) might be due to astrocytic production. In contrast to these findings, however, Hsp20, HspB8 and HspB2B3 did not induce production of TGF-β 1in both SMCs and astrocytes, although these factors are also reported to be upregulated in AD (van der Wal et al., 1993;Calingasan et al., 2002). This suggests that this cytokine might be upregulated by alternative mechanisms or cell types.
Hsp27 is a member of the sHsp family with remarkable capacities compared with the other sHsps tested in this study. Hsp27 was able to induce IL-8 and inhibit TGF-β 1production in both human SMCs and astrocytes in vitro. Furthermore, Hsp27 inhibited CD40 ligand production in astrocytes. Interestingly, IL-8 is a proinflammatory cytokine and TGF-β 1can act as an anti-inflammatory factor by inhibition of local inflammation resulting in reduced tissue injury that may occur as a response to inflammation (Wahl, 1992). Furthermore, the interaction of CD40 ligand with its receptor has been implicated in the modulation of anti-inflammatory responses (Liu et al., 2010). Thus, Hsp27 may exert a proinflammatory effect, both through inducing a proinflammatory reaction (e.g., IL-8) and reducing the production of the anti-inflammatory factors (e.g., CD40 ligand and TGF-β 1) (Liu et al., 2010). In addition, Hsp27 may also function as an indirect anti-apoptotic molecule (Concannon et al., 2003) by inhibiting the proapoptotic proteins caspase-3 (Stetler et al., 2009) and Bax (Havasi et al., 2008). Since both TGF-β 1and CD40 ligand may be involved in apoptosis during inflammation (Calingasan et al., 2002;Schuster and Krieglstein, 2002), reduced TGFβ1 and CD40 ligand levels induced by Hsp27 may add to the anti-apoptotic effect of Hsp27. Furthermore, in transgenic mice models for AD it has been demonstrated that TGF-β 1overexpression may lead to Aβ deposits in cerebral blood vessels and meningeal vessels (Wyss-Coray et al., 1997). Moreover, elevated levels of CD40 ligand may lead to endothelial dysfunction and atherothrombosis, whereas inhibition of CD40/CD40 ligand interaction may prevent atherogenesis in animal models (Urbich and Dimmeler, 2004;Chakrabarti et al., 2010;Dominguez-Rodriguez et al., 2010;Yoshioka et al., 2010). Thus, since Hsp27 affects the expression of TGF-β 1and CD40 ligand, Hsp27 may create a proinflammatory environment, likely both by reducing the production of anti-inflammatory factors and inducing production of proinflammatory cytokines, inhibit apoptotic processes and may alter the vascular micro-environment. However, more study is required to elucidate the exact role of Hsp27 in neurovascular inflammation in AD.
It has been suggested that Aβ itself can induce neuroinflammation (Heneka et al., 2010). In our study, however, Aβ 1–40, Aβ 1–42, and d-Aβ 1–40had no effect on the production of inflammatory factors by SMCs and astrocytes. Previously, we also demonstrated that Aβ did not induce IL-6 production by cerebrovascular cells and astrocytes (Wilhelmus et al., 2009). However, in the same study it was shown that Aβ slightly induced IL-6 production by microglia (Wilhelmus et al., 2009). In addition, in another study dose-dependent increases of IL-8 and MCP-1 production by human brain microglia were observed after exposure to Aβ (Lue et al., 2001). Together, these studies suggest that in the brain, microglial cells may be particularly susceptible to Aβ, resulting in an inflammatory reaction, but that other cerebral cell types, such as vascular cells and astrocytes, do not respond to Aβ in a proinflammatory way, but may be stimulated to do so by sHsps.
In conclusion, Hsp20, HspB8 and HspB2 are associated with (cap)CAA and dyshoric angiopathy in AD brains with severe CAA pathology. In addition, colocalization of these sHsps with ICAM-1 around Aβ-laden vessels was observed. Furthermore, we demonstrated that Hsp20, HspB8 and HspB2B3 induced the production of inflammatory factors in vitro, suggesting that these sHsps might be among the key mediators of the inflammatory reactions associated with (cap)CAA and dyshoric angiopathy. An interesting role for Hsp27 was found, since this sHsp seems to induce a proinflammatory effect by reducing the normal anti-inflammatory effect in human SMC and astrocytes in vitro. Furthermore, although it has been suggested that Aβ itself can induce inflammation (Heneka et al., 2010), we did not observe such an effect in cultured SMCs and astrocytes. The results of this study provide new insights in the inflammatory reactions associated with AD and CAA and, therefore, might provide interesting new targets for therapeutic intervention in the pathogenesis of AD and CAA.
Footnotes
This study was supported by grants from the Internationale Stichting Alzheimer Onderzoek (ISAO, no. 07510), the Netherlands Organisation for Scientific Research (NWO/ZonMW, Vidi program, no. 917.46.331) and the Hersenstichting Nederland (no. 14F06.18). We thank Dr. D. Schenk for his generous gift of antibodies and Prof. Dr. M. Netea for his generous gift of LPS.
The authors declare no competing financial interests.
Correspondence should be addressed to Dr. I. B. Bruinsma, Department of Neurology, 830 LGEM, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. i.bruinsma@neuro.umcn.nl
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Journal of Neuroscience 17 August 2011, 31 (33) 11992-12000; DOI: 10.1523/JNEUROSCI.0945-11.2011
| https://www.jneurosci.org/content/31/33/11992.full |
NELSON v. PROGRESSIVE CAS | 162 P.3d 1228 (2007) | 3d122811389 | Leagle.com
OPINION CARPENETI Justice. I. INTRODUCTION This case concerns the validity and applicability of a named driver exclusion...3d122811389
NELSON v. PROGRESSIVE CAS. INS. CO.
No. S-11793.
View Case
Cited Cases
Citing Case
162 P.3d 1228 (2007)
Katherine NELSON as assignee of Siuleo Milo Ulisese, an individual, Lilii Ulisese, an individual, Anita Ulisese, an individual, Appellants,
v.
PROGRESSIVE CASUALTY INSURANCE COMPANY, a foreign corporation, Danny Withers, an individual, Matt Dufour, an individual, Appellees.
Supreme Court of Alaska. https://leagle.com/images/logo.png
June 29, 2007.
Rehearing Denied August 8, 2007.
Attorney(s) appearing for the Case
Jason Skala, Law Office of Jason Skala, Eagle River, for Appellant.
Gary A. Zipkin, Guess & Rudd P.C., Anchorage, for Appellees.
Before: FABE, Chief Justice, MATTHEWS, EASTAUGH, BRYNER, and CARPENETI, Justices.
Supreme Court of Alaska.
OPINION
CARPENETI, Justice.
I. INTRODUCTION
This case concerns the validity and applicability of a named driver exclusion in an automobile insurance policy. The pedestrian victim of a hit-and-run accident involving an
[162 P.3d 1230]
unlicensed and uninsured driver sued the driver's parents for negligently entrusting their vehicle to their son. The parents' auto insurance carrier refused to cover the victim's personal injury claim because the parents had previously excluded their son from coverage under the policy. The victim argues that the exclusion of the son under the policy should not bar coverage for the victim's claim against the parents for their negligent entrustment of the vehicle to their son. Because the tort of negligent entrustment rests upon the son's operation of the vehicle, which the parents elected to exclude from their insurance coverage, and because Alaska's insurance laws permit such exclusions, we affirm the superior court's grant of summary judgment to the insurance carrier.
II. FACTS AND PROCEEDINGS
The facts of this case are not in dispute. On June 14, 2001, Siuleo Milo Ulisese, a twenty-one-year old uninsured and unlicensed driver, drove his parents' minivan along Fifth Avenue in downtown Anchorage. The traffic signals at the intersection of Fifth Avenue and C Street were not working. While driving down Fifth Avenue, Siuleo turned left onto C Street, striking and injuring Katherine Nelson as she was crossing in the crosswalk.
Siuleo's parents, Anita and Lilii Ulisese, owned the vehicle Siuleo was operating at the time of the accident. Following the accident, Nelson filed an insurance claim with the Uliseses' automobile insurance carrier, Progressive Casualty Insurance Company. After conducting an investigation, Progressive informed Nelson and the Uliseses that it was denying coverage because Lilii had excluded Siuleo from coverage under the policy. 1Progressive based its denial on the "Named Driver Exclusion" language in the Uliseses' auto insurance policy, which states:
If you have asked us to exclude any person from coverage under this Policy, then we will not provide coverage for any claim arising from an accident or loss involving a vehicle or rental vehicle being operated by the excluded person. THIS INCLUDES ANY CLAIM FOR DAMAGES MADE AGAINST YOU, A RELATIVE, OR ANY OTHER PERSON OR ORGANIZATION THAT IS VICARIOUSLY LIABLE FOR AN ACCIDENT ARISING OUT OF THE OPERATION OF A VEHICLE BY THE EXCLUDED DRIVER.
Progressive further denied coverage on the basis of AS 28.20.440(l), which provides:
Notwithstanding any other provisions of law, a person who resides in the same household as the person named as insured or a person who is a relative of the person named as insured shall be excluded from coverage under a motor vehicle liability policy if the person named as insured requests that the person be excluded from coverage.
Nelson filed a claim against Siuleo for negligence and against the Uliseses for negligently entrusting their car to Siuleo. The claim was forwarded to Progressive. After investigating Nelson's claim, Progressive refused to cover the Uliseses for liability to Nelson or for the cost of defending against Nelson's complaint. The Uliseses agreed to confess judgment to Nelson's claims subject to arbitration on the amount of damages and an agreement by Nelson not to enforce the damage award against the Uliseses. The arbitration award amounted to $177,253 plus costs and fees. Anchorage Superior Court Judge Sen K. Tan confirmed the award. The arbitration award was forwarded to Progressive, which again denied coverage for the Uliseses' claims because "Siuleo Milo[] was an excluded driver; therefore, coverage does not apply for him, or any claims made against Lilii and Anita Ulisese arising out of the operation of a vehicle by the excluded driver."
On March 25, 2004, Nelson, as assignee of the Uliseses' claim, filed a complaint against Progressive. The claim alleged that Progressive and its employees were negligent, that they breached their duty to defend the Uliseses, and that Progressive wrongfully breached its contract with the Uliseses when
[162 P.3d 1231]
it refused to cover the negligent entrustment claim. 2Superior Court Judge Peter A. Michalski granted partial summary judgment to Progressive on the issue of coverage and dismissed Nelson's claims with prejudice. Nelson appeals.
III. STANDARD OF REVIEW
We will affirm summary judgment if there are no issues of material fact and the moving party is entitled to judgment as a matter of law. 3Contract interpretation presents a question of law, which we review de novo. 4When interpreting insurance contracts we look "to the language of the disputed policy provisions, the language of other provisions of the policy, and to relevant extrinsic evidence." 5
IV. DISCUSSION
A. The Excluded Driver Exception to Mandatory Auto Insurance Coverage
Alaska law generally requires Alaska drivers to carry automobile insurance. 6Alaska Statute 28.22.101, a provision of the Alaska Mandatory Automobile Insurance Act (AMAIA), lays out general coverage requirements for motor vehicle insurance in Alaska. It provides that an owner's motor vehicle liability policy must "insure the person named against loss from the liability imposed by law for damages that arise from the ownership, maintenance, or use of a designated motor vehicle." Insurers are generally not permitted to issue auto policies containing provisions which reduce the scope of coverage below the statutory minimum. 7
The AMAIA supplements the Motor Vehicle Safety Responsibility Act (MVSRA). 8The MVSRA requires an uninsured driver who has been involved in an accident to prove financial responsibility for the future by posting a bond or submitting a certificate of insurance. 9The MVSRA also requires automobile insurance policies to provide minimum coverages for a named insured and other persons using a vehicle with the named insured's permission. 10All policies issued in the state must meet the content requirements imposed by the MVSRA, regardless of whether the policies were required as proof under the act.
The AMAIA and the MVSRA coexist as part of Alaska's Uniform Vehicle Code. 11They are not, however, coextensive. 12As noted, the AMAIA "supplements, but does not supplant" the MVSRA. 13
In 1997 the legislature enacted an exception to these general coverage requirements. 14Alaska Statute 28.20.440( l) provides:
Notwithstanding any other provisions of law, a person who resides in the same household as the person named as insured or a person who is a relative of the person named as insured shall be excluded from coverage under a motor vehicle liability policy if the person named as insured requests that the person be excluded from coverage.
Subsection .440(
l
) thus permits named insured policyholders to exclude select individuals
[162 P.3d 1232]
from coverage. In this case, the Uliseses endorsed an exclusion that exempted their son Siuleo from coverage under their auto policy. Because Siuleo was excluded under the policy, Progressive refused coverage for Nelson's claim.
Nelson raises two arguments in support of her assertion that Progressive should cover her negligent entrustment claim: (1) because negligent entrustment is an independent tort, the claim does not "arise from" Siuleo's operation of the car; and (2) the named insured exclusion is unenforceable because it is ambiguous and contrary to Alaska law. We consider each in turn.
B. Nelson's Claim of Negligent Entrustment "Arises From" Siuleo's Negligent Act.
Alaska recognizes the common law tort of negligent entrustment and follows the definition in the Restatement (Second) of Torts § 390 (1965), which states:
One who supplies directly or through a third person a chattel for the use of another whom the supplier knows or has reason to know to be likely because of his youth, inexperience, or otherwise, to use it in a manner involving unreasonable risk of physical harm to himself and others whom the supplier should expect to share in or be endangered by its use, is subject to liability for physical harm resulting to them.[15]
Nelson relies on our discussion of negligent entrustment in Ardinger v. Hummell 16to support her claim that because negligent entrustment is considered an independent cause of action, it arises from the independent negligence of the entrusting defendant and is therefore complete upon the act of entrustment. In Ardinger,we noted that negligent entrustment is "an independent cause of action against the [vehicle] owner and is not dependent on theories of agency, joint venture, or other forms of vicarious liability." 17Nelson asserts that Form 9330 of the Progressive policy, which exempts from coverage claims that "aris[e] from an accident or loss involving a vehicle . . . operated by the excluded person" does not bar coverage because her claim arose at the moment the Uliseses entrusted their vehicle to Siuleo. In other words, Nelson contends that her claim arose beforeSiuleo began driving the vehicle.
Ardingerdoes not go as far as Nelson would propose. Ardingerindicates that an entrustor need not actively participate in or direct the entrustee's actions in order to be held liable for foreseeable harm done by the entrustee. 18This does not, however, mean that the entrustor's liability did not "arise from" the entrustee's negligence. The entrustee's act, and the resulting injury, are still required. 19
Nelson relies on the Kansas Supreme Court case of
McCart v. Muir
20
to support her argument that liability for negligent entrustment "arises from the act of entrustment, not the relationship of the parties."
21
Nelson's reliance is misplaced. In
McCart,
a jury found the father of a negligent driver liable for negligently entrusting a car to his son.
22
The issue in
McCart
was whether an
[162 P.3d 1233]
entrustor must pay for an entrustee's portion of the total negligence in apportioning fault. Answering in the negative, McCartheld that the jury should have been instructed on comparative negligence because "[t]he nature and extent of negligence of the entrustor and entrustee are separate and distinct. The percentages of fault may be different in amount and should be determined separately." 23 McCartwas concerned with comparative liability. Nowhere does McCartsuggest that an entrustee's negligence in producing the injury is not a required element of the claim. On the contrary, the court noted "all elements of negligent entrustment were shown: (1) the father . . . was instrumental in furnishing the motor vehicle to his son, Stephen; (2) the father knew or should have known Stephen was an incompetent driver; and (3) the negligence of Stephen in operating the vehicle was a cause of the damages." 24
Several courts have concluded that where the entrustee's excluded act is a "but for" cause of the injury, the injury is not covered under any theory of liability. 25The Ninth Circuit drew this same conclusion when interpreting Alaska law in Allstate Insurance Co. v. Ellison. 26In upholding an exclusion in a homeowner's policy for injuries arising out of the use of an airplane, the court stated: "Negligent entrustment requires both negligent use by the entrustee and negligence by the entrustor. Recovery must depend on the ownership or the use of the excluded vehicle." 27The Wisconsin Supreme Court echoed this reasoning in Bankert v. Threshermen's Mutual Insurance Co., 28noting that "[the] negligent entrustment [of an automobile] is irrelevant unless the person to whom [the vehicle] is entrusted acts in a negligent manner (creates an unreasonable risk) and in fact inflicts injury as the result of such conduct." 29
We cited
Ellison
with approval in
Jones v. Horace Mann Insurance Co.,
30
"a case in which a plaintiff unsuccessfully sought to recover damages for negligent entrustment under a homeowner's policy that contained an exclusion covering motorized vehicles."
31
The victim in
Jones
was injured in an accident involving a snowmachine being operated by a ten-year old friend. The victim sued the driver's parents for negligent entrustment, and the homeowner's insurer denied coverage. The exclusion at issue read: "This policy does not apply to bodily injury or property damage which results directly or indirectly from . . . the ownership, operation, maintenance, use, occupancy, renting, loaning, entrusting, supervision, loading or unloading of motorized vehicles . . . owned or operated by or rented or loaned to an insured."
32
We held that the policy did not cover the accident itself, and for that reason concluded that a change in the legal theory of liability did not give rise to coverage.
33
Nelson attempts to distinguish
Jones
from the present case by arguing that
Jones
involved an exclusion for a specific instrumentality (a snowmachine), whereas the case before us involves an exclusion for a specific driver (Siuleo Ulisese). This difference does not distinguish the case. Other jurisdictions considering negligent entrustment cases have
[162 P.3d 1234]
consistently held that the analysis of exclusionary language is not limited to the type of policy at issue. 34
We therefore hold that any liability on the part of the Uliseses for their alleged negligent entrustment necessarily required the underlying negligence of Siuleo in operating the vehicle.
C. Nelson's Interpretation of the Policy Is Unreasonable.
Nelson argues that the named driver exclusion is ambiguous and that the Uliseses did not understand it. Nelson further asserts that the last clause of the final sentence excludes only vicarious liability, not negligent entrustment claims, and "limits the scope of the exclusion." We consider these arguments in turn.
1. The policy is not ambiguous.
Nelson's first argument is that the term "arising from" in the policy is ambiguous. Progressive Form 9330, the named driver exclusion election, states:
No coverage is provided for any claim arising from an accident or loss that occurs while a covered vehicle . . . is operated by the excluded driver(s). THIS INCLUDES ANY CLAIM FOR DAMAGES MADE AGAINST YOU, A RELATIVE, OR ANY OTHER PERSON OR ORGANIZATION THAT IS VICARIOUSLY LIABLE FOR AN ACCIDENT ARISING OUT OF THE OPERATION OF A . . . VEHICLE BY THE EXCLUDED DRIVER.
(Emphasis added, capitalization in the original.)
Ambiguity will be found "where the contract as a whole and all extrinsic evidence support two different interpretations, both of which are reasonable." 35A contract provision is considered ambiguous if "it is reasonably susceptible to more than one interpretation." 36We emphasize that only where inconsistent, but reasonable, interpretations of the contract are possible will ambiguity be found: The mere fact that the parties disagree about the proper interpretation of the contract does not mean that the contract is ambiguous. 37
We have already determined that an entrustee's negligent act is a necessary element of any negligent entrustment claim against the entrustor. Nelson's claim for recovery against Progressive therefore necessarily "arises from" Siuleo's act of driving the automobile. 38Moreover, the policy's exclusion plainly indicates that any claim arising from Siuleo's operation of the automobile is not covered. Applying a reasonable interpretation of the phrase to the facts presented here, we are unable to find any ambiguity. 39
[162 P.3d 1235]
2. Nelson's interpretation is unreasonable.
Nelson might still prevail despite our conclusion that this policy is not ambiguous, for we need not find that an ambiguity exists to construe the policy under the "reasonable expectations" doctrine. 40This implicates her second argument: that the last clause of the final sentence of the exclusion excludes only vicarious liability, not negligent entrustment claims, and "limits the scope of the exclusion." And because an insurance policy is a contract of adhesion, "we construe it to give effect to the insured's reasonable expectations." 41Thus "the objectively reasonable expectations of applicants and intended beneficiaries regarding the terms of insurance contracts will be honored even though painstaking study of the policy provisions would have negated those expectations." 42We discern "reasonable expectations" from "the language of the disputed provisions, other provisions, and relevant extrinsic evidence. . . . " 43
But Nelson's claim is supported by none of these sources. As to the language of the disputed provision, Nelson argues that "vicariously liable" modifies "you"—and thus that an insured is able to take advantage of the exclusion only if his or her liability is vicarious, a grammatically tortured reading of the provision. Both the placement and language choice indicate that the provision is broad in excluding coverage: excluded under this provision are the insured, relatives of the insured, and persons or organizations vicariously liable for the accident. Any other interpretation of the exclusion would strain credulity and defy reasonable expectations. 44As to other provisions, there are no other provisions in the contract that support this interpretation. Finally, as to extrinsic evidence, Nelson provides no evidence supporting the Uliseses' belief that they would be covered, other than her own assertion. On the contrary, the record reflects that the Uliseses elected to remove Siuleo from the policy at two different times. In 2000 the Uliseses listed three members of their household as excluded drivers. The auto policy premium was $1,427. In February 2001 Lilii added Siuleo to the policy, and the premium increased to $3,859. In March 2001 Siuleo was again removed from the policy, and the policy premiums returned to $1,427. Given the repeated fluctuations in policy premiums and corresponding financial savings in exchange for the exclusions, 45Nelson has failed to show that the Uliseses maintained a reasonable expectation of coverage for injuries resulting from Siuleo's operation of the vehicle.
D. Progressive's Refusal To Cover Negligent Entrustment Claims Against the Named Insured Does Not Violate AS 28.20.440(
l
).
Nelson next argues that Progressive's named driver exclusion is impermissible under Alaska's automobile insurance statutes. She contends that while AS 28.20.440(
l
) contemplates exclusion of a named driver, the exclusion cannot be read to preclude liability coverage for the named policyholders (Lilii and Anita Ulisese). Nelson argues subsection .440(
l
) thus conflicts with the statutorily mandated minimum liability protection required
[162 P.3d 1236]
by AS 28.22.101. She further asserts that Progressive Form 9330 exceeds the permissible scope of subsection .440( l).
In response, Progressive counters that in enacting subsection .440( l), the legislature carved out a limited exception to Alaska's statutorily mandated minimum liability coverage requirements. For the reasons set forth below, we agree.
1. The named driver exclusion is a valid exception to statutorily mandated liability coverage.
Nelson's first argument is that application of the named driver exclusion to her claims against the Uliseses improperly negates the Uliseses' statutorily mandated minimum liability coverage. 46Alaska Statute 28.22.101 requires an owner's automobile policy to "insure the person named against loss from the liability imposed by law for damages that arise from the ownership, maintenance, or use of a designated motor vehicle." It provides for a named insured's liability coverage up to statutorily mandated limits. 47Lilii and Anita Ulisese, as the named insureds, maintained liability coverage under the Progressive policy.
Alaska Statute 28.20.440(b)(2), part of the MVSRA, also requires that an owner's automobile insurance policy insure the named insured and every other person using the vehicle with their permission against loss "for damages arising out of the ownership, maintenance, or use of the vehicle." The stated policy behind the MVSRA is to ensure that "motorists be financially responsible for their negligent acts so that innocent victims of motor vehicle accidents may be recompensed for the injury and financial loss inflicted upon them." 48
However, subsection .440( l), which provides for a specific exception from policy coverage for a named driver, can be read in harmony with the more general provisions of AS 28.20.440 and AS 28.22.101. 49The inclusion of the phrase "[n]otwithstanding any other provisions of law" plainly indicates that subsection .440( 1) was intended to be an exception to other potentially conflicting laws. Insurers commonly allow their insureds to use named driver exclusions to avoid covering high-risk drivers where the premium for such coverage would be cost prohibitive to the named insured. 50Where the loss giving rise to damages arises from Siuleo's driving, subsection .440( l) precludes coverage under the Uliseses' own liability policy for their negligent entrustment. The minimum liability coverage otherwise required of the Uliseses is thus circumscribed, but only to the extent that the claim arose out of Siuleo's operation of a vehicle.
Other jurisdictions have upheld named driver exclusions as permissible exemptions to statutorily mandated minimum liability coverage.
51
In upholding the validity of named driver exclusions, courts have relied on public policy rationales that balance cost reduction with the desire to encourage the
[162 P.3d 1237]
procurement of insurance coverage. 52
The legislative history of House Bill 218, which became subsection .440( l), indicates that the legislature was aware of the potential dangers of the named driver exclusion. Minutes of a House Labor and Commerce Committee meeting considering HB 218 reveal the committee's concern that parents who elected to exclude a child from coverage might be held personally liable with no insurance protection for the child's auto accident. 53Committee testimony in favor of the exclusion noted, however, that the exclusion would enable a household with a high-risk driver to maintain auto coverage by excluding the high-risk driver, while encouraging the excluded driver to obtain his or her own policy. 54
In providing for the exclusion, the legislature offered insureds a chance to avoid excessive premiums they would otherwise be required to pay if they could not exclude a high-risk driver. Ultimately, this helps to minimize the risk that a policyholder may elect to forgo coverage altogether. 55It also encourages responsibility on the part of policyholders and excluded drivers: Policyholders are given a powerful economic incentive to ensure that an excluded driver does not operate a policyholder's vehicle, while the excluded driver is encouraged to obtain his own insurance. 56
Forcing an insurer to provide liability coverage for claims arising out of the excluded driver's use of the vehicle also obviates the practical effect of the exclusion. It skirts a reasonable reading of the exclusion's plain language and give insureds the benefit of a bargain for which they did not pay. As the Arizona Court of Appeals noted in an analogous case:
[I]t is inconceivable that the legislature would purposely enact statutory language that authorized the insurer to exclude coverage for personal liability incurred by the unacceptable driver and to exclude vicarious liability incurred due to the unacceptable driver's conduct, but not to exclude coverage for the named insured's personal liability for negligently entrusting a vehicle to the same unacceptable driver.[57]
In light of the countervailing legislative policies at issue, the legislature's concern with enabling households to secure affordable insurance, and the plain language of subsection .440( l), we hold that the named driver exclusion is a permissible exception to Alaska's minimum liability coverage provisions. 58
2. The Division of Insurance approved Form 9330.
Nelson also argues that the named driver exclusion in Progressive's Form 9330 exceeds the scope of AS 28.20.440(
l
), citing the following language on Form 9330: "WARNING: If you have asked us to exclude coverage under this policy for any person, this policy will not meet the minimum coverage requirements of either Alaska's mandatory automobile insurance or financial responsibility laws." Nelson contends that subsection .440(
l
) does not contemplate that insurers could exclude the named policyholder from coverage, and asserts that Progressive's
[162 P.3d 1238]
warning on Form 9330 indicated it "knew its attempt to limit coverage is prohibited by law."
On the contrary, however, Progressive's warning was in compliance with Division of Insurance regulations intended to make policyholders aware of the law. The Division of Insurance recognized that subsection .440( l) allowed policyholders to exclude members of their household from their policy in exchange for a reduction in premium payments. The Division of Insurance bulletin 97-07 states:
A named driver exclusion should be signed by the named insured each policy period, and a policy with a named driver exclusion should carry a warning that the policy may be inadequate to satisfy the obligations of a motor vehicle owner or operator under the Alaska Motor Vehicle Responsibility Act or the Alaska Mandatory Insurance Law.
Bulletin 98-10 superseded bulletin 97-07. It required insurers to file and receive approval from the director of the division for policy forms that comply with subsection .440( l). 59Bulletin 98-10 states: "[a]n automobile liability insurance policy that limits coverage for named persons other than as specified in AS 28.20.440( l) must clearly indicate that the policy does not meet the minimum coverage standards of either Alaska's mandatory automobile insurance or financial responsibility laws." Bulletin 98-10 requires that exclusions that go beyond AS 28.20.440( l) must be reviewed by the Division of Insurance. Progressive submitted, and the division approved, Progressive's Form 9330.
We have not directly addressed what weight we give to Division of Insurance approvals of insurance forms. 60We have previously recognized that other jurisdictions have suggested that courts could give substantial deference to such approvals. 61In Government Employees Insurance Co. v. Graham-Gonzalez, 62we looked to the division's exercise of its delegated authority to regulate forms under Title 21, and its subsequent approval of the application form in question, in finding that a statute requiring insurers to offer under insured motorist coverage did not require application forms to state the amount of the policy premium. We noted that even if we applied our independent judgment, "the division's approval of forms . . . would be entitled to some deference. In such cases this court gives `some weight to what the agency has done, especially where the agency interpretation is longstanding.'" 63
The Division of Insurance was concerned about policyholders unwittingly executing named driver exclusions without understanding the scope of potential risks involved. The division encouraged insurance companies to develop a disclosure form. Progressive included a plain warning on Form 9330 notifying insureds of the risks of the exclusion.
64
It appears the warning language on Form 9330 was in response to the division's requirements. The division required insurers
[162 P.3d 1239]
to obtain approval from the director of the division for this exclusion, and Progressive did so. The division approved Form 9330. Lilii Ulisese signed it. The division clearly intended that Progressive's exclusion would eliminate a named policyholder's coverage for claims arising out of the excluded driver's operation of the vehicle.
As in Graham-Gonzalez,it is unnecessary for us to determine the precise standard of review we should apply to the division's approval of Form 9330. 65Even if we give only some weight to the division's approval of Form 9330, it is consistent with our view of subsection .440( l). We have already noted that the purpose of subsection .440( l) is to allow policyholders to obtain affordable auto insurance by giving them the option to exclude a high-risk member of their household from their policy. The division approved the form, and in doing so must have contemplated the potential risks that could arise. For these reasons we find that subsection .440( l) and Form 9330 provide a narrow exception to the minimum liability coverage otherwise required by AS 28.20 and AS 28.22. 66
V. CONCLUSION
The superior court correctly determined as a matter of law that the named driver exclusion in the Uliseses' insurance policy operated to exclude Nelson's claim for negligent entrustment. The excluded activity, Siuleo's operation of the vehicle, is an indispensable element of a claim of negligent entrustment. The Progressive exclusion is neither ambiguous nor illegal. Finally, AS 28.22.440( l) sets forth a limited exception to the statutorily mandated liability coverage provisions otherwise required in AS 28.20 and AS 28.22. We therefore AFFIRM the decision of the superior court.
FootNotes
1. It is undisputed that on March 5, 2001 Lilii Ulisese endorsed Progressive Form 9330, entitled "NAMED DRIVER EXCLUSION ELECTION," a provision of the Uliseses' auto policy that excluded Siuleo from coverage.
2. Nelson's claims against Progressive claims adjusters Danny Withers and Matt Dufour are not at issue in this appeal.
3. Jones v. Horace Mann Ins. Co.,937 P.2d 1360, 1361 (Alaska 1997).
4. Id.
5. Cox v. Progressive Cas. Ins. Co.,869 P.2d 467, 468 n. 1 (Alaska 1994).
6. Progressive Ins. Co. v. Simmons,953 P.2d 510, 521 n. 13 (Alaska 1998).
7. Burton v. State Farm Fire & Cas. Co.,796 P.2d 1361, 1363 (Alaska 1990).
8. AS 28.20.010-.640. "[A]lthough the MVSRA has never been a mandatory insurance law, as of 1968 the act's policy content requirements became mandatory for all policies written in the state."
Simmons,
953 P.2d at 520.
9. SeeAS 28.20.010.
10. AS 28.20.440(b)(2).
11. Simmons,953 P.2d at 521.
12. Id.at 520-21.
13. Id.
14. Ch. 81, § 113, SLA 1997.
15.
See Neary v. McDonald,
956 P.2d 1205
, 1208 (Alaska 1998) (applying Restatement (Second) of Torts § 390 to determine whether parents had sufficient control of their son's car to support negligent entrustment claim against them by motorcyclist injured in collision with son's car).
16.982 P.2d 727(Alaska 1999).
17. Id.at 733 (quoting Karen L. Ellmore, Annotation, Negligent Entrustment of Motor Vehicle to Unlicensed Driver,55 A.L.R.4th 1100, 1106 (1987)).
18. Id.
19.
See, e.g.,
RESTATEMENT (SECOND) OF TORTS § 390 cmt. b, illus. 4:
A lends his car to his friend B for B to use to drive a party of friends to a country club dance. A knows that B has habitually become intoxicated at such dances. On the particular occasion B becomes intoxicated and while in that condition recklessly drives the car into the carefully driven car of C, and causes harm to him. A is subject to liability to C.
(Emphasis added.)
20.230 Kan. 618,641 P.2d 384(1982).
21. Id.at 389-90.
22. Id.at 387.
23. Id.at 389.
24. Id.at 388 (emphasis added).
25.
See
Jay M. Zitter, Annotation,
Validity, Construction, and Application of "Named Driver Exclusion" in Automobile Insurance Policy,
33 A.L.R.5th 121, 199-200 (1995).
26.
757 F.2d 1042
, 1045 (9th Cir.1985). The disputed exclusion stated: "We do not cover bodily injury or property damage arising out of the ownership, maintenance, use, loading or unloading of aircraft."
Id.
at 1043-44.
27. Id.at 1045.
28.110 Wis.2d 469,329 N.W.2d 150(1983).
29. Id.at 153.
30.937 P.2d 1360(Alaska 1997).
31. Id.at 1367.
32. Id.
33.
Id.
at 1367.
See also Northern Ins. Co. of New York v. Ekstrom,
784 P.2d 320
, 323 (Colo.1989) ("[The term] `arising out of' has been construed to bar coverage where, but for the covered cause of loss, the injury would not have occurred. . . . The exclusion applies to a specific instrumentality, namely an automobile, rather than a theory of recovery.").
34.
See, e.g., State Farm Mut. Auto. Ins. Co. v. Graham,
860 P.2d 566
, 567-68 (Colo.App.1993) (relying on previous case involving motor vehicle exclusion in homeowner policy to decide case involving named driver exclusion);
Pierce v. Oklahoma Prop. & Cas. Ins. Co.,
901 P.2d 819
, 823-24 (Okla.1995) (relying on previous case involving excluded instrumentality clause in homeowner's policy to decide case involving named driver exclusion).
35. C.P. ex rel. M.L. v. Allstate Ins. Co.,996 P.2d 1216, 1222 at n. 38 (Alaska 2000).
36. Id.
37. Jarvis v. Aetna Cas. & Sur. Co.,633 P.2d 1359, 1363 (Alaska 1981).
38.
Cf. New York Life Insur. Co. v. Rogers,
641 P.2d 218
, 222 (Alaska 1982) (death likely due to hypothermia in water after airplane crash excluded from coverage where it "result[ed] from" airplane travel).
39. In determining whether a policy exclusion precluded claims "result[ing] from" airplane travel, we noted "[t]he question whether such a death `results from' travel in an airplane must be answered by applying a reasonable interpretation of the phrase to the facts presented."
Id. See also McCauley v. Metropolitan Prop. & Cas. Ins. Co.,
109 Wn.App. 628
,
36 P.3d 1110
, 1113 (Div. 1 1999) ("The phrase `arising out of' means `originating from,' `having its origin in,' `growing out of,' or `flowing from'");
State Farm Mut. Auto. Ins. Co. v. Graham,
860 P.2d 566
, 567 (Colo.App.1993), (concluding phrase "arising out of" not ambiguous in a claim for negligent entrustment as "such a claim was `related to,' `flowed from,' and would not exist `but for' the acts of the entrusted driver").
But see, e.g., Pablo v. Moore,
298 Mont. 393,
995 P.2d 460
, 462-64 (2000) (applying "minority rule" that looks to specific theory of coverage, rather than underlying cause of injury, to determine coverage and concluding phrase "arising out of" ambiguous in policy exclusion);
Marquis v. State Farm Fire & Cas. Co.,
265 Kan. 317
,
961 P.2d 1213
(1998) (same).
40. West v. Umialik Ins. Co.,8 P.3d 1135, 1138 (Alaska 2000).
41. Id.; C.P. ex rel. M.L. v. Allstate Ins. Co.,996 P.2d 1216, 1222 (Alaska 2000).
42. Bering Strait Sch. Dist. v. RLI Ins. Co.,873 P.2d 1292, 1295 (Alaska 1994) (quoting Robert Keeton, Basic Text on Insurance Law § 6.3(a), at 351 (1971)).
43. Williams v. Crawford,982 P.2d 250, 253 (Alaska 1999).
44.
See Ness v. Nat'l Indem. Co. of Nebraska,
247 F.Supp. 944
, 947 (D.Alaska 1965) ("A court cannot and should not do violence to the plain terms of a contract by artificially creating ambiguity where none exists. In situations in which reasonable expectations favor the insurer, and any other would be strained and tenuous, no compulsion exists to torture or twist the language of the contract.").
45. Some courts considering the validity of named driver exclusions have analyzed whether the exclusion is supported by consideration, as in the form of lower premiums.
See
7A LEE R. RUSS ET AL., COUCH ON INSURANCE § 110:22 (3d ed. 1995).
46.
See Ward v. Baker,
188 W.Va. 569
,
425 S.E.2d 245
(1992) (holding named driver exclusion of no force or effect up to limits of state's mandatory minimum insurance coverage limits).
47. AS 28.22.101(a).
48. AS 28.20.010.
49.
Progressive Ins. Co. v. Simmons,
953 P.2d 510
, 516 (Alaska 1998) ("To determine whether two statutory provisions conflict, we must interpret them together, in context with other pertinent provisions rather than in isolation, and with a view towards producing a harmonious whole.").
50.
See
Jay M. Zitter, Annotation,
Validity, Construction, and Application of "Named Driver Exclusion" In Automobile Insurance Policy,
33 A.L.R.5th 121, 137-38 (1995).
51.
See, e.g., Lopez v. Dairyland Ins. Co.,
890 P.2d 192
(Colo.App.1994) (holding named driver exclusion valid under statutory scheme mandating insurers offer uninsured motorist coverage);
State Farm Mut. Auto. Ins. Co. v. Washington,
641 A.2d 449
(Del.1994) (holding named driver exclusion valid so long as not used to delete uninsured motorist coverage);
Pierce v. Oklahoma Prop. & Cas. Ins. Co.,
901 P.2d 819
(Okla. 1995) (holding named driver exclusion based on poor driving record of excluded individual consistent with compulsory liability insurance laws);
Tapio v. Grinnell Mut. Reinsurance,
619 N.W.2d 522
(S.D.2000) (upholding named driver exclusion).
But see Ward v. Baker,
188 W.Va. 569
,
425 S.E.2d 245
(1992) (holding named driver exclusion of no force or effect up to limits of state's mandatory minimum insurance coverage limits).
52.
See, e.g., St. Paul Fire & Marine Ins. Co. v. Smith,
337 Ill.App.3d 1054
,
272 Ill.Dec. 666
,
787 N.E.2d 852
, 858 (2003) (discussing public policy rationales of sister states in upholding named driver exclusion);
Pierce,
901 P.2d at 823 (same).
But see Iowa Mut. Ins. Co. v. Davis,
231 Mont. 166,
752 P.2d 166
(1988) ("Although not expressly prohibited . . . a named driver exclusion is contrary to the public policy of [Montana's mandatory insurance statutes], and is, therefore, invalid.").
53. 1997-98 Minutes of the House Labor & Commerce Committee, May 1, 1997, at 328.
54. Id.
55. See Tapio,619 N.W.2d at 525.
56.
See Zamora v. Dairyland County Mut. Ins. Co.,
930 S.W.2d at 739, 741 (Tex.App.1996) (holding that named driver exclusion furthered public policy by enabling families with members having bad driving records to secure affordable insurance and deterred insured drivers from entrusting automobiles to unsafe drivers).
57. State Farm Auto. Ins. Co. v. Dressler,153 Ariz. 527,738 P.2d 1134, 1138 (Ariz.App.1987).
58. Our decision today is confined to the named driver exclusion as it applies to liability coverage. We do not reach the issue of whether the named driver exclusion is valid when uninsured or underinsured motorist coverage is at issue.
59. Insurance forms made part of a policy, including Progressive Form 9330, are subject to state regulation. Alaska Statute 21.42.120 requires forms that are to become part of an insurance policy to be filed and approved by the director of the Division of Insurance.
60.
See Gov't Employees Ins. Co. v. Graham-Gonzalez,
107 P.3d 279
, 286 (Alaska 2005) (noting that independent judgment standard typically applies to question of law unless issue involves agency expertise or determination of fundamental policy questions on subjects committed to the agency).
61.
Id.
(citing
McTaggart v. Liberty Mut. Ins.,
267 Kan. 641
,
983 P.2d 853
, 857-58 (1999) (noting that "the interpretation of a statute by an administrative agency charged with the responsibility of enforcing that statute is entitled to judicial deference")).
See also Lee v. John Deere Ins. Co.,
208 Ill.2d 38
,
280 Ill.Dec. 523
,
802 N.E.2d 774
, 779 (2003) (noting that approval of director of division of insurance is "entitled to great weight, although it is not conclusive on the courts").
62. 107 P.3d at 286.
63. Id.(quoting Diaz v. Silver Bay Logging, Inc.,55 P.3d 732, 741 (Alaska 2002)).
64. "Because named driver exclusions eliminate significant coverage, such exclusions must be accompanied by `strict requirements in the policies so as to insure the insured's full knowledge and consent to the endorsement.'"
Phoenix Indem. Ins. Co. v. Pulis,
129 N.M. 395
,
9 P.3d 639
, 643 (2000) (citing Jay M. Zitter, Annotation,
Validity, Construction and Application of "Named Driver Exclusion" in Automobile Insurance Policy,
33 A.L.R.5th 121, § 2[a] at 137-38 (1995)).
65. Graham-Gonzalez,107 P.3d at 287.
66. Nelson finally argues that a "deemer clause" in the policy's general provisions, which provides that if any part of the policy fails to conform with Alaska law "it shall be deemed amended to conform with state requirements," mandates coverage in this case. Because we have held that the named driver exclusion is valid, and Nelson's argument on this point presupposes the illegality of the exclusion, her argument fails.
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Water | Free Full-Text | Urban Water Cycle Simulation/Management Models: A Review
Urban water management is increasingly important given the need to maintain water resources that comply with global and local standards of quantity and quality. The effective management of water resources requires the optimization of financial resources without forsaking social requirements. A number of mathematical models have been developed for this task; such models account for all components of the Urban Water Cycle (UWC) and their interactions. The wide range of models entails the need to understand their differences in an effort to identify their applicability, so academic, state, and private sectors can employ them for environmental, economic, and social ends. This article presents a description of the UWC and relevant components, a literature review of different models developed between 1990 and 2015, and an analysis of several case studies (applications). It was found that most applications are focused on new supply sources, mainly rainwater. In brief, this article provides an overview of each model’s use (primarily within academia) and potential use as a decision-making tool.
Urban Water Cycle Simulation/Management Models: A Review
by Carlos Andrés Peña-Guzmán 1,2,* , Joaquín Melgarejo 2 , Daniel Prats 2 , Andrés Torres 3 and Sandra Martínez 4
1
Environmental Engineering Program, Universidad Santo Tomas, 110231426 Bogotá, Colombia
2
Institute of Water and Environmental Sciences, Universidad de Alicante, San Vicente del Raspeig Route, s/n, 03690 Alicante, Spain
3
Civil Engineering Program, Pontificia Universidad Javeriana, 110231594 Bogotá, Colombia
4
Matanza Riachuelo Catchment Authority (ACUMAR), Esmeralda 255 PB, C1033AAJ Ciudad Autónoma de Buenos Aires, Argentina
Author to whom correspondence should be addressed.
Water 2017 , 9 (4), 285; https://doi.org/10.3390/w9040285
Received: 19 January 2017 / Revised: 8 April 2017 / Accepted: 16 April 2017 / Published: 19 April 2017
Abstract
Urban water management is increasingly important given the need to maintain water resources that comply with global and local standards of quantity and quality. The effective management of water resources requires the optimization of financial resources without forsaking social requirements. A number of mathematical models have been developed for this task; such models account for all components of the Urban Water Cycle (UWC) and their interactions. The wide range of models entails the need to understand their differences in an effort to identify their applicability, so academic, state, and private sectors can employ them for environmental, economic, and social ends. This article presents a description of the UWC and relevant components, a literature review of different models developed between 1990 and 2015, and an analysis of several case studies (applications). It was found that most applications are focused on new supply sources, mainly rainwater. In brief, this article provides an overview of each model’s use (primarily within academia) and potential use as a decision-making tool.
Keywords:
urban water cycle
;
integrated management of urban water
;
computational models
1. Introduction
The continuous growth of urban areas across the globe is directly tied to rapid economic, population, and infrastructure growth [ 1 , 2 ]. Currently, urban areas account for more than half of the world’s population; more than 500 cities already have more than a million inhabitants [ 3 , 4 ]. It is estimated that in 1900, only 9% of the world’s population lived in urban areas; by the 1980s, urban population had increased to 40% globally. By 2000, this figure had reached 50%, and it is expected to reach 60% by 2025 [ 5 ].
For urban populations, the importance of water cannot be overestimated. Its management is a challenge in terms of sustainability and administration, for cities have short time frames in which to offer the best possible water administration, wastewater collection, rainwater harvesting, and effective water treatment without generating negative environmental, social, sanitary, or health effects [ 6 ].
Over the last two decades, computational models have gained recognition as effective tools for addressing the aforementioned challenges. These models allow for the achievement of policy objectives [ 7 ], evaluation of the feasibility of different solutions for specific problems [ 8 , 9 ], and proper decision-making for urban water management [ 10 ].
Historically, these models have encompassed a number of different approaches, from individual perspectives to more holistic visions, bringing together natural water flows, piping flows, and various subsystems (ecological, environmental, socioeconomic, and political) [ 11 , 12 ]. Initially developed approximately two decades ago, these models were primarily employed to understand the behavior and interactions of urban drainage, treatment systems, and bodies of water. Such models were presented in Denmark in 1992 at the INTERURBA conference “Interactions between Sewers, Treatment Plants and Receiving Waters in Urban Areas” , and they were geared toward identifying relations, impacts, and possible controls [ 13 , 14 ]. At INTERURBA II in Portugal (2001), these models were expanded to include rainwater management [ 15 , 16 ]. As the relations between model components and water supply began to be captured and expressed, researchers began to concentrate their efforts on the development of models that were more comprehensive in terms of elements and interactions [ 17 ]. In Austria, INTERURBA III took place in 2013. This iteration was titled “ Modeling the urban water cycle as integral part of the city ”, and its objective was to study the interactions between models used for management of urban water and socioeconomically feasible urban development [ 14 ].
The incorporation of all components of the Urban Water Cycle (UWC) has improved the management of urban water resources and the development of different component systems, including supply, treatment, distribution, consumption, wastewater collection, drainage, and quality and quantity control of surface and groundwater sources [ 12 , 15 , 18 , 19 , 20 , 21 , 22 ].
As per Renouf and Kenway [ 23 ], UWC modeling was previously based on the quantitative simulation of anthropogenic flows given by water use, along with the simulation of water flows. UWC models factored in balances of mass, energy, and flow [ 9 , 20 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ] until artificial-intelligence models were implemented [ 35 , 36 ]. All UWC models studied in this review, however, have been adapted to different temporal and spatial scales.
As proposed by Mitchell et al. [ 37 ], there are more than 65 commercial or free models that rely on partial or total combinations of UWC elements. Bach et al. [ 15 ] classified them according to four levels, each of which reflects the degree of integration: Integrated Component-based Models, Integrated Urban Drainage Models (IUDMs) or Integrated Water Supply Models (IWSMs), Integrated Urban Water Cycle Models (IUWCMs), and Integrated Urban Water System Models (IUWSMs).
It is crucial for researchers, academics, administrators of urban water resources, and urban-infrastructure planners and designers to learn about these models and their varied applications because they can be used to devise integrated solutions for the different UWC components. The use of these models may help ensure the feasibility of solid economic investments—and establish technical arguments—for the creation of policies and guidelines geared towards sustainability.
This article presents a review of UWC software and models designed for integrated urban water management. This review was based on two parts: models developed between 1990 and 2015 that included all UWC components (IUWCMs and IUWSMs) and different applications of these models between 1990 and 2016. The paper is divided into three parts: an introduction to UWC, a description of the models reviewed, and case studies (applications) of these models.
2. Urban Water Cycle
Based on the literature review, a blanket definition of the UWC concept can be articulated as follows: The spatiotemporal interaction between water and hydrological processes, as well as supply, treatment, distribution, consumption, collection, provision, and reuse carried out in urban or partially urban areas.
This cycle has four main inputs: water, contaminants, energy, and chemicals, as can be observed in Figure 1 . The first, and most essential, for this cycle is water, which comes from two primary sources: supply sources (e.g., surface water and/or groundwater), and precipitation. These inputs allow for the calculation of balances and hydric consumption within the UWC [ 26 , 29 , 38 , 39 ]. The second input refers to contaminants, which are closely linked to water flows, for these flows are the transportation medium and/or input to the cycle. Contaminants enter the cycle via surface water and/or groundwater flows, wastewater water flows from property-related uses, treatment of wastewater flows, and, lastly, rainwater flows associated with atmospheric water, different surfaces, and chemical use associated with these surfaces [ 40 ].
Figure 1. Urban Water Cycle (UWC). Adapted from [ 58 ].
The third input, energy, is highly consequential within the UWC because of the costs and environmental effects attributable to greenhouse gases and the use of natural resources [ 41 , 42 , 43 , 44 , 45 , 46 ]. Energy use is principally related to the function of treatment systems, water supply, and thermal water heating [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. Moreover, during wastewater treatment, biogas is produced by the digestion of organic compounds [ 48 , 56 , 57 ].
The fourth and final input refers to chemicals used to treat wastewater and drinking water; special emphasis is placed on the costs associated with chemicals in terms of the operation of these treatment processes as well as their potential environmental and health impacts [ 34 , 59 , 60 ].
However, the cycle’s behavior, along with that of inputs, is modified by external and internal factors involved in any process. These factors intervene both directly and indirectly within each input, thereby increasing the entire cycle’s complexity. See Table 1 for more information on this complexity.
Table 1. Internal and external factors of the UWC.
3. Description of Models of UWC Processes
To implement models for UWC management, a comprehensive understanding of these models, their characteristics, and users’ needs must be established. Therefore, in this section, 17 models encountered in the literature review are presented with a presentation of the spatial and temporal characteristics, other characteristics, and simulated processes, among other aspects.
To complement the information regarding UWC models found in
Table 2
, important factors and components are described below. The aquacycle sequentially simulates the balances of the UWC processes of drinking-water supply, hydrology (precipitation and evapotranspiration), and wastewater; these balances are established via loops that cover the entire system on a daily timescale. The amount of “imported” water supply is the sum of the entire population’s water uses in addition to the water utilized for irrigation and water lost due to leaks in the system. Wastewater refers to all imported water and percolation and runoff flow rates. For its part, rainwater is runoff minus percolation and storage. Urban Volume Quality (UVQ) is an expansion of Aquacycle. UVQ is distinguished by its simulation of contaminants; it also assumes that there is no degradation or conversion of the evaluated contaminants and that the user must specify concentrations, loads, and performance of treatments [
29
,
30
]. UVQ and Aquacycle are models with grouped parameters that do not require a large amount of input data, simplifying the use of these models.
Table 2. Description of UWC models.
Originally, the Urban Water Optioneering Tool (UWOT) was proposed to improve WaND-OT1, which simulates the interactions between drinking-water supply, wastewater, and runoff. To create possible scenarios, UWOT has an Excel library with nine applications for microcomponents, two for intermediate levels, and four for the top level. The conditions, operations, and design of each of these applications can be modified [ 9 , 100 ].
WaterCress relies on the concept of nodes. Nodes represent the UWC’s functions, operations, processes, and infrastructure. In total, there are 18 basic nodes, with each having a database with quantity and quality variables [ 105 ]. In turn, these nodes are linked by flows, such as supply and drainage. For drainage, these nodes are subdivided depending on the type of function. They are assigned a predetermined color: pink for water diversions, blue for catchment runoff, green for runoff from a house or urban node, gray for gray water, and black for wastewater [ 25 , 103 ]. With respect to Hydro Planner, this software works with the model E2, which allows for the integrated simulation of various components such as runoff and nutrient and sediment contamination of a water body [ 107 ]. Hydro Planner has seven modules: (1) catchment (simulation of contaminant and runoff processes); (2) water supply; (3) consumption; (4) rainwater (contamination and water flow); (5) wastewater (contamination and water flow); (6) receiving water bodies (contamination and water flow); and (7) integration (networking of modules, input and output calculations, and graphic interface) [ 28 , 108 ]. WaterMet2 quantifies the UWC’s metabolism into four main subsystems: (1) water supply (sources, treatment, and supply); (2) water demand (consumption and water uses); (3) wastewater (separated and combined systems and wastewater treatment); and (4) water treatment (in situ or centralized treatment).
UrbanCycle’s software is characterized by the creation of precipitation and demand data, which can be entered by the user. The software allows for their creation via stochastic models. For rain, the model has the Disaggregated Rectangular Intensity Pulse (DRIP); for demand, it has the Probabilistic Demand Mode. Urban Developer is based on UrbanCycle, which presents four main characteristics: Adaptive time-stepping allows for the simulation of different timescales, primarily as a function of climate conditions in wet season for short periods, in dry season for an adapted period, and in transition for an intermediary period, leading to a computational benefit in terms of calculation time. Canvas represents the system’s graphic interface, for which a number of improvements have been proposed from a structural perspective. Each input node is a component of the UWC, not a system of the UWC. Furthermore, the connections or flow movements are represented by a color that characterizes the type of flow. The configuration of input parameters allows for the modification, copy, and elimination of these parameters (among others) by the user quickly and easily. Finally, it has network nesting, a characteristic that allows for the linking of different spatial scales of the system through subnetworks, which symbolize a node containing all previously established connections.
Dance4Water is based on the Virtual Infrastructure Benchmarking (VIBe) model presented by Sitzenfrei et al. [ 118 , 119 ]. This model creates virtual urban environments that include digital models, water bodies, land use, and urban infrastructure (e.g., sewage and drinking-water distribution systems) [ 123 , 124 , 130 , 131 ]. This model follows a stochastic approach, using multiple layers of cellular automata [ 118 ]. This software presents three linked modules to simulate the entire UWC. The first module, the Urban Development Module (UDM), encompasses actions that create territorial development resulting from population increase or urban-development plans at an annual scale. For this purpose, UrbanSim software was created [ 35 ]. The second is the biophysical module (BMP) [ 122 ], which represents UWC-infrastructure components and performance. Two submodules—city and water-system generator (infrastructure) and performance assessment (performance)—were created as part of the second module. The performance submodule uses SWMM (Storm Water Management Model) software for hydraulic and hydrodynamic calculations that are subsequently included in the model [ 117 ]. The third and final module is the Societal Transition Module (STM) designed for simulating the extent and impact of society on the UWC; the STM also serves as a tool for strategic planning [ 117 , 120 , 132 ].
DUWSiM integrates multiple models, namely climate (LARS-WG stochastic weather generator), land use (MOLAND—Monitoring Land Use/Cover Dynamics), and water balance in urban areas (DUWSiM WB—Dynamic Urban Water Simulation Model Water Balance). This integration is done via a database consisting of different input data, such as socioeconomic, geographical, physical-infrastructure, demand, and climate factors. This database provides data for the water-balance model, which simulates the daily flow of movement of UWC processes (drinking-water supply, rainwater, wastewater, evapotranspiration, percolation, etc.). DMM was developed using the MS-Excel platform, which facilitates user adaptation of the interface. Excel lets the user enter different input values and create scenarios by modifying sustainability indicators; in Excel, calculations are performed in intermediary files. The program has four files: (1) notes, assumptions, and guidelines; (2) user control via an input data file (entered or calculated), for which values display particular characteristics of the study area and concomitant consumption; (3) annual files (annual-scale calculations), which are input data consisting of nine independent spreadsheets that are components of the UWC; and (4) comparison of final results (this spreadsheet presents absolute or relative indicators of the performance of economic, social, environmental, and functional factors).
MIKE URBAN independently (in parallel) simulates water supply, drainage, and wastewater sewage; this software couples 1-D sewer modeling with 2-D overland-flow modeling. It is integrated with the ESRI ArcGIS platform using the “geo-database” concept [
95
]. This assembly uses valuable aspects of GIS, such as network topologies, global-reference coordinates, labels, spatial analysis, and graphical functions, resulting in layers and the ability to connect layers for optimal management [
98
]. Sobek-Urban is an integrated software package consisting of 1DFLOW Rural-Urban-River, Overland flow-2D, Rainfall-runoff (RR), 1DWAQ Water quality and Real-time-Control (RTC). The 1-D flow solves the Saint-Venant equations by means of a finite difference, and the 2-D flow uses a rectangular grid and finite difference framework [
133
].
4. Application of UWC Models
The application of these models has led to mixed results, perhaps a result of these models’ use for myriad purposes including: resource administration, management, and decision-making in the development of cities to manage and control hydric resources in terms of quality and quantity, contamination control with relation to natural resources, infrastructure planning, public-policy evaluation, financial management, and evaluation of socioeconomic development [ 134 ]. Case studies are discussed below.
Firstly, as can be seen in
Table 3
, the primary use of these tools is for calculating hydric balances because such balances allow researchers to determine flows and/or volumes of different types of water in the UWC. These flows are crucial insofar as they represent the cycle’s main inputs and outputs [
38
]. In turn, this facilitates an understanding of water dynamics in urban areas and facilitates the identification of the degree of interrelation during different UWC processes. In addition, the aforementioned balances are an essential source when determining modifications of the hydrological cycle, for the is the most disruptive force with respect to the cycle’s equilibrium [
261
]. In light of the realities of disruption, balances let decision-makers create scenarios for adequate hydric resource management. Mass balances, for their part, are used to estimate contaminant loads because of the direct relationship between water flows and contaminants [
171
].
Table 3. Case studies involving UWC software or approaches.
Secondly, Table 3 demonstrates multiple model applications for the management, calculation, and determination of drinking-water supply and water demand. This is attributable to the effort to decentralize water supply and establish alternate or unconventional sources to meet populations’ water needs without ignoring environmental constraints [ 12 ]. Research has found that urban areas face problems related to inequality, in-home contamination, economy, and infrastructure [ 262 ]. Consequently, within the most commonly employed practices, new sources include: rainwater, reuse of gray water and wastewater, desalinization, and groundwater. To address the aforementioned aspects, many scenarios proposed in the literature include the harvesting of rainwater and the reuse of gray water. This allows for the conservation of hydric resources, the reduction of runoff volume, and the reduction of wastewater and corresponding contaminant loads [ 263 , 264 , 265 , 266 , 267 ].
Thirdly, there is the selection and evaluation of best management practices, which are structural and nonstructural actions aimed at minimizing the impact of urbanization on the natural hydrological cycle [
268
]. These practices offer significant potential for UWC management insofar as they can be applied to any part of the UWC, such as reduction of water demand, management of rainwater, reduction of flooding, control of contamination, mitigation of environmental damage, evaluation of ecological possibilities, and reduction of infrastructure investment [
269
]. Many other applications are affected by the kind of software and the needs proposed by the authors (e.g., hydraulic and flooding applications).
Finally, the software MIKE URBAN and Sobek Urban are primarily used for flooding control, evaluation, monitoring, and optimization of drainage/sewage systems—which is a function of their inclusion of hydraulic and hydrological calculations. It is important to add that both software programs (notably the former) have been heavily employed around the world, although a few applications have involved all UWC components.
Of the more infrequent approaches, social factors are salient. The primary reason for the infrequent inclusion of social factors stems from the fact that most software programs and approaches are focused on technical solutions. Additionally, the inclusion of social factors can be quite complex, a reflection of social dynamics, practices, behaviors, and expectations with regard to water use [
270
]. This complexity may serve as a barrier to the determination of effective water-management strategies [
271
]. That said, to some extent, failing to include social factors generates a disconnect, for there is an undeniable relationship between society and the UWC’s technical elements (
Sociotechnical
, see Sofoulis [
272
]). Thus, there is a glaring need to develop tools that encompass social and economic factors (i.e., a more comprehensive engagement with these factors would improve UWC planning). As posited by Koutiva and Makropoulos [
273
], the use of artificial intelligence has produced tools that can be used for social and economic factors as well as water management. According to the two authors, the most frequently employed artificial-intelligence tools include agent-based modeling, artificial neural networks, Bayesian belief networks, and systems dynamics modeling.
The most frequently used models are Urban Volume and Quality (UVQ), Aquacycle, and MIKE URBAN; each accounted for more than 15 experiments in the literature. In fact, these models were used in more than the 50% of all experiments. After these three, water-balance and life-cycle analyses are next, with each accounting for 10 to 14 experiments (22% of all experiments). UWOT, WaterCress, Urban Metabolism, UrbanCycle, Sobek-Urban and Dance4Water accounted for 5 to 9 experiments each (18% of all experiments). Finally, the remaining models accounted for 1 to 4 experiments each (10% of all experiments).
In terms of year ranges, 60% of reported experiments were conducted between 2012 and 2016. Between 2009 and 2011, this percentage was 20%. Between 2006 and 2008, the percentage was 11%, and between 2003 and 2005, the percentage was 9%. This progressive increase can be attributed to the advent of the concept of Integrated Urban Water Management (IUWM) in the mid-1990s, though IUWM was not widely discussed and adopted until 2000 [ 268 ].
Looking at the geographical distribution of these experiments (see Figure 2 ; darker shading represents more experiments and lighter shading less experiments), the applications of these tools or methodologies have been carried out in a variety of countries. However, Australia has the most applications (41 revealed in the literature review). In that country, Aquacycle, UVQ, WaterCress, Hydro Planner, Urban Cycle, and Dance4Water were the most commonly used software programs. These programs were developed by public and private entities. After Australia, the country with the most frequent use of relevant experiments was Denmark, which conducted experiments using MIKE URBAN, a tool developed and evaluated in the Scandinavian country. The United Kingdom (most commonly using UVQ) and Greece (using Aquacycle and, above all, UWOT, which was developed in Greece) each had six experiments. Other countries, such as South Korea and the United States, had four and five experiments, respectively. There were also 24 countries with less than three recorded experiments each (including countries from continents such as Africa, Latin America, Asia, and Europe).
Figure 2. Experiments reported by country.
Despite the potential for the management and administration of UWC, it is important to mention that, by and large, the use of these tools has been concentrated in academia rather than in decision-making environments. This is explained by a number of different factors—related to institutions, politics, society, economics, laws, and organizations—as well as the absence of institutionality, lack of knowledge regarding relevant tasks, and lack of long-term vision, among others [ 274 , 275 ]. However, academics’ role in this situation cannot be overlooked: Most projects related to these models are focused on obtaining data rather than constructing bridges between investigation and social application. For instance, there is scant direct application of these models in industrial sectors. As per Abbott [ 276 ], this is because the needs within academia and within industrial sectors do not always coalesce. That said, the failure to implement the solutions proposed by UWC models hinders possible determination of the level of population acceptance, which is crucial for establishing the success (or lack thereof) of strategies because many of the experiments discussed herein are based on the decentralization of services and applications in situ [ 277 ].
5. Conclusions
Urban water management is a globally urgent problem and entails a host of pertinent issues related to supplying drinking water, handling wastewater and rainwater, reducing environmental impact and waterborne diseases, and mitigating operational and infrastructure costs. Together, these issues pose a challenge to public administration. A deeper understanding would allow for a holistic view of the UWC as well as the development of appropriate management strategies for water in urban areas. In addition, this deeper understanding would help explain the dynamics and interactions of different processes in the UWC.
The use of innovative software and approaches has gained recognition as an effective means for meeting the aforementioned challenges. Combining software and other approaches allows one to create a decision-making tool that integrates technical, environmental, economic, and social concepts to quickly visualize different trends or possible scenarios. The reliance on these tools has increased notably over the last 15 years, with examples ranging from hydric balances to artificial intelligence, with spatial scales from individual properties to entire regions, and timescales from daily to annual. These advances have helped incorporate as many UWC processes as possible.
These software programs or models have facilitated different applications’ employment as a vehicle for determining new sources of supply, contamination control, reduction of the effects of urbanization on the hydrological cycle, and efficient water use, among others. In so doing, these tools have greatly enhanced the capacity for sustainable alternatives and boosted the ability to efficiently manage financial and hydric resources.
The vast majority of the experiments revealed by the literature review touched on technical solutions or regulations, for the models/approaches studied were shown to be geared towards calculating water balances and the concentration or contaminant loads as water passes through the cycle. Nevertheless, social and ecological factors should not be forsaken if models and their responses are to be more comprehensive, especially in light of the close link between these factors and the UWC [ 5 , 278 ].
Even though most of these tools are available online or by request from the authors, their application has been centered in Australia and Europe, which is primarily explained by two facts. First, model development, which is only done in these two regions, leads to their application in different fields within these regions. Second, research and policies in these regions related to water management in urban areas have gained traction due to the need to conserve water resources or due to the lack of such resources.
The results described in the articles and academic theses reviewed herein demonstrate a high potential for management of the UWC, though its greatest contribution currently is academic; the approaches have not been applied as a decision-making tool by public or governmental entities. This confinement to academia is a serious obstacle to the implementation of the models for economic, social, and environmental means.
Although there are direct relationships between energy systems and different UWC processes, several models and software programs do not include these systems, for the primary objective of these tools is to determine strategies for managing water volume. Yet, many of these tools, when not designed from a holistic perspective, may directly impact infrastructure-investment costs [ 50 ] and/or lead to deleterious environmental effects in the form of greenhouse gases or high energy consumption [ 52 , 279 , 280 ].
Moreover, it is crucial to reinforce the usefulness of these models to evaluate the acceptance of the results obtained and thereby solidify social appropriation of this knowledge by means of strategies that promote implementation in decision-making contexts.
Lastly, this review allows different public and private entities to identify opportunities to use the software and models discussed herein for the management of urban water resources. Doing so would pave the way for the optimization of cities’ economic investments and ensure efficiency of the systems comprising the UWC as well as an environmentally conscious urban development that is future-oriented.
Conflicts of Interest
The authors declare no conflicts of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
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Figure 1. Urban Water Cycle (UWC). Adapted from [ 58 ].
Figure 2. Experiments reported by country.
Table 1. Internal and external factors of the UWC.
UWC Part UWC Component Internal Factor External Factor Source Water supply subsystem Raw-water intake Population, availability, techniques Climate, environment, economy, geography [ 61 , 62 , 63 , 64 , 65 ] Water treatment Population, techniques, quantity, quality, energy Climate, economy, regulations, geography Storage Population, techniques, energy Climate, environment, economy, geography Water supply distribution Population, techniques, quantity, quality, energy Economy, geography, society, culture, environment, regulations Water demand Water consumption Population, weather, population density, land use, equipment, economy Education, territory growth, culture, regulations [ 66 , 67 , 68 , 69 , 70 , 71 ] Wastewater and stormwater subsystem Collection Population, weather, population density, land use, equipment geography, hydraulics, regulations, public health, environment, economy Society, culture, education [ 17 , 72 , 73 , 74 , 75 , 76 , 77 ] Treatment Land use, equipment, geography, regulations, public health, quality, quantity, environment, economy, energy Society, culture, education [ 52 , 53 , 78 , 79 , 80 , 81 ] Receiving Water Equipment, geography, regulations, public health, quality, quantity, ecology, environment, economy Territory growth, type of water-receiving body [ 58 , 82 , 83 , 84 , 85 , 86 ]
Table 2. Description of UWC models.
Model Type of Model Development Team or Institution Country Spatial Scale Time Scale Platform Support Software Simulated Processes Model Emphasis Software Link Source H Hd Hy C S Aquacycle IUWCMs CRCCH Australia Pr, Ne, GNe. Daily Windows X X X Hydric balance. www.toolkit.net.au [ 29 , 87 ] UVQ IUWCMs CSIRO Australia Pr, Ne, GNe, Cit. Daily Windows X X X X Hydric and contaminants balance. [ 30 , 88 , 89 , 90 , 91 ] MIKE URBAN IUWCMs DHI Denmark Ne, GNe, Cit. Hourly and Daily Windows ArcGIS, MOUSE, SWMM5, EPANET2 MIKENET X X X X X Hydrological balance, hydraulic calculations. www.mikepoweredbydhi.com [ 92 , 93 , 94 , 95 , 96 , 97 , 98 ] UWOT IUWCMs The urban water management and hydroinformatics team of the School of Civil Engineering, NTUA Greece IndD, Pr, Ne, GNe, Cit. 10 min to monthly Windows, Linux, Matlab (for optimization) and eLearning platform X X X X Optimization of the development of strategies for UWC management www.watershare.eu [ 9 , 32 , 99 , 100 , 101 ] WaterCress IUWCMs Richard Clark and David Cresswell Australia Pr, Cat. Daily Windows X X X X Hydric and contaminant balance. www.waterselect.com.au [ 25 , 102 , 103 , 104 , 105 ] Sobek-Urban IUWCMs Daltares The Netherlands Cat, Ne, GNe Cit. Minutes and seconds Windows GIS X X X X X Hydrological balance, hydraulic calculations, real-time control, water quality. www.deltares.nl [ 106 ] Hydro Planner IUWCMs CSIRO Australia Ne, Cit, Cat. Daily Windows REsource ALlocation Model (REALM), E2 X X X X Hydric balance. [ 28 , 107 , 108 ] WaterMet2 IUWCMs Exeter University and NTUA Greece and UK Pr, GNe, Ci. Daily Windows X X X X Hydric and contaminants balance, energy, greenhouse gases, chemical material balance. www.emps.exeter.ac.uk [ 24 , 109 , 110 , 111 , 112 ] UrbanCycle IUWCMs University of Newcastle Australia Pr, GNe, Cit. Hourly, daily FORTRAN DRIP, Probabilistic Demand Model X X X Hydric balance. [ 20 , 113 , 114 , 115 ] Urban Developer IUWCMs CRCCH Australia Pr, GNe, Cit. Hourly, daily Windows MUSIC X X X Hydric balance. www.ewater.org.au [ 33 , 116 ] Dance4Water IUWSMs Monash University, University of Innsbruck, Centre for Water Sensitive Cities and Melbourne Water Australia and Austria Pr, Ne, GNe, Cit. Daily Virtual, Web SWMM, UrbanSim X X X X Hydrological balance, hydraulic calculation, UWC-related social factors www.dance4water.org [ 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 ] DUWSiM IUWCMs Lars Willuweit and John J. O’Sullivan University College Dublin Ireland Ne, GNe, Cit. Daily Microsoft Excel LARS-WG, MOLAND X X X X Hydric and contaminant balance. [ 36 ] WaND-OT1 IUWCMs University of Exeter UK IndD, Pr, Ne. Daily Matlab Symulink, Microsoft Excel (VBA) X X X Hydric balance. [ 32 ] DMM IUWCMs or IUWSMs Norwegian University of Science and Technology Norway Ne, Cit. Hourly, daily, monthly, yearly Microsoft Excel X X X Hydric balance energy, greenhouse gases. [ 34 ] Water Balance * IUWCMs or IUWSMs N/A N/A Pr, Ne, GNe, Cit. Hourly, daily, monthly, yearly SIMBOX, Matlab, Phyton, R, Microsoft Excel (VBA), ABIMO, X X X X Hydric and contaminant balance, energy, greenhouse gases, chemical and material balance. [ 26 , 38 , 39 ] Urban Metabolism * IUWCMs or IUWSMs N/A N/A Pr, Ne, GNe, Cit. Hourly, daily, monthly, yearly Excel (VBA), Matlab, Phyton, R. X X X X Hydric and contaminant balance, energy, greenhouse gases, chemical and material balance. [ 31 , 125 , 126 , 127 ] LCA * IUWCMs or IUWSMs N/A N/A Pr, Ne, GNe, Cit. Hourly, daily, monthly, yearly Matlab, Phyton, R, Symulink, Microsoft Excel (VBA), SIMAPRO, GaBi4 X X X X Hydric and contaminant balance, energy, greenhouse gases, chemical and material balance. [ 27 , 128 , 129 ]
Notes: H = hydrological, Hd = hydraulic, Hy = UWC hydric components, C = contaminants, S = strategies for structural management and/or nonstructural action, BMP = best management practices, DRIP = Disaggregated Rectangular Intensity Pulse, VIBe = Virtual Infrastructure Benchmarking, CRCCH = Cooperative Research Centre of Catchment Hydrology, CSIRO = Commonwealth Scientific Industrial and Research Organisation, DHI = Danish Hydraulic Institute, Pr = Property, Ne = neighborhood, GNe = group of neighborhoods, Cit = city, IndD = Individual-dwelling water uses, Cat = catchment, Dance4Water = Dynamic Adaptation for eNabling City Evolution for Water, DUWSiM = Dynamic Urban Water Simulation Model, DMM = Dynamic Metabolism Model, LCA = Life Cycle Assessment, WaterCress = Water-Community Resource Evaluation and Simulation System, UWOT = Urban Water Optioneering Tool, UVQ = Urban Volume and Quality, IUWCM = Integrated Urban Water Cycle Models, IUWSMs = Integrated Urban Water System Models, N/A =Not applicable, VBA = Visual Basic for Applications. *Approach does not refer to specific software.
Table 3. Case studies involving UWC software or approaches.
Model Case Study Country Type of Application WHB C SDDW EISW EIGW RC WWT BMP H F RT RR RGW EGG SF Aquacycle [ 135 ] USA X X [ 136 ] Egypt X X X X [ 137 ] Israel X X X X X [ 138 ] Australia X X X X [ 139 ] Australia X [ 140 ] South Korea X [ 141 ] South Korea X X X X [ 142 ] Australia X X X X [ 143 ] Germany X X X X [ 144 ] France X X X X [ 145 ] Ghana X X X X X [ 146 ] Australia X X [ 147 ] Greece X X X X X X [ 39 ] Australia X X [ 148 ] Spain X X X [ 149 ] South Korea X X X X [ 150 , 151 ] Australia X [ 29 ] Australia X X X X Urban Volume Quality (UVQ) [ 152 ] Australia X X X X X X [ 153 ] Australia X X X X X [ 154 ] Australia X X X X X X [ 155 ] Vanuatu X X X X X X X X [ 156 ] Australia X X X X X X [ 157 ] Austria X X [ 158 ] Australia X X X [ 159 ] Mexico X X X X X [ 160 ] South Korea X X X X [ 161 ] Australia X X X X [ 162 ] Australia X X X X [ 163 ] UK X X X [ 164 ] Australia X X [ 142 ] Australia X X X X X X X [ 165 ] Slovenia X X X [ 166 ] Australia X X X X X [ 167 ] UK X X X [ 168 ] Germany X X X [ 169 ] Slovenia X X X [ 170 ] UK X X X X X X X [ 171 ] Germany X X X X X X MIKE URBAN [ 172 ] Denmark X X [ 173 ] India X X [ 174 ] Denmark X X X [ 175 ] Denmark X X [ 176 ] Denmark X X [ 177 ] India X [ 178 ] Denmark X X [ 179 ] Denmark X X [ 96 ] Lithuania X [ 180 ] Denmark X X [ 181 ] Germany X X [ 182 ] Denmark X X [ 183 ] Sweden X [ 184 , 185 ] Denmark X X [ 185 ] Denmark X [ 186 , 187 ] Bangladesh X X [ 188 ] USA X [ 189 ] Denmark X X [ 190 ] Denmark X X [ 191 ] Australia X X [ 192 ] Japan X Urban Water Optioneering Tool (UWOT) [ 193 ] Greece X [ 194 ] Spain X X X X X [ 195 ] Greece X X [ 196 ] Greece X X X X [ 197 ] Hypothetical X X X X X X X [ 198 ] Greece X X X X X [ 199 , 200 ] Greece X [ 201 ] Hypothetical X X X X X X X [ 202 ] Hypothetical X X X X X X WaterCress [ 203 ] Australia X X [ 204 ] Australia X X [ 205 ] Australia X [ 105 ] Australia X X X X [ 206 ] Australia X [ 104 ] Australia X X X [ 207 ] Australia X X X [ 208 ] Australia X Sobek-Urban [ 209 ] Singapore X X [ 210 ] The Netherlands X [ 211 ] The Netherlands X X [ 212 ] The Netherlands X [ 213 ] The Netherlands X [ 214 ] Singapore X [ 215 ] The Netherlands X Hydro Planner [ 216 ] Australia X X X X X X X X X [ 217 ] Australia X X X X [ 108 ] Australia X X WaterMet2 [ 218 ] Iran X X X X X X [ 219 ] Italia X X [ 220 ] Norway X [ 221 ] Unspecified X X [ 222 ] Unspecified X X X X X X X X [ 112 ] Norway X [ 223 ] Iran X X [ 24 ] Norway X X X X X X X UrbanCycle [ 113 ] Hypothetical X X X X X [ 224 ] Australia X X [ 225 ] Australia X X X [ 226 ] Australia X X [ 227 ] Australia X Urban Developer [ 228 ] Hypothetical X Dance4Water [ 229 ] Austria X X X [ 230 ] Australia X X X [ 121 ] Australia X [ 122 ] Australia X X [ 231 ] Australia X X WaND-OT1 [ 32 ] UK X X X X X Dynamic Metabolism Model (DMM) [ 220 ] Norway X [ 34 , 232 ] Norway X X X DUWSiM [ 233 , 234 ] Ireland X [ 235 ] Australia X X X X X Water Balance [ 236 ] Portugal X X X X [ 237 ] Switzerland X X [ 238 ] USA X [ 239 ] Cyprus X X X [ 240 ] Switzerland X X [ 241 ] USA and Canada X X [ 26 ] Australia X [ 10 ] UK X X X X [ 242 ] Germany X [ 243 ] India X X [ 244 ] Colombia X X X X X Urban Metabolism [ 245 ] Colombia X [ 246 ] UK X X [ 247 ] China X [ 248 ] Canada X [ 249 ] China X [ 250 ] Canada X [ 251 ] China X [ 252 ] USA X X Life Cycle Assessment (LCA) [ 253 ] Hypothetical X X [ 254 ] Spain X X X X X [ 255 ] Spain X X [ 256 ] Norway X X [ 59 ] Norway X [ 257 ] Australia X X X X X [ 258 ] Egypt X [ 259 ] Australia X X [ 260 ] Sweden X X
Notes: WHB = Water or hydrology balance of UWC for managing rainwater or wastewater, C = UWC contaminants, SDDW = Supply and demand of drinking water, EISW = Environmental impact on surface hydric resources, EIGW = Environmental impact on groundwater resources, RC = Rainwater contamination, WWT = Wastewater treatment, BMP = Best management practices, H = Hydraulic, F = Flooding, RT = Rainwater treatment, RR = Rainwater reuse, RGW = Reuse of gray water and sewage, EGG = Energy and greenhouse gases, SF = Social factors.
Peña-Guzmán, C.A.; Melgarejo, J.; Prats, D.; Torres, A.; Martínez, S.
Urban Water Cycle Simulation/Management Models: A Review. Water 2017, 9, 285.
https://doi.org/10.3390/w9040285
AMA Style
Peña-Guzmán CA, Melgarejo J, Prats D, Torres A, Martínez S.
Urban Water Cycle Simulation/Management Models: A Review. Water. 2017; 9(4):285.
https://doi.org/10.3390/w9040285
Chicago/Turabian Style
Peña-Guzmán, Carlos Andrés, Joaquín Melgarejo, Daniel Prats, Andrés Torres, and Sandra Martínez.
2017. "Urban Water Cycle Simulation/Management Models: A Review" Water9, no. 4: 285.
https://doi.org/10.3390/w9040285
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Peña-Guzmán, C.A.; Melgarejo, J.; Prats, D.; Torres, A.; Martínez, S.
Urban Water Cycle Simulation/Management Models: A Review. Water 2017, 9, 285.
https://doi.org/10.3390/w9040285
AMA Style
Chicago/Turabian Style
Peña-Guzmán, Carlos Andrés, Joaquín Melgarejo, Daniel Prats, Andrés Torres, and Sandra Martínez.
2017. "Urban Water Cycle Simulation/Management Models: A Review" Water9, no. 4: 285.
https://doi.org/10.3390/w9040285
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The nature of color: New formula to calculate hue improves accuracy of color analysis | EurekAlert! Science News
Color is crucial in ecological studies, playing an important role in studies of flower and fruit development, responses to heat/drought stress, and plant-pollinator communication. But, measuring color variation is difficult, and available formulas sometimes give misleading results. An improved formula to calculate hue (one of three variables characterizing color), published in the March issue of Applications in Plant Sciences, corrects the popular segment classification method of color quantification and will provide accurate color analysis values.
Formula is key for biological studies involving color analysis, provides correction to segment classification method of color quantification
Botanical Society of America
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A stroll through the produce aisle in your local grocery store exhibits a plethora of vivid colors. From opposing hues, like red apples next to green celery, to subtler variations, such as light to dark purple grapes, every color seems to hold its own unique attraction. Is there a way to precisely measure these hundreds of colors? This is a crucial question for scientists studying the biological importance of color in nature, but measuring color is much more challenging than measuring other characteristics, like size or weight. In recent work, University of Colorado researcher Stacey Smith presents one potential solution: a new formula to calculate hue.
"Previous formulas to measure color only worked for a portion of the color space and could give quite misleading results. For example, both reds and yellow-greens would end up with the same hue value," says Smith. "I felt there was a need to provide a more accessible explanation of this method for quantifying color." The new formula will enable researchers to obtain correct hue values for any color of interest. A full description is available for free viewing in the March issue of
Applications in Plant Sciences
( http://www. bioone.
org/ doi/ pdf/ 10. 3732/ apps. 1300088
).
Interestingly, measuring color is actually a matter of analyzing light waves. When an object is exposed to light, its molecules absorb certain wavelengths and the appearance of color results from the unabsorbed light, which is reflected and filtered through the eye's retina. The ability of living organisms to reflect wavelengths of different portions of the color spectrum results in diverse displays like that of the grocery produce section. More importantly, color is involved in a wide range of biological phenomena. Flowers attract pollinators, fruits attract seed-dispersing animals, plants express stress responses, and organisms communicate with each other in many ways via color. Quantifying these variations is a crucial component of research.
"Color is one of the most conspicuous aspects of biological diversity and often carries adaptive significance," explains Smith, who is interested in understanding how and why new colors evolve in nature. When her research was limited by faulty hue values from previous formulas, she needed a new method to overcome this limitation.
Hue, or the type of color, is one of three components utilized in the segment classification method, one of the most popular systems for defining color. The other two components are brightness (lightness/darkness) and chroma (intensity/saturation). Together, these three variables offer a numeric way to describe the light reflected by an object. To calculate hue, brightness, and chroma, researchers use data from an instrument that can detect reflected light at different wavelengths--a spectrometer.
Using a spectrometer, a specimen is exposed to full white light and the reflected light waves are displayed as a curve on a graph. The size and shape of the curve, called a reflectance curve, is unique to each color. With red to violet wavelengths on the x-axis and 0-100% reflectance on the y-axis, a higher curve at a particular wavelength signifies an increased amount of light reflected at that portion of the spectrum. Researchers use mathematical formulas to calculate values for chroma, hue, and brightness from the reflectance curves.
Smith thoroughly tested the original formulas, developed in 1990 by scientist J. A. Endler, with color samples from the famous 1976
Munsell Book of Color
to pinpoint the specific regions where incorrect values occurred. What she found was an error in the way the original formulas converted Cartesian (x and y) coordinates to polar coordinates. Her results showed that the signs of the Cartesian coordinates, not just the coordinates themselves, were needed to calculate correct hue values.
"Refreshing my knowledge of polar and Cartesian coordinate systems was a challenging aspect of this study, but I'm sure my high school math teacher would be glad that some of those lessons came in handy!" says Smith.
By identifying the weak points of the original color calculations and making necessary changes, Smith's work offers scientists a strong tool for including color analysis in their research. This formula will be critical for scientists studying flower and fruit development, plant nutrient deficiencies, responses to heat and drought stress, and other biological phenomena that result in visible color changes.
"I hope that this new method and the accompanying description will provide users with confidence that they are obtaining the correct values. Any downstream analyses involving those results or any meta-analyses of studies using the segment classification method will rely on the quality of those initial calculations," says Smith.
###
Stacey D. Smith. 2014. Quantifying color variation: Improved formulas for calculating hue with segment classification.
Applications in Plant Sciences
2(3): 1300088. doi:10.3732/apps.1300088.
Applications in Plant Sciences
( APPS
) is a monthly, peer-reviewed, open access journal focusing on new tools, technologies, and protocols in all areas of the plant sciences. It is published by the
Botanical Society of America
, a nonprofit membership society with a mission to promote botany, the field of basic science dealing with the study and inquiry into the form, function, development, diversity, reproduction, evolution, and uses of plants and their interactions within the biosphere. APPS
is available as part of BioOne's Open Access collection
.
For further information, please contact the APPS
staff at apps@botany.org
.
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More on this News Release
The nature of color: New formula to calculate hue improves accuracy of color analysis
Botanical Society of America
Journal
American Journal of Botany
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National Science Foundation
Keywords
BIODIVERSITY BIOLOGY
DEVELOPMENTAL/REPRODUCTIVE BIOLOGY
ECOLOGY/ENVIRONMENT EVOLUTION
FOOD/FOOD SCIENCE NUTRITION/NUTRIENTS
PLANT SCIENCES PLANT SCIENCES
POPULATION BIOLOGY
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Latest content added for The Portal to Texas History Title: The Pony Express (Carthage, Texas) 1948-current
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(Carthage, Tex.), Vol. 53, No. 2, Ed. 1 Thursday, February 28, 2002" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 2, Ed. 1 Thursday, February 28, 2002" src="https://texashistory.unt.edu/ark:/67531/metapth591945/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 53, No. 2, Ed. 1 Tuesday, October 8, 2002 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591868/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591868/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 2, Ed. 1 Tuesday, October 8, 2002" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 2, Ed. 1 Tuesday, October 8, 2002" src="https://texashistory.unt.edu/ark:/67531/metapth591868/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 53, No. 3, Ed. 1 Friday, March 29, 2002 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591937/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591937/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 3, Ed. 1 Friday, March 29, 2002" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 3, Ed. 1 Friday, March 29, 2002" src="https://texashistory.unt.edu/ark:/67531/metapth591937/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 53, No. 3, Ed. 1 Tuesday, October 29, 2002 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591822/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591822/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 3, Ed. 1 Tuesday, October 29, 2002" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 3, Ed. 1 Tuesday, October 29, 2002" src="https://texashistory.unt.edu/ark:/67531/metapth591822/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 53, No. 4, Ed. 1 Tuesday, November 19, 2002 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591874/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591874/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 4, Ed. 1 Tuesday, November 19, 2002" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 4, Ed. 1 Tuesday, November 19, 2002" src="https://texashistory.unt.edu/ark:/67531/metapth591874/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 53, No. 4, Ed. 1 Wednesday, April 17, 2002 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591915/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591915/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 4, Ed. 1 Wednesday, April 17, 2002" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 4, Ed. 1 Wednesday, April 17, 2002" src="https://texashistory.unt.edu/ark:/67531/metapth591915/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 53, No. 5, Ed. 1 Thursday, February 6, 2003 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591853/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591853/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 5, Ed. 1 Thursday, February 6, 2003" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 5, Ed. 1 Thursday, February 6, 2003" src="https://texashistory.unt.edu/ark:/67531/metapth591853/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 53, No. 5, Ed. 1 Tuesday, May 7, 2002 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591829/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591829/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 5, Ed. 1 Tuesday, May 7, 2002" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 5, Ed. 1 Tuesday, May 7, 2002" src="https://texashistory.unt.edu/ark:/67531/metapth591829/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 53, No. 6, Ed. 1 Saturday, March 1, 2003 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591855/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591855/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 6, Ed. 1 Saturday, March 1, 2003" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 6, Ed. 1 Saturday, March 1, 2003" src="https://texashistory.unt.edu/ark:/67531/metapth591855/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 53, No. 7, Ed. 1 Thursday, May 1, 2003 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591778/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591778/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 7, Ed. 1 Thursday, May 1, 2003" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 7, Ed. 1 Thursday, May 1, 2003" src="https://texashistory.unt.edu/ark:/67531/metapth591778/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 54, No. 1, Ed. 1 Tuesday, October 28, 2003 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591849/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591849/"><img alt="The Pony Express (Carthage, Tex.), Vol. 54, No. 1, Ed. 1 Tuesday, October 28, 2003" title="The Pony Express (Carthage, Tex.), Vol. 54, No. 1, Ed. 1 Tuesday, October 28, 2003" src="https://texashistory.unt.edu/ark:/67531/metapth591849/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 54, No. 2, Ed. 1 Tuesday, December 16, 2003 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591927/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591927/"><img alt="The Pony Express (Carthage, Tex.), Vol. 54, No. 2, Ed. 1 Tuesday, December 16, 2003" title="The Pony Express (Carthage, Tex.), Vol. 54, No. 2, Ed. 1 Tuesday, December 16, 2003" src="https://texashistory.unt.edu/ark:/67531/metapth591927/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 54, No. 3, Ed. 1 Thursday, February 26, 2004 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591839/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591839/"><img alt="The Pony Express (Carthage, Tex.), Vol. 54, No. 3, Ed. 1 Thursday, February 26, 2004" title="The Pony Express (Carthage, Tex.), Vol. 54, No. 3, Ed. 1 Thursday, February 26, 2004" src="https://texashistory.unt.edu/ark:/67531/metapth591839/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 55, No. 1, Ed. 1 Tuesday, October 5, 2004 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591760/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591760/"><img alt="The Pony Express (Carthage, Tex.), Vol. 55, No. 1, Ed. 1 Tuesday, October 5, 2004" title="The Pony Express (Carthage, Tex.), Vol. 55, No. 1, Ed. 1 Tuesday, October 5, 2004" src="https://texashistory.unt.edu/ark:/67531/metapth591760/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 55, No. 3, Ed. 1 Friday, December 3, 2004 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591904/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591904/"><img alt="The Pony Express (Carthage, Tex.), Vol. 55, No. 3, Ed. 1 Friday, December 3, 2004" title="The Pony Express (Carthage, Tex.), Vol. 55, No. 3, Ed. 1 Friday, December 3, 2004" src="https://texashistory.unt.edu/ark:/67531/metapth591904/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 55, No. 4, Ed. 1 Thursday, February 24, 2005 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591952/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591952/"><img alt="The Pony Express (Carthage, Tex.), Vol. 55, No. 4, Ed. 1 Thursday, February 24, 2005" title="The Pony Express (Carthage, Tex.), Vol. 55, No. 4, Ed. 1 Thursday, February 24, 2005" src="https://texashistory.unt.edu/ark:/67531/metapth591952/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 55, No. 5, Ed. 1 Monday, March 28, 2005 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591828/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591828/"><img alt="The Pony Express (Carthage, Tex.), Vol. 55, No. 5, Ed. 1 Monday, March 28, 2005" title="The Pony Express (Carthage, Tex.), Vol. 55, No. 5, Ed. 1 Monday, March 28, 2005" src="https://texashistory.unt.edu/ark:/67531/metapth591828/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 55, No. 6, Ed. 1 Tuesday, May 10, 2005 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591888/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591888/"><img alt="The Pony Express (Carthage, Tex.), Vol. 55, No. 6, Ed. 1 Tuesday, May 10, 2005" title="The Pony Express (Carthage, Tex.), Vol. 55, No. 6, Ed. 1 Tuesday, May 10, 2005" src="https://texashistory.unt.edu/ark:/67531/metapth591888/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 56, No. 1, Ed. 1 Monday, September 12, 2005 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591755/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591755/"><img alt="The Pony Express (Carthage, Tex.), Vol. 56, No. 1, Ed. 1 Monday, September 12, 2005" title="The Pony Express (Carthage, Tex.), Vol. 56, No. 1, Ed. 1 Monday, September 12, 2005" src="https://texashistory.unt.edu/ark:/67531/metapth591755/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 56, No. 2, Ed. 1 Friday, September 23, 2005 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591947/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591947/"><img alt="The Pony Express (Carthage, Tex.), Vol. 56, No. 2, Ed. 1 Friday, September 23, 2005" title="The Pony Express (Carthage, Tex.), Vol. 56, No. 2, Ed. 1 Friday, September 23, 2005" src="https://texashistory.unt.edu/ark:/67531/metapth591947/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 56, No. 3, Ed. 1 Monday, October 31, 2005 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591765/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591765/"><img alt="The Pony Express (Carthage, Tex.), Vol. 56, No. 3, Ed. 1 Monday, October 31, 2005" title="The Pony Express (Carthage, Tex.), Vol. 56, No. 3, Ed. 1 Monday, October 31, 2005" src="https://texashistory.unt.edu/ark:/67531/metapth591765/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 56, No. 4, Ed. 1 Monday, December 5, 2005 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591852/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591852/"><img alt="The Pony Express (Carthage, Tex.), Vol. 56, No. 4, Ed. 1 Monday, December 5, 2005" title="The Pony Express (Carthage, Tex.), Vol. 56, No. 4, Ed. 1 Monday, December 5, 2005" src="https://texashistory.unt.edu/ark:/67531/metapth591852/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 56, No. 5, Ed. 1 Wednesday, December 14, 2005 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591786/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591786/"><img alt="The Pony Express (Carthage, Tex.), Vol. 56, No. 5, Ed. 1 Wednesday, December 14, 2005" title="The Pony Express (Carthage, Tex.), Vol. 56, No. 5, Ed. 1 Wednesday, December 14, 2005" src="https://texashistory.unt.edu/ark:/67531/metapth591786/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 56, No. 6, Ed. 1 Thursday, February 16, 2006 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591798/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591798/"><img alt="The Pony Express (Carthage, Tex.), Vol. 56, No. 6, Ed. 1 Thursday, February 16, 2006" title="The Pony Express (Carthage, Tex.), Vol. 56, No. 6, Ed. 1 Thursday, February 16, 2006" src="https://texashistory.unt.edu/ark:/67531/metapth591798/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 56, No. 7, Ed. 1 Friday, May 12, 2006 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591744/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591744/"><img alt="The Pony Express (Carthage, Tex.), Vol. 56, No. 7, Ed. 1 Friday, May 12, 2006" title="The Pony Express (Carthage, Tex.), Vol. 56, No. 7, Ed. 1 Friday, May 12, 2006" src="https://texashistory.unt.edu/ark:/67531/metapth591744/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 57, No. 1, Ed. 1 Wednesday, October 4, 2006 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591776/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591776/"><img alt="The Pony Express (Carthage, Tex.), Vol. 57, No. 1, Ed. 1 Wednesday, October 4, 2006" title="The Pony Express (Carthage, Tex.), Vol. 57, No. 1, Ed. 1 Wednesday, October 4, 2006" src="https://texashistory.unt.edu/ark:/67531/metapth591776/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 57, No. 2, Ed. 1 Monday, October 30, 2006 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591797/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591797/"><img alt="The Pony Express (Carthage, Tex.), Vol. 57, No. 2, Ed. 1 Monday, October 30, 2006" title="The Pony Express (Carthage, Tex.), Vol. 57, No. 2, Ed. 1 Monday, October 30, 2006" src="https://texashistory.unt.edu/ark:/67531/metapth591797/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 57, No. 3, Ed. 1 Friday, December 1, 2006 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591772/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591772/"><img alt="The Pony Express (Carthage, Tex.), Vol. 57, No. 3, Ed. 1 Friday, December 1, 2006" title="The Pony Express (Carthage, Tex.), Vol. 57, No. 3, Ed. 1 Friday, December 1, 2006" src="https://texashistory.unt.edu/ark:/67531/metapth591772/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 57, No. 4, Ed. 1 Thursday, May 10, 2007 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591900/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591900/"><img alt="The Pony Express (Carthage, Tex.), Vol. 57, No. 4, Ed. 1 Thursday, May 10, 2007" title="The Pony Express (Carthage, Tex.), Vol. 57, No. 4, Ed. 1 Thursday, May 10, 2007" src="https://texashistory.unt.edu/ark:/67531/metapth591900/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 58, No. 1, Ed. 1 Thursday, November 1, 2007 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591898/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591898/"><img alt="The Pony Express (Carthage, Tex.), Vol. 58, No. 1, Ed. 1 Thursday, November 1, 2007" title="The Pony Express (Carthage, Tex.), Vol. 58, No. 1, Ed. 1 Thursday, November 1, 2007" src="https://texashistory.unt.edu/ark:/67531/metapth591898/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 58, No. 2, Ed. 1 Monday, December 10, 2007 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591863/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591863/"><img alt="The Pony Express (Carthage, Tex.), Vol. 58, No. 2, Ed. 1 Monday, December 10, 2007" title="The Pony Express (Carthage, Tex.), Vol. 58, No. 2, Ed. 1 Monday, December 10, 2007" src="https://texashistory.unt.edu/ark:/67531/metapth591863/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 58, No. 3, Ed. 1 Thursday, February 21, 2008 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591885/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591885/"><img alt="The Pony Express (Carthage, Tex.), Vol. 58, No. 3, Ed. 1 Thursday, February 21, 2008" title="The Pony Express (Carthage, Tex.), Vol. 58, No. 3, Ed. 1 Thursday, February 21, 2008" src="https://texashistory.unt.edu/ark:/67531/metapth591885/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 58, No. 4, Ed. 1 Monday, May 5, 2008 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591883/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591883/"><img alt="The Pony Express (Carthage, Tex.), Vol. 58, No. 4, Ed. 1 Monday, May 5, 2008" title="The Pony Express (Carthage, Tex.), Vol. 58, No. 4, Ed. 1 Monday, May 5, 2008" src="https://texashistory.unt.edu/ark:/67531/metapth591883/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 59, No. 1, Ed. 1 Tuesday, September 30, 2008 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591763/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591763/"><img alt="The Pony Express (Carthage, Tex.), Vol. 59, No. 1, Ed. 1 Tuesday, September 30, 2008" title="The Pony Express (Carthage, Tex.), Vol. 59, No. 1, Ed. 1 Tuesday, September 30, 2008" src="https://texashistory.unt.edu/ark:/67531/metapth591763/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 59, No. 2, Ed. 1 Thursday, October 30, 2008 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591756/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591756/"><img alt="The Pony Express (Carthage, Tex.), Vol. 59, No. 2, Ed. 1 Thursday, October 30, 2008" title="The Pony Express (Carthage, Tex.), Vol. 59, No. 2, Ed. 1 Thursday, October 30, 2008" src="https://texashistory.unt.edu/ark:/67531/metapth591756/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 59, No. 3, Ed. 1 Tuesday, November 18, 2008 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591824/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591824/"><img alt="The Pony Express (Carthage, Tex.), Vol. 59, No. 3, Ed. 1 Tuesday, November 18, 2008" title="The Pony Express (Carthage, Tex.), Vol. 59, No. 3, Ed. 1 Tuesday, November 18, 2008" src="https://texashistory.unt.edu/ark:/67531/metapth591824/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 59, No. 5, Ed. 1 Tuesday, April 21, 2009 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591789/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591789/"><img alt="The Pony Express (Carthage, Tex.), Vol. 59, No. 5, Ed. 1 Tuesday, April 21, 2009" title="The Pony Express (Carthage, Tex.), Vol. 59, No. 5, Ed. 1 Tuesday, April 21, 2009" src="https://texashistory.unt.edu/ark:/67531/metapth591789/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 59, No. 5, Ed. 1 Wednesday, March 4, 2009 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591941/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591941/"><img alt="The Pony Express (Carthage, Tex.), Vol. 59, No. 5, Ed. 1 Wednesday, March 4, 2009" title="The Pony Express (Carthage, Tex.), Vol. 59, No. 5, Ed. 1 Wednesday, March 4, 2009" src="https://texashistory.unt.edu/ark:/67531/metapth591941/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 59, No. 7, Ed. 1 Wednesday, May 13, 2009 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591750/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591750/"><img alt="The Pony Express (Carthage, Tex.), Vol. 59, No. 7, Ed. 1 Wednesday, May 13, 2009" title="The Pony Express (Carthage, Tex.), Vol. 59, No. 7, Ed. 1 Wednesday, May 13, 2009" src="https://texashistory.unt.edu/ark:/67531/metapth591750/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p> The Pony Express (Carthage, Tex.), Vol. 59, No. 7, Ed. 1 Wednesday, October 28, 2009 2015-03-03T18:33:27-06:00 https://texashistory.unt.edu/ark:/67531/metapth591890/ <p><a href="https://texashistory.unt.edu/ark:/67531/metapth591890/"><img alt="The Pony Express (Carthage, Tex.), Vol. 59, No. 7, Ed. 1 Wednesday, October 28, 2009" title="The Pony Express (Carthage, Tex.), Vol. 59, No. 7, Ed. 1 Wednesday, October 28, 2009" src="https://texashistory.unt.edu/ark:/67531/metapth591890/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
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Latest content added for The Portal to Texas History Title: The Pony Express (Carthage, Texas) 1948-current
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This is a custom feed for browsing The Portal to Texas History Title: The Pony Express (Carthage, Texas) 1948-current
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The Pony Express (Carthage, Tex.), Vol. 51, No. 6, Ed. 1 Thursday, February 1, 2001
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<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591836/"><img alt="The Pony Express (Carthage, Tex.), Vol. 51, No. 6, Ed. 1 Thursday, February 1, 2001" title="The Pony Express (Carthage, Tex.), Vol. 51, No. 6, Ed. 1 Thursday, February 1, 2001" src="https://texashistory.unt.edu/ark:/67531/metapth591836/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
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The Pony Express (Carthage, Tex.), Vol. 51, No. 7, Ed. 1 Sunday, February 11, 2001
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<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591788/"><img alt="The Pony Express (Carthage, Tex.), Vol. 51, No. 7, Ed. 1 Sunday, February 11, 2001" title="The Pony Express (Carthage, Tex.), Vol. 51, No. 7, Ed. 1 Sunday, February 11, 2001" src="https://texashistory.unt.edu/ark:/67531/metapth591788/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
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The Pony Express (Carthage, Tex.), Vol. 51, No. 8, Ed. 1 Monday, February 19, 2001
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https://texashistory.unt.edu/ark:/67531/metapth591910/
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<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591910/"><img alt="The Pony Express (Carthage, Tex.), Vol. 51, No. 8, Ed. 1 Monday, February 19, 2001" title="The Pony Express (Carthage, Tex.), Vol. 51, No. 8, Ed. 1 Monday, February 19, 2001" src="https://texashistory.unt.edu/ark:/67531/metapth591910/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
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The Pony Express (Carthage, Tex.), Vol. 51, No. 9, Ed. 1 Tuesday, March 27, 2001
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<published > 2015-03-03T18:33:27-06:00 </published >
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https://texashistory.unt.edu/ark:/67531/metapth591894/
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<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591894/"><img alt="The Pony Express (Carthage, Tex.), Vol. 51, No. 9, Ed. 1 Tuesday, March 27, 2001" title="The Pony Express (Carthage, Tex.), Vol. 51, No. 9, Ed. 1 Tuesday, March 27, 2001" src="https://texashistory.unt.edu/ark:/67531/metapth591894/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
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The Pony Express (Carthage, Tex.), Vol. 51, No. 10, Ed. 1 Tuesday, May 8, 2001
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The Pony Express (Carthage, Tex.), Vol. 52, No. 1, Ed. 1 Wednesday, September 12, 2001
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The Pony Express (Carthage, Tex.), Vol. 52, No. 2, Ed. 1 Monday, October 1, 2001
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<published > 2015-03-03T18:33:27-06:00 </published >
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https://texashistory.unt.edu/ark:/67531/metapth591884/
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The Pony Express (Carthage, Tex.), Vol. 52, No. 3, Ed. 1 Thursday, October 18, 2001
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The Pony Express (Carthage, Tex.), Vol. 52, No. 4, Ed. 1 Monday, November 12, 2001
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<published > 2015-03-03T18:33:27-06:00 </published >
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The Pony Express (Carthage, Tex.), Vol. 53, No. 1, Ed. 1 Tuesday, September 17, 2002
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<title > ... </title >
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<published > 2015-03-03T18:33:27-06:00 </published >
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https://texashistory.unt.edu/ark:/67531/metapth591746/
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<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591746/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 1, Ed. 1 Tuesday, September 17, 2002" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 1, Ed. 1 Tuesday, September 17, 2002" src="https://texashistory.unt.edu/ark:/67531/metapth591746/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
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The Pony Express (Carthage, Tex.), Vol. 53, No. 2, Ed. 1 Thursday, February 28, 2002
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<title > ... </title >
<link
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<published > 2015-03-03T18:33:27-06:00 </published >
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https://texashistory.unt.edu/ark:/67531/metapth591945/
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<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591945/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 2, Ed. 1 Thursday, February 28, 2002" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 2, Ed. 1 Thursday, February 28, 2002" src="https://texashistory.unt.edu/ark:/67531/metapth591945/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
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The Pony Express (Carthage, Tex.), Vol. 53, No. 2, Ed. 1 Tuesday, October 8, 2002
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<title > ... </title >
<link
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<published > 2015-03-03T18:33:27-06:00 </published >
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https://texashistory.unt.edu/ark:/67531/metapth591868/
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<title >
The Pony Express (Carthage, Tex.), Vol. 53, No. 3, Ed. 1 Friday, March 29, 2002
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591937/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
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https://texashistory.unt.edu/ark:/67531/metapth591937/
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<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591937/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 3, Ed. 1 Friday, March 29, 2002" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 3, Ed. 1 Friday, March 29, 2002" src="https://texashistory.unt.edu/ark:/67531/metapth591937/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
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<title >
The Pony Express (Carthage, Tex.), Vol. 53, No. 3, Ed. 1 Tuesday, October 29, 2002
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591822/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
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https://texashistory.unt.edu/ark:/67531/metapth591822/
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<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591822/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 3, Ed. 1 Tuesday, October 29, 2002" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 3, Ed. 1 Tuesday, October 29, 2002" src="https://texashistory.unt.edu/ark:/67531/metapth591822/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
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<title >
The Pony Express (Carthage, Tex.), Vol. 53, No. 4, Ed. 1 Tuesday, November 19, 2002
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591874/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
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https://texashistory.unt.edu/ark:/67531/metapth591874/
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<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591874/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 4, Ed. 1 Tuesday, November 19, 2002" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 4, Ed. 1 Tuesday, November 19, 2002" src="https://texashistory.unt.edu/ark:/67531/metapth591874/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
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<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591874/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 53, No. 4, Ed. 1 Wednesday, April 17, 2002
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591915/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591915/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591915/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 4, Ed. 1 Wednesday, April 17, 2002" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 4, Ed. 1 Wednesday, April 17, 2002" src="https://texashistory.unt.edu/ark:/67531/metapth591915/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591915/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 53, No. 5, Ed. 1 Thursday, February 6, 2003
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591853/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591853/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591853/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 5, Ed. 1 Thursday, February 6, 2003" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 5, Ed. 1 Thursday, February 6, 2003" src="https://texashistory.unt.edu/ark:/67531/metapth591853/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591853/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 53, No. 5, Ed. 1 Tuesday, May 7, 2002
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591829/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591829/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591829/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 5, Ed. 1 Tuesday, May 7, 2002" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 5, Ed. 1 Tuesday, May 7, 2002" src="https://texashistory.unt.edu/ark:/67531/metapth591829/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591829/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 53, No. 6, Ed. 1 Saturday, March 1, 2003
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591855/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591855/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591855/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 6, Ed. 1 Saturday, March 1, 2003" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 6, Ed. 1 Saturday, March 1, 2003" src="https://texashistory.unt.edu/ark:/67531/metapth591855/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591855/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 53, No. 7, Ed. 1 Thursday, May 1, 2003
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591778/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591778/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591778/"><img alt="The Pony Express (Carthage, Tex.), Vol. 53, No. 7, Ed. 1 Thursday, May 1, 2003" title="The Pony Express (Carthage, Tex.), Vol. 53, No. 7, Ed. 1 Thursday, May 1, 2003" src="https://texashistory.unt.edu/ark:/67531/metapth591778/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591778/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 54, No. 1, Ed. 1 Tuesday, October 28, 2003
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591849/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591849/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591849/"><img alt="The Pony Express (Carthage, Tex.), Vol. 54, No. 1, Ed. 1 Tuesday, October 28, 2003" title="The Pony Express (Carthage, Tex.), Vol. 54, No. 1, Ed. 1 Tuesday, October 28, 2003" src="https://texashistory.unt.edu/ark:/67531/metapth591849/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591849/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 54, No. 2, Ed. 1 Tuesday, December 16, 2003
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591927/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591927/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591927/"><img alt="The Pony Express (Carthage, Tex.), Vol. 54, No. 2, Ed. 1 Tuesday, December 16, 2003" title="The Pony Express (Carthage, Tex.), Vol. 54, No. 2, Ed. 1 Tuesday, December 16, 2003" src="https://texashistory.unt.edu/ark:/67531/metapth591927/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591927/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 54, No. 3, Ed. 1 Thursday, February 26, 2004
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591839/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591839/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591839/"><img alt="The Pony Express (Carthage, Tex.), Vol. 54, No. 3, Ed. 1 Thursday, February 26, 2004" title="The Pony Express (Carthage, Tex.), Vol. 54, No. 3, Ed. 1 Thursday, February 26, 2004" src="https://texashistory.unt.edu/ark:/67531/metapth591839/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591839/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 55, No. 1, Ed. 1 Tuesday, October 5, 2004
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591760/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591760/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591760/"><img alt="The Pony Express (Carthage, Tex.), Vol. 55, No. 1, Ed. 1 Tuesday, October 5, 2004" title="The Pony Express (Carthage, Tex.), Vol. 55, No. 1, Ed. 1 Tuesday, October 5, 2004" src="https://texashistory.unt.edu/ark:/67531/metapth591760/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591760/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 55, No. 3, Ed. 1 Friday, December 3, 2004
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591904/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591904/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591904/"><img alt="The Pony Express (Carthage, Tex.), Vol. 55, No. 3, Ed. 1 Friday, December 3, 2004" title="The Pony Express (Carthage, Tex.), Vol. 55, No. 3, Ed. 1 Friday, December 3, 2004" src="https://texashistory.unt.edu/ark:/67531/metapth591904/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591904/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 55, No. 4, Ed. 1 Thursday, February 24, 2005
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591952/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591952/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591952/"><img alt="The Pony Express (Carthage, Tex.), Vol. 55, No. 4, Ed. 1 Thursday, February 24, 2005" title="The Pony Express (Carthage, Tex.), Vol. 55, No. 4, Ed. 1 Thursday, February 24, 2005" src="https://texashistory.unt.edu/ark:/67531/metapth591952/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591952/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 55, No. 5, Ed. 1 Monday, March 28, 2005
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591828/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591828/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591828/"><img alt="The Pony Express (Carthage, Tex.), Vol. 55, No. 5, Ed. 1 Monday, March 28, 2005" title="The Pony Express (Carthage, Tex.), Vol. 55, No. 5, Ed. 1 Monday, March 28, 2005" src="https://texashistory.unt.edu/ark:/67531/metapth591828/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591828/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 55, No. 6, Ed. 1 Tuesday, May 10, 2005
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591888/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591888/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591888/"><img alt="The Pony Express (Carthage, Tex.), Vol. 55, No. 6, Ed. 1 Tuesday, May 10, 2005" title="The Pony Express (Carthage, Tex.), Vol. 55, No. 6, Ed. 1 Tuesday, May 10, 2005" src="https://texashistory.unt.edu/ark:/67531/metapth591888/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591888/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 56, No. 1, Ed. 1 Monday, September 12, 2005
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591755/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591755/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591755/"><img alt="The Pony Express (Carthage, Tex.), Vol. 56, No. 1, Ed. 1 Monday, September 12, 2005" title="The Pony Express (Carthage, Tex.), Vol. 56, No. 1, Ed. 1 Monday, September 12, 2005" src="https://texashistory.unt.edu/ark:/67531/metapth591755/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591755/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 56, No. 2, Ed. 1 Friday, September 23, 2005
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591947/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591947/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591947/"><img alt="The Pony Express (Carthage, Tex.), Vol. 56, No. 2, Ed. 1 Friday, September 23, 2005" title="The Pony Express (Carthage, Tex.), Vol. 56, No. 2, Ed. 1 Friday, September 23, 2005" src="https://texashistory.unt.edu/ark:/67531/metapth591947/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591947/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 56, No. 3, Ed. 1 Monday, October 31, 2005
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591765/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591765/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591765/"><img alt="The Pony Express (Carthage, Tex.), Vol. 56, No. 3, Ed. 1 Monday, October 31, 2005" title="The Pony Express (Carthage, Tex.), Vol. 56, No. 3, Ed. 1 Monday, October 31, 2005" src="https://texashistory.unt.edu/ark:/67531/metapth591765/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591765/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 56, No. 4, Ed. 1 Monday, December 5, 2005
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591852/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591852/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591852/"><img alt="The Pony Express (Carthage, Tex.), Vol. 56, No. 4, Ed. 1 Monday, December 5, 2005" title="The Pony Express (Carthage, Tex.), Vol. 56, No. 4, Ed. 1 Monday, December 5, 2005" src="https://texashistory.unt.edu/ark:/67531/metapth591852/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591852/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 56, No. 5, Ed. 1 Wednesday, December 14, 2005
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591786/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591786/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591786/"><img alt="The Pony Express (Carthage, Tex.), Vol. 56, No. 5, Ed. 1 Wednesday, December 14, 2005" title="The Pony Express (Carthage, Tex.), Vol. 56, No. 5, Ed. 1 Wednesday, December 14, 2005" src="https://texashistory.unt.edu/ark:/67531/metapth591786/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591786/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 56, No. 6, Ed. 1 Thursday, February 16, 2006
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591798/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591798/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591798/"><img alt="The Pony Express (Carthage, Tex.), Vol. 56, No. 6, Ed. 1 Thursday, February 16, 2006" title="The Pony Express (Carthage, Tex.), Vol. 56, No. 6, Ed. 1 Thursday, February 16, 2006" src="https://texashistory.unt.edu/ark:/67531/metapth591798/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591798/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 56, No. 7, Ed. 1 Friday, May 12, 2006
</title >
<title > ... </title >
<link
href =" https://texashistory.unt.edu/ark:/67531/metapth591744/?q=%22%22~1 " rel =" alternate " />
<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591744/
</id >
<id > ... </id >
<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591744/"><img alt="The Pony Express (Carthage, Tex.), Vol. 56, No. 7, Ed. 1 Friday, May 12, 2006" title="The Pony Express (Carthage, Tex.), Vol. 56, No. 7, Ed. 1 Friday, May 12, 2006" src="https://texashistory.unt.edu/ark:/67531/metapth591744/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591744/small/ " />
</entry >
<entry > ... </entry >
<entry >
<title >
The Pony Express (Carthage, Tex.), Vol. 57, No. 1, Ed. 1 Wednesday, October 4, 2006
</title >
<title > ... </title >
<link
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<published > 2015-03-03T18:33:27-06:00 </published >
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The Pony Express (Carthage, Tex.), Vol. 57, No. 2, Ed. 1 Monday, October 30, 2006
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<published > 2015-03-03T18:33:27-06:00 </published >
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<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591797/"><img alt="The Pony Express (Carthage, Tex.), Vol. 57, No. 2, Ed. 1 Monday, October 30, 2006" title="The Pony Express (Carthage, Tex.), Vol. 57, No. 2, Ed. 1 Monday, October 30, 2006" src="https://texashistory.unt.edu/ark:/67531/metapth591797/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
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The Pony Express (Carthage, Tex.), Vol. 57, No. 3, Ed. 1 Friday, December 1, 2006
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<published > 2015-03-03T18:33:27-06:00 </published >
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<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591772/"><img alt="The Pony Express (Carthage, Tex.), Vol. 57, No. 3, Ed. 1 Friday, December 1, 2006" title="The Pony Express (Carthage, Tex.), Vol. 57, No. 3, Ed. 1 Friday, December 1, 2006" src="https://texashistory.unt.edu/ark:/67531/metapth591772/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
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url =" https://texashistory.unt.edu/ark:/67531/metapth591772/small/ " />
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<entry > ... </entry >
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The Pony Express (Carthage, Tex.), Vol. 57, No. 4, Ed. 1 Thursday, May 10, 2007
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<published > 2015-03-03T18:33:27-06:00 </published >
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<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591900/"><img alt="The Pony Express (Carthage, Tex.), Vol. 57, No. 4, Ed. 1 Thursday, May 10, 2007" title="The Pony Express (Carthage, Tex.), Vol. 57, No. 4, Ed. 1 Thursday, May 10, 2007" src="https://texashistory.unt.edu/ark:/67531/metapth591900/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
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url =" https://texashistory.unt.edu/ark:/67531/metapth591900/small/ " />
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<entry > ... </entry >
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The Pony Express (Carthage, Tex.), Vol. 58, No. 1, Ed. 1 Thursday, November 1, 2007
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<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591898/"><img alt="The Pony Express (Carthage, Tex.), Vol. 58, No. 1, Ed. 1 Thursday, November 1, 2007" title="The Pony Express (Carthage, Tex.), Vol. 58, No. 1, Ed. 1 Thursday, November 1, 2007" src="https://texashistory.unt.edu/ark:/67531/metapth591898/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
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The Pony Express (Carthage, Tex.), Vol. 58, No. 2, Ed. 1 Monday, December 10, 2007
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<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591863/"><img alt="The Pony Express (Carthage, Tex.), Vol. 58, No. 2, Ed. 1 Monday, December 10, 2007" title="The Pony Express (Carthage, Tex.), Vol. 58, No. 2, Ed. 1 Monday, December 10, 2007" src="https://texashistory.unt.edu/ark:/67531/metapth591863/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
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The Pony Express (Carthage, Tex.), Vol. 58, No. 3, Ed. 1 Thursday, February 21, 2008
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<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591885/"><img alt="The Pony Express (Carthage, Tex.), Vol. 58, No. 3, Ed. 1 Thursday, February 21, 2008" title="The Pony Express (Carthage, Tex.), Vol. 58, No. 3, Ed. 1 Thursday, February 21, 2008" src="https://texashistory.unt.edu/ark:/67531/metapth591885/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
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The Pony Express (Carthage, Tex.), Vol. 58, No. 4, Ed. 1 Monday, May 5, 2008
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<published > 2015-03-03T18:33:27-06:00 </published >
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<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591883/"><img alt="The Pony Express (Carthage, Tex.), Vol. 58, No. 4, Ed. 1 Monday, May 5, 2008" title="The Pony Express (Carthage, Tex.), Vol. 58, No. 4, Ed. 1 Monday, May 5, 2008" src="https://texashistory.unt.edu/ark:/67531/metapth591883/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
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url =" https://texashistory.unt.edu/ark:/67531/metapth591883/small/ " />
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<entry > ... </entry >
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The Pony Express (Carthage, Tex.), Vol. 59, No. 1, Ed. 1 Tuesday, September 30, 2008
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<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591763/
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<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591763/"><img alt="The Pony Express (Carthage, Tex.), Vol. 59, No. 1, Ed. 1 Tuesday, September 30, 2008" title="The Pony Express (Carthage, Tex.), Vol. 59, No. 1, Ed. 1 Tuesday, September 30, 2008" src="https://texashistory.unt.edu/ark:/67531/metapth591763/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
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url =" https://texashistory.unt.edu/ark:/67531/metapth591763/small/ " />
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<entry > ... </entry >
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The Pony Express (Carthage, Tex.), Vol. 59, No. 2, Ed. 1 Thursday, October 30, 2008
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<title > ... </title >
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<published > 2015-03-03T18:33:27-06:00 </published >
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<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591756/"><img alt="The Pony Express (Carthage, Tex.), Vol. 59, No. 2, Ed. 1 Thursday, October 30, 2008" title="The Pony Express (Carthage, Tex.), Vol. 59, No. 2, Ed. 1 Thursday, October 30, 2008" src="https://texashistory.unt.edu/ark:/67531/metapth591756/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591756/small/ " />
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<entry > ... </entry >
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The Pony Express (Carthage, Tex.), Vol. 59, No. 3, Ed. 1 Tuesday, November 18, 2008
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<title > ... </title >
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<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591824/
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<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591824/"><img alt="The Pony Express (Carthage, Tex.), Vol. 59, No. 3, Ed. 1 Tuesday, November 18, 2008" title="The Pony Express (Carthage, Tex.), Vol. 59, No. 3, Ed. 1 Tuesday, November 18, 2008" src="https://texashistory.unt.edu/ark:/67531/metapth591824/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
<summary type =" html " > ... </summary >
<media:thumbnail
url =" https://texashistory.unt.edu/ark:/67531/metapth591824/small/ " />
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The Pony Express (Carthage, Tex.), Vol. 59, No. 5, Ed. 1 Tuesday, April 21, 2009
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<published > 2015-03-03T18:33:27-06:00 </published >
<id >
https://texashistory.unt.edu/ark:/67531/metapth591789/
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<summary type =" html " >
<p><a href="https://texashistory.unt.edu/ark:/67531/metapth591789/"><img alt="The Pony Express (Carthage, Tex.), Vol. 59, No. 5, Ed. 1 Tuesday, April 21, 2009" title="The Pony Express (Carthage, Tex.), Vol. 59, No. 5, Ed. 1 Tuesday, April 21, 2009" src="https://texashistory.unt.edu/ark:/67531/metapth591789/small/"/></a></p><p>Newspaper from Panola College in Carthage, Texas that includes news of interest to the college community along with advertising.</p>
</summary >
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url =" https://texashistory.unt.edu/ark:/67531/metapth591789/small/ " />
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The Pony Express (Carthage, Tex.), Vol. 59, No. 5, Ed. 1 Wednesday, March 4, 2009
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<published > 2015-03-03T18:33:27-06:00 </published >
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https://texashistory.unt.edu/ark:/67531/metapth591941/
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<summary type =" html " >
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url =" https://texashistory.unt.edu/ark:/67531/metapth591941/small/ " />
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The Pony Express (Carthage, Tex.), Vol. 59, No. 7, Ed. 1 Wednesday, May 13, 2009
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<published > 2015-03-03T18:33:27-06:00 </published >
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</summary >
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url =" https://texashistory.unt.edu/ark:/67531/metapth591750/small/ " />
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The Pony Express (Carthage, Tex.), Vol. 59, No. 7, Ed. 1 Wednesday, October 28, 2009
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(PDF) Organizational Climate and Culture
PDF | Organizational climate and organizational culture theory and research are reviewed. The article is first framed with definitions of the... | Find, read and cite all the research you need on ResearchGate
Article
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Literature Review
Organizational Climate and Culture
July 2012
Annual Review of Psychology 64(1)
DOI: 10.1146/annurev-psych-113011-143809
Source
PubMed
Authors:
University of Central Florida
Culturefactors
Abstract and Figures
Organizational climate and organizational culture theory and research are reviewed. The article is first framed with definitions of the constructs, and preliminary thoughts on their interrelationships are noted. Organizational climate is briefly defined as the meanings people attach to interrelated bundles of experiences they have at work. Organizational culture is briefly defined as the basic assumptions about the world and the values that guide life in organizations. A brief history of climate research is presented, followed by the major accomplishments in research on the topic with regard to levels issues, the foci of climate research, and studies of climate strength. A brief overview of the more recent study of organizational culture is then introduced, followed by samples of important thinking and research on the roles of leadership and national culture in understanding organizational culture and performance and culture as a moderator variable in research in organizational behavior. The final section of the article proposes an integration of climate and culture thinking and research and concludes with practical implications for the management of effective contemporary organizations. Throughout, recommendations are made for additional thinking and research. Expected final online publication date for the Annual Review of Psychology Volume 64 is November 30, 2012. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
The competing values framework …
Figures - uploaded by
Benjamin Schneider
Author content
Content uploaded by Benjamin Schneider
Author content
Organizational Climate
and Culture
Benjamin Schneider, 1 Mark G. Ehrhart, 2
and William H. Macey 1
1 CEB Valtera, Rolling Meadows, Illinois 60008, 2 Department of Psychology, San Diego
State University, San Diego, California 92182; email: bschneider@executiveboard.com,
mehrhart@mail.sdsu.edu, wmacey@executiveboard.com
Annu. Rev. Psychol. 2013. 64:361–88
First published online as a Review in Advance on
July 30, 2012
The Annual Review of Psychology is online at
psych.annualreviews.org
This article’s doi:
10.1146/annurev-psych-113011-143809
Copyright c
2013 by Annual Reviews.
All rights reserved
Keywords
organizational behavior, organizational effectiveness, data
aggregation, linkage research, organizational values, levels of analysis
Abstract
Organizational climate and organizational culture theory and research
are reviewed. The article is first framed with definitions of the con-
structs, and preliminary thoughts on their interrelationships are noted.
Organizational climate is briefly defined as the meanings people attach
to interrelated bundles of experiences they have at work. Organizational
culture is briefly defined as the basic assumptions about the world and
the values that guide life in organizations. A brief history of climate re-
search is presented, followed by the major accomplishments in research
on the topic with regard to levels issues, the foci of climate research,
and studies of climate strength. A brief overview of the more recent
study of organizational culture is then introduced, followed by samples
of important thinking and research on the roles of leadership and na-
tional culture in understanding organizational culture and performance
and culture as a moderator variable in research in organizational behav-
ior. The final section of the article proposes an integration of climate
and culture thinking and research and concludes with practical impli-
cations for the management of effective contemporary organizations.
Throughout, recommendations are made for additional thinking and
research.
361
PS64CH14-Schneider ARI 8 November 2012 10:21
Contents
F R A M I N GT H E R E V I E W ........... 3 6 2
ORGANIZATIONAL CLIMATE . . . . 363
The Levels-of-Analysis Issue . . . . . . . 363
The Focus of Organizational
Climate Theory, Research, and
P r a c t i c e........................ 3 6 5
O nC l i m a t e S t r e n g t h............... 3 6 7
C l i m a t eS u m m a r y.................. 3 6 8
ORGANIZATIONAL CULTURE . . . 369
A Brief Overview of the
Organizational Culture
Construct and Research
M e t h o d s ........................ 3 6 9
Recent Themes in Organizational
C u l t u r eR e s e a r c h ............... 3 7 1
C u l t u r eS u m m a r y.................. 3 7 6
TOWARD INTEGRATING
CLIMATE AND
CULTURE—WITH PRACTICE
I M P L I C A T I O N S................. 3 7 6
Climate and Culture
R a p p r o c h e m e n t................. 3 7 6
Needed Further Integration . . . . . . . . 377
P r a c t i c eI m p l i c a t i o n s............... 3 7 8
C O N C L U S I O N ..................... 3 8 0
FRAMING THE REVIEW
Organizational climate and organizational
culture are two alternative constructs for
conceptualizing the way people experience and
describe their work settings (including not only
businesses but also schools and governments).
These topics, representing a subset of research
in organizational behavior and organizational
psychology, have never been reviewed in
the Annual Review of Psychology , although
they received some mention as early as 1985
(Schneider 1985). Given this void, we provide
a brief historical overview of thinking and
research on each topic, update the central
issues identified as characterizing these liter-
atures, and provide preliminary thoughts on
integrating them.
Organizational climate may be defined as
the shared perceptions of and the meaning
attached to the policies, practices, and proce-
dures employees experience and the behaviors
they observe getting rewarded and that are
supported and expected (Ostroff et al. 2003,
Schneider & Reichers 1983, Schneider et al.
2011). On the other hand, organizational
culture may be defined as the shared basic as-
sumptions, values, and beliefs that characterize
a setting and are taught to newcomers as the
proper way to think and feel, communicated by
the myths and stories people tell about how the
organization came to be the way it is as it solved
problems associated with external adaptation
and internal integration (Schein 2010, Trice &
Beyer 1993, Zohar & Hofmann 2012). Until
the past two decades or so there have also been
significant differences in the methods used
to study climate and culture, with the former
having been characterized by employee surveys
and the latter by qualitative case studies. A
historical review of the climate and culture
literatures, however, reveals that culture re-
cently has been much more often studied using
surveys, and the issues addressed can both
overlap and be considerably different from the
issues addressed via climate surveys (Schneider
et al. 2011, Zohar & Hofmann 2012).
The relative research interest in the two
constructs has also varied over the decades.
The topic of organizational climate dominated
the early research on the human organizational
environment in the 1960s and 1970s, but it
moved to the background as interest in orga-
nizational culture dominated the 1980s. How-
ever, through the 1990s another transition took
place, and interest in organizational climate ap-
pears to have eclipsed the focus on organiza-
tional culture in more recent years. To illustrate
this shift, we reviewed articles in three of the top
empirical journals in industrial/organizational
psychology ( Journal of Applied Psychology ,
Academy of Management Journal ,a n d Personnel
Psychology ) since the turn of the century (2000–
2012). We counted articles that had as one of
their primary variables organizational climate
or organizational culture, focusing on those that
362 Schneider · Ehrhart · Macey
PS64CH14-Schneider ARI 8 November 2012 10:21
studied them as aggregate constructs (as op-
posed to individual perceptions, preferences, or
beliefs). Our review revealed over 50 articles
that studied organizational climate and fewer
than 10 on organizational culture. Although our
review was limited to three journals and there
are certainly other outlets that do publish more
on organizational culture, we think it is an accu-
rate conclusion that there is currently more of
a focus on organizational climate than organi-
zational culture in the industrial/organizational
psychology research literature.
In this review we describe climate and cul-
ture theory and research with a primary focus
on the recent literature, albeit framed within the
historical developments of both fields. In addi-
tion, we present ways in which organizational
climate and culture complement each other and
can be mutually useful in practice. The review
unfolds as follows. We begin with some early
thinking and research on organizational cli-
mate. Then we introduce the three major ac-
research: ( a ) resolution of what has come to be
called the levels-of-analysis issue; ( b )t h ec r e -
ation of various foci for climate research that
has yielded increased understanding for what
climate is, how to study it, and its potential prac-
tical usefulness; and ( c ) the recent research on
climate strength. In the second major section
of the review, we provide a brief overview of
the construct of organizational culture before
focusing on the four major themes we see in
recent organizational culture research: ( a )l e a d -
ership, ( b ) national culture, ( c ) organizational
effectiveness, and ( d ) organizational culture as
a moderator variable. In the final section, we ex-
plore ways in which climate and culture think-
ing and research can complement each other
both conceptually and practically.
ORGANIZATIONAL CLIMATE
Serious quantitative research on organizational
climate began around 1970 (see the historical
overview in Schneider et al. 2011). Early
research on organizational climate was charac-
it, almost no conceptual orientation to the early
measures designed to assess it, and paradoxi-
cally an almost complete ignoring of the term
“organizational.” Thus, early climate research
(say through the early 1980s) followed a more
traditional individual differences methodology
that was characteristic of the industrial psychol-
ogy of the time. As the field of organizational
culture began to explode in the early 1980s
(following Pettigrew’s introduction of it to
organizational studies in 1979), organizational
climate faded to the background (at least for a
time) as it struggled with the levels-of-analysis
issue. To some degree, the rise in interest in
organizational culture in the 1980s could be
attributed to the fact that it seemed to capture
the richness of the organizational environment
in ways that climate research had not. As
Pettigrew (1990, p. 416) observed, “[There is]
the impression that climate studies have been
boxed in by the appearance in the nest of this
rather overnourished, noisy, and enigmatic
sure from an interloper may, however, be en-
ergizing climate researchers to rethink the role
of climate studies.” Pettigrew was prescient in
his depiction of climate research, given that the
renewed interest in the topic yielded significant
progress in conceptual thinking and research
methodologies (Kuenzi & Schminke 2009).
The Levels-of-Analysis Issue
Although early organizational and management
writings about climate and climate-like con-
structs (e.g., Argyris 1957, Lewin et al. 1939)
focused on aggregates and not individuals,
the early quantitative research on climate that
proliferated in the late 1960s and early 1970s
was done by individual-differences-oriented
industrial psychologists (e.g., Schneider &
Bartlett 1968) and thus tended to focus on the
individual level of analysis. Grappling with this
issue was a major focus of researchers through-
out the 1970s, with some resolution emerging
in the 1980s. In brief, the issue was whether
climate is an individual experience construct
www.annualreviews.org • Organizational Climate and Culture 363
words, there was confusion between the level
of the theory and the level of data and analysis.
Glick (1985) succinctly argued that unless
( a ) climate survey items assessed organizational
functioning, ( b ) the data were aggregated to the
organizational level of analysis, and ( c ) the cli-
mate measurement was focused on important
organizational outcomes (more on this later),
then climate research was not different from
other individual-level attitudinal research.
The clarification of climate as an attribute of
the group or organization was an important
step for climate research, although some
researchers do continue to study climate at the
individual level. However, such research on
psychological climate (e.g., James et al. 2008)
is not relevant for the present review, which is
concerned with organizational climate.
Recent writings by Bliese (2000), Chan
(1998), Klein & Kozlowski (2000), and
LeBreton & Senter (2008) indicate that re-
search on climate is best characterized as a
referent-shift consensus model (Chan 1998).
The referent-shift model uses survey items
that refer to attributes of the unit/organization
rather than individuals’ own perspectives.
Referent-shift consensus items are conceptually
appropriate because they refer to the level to
which individual responses will be aggregated,
and they tend to yield improved consensus
when aggregated (LeBreton & Senter 2008).
Consensus implies that perceptions are
shared. Assessments of “sharedness” have
focused on interrater agreement and/or inter-
rater reliability. Interrater agreement addresses
the extent to which raters provide similar
absolute ratings of climate such that their rat-
ings are interchangeable. The most common
measure of this form of agreement in climate
research is r WG( J) ( James et al. 1984), although
other alternatives such as the average deviation
index (Burke et al. 1999) and a WG (Brown
& Hauenstein 2005), have been proposed.
Commonly accepted standards for legitimizing
aggregation based on agreement are typically
0.70 or higher, although the usefulness of
a broadly applied cutoff has been recently
questioned (see LeBreton & Senter 2008).
Interrater reliability addresses the extent
to which the rank ordering of the ratings is
consistent across people within units. Climate
researchers typically report ICC(1), a ratio of
between-unit variance to total variance (like
analysis of variance, or ANOVA; Bliese 2000),
and as such technically a measure of both
interrater reliability and interrater agreement
(LeBreton & Senter 2008). Although no firm
cutoffs exist for ICC(1), James (1982) reported
a median value of 0.12 among the studies in his
early review, and LeBreton & Senter (2008)
suggested that values of 0.01, 0.10, and 0.25
might be considered small, medium, and large
effects, respectively. It is also common for re-
searchers to report ICC(2) [sometimes also re-
ferred to as ICC(K); LeBreton & Senter 2008].
ICC(2) is an index of the reliability of group
means and is related to ICC(1) as a function
of group size (Bliese 2000), and ICC(2) values
are commonly interpreted in line with other
measures of reliability, with 0.70 or higher
deemed adequate (Bliese 2000, LeBreton &
Senter 2008). Values that high are obviously
quite challenging to achieve with smaller group
sizes (e.g., 5–6 individuals per group).
In sum, it is common practice for cli-
mate researchers to include a measure of
interrater agreement as well as both within-
and between-group interrater reliability to
support aggregation of individual perceptions
to unit and/or organizational levels of analysis.
Furthermore, we emphasize that a key to such
agreement and reliability evidence is the ap-
propriate wording of climate survey items such
that they represent the level of analysis to which
individual perception data will be aggregated.
A very recent levels issue that has emerged
in climate research concerns the study of cli-
mate across multiple levels of analysis. Over
the years, studies of “organizational” climate
have most frequently been studies of organi-
zational subunits and rarely if ever of organiza-
tions themselves, much less of multiple levels of
analysis. In their recent research on safety cli-
mate, Zohar & Luria (2005) demonstrated a sig-
nificant main effect on safety behavior both for
organizations and for subunits (groups) nested
364 Schneider · Ehrhart · Macey
within organizations. In addition, they showed
that subunit safety climate mediated the effects
of organizational safety climate on employee
safety behavior. As Zohar & Hofmann (2012)
note, this means that employees in organiza-
tions are able to distinguish what happens in
their subunits from the larger organizational
focus on safety, but that subunits within a com-
pany have more agreement in their safety cli-
mate perceptions than they have with people
in the subunits of other companies. In short,
levels issues are somewhat complex to concep-
tualize because they exist simultaneously within
and between organizations, but it appears that
the main effects at both levels have meaning for
the people in them and their behavior.
The Focus of Organizational Climate
Theory, Research, and Practice
A second major accomplishment of research on
organizational climate is the development of re-
search on focused climates. By focus we mean
that early climate research might be character-
ized as having little focus on anything besides
what might be called a climate for well-being,
with a strong focus on leadership and supervi-
sory style (Schneider et al. 2011). Industrial psy-
chologists developed early measures of climate
that had between 6 and 10 dimensions, but the
dimensions chosen for study seemed to cover a
variety of territories that emerged from a vari-
ety of researchers. Given this molar conceptual
and measurement approach to climate, validity
studies using such measures produced highly
variable results at best because the generic na-
ture of the climate measured was not useful for
the prediction of specific outcomes.
Schneider (1975) recognized this issue and
proposed that the bandwidth and focus of
climate measures should match the bandwidth
and focus of the outcome to be predicted.
Adopting the personnel selection tactic of
first identifying the outcome of interest, he
suggested that climate measures follow suit. To
clarify the distinction between molar climate
and focused climate, here is what might have
been a typical generic climate item followed by
the strategically focused version of the item:
“My supervisor says a good word whenever he
sees a job well done” versus “My supervisor
says a good word whenever he sees a job done
according to the safety rules” (Zohar 2000).
The two most prevalent examples of re-
search on climates with a specific strategic focus
are in the literatures on climate for customer
service and climate for safety. One of the
strongest tests of the outcomes of service cli-
mate was conducted by Schneider et al. (2009),
who used longitudinal data at the organization
level of analysis to show that companies with
higher levels of service climate had higher cus-
tomer satisfaction and subsequently superior
financial performance. That study replicated
many similar studies on the relationship
between service climate and customer satis-
faction. Indeed, the service climate literature
now includes studies of both antecedents and
consequences of it as well as studies of poten-
tial moderators. For example, Schneider et al.
(2005) found that unit-level customer-oriented
citizenship behavior was a mediator of service
climate’s effects on department-level customer
satisfaction and sales. That study also showed
that service leadership was an important an-
tecedent of service climate. Indeed, our review
showed that leadership has become an impor-
tant antecedent theme in the service climate lit-
erature. For instance, research reveals that both
transformational leadership (Liao & Chuang
2007) and servant leadership (Walumbwa
et al. 2010) are significant predictors of service
climate. Other research has shown that the
leader’s personal characteristics are also impor-
tant to consider, such that a manager’s service
orientation was shown to fully mediate the re-
lationship between their core-self-evaluations
and the service climate of their department
(Salvaggio et al. 2007). In addition to leader-
ship, other antecedents that have been shown to
predict service climate include organizational
resources and unit-level engagement (Salanova
et al. 2005) as well as high performance work
practices (Chuang & Liao 2010). Finally, in
terms of moderators of the climate-outcome
relationship, Dietz et al. (2004) showed that
www.annualreviews.org • Organizational Climate and Culture 365
service climate had stronger effects when
customer contact was higher, and Mayer et al.
(2009a) replicated that finding, also showing
that the effects of service climate were stronger
when the product was more intangible and
when service employee interdependence was
higher.
The literature on safety climate has touched
on many of the same general themes as the
service climate literature, including consistent
validation of the construct. Thus, meta-analytic
evidence supports the consistent relationship
between safety climate and accidents (Christian
et al. 2009, Clarke 2006), although Beus et al.
(2010b) suggested that there may be reciprocal
effects between safety climate and accidents,
such that increased levels of accidents influence
the shared perceptions of the unit’s (poor)
climate for safety. A safety climate is not only
related to accidents but also the reporting
of those accidents, such that underreporting
is significantly higher in organizations with
poor safety climates (Probst et al. 2008). The
antecedents of safety climate have included
general transformational leadership (Zohar &
Tenne-Gazit 2008), safety-specific transfor-
mational leadership (Barling et al. 2002), the
safety climate of higher organizational levels
(Zohar & Luria 2005), and both management-
employee relations and organizational support
(Wallace et al. 2006). In terms of outcomes
of safety climate, recent research by Neal
& Griffin (2006) used longitudinal data to
demonstrate how safety climate influences
individual-level safety motivation and safety
behavior, which in the aggregate predicts acci-
dent rates in the work unit. Finally, there is also
evidence for moderators of the outcomes of
safety climate. For instance, Hofmann & Mark
(2006) showed in a sample of nurses that safety
climate had a stronger influence on decreasing
back injuries and medication errors when
complexity of the patient’s condition was high.
In addition to studying specific focused cli-
mates for tangible outcomes, scholars have
studied climates for various organizational pro-
cesses. In this research, the measurement of
climate targets the organizational process of
interest rather than the strategic outcome of
interest. Some of the earliest work on process
climates focused on procedural justice climate
(e.g., Naumann & Bennett 2000). Recent re-
search in that area has demonstrated that proce-
dural justice climate could be predicted by team
size and team collectivism (Colquitt et al. 2002),
servant leadership (Ehrhart 2004, Walumbwa
et al. 2010), and leader personality (Mayer
et al. 2007). In addition, procedural justice cli-
mate is related to unit-level outcomes such as
turnover and customer satisfaction (Simons &
Roberson 2003), team performance and absen-
teeism (Colquitt et al. 2002), and unit-level cit-
izenship behavior (Ehrhart 2004), as well as
individual-level attitudes and citizenship behav-
ior (Liao & Rupp 2005, Naumann & Bennett
2000, Walumbwa et al. 2010). Moreover, the
cross-level effects of justice climate are mod-
erated by both individual ( justice orientation;
Liao & Rupp 2005) and structural attributes
(group power distance; Yang et al. 2007).
Interest has recently increased in another
process climate: diversity climate. Several re-
cent examples are notable. For instance, McKay
et al. (2008) showed that gaps in perfor-
mance between racial/ethnic groups were sig-
nificantly smaller when the organization was
more supportive of diversity. Pugh et al. (2008)
found that workforce racial diversity was more
strongly related to diversity climate when the
community in which the organizational unit is
based is less diverse. McKay et al. (2009) found
that unit sales improvements were most positive
when managers and subordinates both reported
that their organization had a supportive diver-
sity climate. Finally, Gonzalez & DeNisi (2009)
showed that racial/ethnic diversity was pos-
itively related to organizational performance
when diversity climate was positive.
Other examples of process climates that have
been the focus of recent research include eth-
ical climate (Martin & Cullen 2006, Mayer
et al. 2009b, Schminke et al. 2005), empower-
ment climate (Chen et al. 2007, Seibert et al.
2004), voice climate (Morrison et al. 2011),
and climate for initiative (Baer & Frese 2003,
Michaelis et al. 2010). Indeed, it is reasonable
366 Schneider · Ehrhart · Macey
to suggest that any and all organizational pro-
cesses might be usefully studied and understood
through a climate lens. For example, one might
conceptualize in climate terms such diverse or-
(Weick & Quinn 1999), performance appraisal
(Rynes et al. 2005), work motivation (Latham
& Pinder 2005), and trust in organizations
(Kramer 1999). The study of these from a cli-
mate perspective could yield new insights into
the sets of contextual process variables that are
their correlates and perhaps their antecedents.
In sum, the change to a strategic outcome
and process focus for climate research has sig-
nificantly improved not only the validity of cli-
mate research but also the understanding of the
contexts that likely yield these focused climates.
As such, the development of this more focused
approach has resulted in the climate construct
being more available to practitioners because
it literally has focused on important organiza-
tional processes and outcomes and has indicated
specific practices and behaviors that might serve
as interventions in organizations to enhance
performance in those areas (Burke 2011).
One topic that has yet to receive much re-
search attention, however, is the issue of the
Schneider et al. (2011) have proposed that pro-
cess climates might be conceptualized as a foun-
dation for outcome climates. That is, when
workers perceive that their organization is con-
cerned about their well-being through its em-
phasis on fairness, diversity, ethics, trust, and
so forth, they are more amenable to the ef-
forts of management to focus on strategic out-
comes of value to the organization. Schneider
et al. (1998) and Wallace et al. (2006) have pro-
vided empirical support for the idea that cli-
mates focused on specific outcomes require that
the foundations on which they are built (foun-
dational climates) be in place for the strate-
gic climates to have an opportunity to emerge.
Recent research by Schulte et al. (2009) sup-
ports this general premise by showing that it is
the configuration of employee-supportive ele-
ments and strategy-focused elements (in their
case, the focus on service) that matters most for
relevant strategic outcomes (such as financial
performance and customer satisfaction). Fur-
be a threshold of climate for well-being that
is needed to build a strategic climate and that
a moderate climate for well-being may suffice.
Along similar lines, McKay et al. (2011) found
support in a sample of retail stores for a three-
way interaction between diversity climate, ser-
vice climate, and minority representation in
the stores to predict customer satisfaction; the
graphs of this interaction indicated that cus-
tomer satisfaction was generally highest when
both diversity climate and service climate levels
were high. More research along these lines that
conceptually integrates focused climates and
molar climates and that simultaneously studies
multiple focused climates is needed.
On Climate Strength
In a prior section on levels issues we addressed
the variety of techniques researchers employ to
defend aggregation of individual perceptions to
yield a score representative of the larger unit of
analysis of interest. Researchers have more re-
cently raised the following interesting question:
ability in consensus within the units or organi-
zations being studied? This is a question about
the relative strength of the climate across set-
tings and the impact that differences in climate
strength may have. The fundamental idea be-
hind climate strength is not new, being related
to the concept of situational strength (Mischel
1976), a construct that has received renewed
interest in recent years by Meyer, Dalal, and
colleagues (Meyer & Dalal 2009; Meyer et al.
2009, 2010). As Zohar (2000; Zohar & Luria
2005) has noted, a weak climate can result when
policies and procedures are inconsistent and/or
when the practices that emerge from policies
and procedures reveal inconsistencies.
Research on climate strength has focused on
molar/generic climate (e.g., Gonz ´
alez-Rom ´
a
et al. 2002, Lindell & Brandt 2000) as well as
a number of focused climates, including proce-
dural justice climate (e.g., Colquitt et al. 2002),
service climate (e.g., Schneider et al. 2002), and
www.annualreviews.org • Organizational Climate and Culture 367
safety climate (e.g., Zohar & Luria 2004, 2005).
The usual model guiding such work is that cli-
mate strength will moderate the relationship
between the climate and outcomes of inter-
est such that the relationship will be stronger
when climate strength is high. On a conceptual
level, this interaction is expected because the
more consistent the experiences of employees,
the more likely employees are to behave con-
sistently as a collective such that there should
be more positive outcomes on the positive end
and more negative outcomes on the low end.
On a measurement level, high consensus (low
variability within units) provides for a more reli-
able mean, and with a more reliable mean there
should be greater validity in conceptually rel-
evant relationship with outcomes. Recent re-
search has provided some promising evidence in
support of the moderating effect of strength on
the relationship between climate level and out-
comes (Colquitt et al. 2002, Gonz ´
alez-Rom ´
a
et al. 2002, Schneider et al. 2002). An interest-
ing corollary finding from the Schneider et al.
(2002) article was that the less consensus there
was among employees in bank branches (the
weaker the service climate was), the higher was
the variance in branch customer perceptions of
the service quality they received.
But not all studies reveal a significant mod-
erator effect for climate strength in predict-
ing outcomes (Dawson et al. 2008, Lindell
& Brandt 2000, Rafferty & Jimmieson 2010,
Schneider et al. 2002, Sowinski et al. 2008,
Zohar & Luria 2004). We must be tentative in
offering an explanation for this inconsistency in
findings, but we propose that a likely crucial is-
sue presents an interesting paradox as follows:
Climate researchers spent decades attempting
to write items for climate surveys such that the
consensus indicators discussed earlier would be
high, legitimating aggregation. But in order to
have a moderator there must be significant vari-
ability across units in consensus; if consensus
is uniformly high, then climate strength will
not serve as a moderator. Indeed, several of the
studies that did not find support for strength as a
moderator seem to have had quite low variabil-
ity in the level of agreement across units (e.g.,
Dawson et al. 2008, Sowinski et al. 2008, Zohar
& Luria 2004).
More research on the conditions under
which climate strength will function as hypoth-
esized is clearly required, but there is beginning
to be some evidence on the conditions most
likely to elicit strong versus weak climates.
For example, climates have been found to
be stronger when units are smaller and less
diverse (Colquitt et al. 2002), when within-
unit social interaction is high (Gonz ´
alez-Rom ´
a
et al. 2002), when the unit’s communication
network is more dense (Zohar & Tenne-
Gazit 2008), when units are more interde-
pendent and have higher group identification
(Roberson 2006), when units are more cohe-
sive (Luria 2008), and when average unit tenure
is higher (Beus et al. 2010a). The most com-
monly studied antecedent of climate strength
has been leadership, with research showing
that units have stronger climates when lead-
ers are described as providing more infor-
mation (Gonz ´
alez-Rom ´
a et al. 2002), being
more straightforward and having less vari-
able behavior patterns (Zohar & Luria 2004),
and being more transformational (Luria 2008,
Zohar & Luria 2004, Zohar & Tenne-Gazit
2008). In sum, when work units interact more,
communicate more, and are more interdepen-
dent, and when leaders communicate more and
share a clear strategic vision for the work, then
the climate in those units will be stronger.
Although progress has been made in re-
search on climate strength, there are still ques-
tions that need to be answered. Nevertheless,
from a practical vantage point, what we can con-
clude is that a positive and strong climate is usu-
ally superior to a weak climate and for sure is
superior to a negative climate, so the implica-
tions for practice are clear: In order to maximize
the likelihood of achieving the organization’s
process and outcome performance goals, it is
essential to consistently and forcefully promote
a positive focused climate.
Climate Summary
A half century of thinking and research has pro-
duced a significant literature on organizational
368 Schneider · Ehrhart · Macey
climate. Perhaps the major outcome of this
area of research for psychology has been the
acceptance of a level of theory and data other
than the individual as relevant and important
in organizational psychological research and
practice. Thus, the resolution of the level-of-
analysis issue has been central to positioning
organizational climate as an integral and inte-
grating conceptual force in the larger world of
organizational psychology and organizational
behavior. Testament to this enlarged role
for the construct is The Oxford Handbook of
Organizational Climate and Culture (Schneider
& Barbera 2013), in which the research and
practice related to the major topics in organiza-
tional psychology are approached from climate
(and culture) perspectives. More specifically,
the handbook chapters reveal ways in which
climate and culture are both influenced by and
have influence on more fundamental orga-
nizational psychology issues, from personnel
selection to organizational change.
Particularly for the world of practice, the
emphasis on focused climates (e.g., climates for
service, safety, justice, ethics) that currently ex-
ists has revealed insight into organizational pro-
cesses and the various climates they produce
for people as well as robust evidence for the
validity of climate perceptions for understand-
ing and predicting important specific organiza-
tional outcomes such as accidents and customer
satisfaction. Although this specific focus for
climate research has improved the prediction
and understanding of specific outcomes, issues
about the variability in the prediction of more
global measures of organizational effectiveness
based on climate measures have not received
much attention. In an exception, Kuenzi (2008)
showed that molar climate can in fact be use-
ful in understanding global performance when
conceptualized and studied through the com-
peting values framework (Quinn & Rohrbaugh
1983, Weick & Quinn 1999). More research
of this sort, utilizing a common framework and
measure across various global performance out-
comes, is needed.
We emphasize that organizations do not
have a singular climate but rather multiple
simultaneous climates of both the process and
strategic outcome sort. Although this may be
obvious, it is also true that there has been very
little theory and research on the issue of multi-
ple climates (Zohar & Hofmann 2012). Theory
and research on such possible additive and in-
teractive effects from multiple climates would
be useful, especially when such multiple cli-
mates include both process and outcome foci
for climate as well as molar climates.
ORGANIZATIONAL CULTURE
The review of the organizational culture con-
struct and research on it traces a different path
from that for organizational climate. This is
true basically because there were few level-of-
analysis issues to deal with in the organizational
culture world. Emerging from a conceptual and
methodological base in anthropology, the col-
lective was the natural unit of theory and anal-
ysis, with individual differences an irrelevant
idea. Instead, while the climate literature in the
1980s struggled with the levels issues, the cul-
ture literature of the same era somewhat para-
doxically struggled with success in the world of
management consulting. That is, culture very
quickly became the darling of the management
consulting world, with books such as In Search of
Excellence (Peters & Waterman 1982) and Cor-
porate Culture: The Rites and Rituals of Organi-
zational Life (Deal & Kennedy 1982) attracting
headlines. From an academic standpoint, this
presented some issues because academics were
not quite sure about what culture was and what
it represented—and even whether it was appro-
priate to try to link organizational culture with
the financial success of corporations (Siehl &
Martin 1990).
A Brief Overview of the
Organizational Culture Construct
and Research Methods
Although the construct of culture itself has a
long history in anthropology, and the term had
been used in earlier writings on organizations
(Alvesson & Berg 1992, Trice & Beyer 1993),
www.annualreviews.org • Organizational Climate and Culture 369
what Pettigrew (1979) did in introducing the
topic to organizational studies was to legitimize
the concept in all of its potential richness. He
did this by showing how the concepts of beliefs,
ideology, language, ritual, and myth could be
applied to the study of organizations (Alvesson
& Berg 1992), as complex as that obviously
would be. This complexity scared neither
culture scholars nor practitioners, the former
group feeling liberated by the ambiguity the
definition(s) presented, permitting them to ex-
plore culture as they saw fit, and the latter group
identifying with the ambiguity as a realistic
picture of the world in which they functioned.
At a more macro conceptual level, the best
way to distinguish definitional (and method-
ological) approaches to culture is by a focus
on culture as something an organization has
versus something an organization is (Smircich
1983). From the “organizations have cultures”
perspective, researchers are concerned with
the ways in which organizations differ and are
usually pragmatic in terms of their focus on
organizational effectiveness and organizational
change (Alvesson 2002, Weick & Quinn 1999).
The research approach from this perspective
is typically comparative—to explore those
attributes of organizations that differentiate
the more effective from the less ef fective (e.g.,
Sackmann 2011)—which explains why survey
approaches have dominated research on culture
from this perspective. In contrast, from the
“organizations are cultures” perspective, the
researcher’s goal is description and understand-
ing, including how organizational members
develop meaning and come to share the very
basic assumptions—the root metaphors (Smir-
cich 1983)—that guide the way they as the
organization function. The research approach
here tends to be inductive (Ashkanasy et al.
2000a), using a native-view paradigm (Gregory
1983, Louis 1990) to report how insiders
experience their organizations (e.g., an emic
perspective). From a methodological stand-
point, researchers from this perspective almost
exclusively use qualitative methods in their
research, as those permit the identification of
the unique manifestations of culture in settings
and permit the identification of ambiguity in
“the” culture as an attribute of a setting.
Simply stated, there is not agreement on
what culture is nor how it should be studied,
but the issues have been somewhat clarified.
For every definition of what culture is, there
is an important contrary view. For example, in
most definitions of culture the idea that it is
shared is present. Yet one of the most widely
influential perspectives on culture, by Martin
(1992, 2002), indicates that this integrationist
idea about culture is but one of three perspec-
tives, the other two being a fragmented view
and a differentiated view. The integrationist
view is that organizations are or have one
culture shared by all; conflict and ambiguity
and differences are ignored and, if mentioned,
are seen as something to fix or an aberration.
The fragmented perspective focuses on am-
biguity; it forcefully denies the necessity for
sharedness, arguing that it is unlikely that
people in an organization at different levels
and in different positions/occupations—and
with different personalities—would have the
same experiences and attach the same meaning
to the organization and what it values. The
differentiation perspective is a compromise
position. It notes that people occupy sub-
cultures in organizations (by function, by
occupation, by gender, and so forth) and thus
may have different experiences and may even
attach different meaning to the same events.
Martin (2002) has recently advocated for a
three-perspective theory of culture, in which all
three perspectives are applied simultaneously.
Building on our discussions of both climate
and culture thus far, it may be useful to think of
the three perspectives as addressing the general
culture (integration), subcultures (differentia-
tion), and culture strength (fragmentation) in
organizations at the same time. Along these
lines, Yammarino & Dansereau (2011) identify
a series of climate and culture studies in which
levels-of-analysis issues, especially multilevel
issues, are present and discuss the ways in which
these issues may be simultaneously studied.
In organizational culture research, the issue
of levels has typically concerned the extent to
370 Schneider · Ehrhart · Macey
which the facets of culture are more or less eas-
ily observable. These different levels have been
conceptualized in a variety of similar ways, but
the most commonly referred to framework on
the levels of culture is Schein’s (2010). He pro-
posed three levels of organizational culture: ar-
tifacts, espoused beliefs and values, and under-
lying assumptions. Artifacts represent the outer
layer of culture and include rituals, language,
myths, dress, and the organization of space.
They are the most readily accessible to out-
siders but also the most ambiguous in terms
of the underlying meaning they may represent.
Thus, although many artifacts may look the
same across organizations, the meaning(s) as-
cribed to them may be quite different. Schein’s
next level of culture is espoused values, or the
values that are reported by management as core
to the organization but that may or may not re-
flect the reality in the organization for mem-
bers. Schein’s third level concerns what he (and
others) term the underlying assumptions of or-
ganizational life. These indicate why organiza-
tional members go about their day-to-day work
lives as they do, and they are frequently so in-
grained that they cannot necessarily be easily
articulated, requiring in-depth interviewing to
illuminate them.
Recent Themes in Organizational
Culture Research
In this section, we attempt to summarize the re-
cent empirical literature on organizational cul-
ture. We do not provide an exhaustive review,
but instead identify key themes and exemplars
in the literature of each. The themes we fo-
cus on are ( a ) leadership, ( b ) national culture,
( c ) organizational effectiveness, and ( d )o r g a n i -
zational culture as a moderator variable.
One theme we do not include is research
on person-organization fit. The main idea of
person-organization fit involves the extent to
which there is an alignment between an in-
dividual’s values and the values (or culture)
of their current or potential organization. Al-
though culture is central to this literature, the
focus is on the consequences of fit for individ-
uals, their subjective fit perceptions, or their
preferences for an organization’s culture (for
a review, see Ostroff & Judge 2007). Given
our focus on aggregate perceptions of organi-
zational culture, we do not review these studies
(although we do note there are exceptions that
do include aggregate indicators of organization
culture, such as recent research by Anderson
et al. 2008).
Leadership and organizational culture. The
most commonly discussed source for the or-
ganization’s assumptions and values is the
founder of the organization and his/her leader-
ship. Schein’s (2010, p. 236) culture-embedding
mechanisms describe what leaders do to articu-
late their values (primary mechanisms) and re-
inforce them (secondary mechanisms):
Primary embedding mechanisms
What leaders pay attention to, measure,
and control on a regular basis
How leaders react to critical incidents and
organizational crises
How leaders allocate resources
How leaders allocate rewards and status
How leaders recruit, select, promote, and
excommunicate
Secondary embedding mechanisms
Organizational design and structure
Organizational systems and procedures
Rites and rituals of the organization
Design of physical space, facades, and
buildings
Stories about important events and
people
Formal statements of organizational phi-
losophy, creeds, and charters
Schein argues that these cultural embedding
mechanisms have an impact on culture to the
e x t e n tt h a tt h e ya r ef o u n dt ob eu s e f u lb yt h e
organization in coping with the world in which
it functions. In other words, what determines
whether certain behaviors and values espoused
by management ultimately become assump-
tions is whether those behaviors and values
lead to success.
Although the theoretical literature on orga-
nizational culture is replete with discussions of
the influence the founder and upper manage-
ment have on an organization’s culture, empir-
ical studies of that relationship are hard to find.
Nevertheless, we highlight three recent studies
here that provide some insight into the role of
leaders in organizational culture. Berson et al.
(2008) examined the relationship between CEO
values, organizational culture, and firm perfor-
mance in a sample of 26 Israeli companies. Sup-
porting their three primary hypotheses, they
found that the CEO value of self-direction was
positively associated with an innovative culture,
security value was positively related to a bureau-
cratic culture, and benevolence value was pos-
itively associated with a supportive culture. In
addition, these culture dimensions were subse-
quently related to several indices of organiza-
tional performance (including sales growth and
efficiency).
cused on leader behavior (not leader values).
Ogbonna & Harris (2000) examined the extent
to which the effects of three styles of leadership
(supportive, participative, and instrumental)
on organizational performance were mediated
by organizational culture. They found partial
support for culture as a mediator, with some
leader behaviors having direct effects on per-
formance. Finally, Tsui et al. (2006b) focused
on the extent to which strength (consistency) of
leadership was associated with the strength of
the culture. Although they generally found that
strength of leadership and strength of culture
were related, they also identified exceptions
to that relationship and clarified the reasons
for the exceptions in follow-up interviews.
Those interviews revealed that some leaders
are able to build a strong culture through
institution-building behaviors (working in the
background to build strong organizational
systems) rather than performance-building
behaviors (showing energy and articulating a
influence culture is needed, especially research
focusing on the effects of Schein’s (2010)
culture-embedding behaviors.
National culture and organizational cul-
ture. Multiple recent studies focus on the re-
lationship between organizational culture and
organizational effectiveness in dif ferent coun-
tries (e.g., Fey & Denison 2003, Lee & Yu
2004, Xenikou & Simosi 2006) or the mea-
surement of organizational culture in countries
outside the United States (e.g., Lamond 2003,
Tsui et al. 2006a), but the primary theoretical
issue of interest when it comes to national cul-
ture is the extent to which it shapes the cul-
tures of the organizations within it. This issue
has been of interest to researchers since the in-
fluential work of Hofstede (1980). In general,
the results show that when national culture is
correlated with the organizational culture of
companies within them, a significant main ef-
fect invariably is found (Gelfand et al. 2007).
The most thorough test of this relationship in
recent years has been provided by the Global
Leadership and Organizational Behavior Effec-
tiveness (GLOBE) project (House et al. 2004),
which collected data on societal culture, or-
ganizational culture, and leadership from over
17,000 people representing 62 societal cultures
and 951 organizations. Brodbeck et al. (2004)
used a subsample of that database with ade-
quate representation within organizations and
across countries and industries and showed that
culture explained between 21% and 47% of
the variance (with an average of 32.7%) across
their nine organizational culture practice di-
mensions. In addition, they found that societal
culture had much stronger effects than either
industry or the society-by-industry interaction.
Two important points should be made
in the light of this finding. First, national
culture has an impact on organizational cul-
ture. Second, the impact leaves considerable
variability in the organizational culture profiles
possible; national culture is influential but not
determinant. Indeed, Sagiv et al. (2011) report
that within organizations and nations there is
also significant variability in individual values.
From this review, it is possible to provide some
potential resolution of the theoretical issue
with regard to the integrationist versus the dif-
ferentiated culture, and it is in agreement with
372 Schneider · Ehrhart · Macey
Martin’s (2002, p. 151) proposal that these can
exist simultaneously as a function of the lens
through which culture is viewed. Thus, through
a macro lens, one might reveal whole nations as
distinctive cultures but also differences between
nations; a macromicro lens would reveal dis-
tinctive cultures for organizations as well as dif-
ferences between organizations within a nation;
a micro lens would reveal within-organization
subcultures; and yet an even more refined view
would reveal within-organization individual
differences. More such multilevel research on
organizational culture is obviously needed.
Culture and organizational performance.
The idea that organizations have cultures
yields a focus on the relationship between
organizational culture and organizational
effectiveness. A recent review of the work
on this possible relationship makes it clear
that such research will necessarily be based
on survey measures of organizational culture
(Sackmann 2011). Sackmann notes that such
research is fraught with difficulties with regard
to ( a ) what levels of culture should be the focus
of assessments (e.g., myths, stories, values,
behavior), ( b ) the unit of analysis for assessment
(subcultures within organizations versus whole
organizations), and ( c ) the content dimensions
along which assessments might best be made
(e.g., employee experiences, socialization
tactics, leadership actions). Because of these
difficulties, a relationship with organizational
performance outcomes has been difficult to
consistently establish (Wilderom et al. 2000).
Nevertheless, a comparison of the Wilderom
et al. (2000) review with the Sackmann (2011)
review indicates that not only is there much
interest in this relationship, but also that
support for that relationship is growing.
Our review of recent (2000–2012) studies
examining the relationship between organiza-
tional culture and performance revealed a va-
riety of approaches to the issue, with consis-
tent significant findings. Studies relied on a
variety of fairly traditional outcomes, includ-
ing objective financial measures of performance
(e.g., Gregory et al. 2009, Kotrba et al. 2012,
Lee & Yu 2004), customer satisfaction (e.g.,
Gillespie et al. 2008), goal achievement (e.g.,
Xenikou & Simosi 2006), and top management
reports (e.g., Chan et al. 2004, Glisson et al.
2008). Other less traditional indices of effec-
tiveness were also studied, for example, the
percentage of women in management (Bajdo
& Dickson 2001) or the odds of children re-
ceiving mental health care (Glisson & Green
2006). Some studies included mediators of
the culture-performance relationship (e.g., atti-
tudes in Gregory et al. 2009), whereas others in-
cluded interactive effects among dimensions of
culture (Kotrba et al. 2012), with organizational
practices (Chan et al. 2004), or with industry
characteristics (Sørensen 2002). Researchers
also used a variety of measures of culture:
The Organizational Culture Inventory (Cooke
& Lafferty 1989), the Denison Organizational
Culture Survey (Denison 1990), and the Orga-
nizational Culture Profile (OCP; O’Reilly et al.
1991) seemed particularly common.
Using the competing values framework
(CVF; Quinn & Rohrbaugh 1983) as a foun-
dation, Hartnell et al. (2011) provided perhaps
the most comprehensive test of the relationship
between organizational culture and organiza-
tional performance. The CVF is characterized
by two sets of competing values with bipolar
dimensions defining four cells. The bipolar
dimensions are flexibility versus stability in
structure and an internal versus an external
focus. Although more complex than we can re-
port in detail here, the 2 × 2 framework yields
four cells with conceptually competing values
about what is important in organizations, the
ways those values are manifest in organiza-
tions, and the likelihood of success in different
domains of organizational performance. The
four cells are named Clan (internal and flexible
with a focus on people), Adhocracy (external
and flexible with a focus on growth), Market
(external and stable with a focus on competi-
tion), and Hierarchy (internal and stable with
a focus on organizational structure). Table 1
shows in detail the ways the four organizational
culture cells hypothetically get played out with
regard to basic assumptions, beliefs, values, and
www.annualreviews.org • Organizational Climate and Culture 373
Table 1 The competing values framework
Culture type Assumptions Beliefs Values
Artifacts
(behaviors)
Effectiveness
criteria
Clan Human affiliation People behave
appropriately when
they have trust in,
loyalty to, and
membership in the
organization
Attachment,
affiliation,
collaboration,
trust, and support
Teamwork,
participation,
employee
involvement, and
open
communication
Employee
satisfaction and
commitment
Adhocracy Change People behave
appropriately when
they understand the
importance and impact
of the task
Growth,
stimulation,
variety, autonomy,
and attention to
detail
Risk taking,
creativity, and
adaptability
Innovation
Market Achievement People behave
appropriately when
they have clear
objectives and are
rewarded based on their
achievements
Communication,
competition,
competence, and
achievement
Gathering customer
and competitor
information, goal
setting, planning
task focus,
competitiveness,
and aggressiveness
Increased market
share profit,
product quality,
and productivity
Hierarchy Stability People behave
appropriately when
they have clear roles
and procedures are
formally defined by
rules and regulations
Communication,
routinization,
formalization
Conformity and
predictability
Efficiency,
timeliness, and
smooth
functioning
From Hartnell CA, Ou AY, Kinicki A. 2011. Organizational culture and organizational effectiveness: a meta-analytic investigation of the competing values
framework. Journal of Applied Psychology 96:677–694, figure 2, p. 679. Copyright c
2011 by the American Psychological Association; reprinted with
behaviors (from Hartnell et al. 2011, p. 679,
and based on Quinn & Kimberly 1984). Thus,
the CVF takes the complex notion of different
levels at which culture exists in companies
and with different foci and proposes that the
different levels of cultural variables do not
exist randomly but tend to be associated with
conceptually similar variables and that the
likelihood of success for an organization is a
function of the focus (e.g., employee well-being
versus increased market share) of the assump-
tions, beliefs, values, and behavior that accrue in
organizations.
In their meta-analysis, Hartnell et al. (2011)
explored the structure of the CVF as well as
the relationship between CVF dimensions and
three indicators of organizational effectiveness
(employee attitudes, operational performance,
and financial performance). They found that for
the most part, the CVF behaved as predicted,
with organizations that were more Clan-like
having employees who were more satisfied and
committed, whereas those with a more market
orientation had superior operational and finan-
cial performance. Perhaps most interestingly,
the Hartnell et al. (2011) findings suggest that
although some foci are superior for some cri-
teria (as just reviewed), organizations scoring
higher on the four cells generated in the frame-
work also were more successful across all three
effectiveness criteria. This finding is explained
by Hartnell et al. (2011, p. 687) as follows:
“ ... [T]he culture types in opposite quadrants
are not competing or paradoxical. Instead they
374 Schneider · Ehrhart · Macey
coexist and work together ... [C]ompeting val-
ues may be more complementary than contra-
dictory.” In short, organizations that do many
things well are more generally more effective,
and organizations that in addition have a focus
on different kinds of outcome criteria will be
even more effective on those outcomes.
There are at least three avenues for future
research that would deepen our understanding
of the relationship between culture and per-
formance. One would be to more clearly ar-
ticulate (and measure) the role of the multi-
ple levels of culture in this relationship. Thus,
what most quantitative measures of culture cap-
ture are the espoused values and/or behavioral
norms in organizations and not the full rich-
ness of the construct—including myths, stories,
and socialization tactics. Such a narrow view of
culture is one reason why researchers from the
“organizations are culture” tradition strongly
discourage quantitative culture measures. Sec-
ond, most research on culture focuses on the
direct relationship between culture and perfor-
mance, but almost all theory related to how
culture impacts performance would conceptu-
alize it in a more moderated/mediated fashion
(as we will shortly review). By this we mean it
explores simultaneously the cultural levels and
the various foci with an addition of more spe-
cific process and content dimensions of behav-
ior a la the climate research we recommended
earlier. More research capturing this complex-
ity would be beneficial. Finally, there are many
contextual social, economic, and political rea-
sons why organizational culture will not have
an impact (or at least as much of an impact) on
organizational performance. More clarification
of how context (e.g., national culture, industry,
economic perturbations, product/service char-
acteristics) moderates the culture-performance
relationship would help identify when culture
has its strongest (and weakest) effects.
Organizational culture as a moderator vari-
able. The final theme we highlight in recent
literature on organizational culture is research
that focuses on organizational culture as a con-
textual variable that moderates relationships
between and among other constructs. Below,
we highlight three studies that take this ap-
proach.
Erdogan et al. (2006) investigated whether
specific dimensions of organizational culture
(as measured by the OCP) would weaken or
strengthen the relationship between organi-
zational justice and leader-member exchange
(LMX). Their logic was that the culture of the
organization influences aspects of social rela-
tionships more or less salient to organizational
members. In line with their hypotheses, they
found that in cultures with high respect for peo-
ple, the relationship between interpersonal jus-
tice and LMX was stronger, and in cultures high
in aggressiveness, the relationship between dis-
tributive justice and LMX was stronger. In con-
trast, in cultures high in team orientation, the
relationships between both types of justice and
LMX were weaker, mainly because employees
in those cultures tended to have higher-quality
LMX relationships across the board.
Another example of the “culture as modera-
tor” approach comes from Chatman & Spataro
(2005). Their focus was on the relationship be-
tween being demographically different and co-
operative behavior. Based on social categoriza-
tion theory, they hypothesized that those who
are demographically different will tend to show
less cooperative behavior because they are more
likely to be categorized as part of the out-group.
However, using sex, race, and nationality as
their demographics and the OCP as their mea-
sure of culture, they were able to show that
a collectivistic culture counteracted these ef-
fects and resulted in significantly higher levels
of cooperation among those who were demo-
graphically different. Thus, they concluded that
the work environment in terms of its culture
resulted in people looking beyond individual
demographic differences and focusing on the
group and the achievement of the group’s goals.
Finally, Bezrukova et al. (2012) studied cul-
ture as a moderator of the relationship between
group fault lines and performance. Specifically,
they examined group fault lines from an in-
formational diversity perspective, including ed-
ucational, tenure, and functional background,
www.annualreviews.org • Organizational Climate and Culture 375
and found that stronger fault lines were nega-
tively related to performance as measured by
group stock options and bonuses. However,
they found that a results-focused culture mod-
erated that relationship, but more importantly,
that it was the alignment of the group’s results-
focused culture and the department’s results-
focused culture that was critical. Thus, this re-
search takes the relatively rare step of examining
culture at multiple levels simultaneously, sim-
ilar to Zohar & Luria’s (2005) approach with
safety climate that we highlighted in the sec-
tion on climate.
Culture Summary
Pettigrew (1979) added new dimensions to
the study of organizational behavior when he
promoted a culture focus for organizational
research. His emphasis on the relevance of
myths, values, and history for understanding
what organizations are was instructive to both
researchers and practitioners. Although there
were debates for decades about how to study or-
ganizational culture, including on what facets of
organizations one might focus and whether cul-
ture should be expected to be related to organi-
zational performance, since the turn of the mil-
lennium survey approaches have become more
common, and increasingly there is an empha-
sis on the organizational performance conse-
quences of organizational culture.
The work of Schein (1985, 2010) indicates
that it is agreed by most that a major building
block for organizational culture is attributable
to the early decisions founders make about
structures and organizing principles and to
what ends valuable resources will be expended.
In addition, based largely on Schein’s writings,
the idea that culture manifests itself at differ-
ent levels (artifacts, values, assumptions) of or-
ganizations also has been accepted. Martin’s
(2002) conceptualization of cultures being si-
multaneously macro and micro in form also
seems to have been accepted but with less uni-
versality. We have found Martin’s perspective
useful here for understanding how national, or-
ganizational, and subcultural perspectives may
be simultaneously relevant, but the explication
of each depends on the lens through which or-
ganizational culture is viewed.
In particular, we spent considerable time
outlining the CVF of Quinn & Rohrbaugh
(1983), especially via the recent meta-analysis of
research within that framework (Hartnell et al.
2011). CVF is an elegant way to summarize
the wide range of issues that have been stud-
ied under the culture rubric, revealing how they
combine to produce particular foci for organi-
zations on outcomes. The finding that the cells
in the framework are positively related suggests
that organizations that do some things appro-
priately also are likely doing many other things
appropriately. The challenge, of course, is to
make that happen (Burke 2011, Weick & Quinn
1999).
TOWARD INTEGRATING
CLIMATE AND CULTURE—WITH
PRACTICE IMPLICATIONS
Molloy et al. (2011) have written convincingly
about the difficulties in crossing levels of anal-
ysis when more than one discipline is involved,
and Reichers & Schneider (1990) decried the
fact that climate and culture research of that
era was characterized by parallel but not over-
lapping tracks of scholarship. Fortunately, both
within the study of climate and within the study
of culture, progress has been made in overcom-
ing the difficulties identified by Molloy et al.
and bridging the parallel tracks identified by
Reichers and Schneider.
Climate and Culture Rapprochement
For example, as reviewed above, psychologists
have moved from a study of climate that was
at the individual level of analysis to a unit and
organizational focus, and culture researchers
(e.g., Martin 2002) have promoted the idea that
cultures can manifest themselves simultane-
ously such that there are common experiences,
clusters of people with different experiences,
and unique experiences as well. Climate
researchers have realized that a focus for their
376 Schneider · Ehrhart · Macey
efforts (e.g., service, safety) might yield supe-
rior results in validity research against specific
outcomes, and the recent Hartnell et al. (2011)
meta-analysis of the CVF reveals a similar re-
sult for culture researchers: A focus on the Clan
quadrant values and behavior yields superior
employee satisfaction, whereas a focus on the
Market quadrant values and behavior yields su-
perior operational and financial performance.
Perhaps most notably, Schein, who in the
earlier editions of his book (1985, 1992) barely
mentioned climate (simply lumping climate in
with “artifacts”), has more recently (2004, 2010)
characterized climate as providing the behav-
ioral evidence for the culture of a setting, such
that those behaviors form the bases for employ-
ees’ conclusions about the values and beliefs
that characterize their organization. In line with
this view, he stated in his introductory chapter
to the 2000 Handbook of Culture and Climate that
“to understand what goes on in organizations
and why it happens in the way it does , one needs
several concepts. Climate and culture, if each
is carefully defined, then become two crucial
building blocks for organizational description
and analysis” (Schein 2000, pp. xxiv–xxv; italics
in original). We agree with this interpretation
of the relationship between climate and culture
and of their mutually reinforcing properties.
The CVF (Hartnell et al. 2011, Quinn &
Rohrbaugh 1983) as represented in Table 1
provides a possible framework for more such
integration across climate and culture per-
spectives. Climate researchers have studiously
avoided the assessment of values and basic
assumptions, viewing them perhaps as “soft”
and therefore not immediately under manage-
ment control. Certainly climate researchers
could assess, in addition to policies, practices,
and procedures, the values these might imply
to organizational members—values for cus-
tomer satisfaction, for example. And culture
researchers have avoided a focus on specific
criteria, whether it be strategic issues such as
customer satisfaction on the one hand or pro-
cess issues such as trust on the other hand. One
exception can be found in recent work by Deni-
son, who markets a well-researched culture
inventory ( http://www.denisonconsulting.
com/advantage/researchModel/model.aspx )
and who has developed a module focusing
on trust—he could also of course have more
focused modules on other outcomes or pro-
cesses as well, for example, on customer
satisfaction.
An especially attractive feature of Table 1
is that it reveals the variety of values and be-
haviors that might be appropriate to create a
culture of well-being or a culture of innova-
tion, and this notion of a culture for something
might help make the culture concept less com-
plex both in research and practice. Recall that
in early climate research it seems that the focus
for such work was implicitly a climate for well-
being. Recall also that in our review of climate
we suggested that this climate for well-being
might serve as a foundation on which more
specifically focused climates might be built. The
CVF, following the work of Kuenzi (2008),
indicates that such a focus on well-being (a
Clan culture) might serve as a foundation for
more molar achievement, market, and opera-
tional/technical foci, and that these, in turn,
might serve as foundations for more specifically
focused strategic climates.
Needed Further Integration
But while the CVF offers the potential for
increased integration of climate and culture
research and the two approaches have become
more like each other, we believe there are
more ways in which they can learn from
each other—and indeed from themselves.
For example, in regard to the latter, a central
variable in early writings on organizational
culture—socialization experiences (Louis
1990, Trice & Beyer 1993)—paradoxically has
gone missing in action. In the 2000 edition
of the Handbook of Organizational Culture and
Climate (Ashkanasy et al. 2000b), there was
a chapter by Major (2000) on socialization,
but the word is not even indexed in the 2011
edition. It is not that research on socialization
has not been occurring. The issue is that
the research has focused primarily on the
www.annualreviews.org • Organizational Climate and Culture 377
tactics individuals report experiencing during
socialization (see the meta-analysis by Bauer
et al. 2007) or perhaps the effects of individuals’
proactivity during socialization (for a review,
see Bindl & Parker 2010), but less so the role
the socialization plays in the perpetuation
of organizational culture to new members.
In short, both culture and climate measures
should focus on the socialization experiences of
newcomers to settings precisely because they
are newcomers, and everything that happens to
them is new and likely to enter awareness—and
have a long-term impact (Louis 1990, Scandura
2002, Van Maanen 1975).
The mention of newcomers also raises the
issue of the development of organizations over
time and the resultant changes in climate and
culture that might be expected. Schein (1985,
1992, 2004, 2010) has consistently explored the
issue of organizational life cycle and the im-
plications of such for ( a ) the leadership de-
mands on managers and ( b ) the resultant cul-
tures to be expected as organizations enter and
pass through various stages of life. The issues
are noticeably absent from the literature on or-
ganizational climate. Perhaps this is because of
the more quantitative orientation of climate re-
searchers and the difficulty of accessing data
across multiple time points over enough time
to meaningfully study such issues, particularly
when the focus is on entire organizations and
not just subunits. Nevertheless, research along
these lines is needed. Presumably, organiza-
tions have a clearly identified and communi-
cated strategy early in their life cycle (Flamholtz
& Randle 2011), but as the organization grows
in terms of numbers and sales, and perhaps
spreads out geographically, it would be useful to
know how organizations continue to maintain
a strong strategic climate. Another example of
potentially beneficial research along these lines
would be on how major organizational changes
such as mergers, acquisitions, or restructuring
affect the climate of the organization and its
strength.
One useful lens for exploring the interre-
culture is that of organizational change. The
question is this: If someone wanted to change
an organization and improve its performance,
should they change the culture? The climate?
Both? If there are assumptions and values in
the organization that are preventing the orga-
nization from achieving its potential, then those
need to be addressed. But just having the “right”
culture will be unlikely to result in high perfor-
mance unless management has created a strate-
gic climate that communicates exactly what the
goals of the organization are and that orga-
nizes the various processes and procedures in
the organization around their achievement. On
the flip side, management’s efforts to build a
strategic climate will struggle if they contra-
dict deeply held assumptions in the organiza-
tion (Schein 2000). Another way to think about
this issue and to demonstrate the linkages be-
tween climate and culture would be to ask how
change is viewed by the executives who would
be responsible for making such change happen.
point next.
Practice Implications
Executives have little concern for the distinc-
tions we have made between culture and cli-
mate. Indeed, culture is their commonly used
term. As an example, in the wake of the 2005 BP
Texas City catastrophe, the independent panel
widely known as the Baker Committee con-
ducted a review of BP’s “safety culture.” The
ensuing report (Baker et al. 2007) includes the
item content of a “safety culture survey” pre-
pared by an independent consulting firm. This
survey is a clear example of a safety climate
survey with its focus on policies, practices and
procedures, and behaviors that (fail to) get re-
warded, supported, and expected. The panel
calls this a culture survey because they implicitly
understand that ( a ) executive interest in “cor-
porate culture” is in creating processes that are
reinforcing of the core values underlying ex-
isting strategy, ( b ) a focused strategy requires
processes that are focused on valued outcomes
such processes do values actually get embedded
378 Schneider · Ehrhart · Macey
and become self-sustaining within the organi-
zation to serve as guideposts for organization
members. Thus, contemporary popular busi-
ness writers consider corporate culture to have
the potential to “outlast any one charismatic
leader” (Heskett et al. 2008).
In short, executives use corporate culture in
a more expansive way than we have articulated
in terms of the scholarly views we presented.
Conversationally, the extended corporate vo-
cabulary embraced by the term culture includes
a broad range of intangible assets (or liabilities)
such as image, brand, and the like. Such id-
iosyncratic frameworks may not have a founda-
tion in scholarship, but they nonetheless serve
as working frames of reference for culture as
interpreted by executives.
Issues of importance to executives are
( a ) knowing the corporate culture, ( b ) chang-
ing the corporate culture, and/or ( c ) leveraging
the corporate culture to create competitive ad-
vantage. Questions of “knowing” are relevant
because the value of culture, like all intangible
assets, is unknown. Both efforts to change and
to leverage the culture are in fact dependent on
the understanding of what that culture is, and
perhaps the direction in which it is moving, an
observation we return to shortly.
Knowing the culture. Of course, executives
are agnostic with respect to how best to mea-
sure culture. They do care about the ability to
make comparisons, though, leading to a natural
inclination to hire consultants who can provide
comparisons to benchmarks (e.g., industry
comparisons, comparisons to the Best Compa-
nies to Work For or Most Admired Companies
lists) that most interest them. Essential here
is a quantitative measure that can be charac-
terized by some finite number of (universal?)
dimensions that are common across different
organizations, with the measured constructs
varying considerably. It is interesting to spec-
culture most in keeping with the values they
wish to endorse and their strategic outcomes
of interest a la the Quinn & Rohrbaugh (1983)
CVF, and that best fit a felt need for knowledge
about a specific facet of culture/climate (such as
safety or service). Executives who believe that
culture is important purchase such measures
and take action on results because of their
beliefs in the importance of the intangible they
confront in all of their activities.
From a practical standpoint, as from an
academic standpoint, the emphasis on intangi-
bles makes a complete reliance on quantitative
approaches unsatisfactory to executives. This
is true because the very vocabulary that is
imposed by such measures on the description
of the culture may be quite different from that
used by those who experience it (Denison &
Spreitzer 1991). Indeed, it seems reasonable
to predict that the relatively near-term future
of culture measurement may drift toward the
ad hoc, textual-based reflections of verbal and
natural language-processing mechanics now
in vogue for measuring political and consumer
sentiment (e.g., Pang & Lee 2008).
Changing the culture. Knowing the culture
is almost always considered in the context of
a felt need for cultural change or to ensure
preservation of what is held as core to how the
organization creates value. Indeed, interven-
tions focused on cultural change often focus on
closing the gap between existing and desired
cultures, and these are typically captured in
measures by asking respondents for both kinds
of data. The underlying assumption (hope?) is
that, with knowledge, culture can be changed
through the right action. Executives implicitly
understand that they have somewhat limited
direct influence on effecting change because so
many issues must be addressed simultaneously
throughout the firm. Their job is to establish
the mission and support the interventions
necessary to embed the processes necessary
to begin redirection—always understanding
significant role in who they are and what they
can become (Burke 2011).
By itself, change is elusive to measure, and
as such, models of corporate culture include
dimensions that reflect constructs such as
www.annualreviews.org • Organizational Climate and Culture 379
adaptability; indeed, Kotter & Heskett (1992)
make adaptability a central feature of orga-
nizational effectiveness, arguing that today’s
change necessarily precedes the necessity to
change tomorrow. It is worth adding that the
practical interest is not just in the direction
of change, but also in the pace of that change
(Flamholtz & Randle 2011).
Leveraging culture for competitive ad-
vantage. The underlying theme of many
conversations about culture is how it can be
leveraged as an asset. Culture is a focus for
competitive advantage when it is different from
other cultures and the elements that constitute
it are difficult to imitate (Ployhart 2012).
“The elements that constitute it” are based
on the processes that get embedded through
knowledge and change with the resultant
climates they create for the behaviors required
for success. Culture, then, yields competitive
advantage as the result of a cycle beginning with
the development of a unique mission statement
enacted by support for the unique processes
necessary to embed the mission’s values and
to create the focused strategic and process
climates that serve as guidelines for behavior.
In short, doing better than what others are
doing is not the key to competitive advantage.
In sum, the most successful executives im-
plicitly understand how climate and culture
are necessarily linked and the complex steps
required for achieving competitive advantage.
When the culture sought is unique, when the
climates created are unique in their complex
simultaneous focus on important internal or-
ganizational processes (e.g., fairness, ethics, in-
clusion) and strategic outcomes (e.g., service,
safety, innovation), then competitive advantage
is possible. A silver bullet still does not exist,
and the best executives know and understand
this truth.
CONCLUSION
Organizational climate and culture offer
overlapping perspectives for understanding the
kinds of integrative experiences people have
in work settings—or in any organizational
settings. The constructs address the meaning
people attach to their experiences of how the
organization works (process climates), the
strategic foci the organization has (strategic
climates), and the values they attribute to the
setting (culture), all in attempts to make sense of
their experiences (Weick & Quinn 1999). The
climate literature has focused on what Schein
(2010) calls the culture-embedding mecha-
nisms of organizations, the tangibles enacted by
leaders by which they express their values and
basic assumptions (Quinn & Rohrbaugh 1983)
and by which they attempt to focus the energies
and competencies of the people in the setting.
These processes and activities are designed
to yield behaviors that pursue organizational
goals and objectives, and it is these behaviors
that come to characterize whole organizations
and subcultures within them (Martin 2002).
Climate scholars have for the past 25 years
been dealing with more tangible policies,
practices, and procedures as the causes of the
experiences people have, focusing their efforts
on understanding how workers experience
the strategic initiatives of management (e.g.,
service, safety, innovation) and the internal
processes accompanying them (e.g., fairness,
ethics, inclusion). Progress has now been made
in understanding when people do not agree on
those climates (i.e., climate strength), but there
is not much work at all on conceptualizing
and understanding how multiple climates in
organizations interact and/or even conflict
with each other (Kuenzi & Schminke 2009).
Culture scholars have taken two directions
in their efforts to conceptualize and understand
organizational culture. When culture is studied
as something organizations are ,t h ef o c u si s
on their uniqueness and what the specific
peculiarities of their “artifacts” (i.e., myths,
stories, and socialization tactics) tell us about
the values and basic assumptions of the people
there. Alternatively, when culture is studied
as something organizations have , comparative
organizational culture research yields quan-
titative assessments of the ways organizations
display their values for and basic assumptions
380 Schneider · Ehrhart · Macey
about people, achievement, formalization, and
growth (a la the competing values framework
shown in Table 1 ). Surveys designed to assess
these inclinations share much in common with
climate surveys, with the CVF providing more
focus for such assessments than has been true
of culture research in the past.
We obviously see these two perspectives as
being useful ways to conceptualize and under-
stand people’s experiences at work. Climate
offers an approach to the tangibles on which
managers can focus to generate the behaviors
fers the intangibles that likely accrue to produce
the deeper psychology of people in a setting.
The psychology of how people experience their
work environment is difficult to assess but is
likely what implicitly directs them in their daily
lives, so it is important to understand. When a
change in what directs people and their daily
lives is required, then a focus on tangibles is the
way to achieve it. As such, the conceptual con-
nection between climate and culture is clear—
and deserving of future research.
SUMMARY POINTS
1. Organizational climate emerges in organizations through a social information process
that concerns the meaning employees attach to the policies, practices, and procedures
they experience and the behaviors they observe being rewarded, supported, and expected.
2. Organizational climate research that has a focus on a strategically relevant outcome
(safety, service) and/or process (fairness, ethics) is superior in understanding specific
relevant outcomes to research on climate that is generic with no specific focus.
3. The aggregation of individual perceptions of climate into higher levels of analysis is
accomplished both through the survey items that are written to capture climate (they
are written to describe the level to which the data will be aggregated) and through the
statistical procedures used to defend such aggregation.
ceptions) reveals that strength frequently moderates the relationship between climate
aggregate means and outcomes of interest.
5. Organizational culture concerns the implicit values, beliefs, and assumptions that em-
ployees infer guide behavior, and they base these inferences on the stories, myths, and
socialization experiences they have and the behaviors they observe (especially on the part
of leaders) that prove to be useful and promote success.
6. Organizational culture may exist as an inclusive organizational construct for a whole
organization but also simultaneously in the form of subcultures (e.g., based on level in
the organization or occupation) and also in ways that suggest a lack of integration (the
culture is fragmented).
7. Early research on organizational culture was predominantly via the qualitative case-
method (emic), but more recently survey procedures have become predominant due to
the comparative opportunities they present as well as the potential they offer for links to
organizational performance outcomes across settings.
8. An integration of climate and culture theory and research has useful implications for
practice, especially vis- `
a-vis practice that yields data suggestive of organizational changes
that might yield improvements in organizational behavior and performance.
www.annualreviews.org • Organizational Climate and Culture 381
FUTURE ISSUES
1. Research that simultaneously studies macro generic climate, multiple strategically fo-
life.
2. Research linking the fundamental beliefs, values, and assumptions that characterize cul-
ture research with the policies, practices, and procedures and accompanying behaviors
that are typical of climate research.
3. Research on boundary conditions surrounding the outcome and process-focused climate
studies in which links with important unit/organizational performance indicators are
studied.
4. Research on the contributions human resource management practices make to the emer-
gence and strength of climate and culture in organizations.
5. Research on the contributions of operations management, finance, legal, marketing, and
other departments/functions to the experienced climate and couture of an organization.
6. Longitudinal research on the likely feedback loops in climate and culture research, es-
pecially feedback loops between outcomes and climate/culture.
7. Research on climate and culture as brand image extending beyond the boundaries of the
organization with regard to image as a potential employer, service or product provider,
and object of investment.
8. Research on the life cycles of organizations and the ways in which climate and culture
change over time as a function of the stages of the life cycle.
DISCLOSURE STATEMENT
The authors are not aware of any affiliations, memberships, funding, or financial holdings that
might be perceived as affecting the objectivity of this review.
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81
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PS64CH14-Schneider ARI 8 November 2012 10:21
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388 Schneider · Ehrhart · Macey
... Previous research on organizational climate has shown that organizations affect their employees' attitudes and behavior in a wide range of areas
(Schneider et al., 2013
(Schneider et al., , 2017. However, less is known about how far the effects of organizational climate reach into employees' private life. ...
... However, less is known about how far the effects of organizational climate reach into employees' private life. In addition, the mechanisms underlying the effects of organizational climate on employees' attitudes are poorly understood
(Schneider et al., 2013
(Schneider et al., , 2017. The present paper aims to address these two research gaps. ...
... Consequently, organizations have a high potential to affect their employees' attitudes and behavior both within and outside work. A framework to bundle and examine these influences of organizations, supervisors, and coworkers on employees' attitudes and behavior is organizational climate, which is defined as employees' perceptions of the organizational practices, policies, and procedures that are supported and expected within the workplace
(Schneider et al., 2013
(Schneider et al., , 2017. ...
Organizations affect their employees' vaccine readiness: A self-perception theory perspective
Over the past 3 years, employees have constantly witnessed how their organizations have responded to the challenges posed by the COVID-19 pandemic. Here, we hypothesize that employees' perceptions of the COVID-19 safety climate of their organization positively affect their vaccine readiness. To examine the underlying mechanisms of this effect, we use a self-perception theory lens. Thus, we hypothesize that an organization's COVID-19 safety climate affects employees' COVID-19 vaccine readiness through employees' adherence to COVID-19 guidelines. We conducted a time-lagged study over the time span of 1 year (N = 351) to test our hypotheses. In general, results support our hypotheses. In particular, results showed that perceived COVID-19 safety climate assessed at an early stage of the pandemic (April 2020, when no vaccines were available) predicted employees' COVID-19 vaccine readiness more than a year later. In line with self-perception theory, this effect was mediated by employees' adherence to COVID-19 guidelines. The present study provides theoretical insight into the underlying mechanisms of organizational climate on employees' attitudes. From a practical perspective, our results suggest that organizations are a powerful lever for promoting vaccine readiness.
... The PO-fit was high at the beginning of the study before they started adding feedback but decreased throughout the study. This might indicate that the implementation of feedback was altering the local organization culture leading to a poorer PO-fit and a negative organizational climate
(Schneider et al., 2013)
. An interaction effect of patient factors, provision of feedback and therapist characteristics was also found in this study, when the influence of therapists' regulatory focus was observed. ...
... This difference in centres is hypothesized to be linked to a changing organizational climate in the centre, with the lowest regular use of PCOMS
(Schneider et al., 2013)
. As described in the study protocol (Bovendeerd et al., 2019), the centres were recruited in a Mindfit However, when we analyse the therapists comments administered at the end of the patient inclusion period, it is remarkable that increased workload is never mentioned as a reason to neglect SCF in the low SCF use centre. ...
The effect of therapist characteristics on the use and outcome of systematic client feedback in outpatient mental healthcare
CLIN PSYCHOL PSYCHOT
Bram Bovendeerd
Kim de Jong
Izaäk W de Groot
Jos de Keijser
Objective:
Therapist characteristics are known to affect treatment outcome in general and could also influence the use of systematic client feedback (SCF). The current study explores the effect of feedback orientation, regulatory focus, self-efficacy, attitude towards feedback resources and perceived feedback validity on the use and outcome of SCF in outpatient mental healthcare.
Method:
The data of therapists (n = 12) and patients (n = 504) of two outpatient centres offering brief psychological treatment were analysed when SCF, based on the Partners for Change Outcome Management System (PCOMS), was added to treatment as usual. The data of therapists were obtained through a therapist questionnaire composed of relevant characteristics from feedback studies in social and organizational psychology. The effect on the use of SCF was analysed using logistic regression; whereas, the effect on outcome was assessed using a two-level multilevel analysis. Regular use of SCF and the Outcome Questionnaire (OQ-45) were used as outcome variables. DSM-classification, sex and age of each patient were included as covariates.
Results:
High perceived feedback validity significantly increased the use of SCF. No significant therapist characteristics effects were found on outcome, but high promotion focus was associated with treating more complex patients.
Conclusions:
The perceived feedback validity of SCF is likely to have an influence on its use and is probably affected by the changes in the organizational climate.
... On a broader perspective, organizations could minimize the negative impact of organizational dehumanization by reshaping the organizational climate. According to both Schneider and Reichers (1983) and
Schneider et al. (2013)
, "organizational climate" refers to the shared perceptions of and the meaning attached to the policies, practices, and procedures employees experience, along with the behaviors that are expected to be supported or rewarded. As suggested by the recent meta-analysis by Eisenberger et al. (2019), the employee-organizational relationship has been deteriorating over the last 20 years. ...
The Relationship Between Organizational Dehumanization and Family Functioning
Organizational dehumanization may affect employees’ work behaviors and well-being. However, whether the impact of organizational dehumanization goes beyond the work domain and influences family functioning remains unclear. Following the spillover theory, this study examines the association between employees’ perception of organizational dehumanization and family functioning. Path analysis was used on a two-wave dataset of 372 participants. Results showed that organizational dehumanization at T1 significantly predicted family functioning at T1. Similarly, dehumanization at T2 significantly predicted family functioning at T2. However, organizational dehumanization at T1 did not predict family functioning at T2 when family functioning at T1 was considered. Limitations and implications are discussed.
... Subsequent models have developed Turner's ideas, and, in particular, have placed organisational culture at the centre of explanations for why institutions fail (Reason, 1990;Roberts et al., 2001;Westrum, 2004). Organisational culture refers to the common ways in which people of an organisation understand the world (e.g., in terms of values, beliefs) and behave accordingly (Chatman & O'Reilly, 2016;Schein, 1984;
Schneider et al., 2013)
. ...
It depends who you ask: Divergences in staff and external stakeholder narratives about the causes of a healthcare failure
Article
Tom W. Reader
Investigations of institutional failure in healthcare typically use staff narratives to identify the cultural factors contributing to the incident. But, to what extent can staff, who are embedded in the culture and who were part of the failing, reflect on and report on the culture? We investigate this by comparing 40 witness statements from staff and 53 witness statements from patients and relatives collected by a public inquiry into a major UK healthcare failure (Clostridium difficile outbreak). Through quantitative text analysis, we found that, while staff and external stakeholders both recognised problems in care, they diverged on the factors considered paramount. Staff emphasised underlying factors such as under‐resourcing and training (causal culture), while patients and relatives emphasised corrective behaviours such as communication for identifying and taking precautions against the spread of C. difficile (corrective culture). The results indicate that patients and relatives may be able to report on cultural factors that staff do not report or are unaware of, thus allowing a more complete analysis. Even in light of an institutional failure, staff may have incomplete accounts of the contributing cultural factors, with implications for learning and postincident improvement.
... We argue that workers' impressions of the workplace environment-which we define as workers' impressions of the organization's written policies, the processes that translate these policies into tacit guidelines, the practices that are rewarded and supported, and the norms typically observed among coworkers-are indicative of the level of satisfaction and productivity in the workplace, serve as the primary drivers of social norms within organizations
[16]
. Workplace environment evaluations are a reflection of employees' professed values and behavioral standards, as well as the value-based frameworks they bring to the table to interpret data in the workplace [17][18][19]. ...
Green HRM: the link between environmental and employee performance, moderated by green work climate perception
Sustainable organizations think about how their operating systems impact the environment. In this regard, organizations can prevent environmental pollution by adopting green human resource management practices resulting in the development of environmentally responsible behavior among employees. The aim of this study is to provide an understanding of how organizations transform human resource management practices into green human resource management practices that enhance environmental performance and further lead to green employee performance moderated by employee perceptions of a green work climate. This study has used a quantitative research approach. Data analysis uses an approach structural equation modeling-partial least squares supported by the Smart-PLS 3 computer software program. The selected sample is the hospitality sector in Indonesia. The results of the study show that green human resource management has a positive effect on environmental performance. Environmental performance has a positive effect on employee green performance. Employees' green work climate perceptions have a positive effect on employees' green performance. Employees' green work climate perceptions do not moderate the effect of environmental performance on employees' green performance. The implications of the magnitude of the results, opinions and responses of other sustainability stakeholders can add important findings for further research.
ΗΘΙΚΗ ΤΩΝ ΕΠ-ΣΕΩΝ ΤΕΛΙΚΟ 01.08.2022
Alexandros Koliopoulos
Sotiria Triantari
Knowledge Sharing in der betrieblichen Praxis – Empirische Befunde einer Fallstudie bei einem mittelständischen IT-Dienstleister
Sophia T. Gentner
Stefanie Birkle
Jürgen Seifried
A Review on the Impact of Workplace Culture on Employee Mental Health and Well-Being
Purpose: This review paper's objective is to look into how workplace culture affects the results of employee mental health and well-being. The review will cover the body of research on the subject and offer a thorough grasp of the elements that influence both healthy and unhealthy workplace cultures. Methodology: The systematic search and selection of pertinent studies on workplace culture and employee mental health and well-being will be the emphasis of this review study. Several peer-reviewed academic research examine and take into account the study's theoretical foundations. The majority of the information used in this article is taken from secondary sources. Journal articles and academic research publications provide secondary data. Findings: The findings demonstrate that organisational culture has a major impact on the mental health and wellbeing of employees. Through developing supportive leadership, social support, suitable job expectations, work-life balance, and effective regulations, healthy workplace cultures that promote employee mental health and well-being can be improved. The outcomes of employee mental health and well-being, however, can be negatively impacted by unfavourable workplace cultures, which are defined by unsupportive leadership, a lack of social support, excessive job demands, a lack of work-life balance, and insufficient policies. The study also discusses opportunities for future research, such as the need to look into the potential effects of workplace culture on certain mental diseases and the moderating effects of individual traits. Originality/Value: By offering an exhaustive synthesis of the body of research on the subject, this review paper makes a significant contribution to the body of knowledge on workplace culture and employee mental wellbeing and well-being. The study report will also offer useful recommendations for businesses, decision-makers, and practitioners on how to foster supportive work environments and enhance employee mental health and wellbeing. Overall, this review paper significantly contributes to our understanding of how workplace culture affects outcomes related to employee mental health and well-being. Paper Type: Literature Review
Safety voice climate: A psychometric evaluation and validation
May 2023
J SAFETY RES
Gro Ellen Mathisen
Tore Tjora
CEO Personality: The Cornerstone of Organizational Culture?
May 2023
GROUP ORGAN MANAGE
Charles O'Reilly
Xubo Cao
Donald Sull
Organizational culture is widely seen as an important element in a firm’s success or failure. While there is almost universal agreement that leaders define and shape organizational culture, there is little research exploring how and why they do this. We propose that a leader’s personality and values are the cornerstone of organizational culture. Using a validated natural language processing instrument, we used earnings call data to collect data on the personalities of 460 CEOs in 309 firms and matched this to organizational culture ratings based on Glassdoor employee ratings for the period 2015–2019. Results show strong, interpretable associations between a CEO’s personality and the culture of the firm—and this association is strengthened the longer the CEO is in the role. Further, by examining 128 succession events during this period, we also show that, consistent with attraction-similarity-retention logic, there is some weak evidence that the existing culture of a firm can be related to the selection of a new CEO. We discuss the implications of these findings for future research on organizational culture.
PEOPLE AND ORGANIZATIONAL CULTURE: A PROFILE COMPARISON APPROACH TO ASSESSING PERSON-ORGANIZATION FIT
Answers to twenty questions about inter-rater reliability and inter-rater agreement
Organizational Culture and Climate
Although there have been several attempts to address the conceptual ambiguities in the literature discussing organizational climate, organizational culture, and their interrelationship, there remains much confusion and a general lack of clarity about what these two constructs represent, as well as how they may interrelate. In order to provide some clarity, we provide a comprehensive review of both constructs and conclude with a model describing how organizational climate can be viewed as a bottom-up (i.e., flowing from employee perceptions) indicator of the underlying core values and assumptions that form the organization's culture. Recommendations for researchers seeking to investigate organizational climate and culture, as well as suggestions for future research, are discussed throughout the chapter.
Social Media Sentiment Analysis for Opinion Mining
Sudha M.K.
Service Climate Effects on Customer Attitudes: An Examination of Boundary Conditions
ACAD MANAGE J
S. Douglas Pugh
Making ethical climate a mainstream management topic: A review, critique, and prescription for the empirical research on ethical climate
David M. Mayer
M. Kuenzi
Rebecca Greenbaum
Organizational culture and effectiveness: Can American theory be applied in Russia?
CF Carl
Multi-level issues in organizational culture and climate research
Francis J. Yammarino
Fred Dansereau
The establishment years: A dependence perspective
Terri A. Scandura
Organisational change and development
Karl E. Weick
Robert E. Quinn
Recent analyses of organizational change suggest a growing concern with the tempo of change, understood as the characteristic rate, rhythm, or pattern of work or activity. Episodic change is contrasted with continuous change on the basis of implied metaphors of organizing, analytic frameworks, ideal organizations, intervention theories, and roles for change agents. Episodic change follows the sequence unfreeze-transition-refreeze, whereas continuous change follows the sequence freeze-rebalance-unfreeze. Conceptualizations of inertia are seen to underlie the choice to view change as episodic or continuous.
| https://www.researchgate.net/publication/230628709_Organizational_Climate_and_Culture |
References in: Measurement in Science - PhilPapers
References in:
Measurement in Science
Eran Tal
Stanford Encyclopedia of Philosophy ( 2015 )
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Psychometrics is one of the main approaches to social scientific measurement. It is relied upon in drug testing, economic policymaking, recruitment, and other decision-making contexts. The first aim of this article is to introduce philosophers to key aspects of psychometrics, namely, classical test theory, item response theory, and construct validity. The second aim is to show how a debate on the nature of psychological attributes manifests in psychometrics. In this debate, realists claim that psychometric measures are indicators of independently existing ( ... ) qualities, while operationalists argue that a measure defines its target attribute. The third and final aim is to argue that despite its poor reputation among philosophers, operationalism is a viable approach to psychometrics. ( shrink )
No categories
The Complementarity of Psychometrics and the Representational Theory of Measurement. Elina Vessonen - 2020 - British Journal for the Philosophy of Science 71 (2):415-442. details Psychometrics and the representational theory of measurement are widely used in social scientific measurement. They are currently pursued largely in isolation from one another. I argue that despite their separation in practice, RTM and psychometrics are complementary approaches, because they can contribute in complementary ways to the establishment of what I argue is a crucial measurement property, namely, representational interpretability. Because RTM and psychometrics are complementary in the establishment of representational interpretability, the current separation of measurement approaches is unfounded. 1Introduction2Two ( ... ) Approaches to Measurement 2.1Representational theory of measurement2.2Psychometrics2.3Representational interpretability3Complementarity, Conceptually 3.1Representational theory of measurement: Conditions of representational interpretability3.2Psychometrics: Evidence of representational interpretability4Complementarity in Action 4.1What is the Rasch model?4.2Rasch and conjoint measurement5Conclusion: Critics and Fruits of Complementarity. ( shrink ) Science, Logic, and Mathematics Direct download (7 more) Export citation Bookmark 3 citations
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The story of how Perrin’s experimental work established the reality of atoms and molecules has been a staple in (realist) philosophy of science writings (Wesley Salmon, Clark Glymour, Peter Achinstein, Penelope Maddy, …). I’ll argue that how this story is told distorts both what the work was and its significance, and draw morals for the understanding of how theories can be or fail to be empirically grounded.
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Measurement in Science in General Philosophy of Science
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This article develops a model-based account of the standardization of physical measurement, taking the contemporary standardization of time as its central case study. To standardize the measurement of a quantity, I argue, is to legislate the mode of application of a quantity concept to a collection of exemplary artefacts. Legislation involves an iterative exchange between top-down adjustments to theoretical and statistical models regulating the application of a concept, and bottom-up adjustments to material artefacts in light of remaining gaps. The model-based ( ... ) account clarifies the cognitive role of ad hoc corrections, arbitrary rules, and seemingly circular inferences involved in contemporary timekeeping, and explains the stability of networks of standards better than its conventionalist and constructivist counterparts. 1 Introduction2 Making Time Universal2.1 Stability and accuracy2.2 Multiple realizability2.3 The challenges of synchronicity2.4 Divergent standards2.5 The leap second3 The Two Faces of Stability3.1 An explanatory challenge3.2 Conventionalist explanations3.3 Constructivist explanations4 Models and Standardization4.1 A third alternative4.2 Stability reconceived4.3 Legislative freedom4.4 Discovering gaps4.5 Nature and society entangled4.6 Remark on scope5 Conclusions. ( shrink )
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Old and New Problems in Philosophy of Measurement. Eran Tal - 2013 - Philosophy Compass 8 (12):1159-1173.
The philosophy of measurement studies the conceptual, ontological, epistemic, and technological conditions that make measurement possible and reliable. A new wave of philosophical scholarship has emerged in the last decade that emphasizes the material and historical dimensions of measurement and the relationships between measurement and theoretical modeling. This essay surveys these developments and contrasts them with earlier work on the semantics of quantity terms and the representational character of measurement. The conclusions highlight four characteristics of the emerging research program in ( ... ) philosophy of measurement: it is epistemological, coherentist, practice oriented, and model based. ( shrink )
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Eudoxos and dedekind: On the ancient greek theory of ratios and its relation to modern mathematics. Howard Stein - 1990 - Synthese 84 (2):163 - 211. details History of Mathematics in Philosophy of Mathematics Direct download (4 more) Export citation Bookmark 22 citations
Securing the Empirical Value of Measurement Results. Kent W. Staley - 2020 - British Journal for the Philosophy of Science 71 (1):87-113.
Reports of quantitative experimental results often distinguish between the statistical uncertainty and the systematic uncertainty that characterize measurement outcomes. This article discusses the practice of estimating systematic uncertainty in high-energy physics. The estimation of systematic uncertainty in HEP should be understood as a minimal form of quantitative robustness analysis. The secure evidence framework is used to explain the epistemic significance of robustness analysis. However, the empirical value of a measurement result depends crucially not only on the resulting systematic uncertainty estimate, ( ... ) but on the learning aims for which that result will be used. Important conceptual and practical questions regarding systematic uncertainty assessment call for further investigation. _1_ Introduction _2_ Systematic Uncertainty: The Very Idea _3_ Systematic Uncertainty in High-Energy Physics _4_ Methodological Debates in High-Energy Physics _5_ The Secure Evidence Framework _6_ Systematic Uncertainty Assessment as Robustness Analysis _7_ Security and Sensitivity _8_ Conclusion Appendix. ( shrink )
Measurement in Science in General Philosophy of Science
Particle Physics in Philosophy of Physical Science
The operational analysis of psychological terms. B. F. Skinner - 1945 - Psychological Review 52 (5):270-277. details No categories Direct download (3 more) Export citation Bookmark 247 citations
The concept of observation in science and philosophy. Dudley Shapere - 1982 - Philosophy of Science 49 (4):485-525.
Through a study of a sophisticated contemporary scientific experiment, it is shown how and why use of the term 'observation' in reference to that experiment departs from ordinary and philosophical usages which associate observation epistemically with perception. The role of "background information" is examined, and general conclusions are arrived at regarding the use of descriptive language in and in talking about science. These conclusions bring out the reasoning by which science builds on what it has learned, and, further, how that ( ... ) process of building consists not only in adding to our substantive knowledge, but also in increasing our ability to learn about nature, by extending our ability to observe it in new ways. The argument of this paper is thus a step toward understanding how it is that all our knowledge of nature rests on observation. ( shrink )
Observation in Science in General Philosophy of Science
Foundational aspects of theories of measurement. Dana Scott & Patrick Suppes - 1958 - Journal of Symbolic Logic 23 (2):113-128. details Logic and Philosophy of Logic Measurement in Science in General Philosophy of Science Direct download (9 more) Export citation Bookmark 66 citations
The Principles of Mathematics. Bertrand Russell - 1903 - Revue de Métaphysique et de Morale 11 (4):11-12. details No categories Direct download Export citation Bookmark 661 citations
Strategies for conceptual change: Ratio and proportion in classical Greek mathematics. Paul Rusnock & Paul Thagard - 1995 - Studies in History and Philosophy of Science Part A 26 (1):107-131. details …all men begin… by wondering that things are as they are…as they do about…the incommensurability of the diagonal of the square with the side; for it seems wonderful to all who have not yet seen the reason, that there is a thing which cannot be measured even by the smallest unit. But we must end in the contrary and, according to the proverb, the better state, as is the case in these instances too when men learn the cause; for there ( ... ) is nothing which would surprise a geometer so much as if the diagonal turned out to be commensurable. ( shrink ) Ancient Greek and Roman Philosophy, Miscellaneous in Ancient Greek and Roman Philosophy History of Mathematics in Philosophy of Mathematics Incommensurability in Science in General Philosophy of Science Science, Logic, and Mathematics Direct download (3 more) Export citation Bookmark 3 citations
The epistemology of a spectrometer. Daniel Rothbart & Suzanne W. Slayden - 1994 - Philosophy of Science 61 (1):25-38.
Contrary to the assumptions of empiricist philosophies of science, the theory-laden character of data will not imply the inherent failure (subjectivity, circularity, or rationalization) of instruments to expose nature's secrets. The success of instruments is credited to scientists' capacity to create artificial technological analogs to familiar physical systems. The design of absorption spectrometers illustrates the point: Progress in designing many modern instruments is generated by analogically projecting theoretical insights from known physical systems to unknown terrain. An experimental realism is defended.
Atomic and Molecular Physics in Philosophy of Physical Science
Epistemology of Specific Domains, Misc in Epistemology
Experimentation in Science in General Philosophy of Science
Quine-Duhem Thesis in General Philosophy of Science
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Varieties of Scientific Realism in General Philosophy of Science
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The objectivity of scientific measures. Sally Riordan - 2015 - Studies in History and Philosophy of Science Part A 50:38-47. details Scientific Practice in General Philosophy of Science Direct download (3 more) Export citation Bookmark 8 citations
The nature of number. Peter Forrest & D. M. Armstrong - 1987 - Philosophical Papers 16 (3):165-186.
The article develops and extends the theory of Glenn Kessler (Frege, Mill and the foundations of arithmetic, Journal of Philosophy 77, 1980) that a (cardinal) number is a relation between a heap and a unit-making property that structures the heap. For example, the relation between some swan body mass and "being a swan on the lake" could be 4.
Mathematical Aristotelianism in Philosophy of Mathematics
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Computer Simulation, Measurement, and Data Assimilation. Wendy S. Parker - 2017 - British Journal for the Philosophy of Science 68 (1):273-304. details This article explores some of the roles of computer simulation in measurement. A model-based view of measurement is adopted and three types of measurement—direct, derived, and complex—are distinguished. It is argued that while computer simulations on their own are not measurement processes, in principle they can be embedded in direct, derived, and complex measurement practices in such a way that simulation results constitute measurement outcomes. Atmospheric data assimilation is then considered as a case study. This practice, which involves combining information ( ... ) from conventional observations and simulation-based forecasts, is characterized as a complex measuring practice that is still under development. The case study reveals challenges that are likely to resurface in other measuring practices that embed computer simulation. It is also noted that some practices that embed simulation are difficult to classify; they suggest a fuzzy boundary between measurement and non-measurement. 1 Introduction2 A Contemporary View of Measurement3 Three Types of Measurement4 Can Computer Simulations Measure Real-World Target Systems?5 Case Study: Atmospheric Data Assimilation5.1 Why data assimilation?5.2 A complex measuring practice under development5.3 Epistemic iteration6 The Boundaries of Measurement7 Epistemology, Not Terminology. ( shrink ) Measurement in Science in General Philosophy of Science Science, Logic, and Mathematics Scientific Instruments in General Philosophy of Science Simulation in Science in General Philosophy of Science Direct download (3 more) Export citation Bookmark 32 citations
Measurement, coordination, and the relativized a priori. Flavia Padovani - 2015 - Studies in History and Philosophy of Science Part B: Studies in History and Philosophy of Modern Physics 52 (Part B):123-128. details The A Priori in Epistemology Direct download (2 more) Export citation Bookmark 4 citations
Measurement. Ernest Nagel & C. G. Hempel - 1931 - Erkenntnis 2 (1):313-335. details Measurement in Science in General Philosophy of Science Direct download (3 more) Export citation Bookmark 23 citations
The metaphysics of quantity. Brent Mundy - 1987 - Philosophical Studies 51 (1):29 - 54.
A formal theory of quantity T Q is presented which is realist, Platonist, and syntactically second-order (while logically elementary), in contrast with the existing formal theories of quantity developed within the theory of measurement, which are empiricist, nominalist, and syntactically first-order (while logically non-elementary). T Q is shown to be formally and empirically adequate as a theory of quantity, and is argued to be scientifically superior to the existing first-order theories of quantity in that it does not depend upon empirically ( ... ) unsupported assumptions concerning existence of physical objects (e.g. that any two actual objects have an actual sum). The theory T Q supports and illustrates a form of naturalistic Platonism, for which claims concerning the existence and properties of universals form part of natural science, and the distinction between accidental generalizations and laws of nature has a basis in the second-order structure of the world. ( shrink )
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Models, measurement and computer simulation: the changing face of experimentation. Margaret Morrison - 2009 - Philosophical Studies 143 (1):33-57. details The paper presents an argument for treating certain types of computer simulation as having the same epistemic status as experimental measurement. While this may seem a rather counterintuitive view it becomes less so when one looks carefully at the role that models play in experimental activity, particularly measurement. I begin by discussing how models function as “measuring instruments” and go on to examine the ways in which simulation can be said to constitute an experimental activity. By focussing on the connections ( ... ) between models and their various functions, simulation and experiment one can begin to see similarities in the practices associated with each type of activity. Establishing the connections between simulation and particular types of modelling strategies and highlighting the ways in which those strategies are essential features of experimentation allows us to clarify the contexts in which we can legitimately call computer simulation a form of experimental measurement. ( shrink ) Moral Status of Artificial Systems in Philosophy of Cognitive Science Simulation and Reality in Philosophy of Computing and Information Simulation in Science in General Philosophy of Science The Nature of Models in General Philosophy of Science Direct download (4 more) Export citation Bookmark 71 citations
The Mismeasure of Consciousness: A problem of coordination for the Perceptual Awareness Scale. Matthias Michel - 2018 - Philosophy of Science (5):1239-1249.
As for most measurement procedures in the course of their development, measures of consciousness face the problem of coordination, i.e., the problem of knowing whether a measurement procedure actually measures what it is intended to measure. I focus on the case of the Perceptual Awareness Scale to illustrate how ignoring this problem leads to ambiguous interpretations of subjective reports in consciousness science. In turn, I show that empirical results based on this measurement procedure might be systematically misinterpreted.
Consciousness and Neuroscience in Philosophy of Cognitive Science
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Numbers, ratios, and structural relations. Joel Michell - 1993 - Australasian Journal of Philosophy 71 (3):325 – 332. details Mathematical Aristotelianism in Philosophy of Mathematics Measurement in Science in General Philosophy of Science Numbers in Philosophy of Mathematics Quantities in Metaphysics Direct download (2 more) Export citation Bookmark 4 citations
Numbers as quantitative relations and the traditional theory of measurement. Joel Michell - 1994 - British Journal for the Philosophy of Science 45 (2):389-406.
The thesis that numbers are ratios of quantities has recently been advanced by a number of philosophers. While adequate as a definition of the natural numbers, it is not clear that this view suffices for our understanding of the reals. These require continuous quantity and relative to any such quantity an infinite number of additive relations exist. Hence, for any two magnitudes of a continuous quantity there exists no unique ratio. This problem is overcome by defining ratios, and hence real ( ... ) numbers, as binary relations between infinite standard sequences. This definition leads smoothly into a new definition of measurement consonant with the traditional view of measurement as the discovery or estimation of numerical relations. The traditional view is further strengthened by allowing that the additive relations internal to a quantity are distinct from relations observed in the behaviour of objects manifesting quantities. In this way the traditional theory can accommodate the theory of conjoint measurement. This is worth doing because the traditional theory has one great strength lacked by its rivals: measurement statements and quantitative laws are able to be understood literally. 1 This paper was completed in 1990-1. while the author was a visiting scholar at the Irvine Research Unit in Mathematical Behavioral Sciences. University of California. Irvine. The author wishes to thank the Director. Professor R. D. Luce, for the generous provision of space and facilities within the Unit and for his critical comments upon some of the ideas expressed herein: Professor L. Narens. for his trenchant criticisms: and the University of Sydney, for granting Special Study Leave and financial assistance to make the visit possible. ( shrink )
Mathematical Aristotelianism in Philosophy of Mathematics
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The origins of the representational theory of measurement: Helmholtz, Hölder, and Russell. Joel Michell - 1993 - Studies in History and Philosophy of Science Part A 24 (2):185-206. details It has become customary to locate the origins of modern measurement theory in the works of Helmholtz and Hölder. If by ‘modern measurement theory’ is meant the representational theory, then this may not be an accurate assessment. Both Helmholtz and Hölder present theories of measurement which are closely related to the classical conception of measurement. Indeed, Hölder can be interpreted as bringing this conception to fulfilment in a synthesis of Euclid, Newton, and Dedekind. The first explicitly representational theory appears to ( ... ) have been Russell's. He rejected the traditional concept of quantity and its connection to number, making the use of number in quantitative science problematical. He solved the problem via representationalism. ( shrink ) Bertrand Russell in 20th Century Philosophy Measurement in Science in General Philosophy of Science Direct download (4 more) Export citation Bookmark 14 citations
Bertrand Russell's 1897 critique of the traditional theory of measurement. Joel Michell - 1997 - Synthese 110 (2):257-276.
The transition from the traditional to the representational theory of measurement around the turn of the century was accompanied by little sustained criticism of the former. The most forceful critique was Bertrand Russell''s 1897 Mind paper, On the relations of number and quantity. The traditional theory has it that real numbers unfold from the concept of continuous quantity. Russell''s critique identified two serious problems for this theory: (1) can magnitudes of a continuous quantity be defined without infinite regress; and (2) ( ... ) can additive relations between such magnitudes exist if magnitudes are not divisible? The present paper shows how the traditional theory answers these questions and compares the traditional and representational theories as contributions to our understanding of the logic of application. ( shrink )
Bertrand Russell in 20th Century Philosophy
Quantities in Metaphysics
Clinical outcome measurement: Models, theory, psychometrics and practice. Leah McClimans , John Browne & Stefan Cano - 2017 - Studies in History and Philosophy of Science Part A 65:67-73. details Science, Logic, and Mathematics Direct download (3 more) Export citation Bookmark 10 citations
Computer simulation and the features of novel empirical data. Greg Lusk - 2016 - Studies in History and Philosophy of Science Part A 56:145-152.
In an attempt to determine the epistemic status of computer simulation results, philosophers of science have recently explored the similarities and differences between computer simulations and experiments. One question that arises is whether and, if so, when, simulation results constitute novel empirical data. It is often supposed that computer simulation results could never be empirical or novel because simulations never interact with their targets, and cannot go beyond their programming. This paper argues against this position by examining whether, and under ( ... ) what conditions, the features of empiricality and novelty could be displayed by computer simulation data. I show that, to the extent that certain familiar measurement results have these features, so can some computer simulation results. ( shrink )
Science, Logic, and Mathematics
The Nature of Models in General Philosophy of Science
Theories and Models in General Philosophy of Science
The function of measurement in modern physical sciences. Thomas S. Kuhn - 1961 - Isis 52:161-193. details Measurement in Science in General Philosophy of Science Thomas Kuhn in 20th Century Philosophy Direct download (2 more) Export citation Bookmark 78 citations
The Epistemological Foundations of Scientific Observation. Vincent Israel-Jost - 2011 - South African Journal of Philosophy 30 (1):29-40.
In the philosophy of science, it is a rather undisputed idea that our concepts, conceptions and theories are strongly constrained by what we observe. But the epistemic authority of observation is threatened by its widely acknowledged lack of autonomy: to have observation yield knowledge through observation reports, one has to already possess a conception of (some aspects of) the self and the world. My goal in this paper is to give a satisfying account of the concept of observation, one that ( ... ) reconciles these two seemingly incompatible yet indisputable aspects of observation: its epistemic authority and its lack of autonomy. My main suggestion is that observation reports can be characterized by a form of uniqueness, namely, that no other judgment that would contradict an observation report could rationally be sustained. I will show that this claim is consistent with the two aforementioned features of observation by using Anil Gupta's innovative treatment of the contribution of experience to knowledge in his recent Empiricism and Experience (2006) based on the logic of interdependent definitions. ( shrink )
Scientific Practice in General Philosophy of Science
Hubris to humility: Tonal volume and the fundamentality of psychophysical quantities. Alistair M. C. Isaac - 2017 - Studies in History and Philosophy of Science Part A 65:99-111. details Psychophysics measures the attributes of perceptual experience. The question of whether some of these attributes should be interpreted as more fundamental, or “real,” than others has been answered differently throughout its history. The operationism of Stevens and Boring answers “no,” reacting to the perceived vacuity of earlier debates about fundamentality. The subsequent rise of multidimensional scaling (MDS) implicitly answers “yes” in its insistence that psychophysical data be represented in spaces of low dimensionality. I argue the return of fundamentality follows from ( ... ) a trend toward increasing epistemic humility. Operationism exhibited a kind of hubris in the constitutive role it assigned to the experimenter’s presuppositions that is abandoned by the algorithmic methods of MDS. This broad epistemic trend is illustrated by following the trajectory of research on a particular candidate attribute: tonal volume. ( shrink ) Science, Logic, and Mathematics Direct download (3 more) Export citation Bookmark 4 citations
Psychological Measurement and Methodological Realism. S. Brian Hood - 2013 - Erkenntnis 78 (4):739-761.
Within the context of psychological measurement, realist commitments pervade methodology. Further, there are instances where particular scientific practices and decisions are explicable most plausibly against a background assumption of epistemic realism. That psychometrics is a realist enterprise provides a possible toehold for Stephen Jay Gould’s objections to psychometrics in The Mismeasure of Man and Joel Michell’s charges that psychometrics is a “pathological science.” These objections do not withstand scrutiny. There are no fewer than three activities in ongoing psychometric research which ( ... ) presuppose a commitment to a minimal epistemic realism. Those activities include selecting between different models for representing data, estimating ability in the context of item response theory, and the move to make the individual the fundamental unit of analysis in psychometrics thereby calling for a shift in what sorts of data are evidentially relevant. In none of these activities are the commitments and disregard for evidence that Gould and Michell find objectionable or “pathological.”. ( shrink )
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Nature from within: Gustav Theodor Fechner and His Psychophysical Worldview. Lawrence A. Shapiro - 2005 - Mind 114 (455):739-743. details Metaphysics of Mind in Philosophy of Mind Direct download (7 more) Export citation Bookmark 11 citations
Fechner's impact for measurement theory. Michael Heidelberger - 1993 - Behavioral and Brain Sciences 16 (1):146-148. details Philosophy of Cognitive Science Philosophy of Consciousness in Philosophy of Mind Psychophysics in Philosophy of Mind Direct download (4 more) Export citation Bookmark 8 citations
Nature From Within: Gustav Theodor Fechner and His Psychophysical Worldview. Michael Heidelberger & Translator: Cynthia Klohr - 2004 - Pittsburgh: University of Pittsburgh Press. details Michael Heidelberger's exhaustive exploration of Fechner's writings, in relation to current issues in the field, successfully reestablishes Fechner'... Panpsychism in Philosophy of Mind Direct download (3 more) Export citation Bookmark 28 citations
Paradigmatic experiments: The ultimatum game from testing to measurement device. Francesco Guala - 2008 - Philosophy of Science 75 (5):658-669.
The Ultimatum Game is one of the most successful experimental designs in the history of the social sciences. In this article I try to explain this success—what makes it a “paradigmatic experiment”—stressing in particular its versatility. Despite the intentions of its inventors, the Ultimatum Game was never a good design to test economic theory, and it is now mostly used as a heuristic tool for the observation of nonstandard preferences or as a “social thermometer” for the observation of culture‐specific norms. ( ... ) †To contact the author, please write to: Department of Sociology and Philosophy, University of Exeter, Amory Building, Exeter EX4 4DT, UK; e‐mail: f.guala@ex.ac.uk. ( shrink )
Game Theory, Misc in Philosophy of Action
Operationalism. D. A. Gillies - 1972 - Synthese 25 (1-2):1 - 24. details Operationalism in General Philosophy of Science Direct download (4 more) Export citation Bookmark 12 citations
Outline of a general model of measurement. Aldo Frigerio , Alessandro Giordani & Luca Mari - 2010 - Synthese 175 (2):123-149.
Measurement is a process aimed at acquiring and codifying information about properties of empirical entities. In this paper we provide an interpretation of such a process comparing it with what is nowadays considered the standard measurement theory, i.e., representational theory of measurement. It is maintained here that this theory has its own merits but it is incomplete and too abstract, its main weakness being the scant attention reserved to the empirical side of measurement, i.e., to measurement systems and to the ( ... ) ways in which the interactions of such systems with the entities under measurement provide a structure to an empirical domain. In particular it is claimed that (1) it is on the ground of the interaction with a measurement system that a partition can be induced on the domain of entities under measurement and that relations among such entities can be established, and that (2) it is the usage of measurement systems that guarantees a degree of objectivity and intersubjectivity to measurement results. As modeled in this paper, measurement systems link the abstract theory of measuring, as developed in representational terms, and the practice of measuring, as coded in standard documents such as the International Vocabulary of Metrology. ( shrink )
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Can a theory-Laden observation test the theory? A. Franklin , M. Anderson , D. Brock , S. Coleman , J. Downing , A. Gruvander , J. Lilly , J. Neal , D. Peterson , M. Price , R. Rice , L. Smith , S. Speirer & D. Toering - 1989 - British Journal for the Philosophy of Science 40 (2):229-231. details Aspects of Consciousness in Philosophy of Mind Observation in Science in General Philosophy of Science Theory Change in General Philosophy of Science Direct download (10 more) Export citation Bookmark 22 citations
Calibration. Allan Franklin - 1997 - Perspectives on Science 5 (1):31-80.
Calibration, the use of a surrogate signal to standardize an instrument, is an important strategy for the establishment of the validity of an experimental result. In this paper, I present several examples, typical of physics experiments, that illustrate the adequacy of the surrogate. In addition, I discuss several episodes in which the question of calibration is both difficult to answer and of paramount importance. These episodes include early attempts to detect gravity waves, the question of the existence of a 17–keV ( ... ) neutrino, and the question of the existence of a Fifth Force in gravity. I argue that in these more complex cases, the adequacy of calibration, in an extended sense, was both considered and established. ( shrink )
Science, Logic, and Mathematics
Construct validity in psychological tests – the case of implicit social cognition. Uljana Feest - 2020 - European Journal for Philosophy of Science 10 (1):1-24. details This paper looks at the question of what it means for a psychological test to have construct validity. I approach this topic by way of an analysis of recent debates about the measurement of implicit social cognition. After showing that there is little theoretical agreement about implicit social cognition, and that the predictive validity of implicit tests appears to be low, I turn to a debate about their construct validity. I show that there are two questions at stake: First, what ( ... ) level of detail and precision does a construct have to possess such that a test can in principle be valid relative to it? And second, what kind of evidence needs to be in place such that a test can be regarded as validated relative to a given construct? I argue that construct validity is not an all-or-nothing affair. It can come in degrees, because both our constructs and our knowledge of the explanatory relation between constructs and data can vary in accuracy and level of detail, and a test can fail to measure all of the features associated with a construct. I conclude by arguing in favor of greater philosophical attention to processes of construct development. ( shrink ) Cognitive Psychology in Philosophy of Cognitive Science Social Psychology in Philosophy of Cognitive Science Direct download (3 more) Export citation Bookmark 7 citations
The Aim and Structure of Physical Theory. Pierre Maurice Marie Duhem - 1954 - Princeton: Princeton University Press.
This classic work in the philosophy of physical science is an incisive and readable account of the scientific method. Pierre Duhem was one of the great figures in French science, a devoted teacher, and a distinguished scholar of the history and philosophy of science. This book represents his most mature thought on a wide range of topics.
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A theory of measurement. Herbert Dingle - 1950 - British Journal for the Philosophy of Science 1 (1):5-26. details Measurement in Science in General Philosophy of Science Science, Logic, and Mathematics Direct download (10 more) Export citation Bookmark 19 citations
The Scientific Image. William Demopoulos & Bas C. van Fraassen - 1982 - Philosophical Review 91 (4):603. details 20th Century Philosophy, Misc in 20th Century Philosophy Direct download (4 more) Export citation Bookmark 1694 citations
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IJMS | Free Full-Text | The Role of Heat Shock Proteins in the Pathogenesis of Polycystic Ovarian Syndrome: A Review of the Literature
Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and post-menopausal women. PCOS is a multifactorial heterogeneous disorder associated with a variety of etiologies, outcomes, and clinical manifestations. However, the pathophysiology of PCOS is still unclear. Heat shock proteins (HSPs) have recently been investigated for their role in the pathogenesis of PCOS. HSPs are a class of proteins that act as molecular chaperones and maintain cellular proteostasis. More recently, their actions beyond that of molecular chaperones have highlighted their pathogenic role in several diseases. In PCOS, different HSP family members show abnormal expression that affects the proliferation and apoptotic rates of ovarian cells as well as immunological processes. HSP dysregulation in the ovaries of PCOS subjects leads to a proliferation/apoptosis imbalance that mechanistically impacts follicle stage development, resulting in polycystic ovaries. Moreover, HSPs may play a role in the pathogenesis of PCOS-associated conditions. Recent studies on HSP activity during therapeutic interventions for PCOS suggest that modulating HSP activity may lead to novel treatment strategies. In this review, we summarize what is currently known regarding the role of HSPs in the pathogenesis of PCOS and their potential role in the treatment of PCOS, and we outline areas for future research.
The Role of Heat Shock Proteins in the Pathogenesis of Polycystic Ovarian Syndrome: A Review of the Literature
by Sara Anjum Niinuma 1 , Laila Lubbad 1 , Walaa Lubbad 1 , Abu Saleh Md Moin 2 and Alexandra E. Butler 2,*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023 , 24 (3), 1838; https://doi.org/10.3390/ijms24031838
Received: 30 November 2022 / Revised: 31 December 2022 / Accepted: 3 January 2023 / Published: 17 January 2023
(This article belongs to the Special Issue Polycystic Ovary Syndrome: From Molecular Mechanisms to Therapies 2.0 )
Abstract
Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and post-menopausal women. PCOS is a multifactorial heterogeneous disorder associated with a variety of etiologies, outcomes, and clinical manifestations. However, the pathophysiology of PCOS is still unclear. Heat shock proteins (HSPs) have recently been investigated for their role in the pathogenesis of PCOS. HSPs are a class of proteins that act as molecular chaperones and maintain cellular proteostasis. More recently, their actions beyond that of molecular chaperones have highlighted their pathogenic role in several diseases. In PCOS, different HSP family members show abnormal expression that affects the proliferation and apoptotic rates of ovarian cells as well as immunological processes. HSP dysregulation in the ovaries of PCOS subjects leads to a proliferation/apoptosis imbalance that mechanistically impacts follicle stage development, resulting in polycystic ovaries. Moreover, HSPs may play a role in the pathogenesis of PCOS-associated conditions. Recent studies on HSP activity during therapeutic interventions for PCOS suggest that modulating HSP activity may lead to novel treatment strategies. In this review, we summarize what is currently known regarding the role of HSPs in the pathogenesis of PCOS and their potential role in the treatment of PCOS, and we outline areas for future research.
Keywords:
polycystic ovary syndrome
;
heat shock proteins
;
therapeutics
;
insulin
1. Introduction to Polycystic Ovarian Syndrome
Affecting approximately 6–10% of women of reproductive age, PCOS is the most common endocrine disorder and cause of anovulatory infertility in women [
1
,
2
,
3
]. Diagnostic criteria for PCOS were established and accepted by the European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine (ESHRE/ASRM) in Rotterdam in 2003, and these Rotterdam consensus guidelines are the most widely accepted and commonly used
criteria for PCOS diagnosis. For diagnosis, the presence of two out of three diagnostic criteria is required: (1) oligo- or anovulation, (2) biochemical or clinical hyperandrogenism (clinical signs being acne, hirsutism, and androgenetic alopecia), and (3) characteristics of polycystic ovarian morphology (PCOM) as assessed by ultrasound scanning of the ovaries (an ovary with
≥
20 follicles, with a diameter of 2–9 mm and/or volume
≥
10 cm
3
) [
4
].
In a healthy female ovary, an egg/ovum is released once a month and will either be fertilized or released during menstruation. In women with PCOS, a variety of factors can prevent the egg from being released from the ovary, which is referred to as anovulation. Antral follicles and immature eggs are arrested at the preovulatory stage, leading to the formation of small cysts in the ovary. Consequently, this results in irregular menstrual cycles and an increased likelihood of infertility [ 1 ].
Multiple factors, including disturbances in the release of gonadotropins, cause anovulation in women with PCOS. This is largely due to abnormal regulation of the secretion of hormones by the hypothalamus [
5
]. A high frequency of luteinizing hormone (LH) pulses leads to the high LH:follicle stimulating hormone (FSH) ratio commonly found in women with PCOS [
1
]. FSH levels become relatively low, causing follicles in the ovary to become resistant to the hormone. This interferes with normal follicular growth, which is also believed to be due to elevated anti-Mullerian hormone levels [
2
]; however, the raised LH:FSH ratio is not used for the diagnosis of PCOS [
6
].
PCOS is a heterogeneous disorder clinically manifested by hirsutism, acne, irregular periods, and other features, as illustrated in Figure 1 . These symptoms are largely due to increased androgen levels in women with PCOS. Androgens have an inhibitory effect on the production of sex-binding globulin in the liver, leading to acne, hirsutism, and, less commonly, androgenetic alopecia due to elevated circulating testosterone [ 7 ]. Additionally, androgens prevent the maturation of the dominant follicle and the apoptosis of smaller follicles in the ovary, which causes the characteristic formation of cysts around the border of each ovary [ 7 ]. Estrogen dominance and slightly elevated prolactin levels are also notable reasons underlying the irregular menstrual cycles, mood disturbances, headaches, bloating/weight gain, and infertility [ 8 ]. Other major manifestations of PCOS, in particular insulin resistance and hyperinsulinemia, also play a role in the folliculogenesis and maintenance of hyperandrogenemia. Elevated circulating insulin stimulates LH to increase androgen formation in ovarian theca cells [ 2 ]. This leads to reproductive and metabolic abnormalities and increased inflammation in women with PCOS.
Figure 1. The clinical manifestations of PCOS in women.
Several factors play a role in the pathophysiology of PCOS, a key one being oxidative stress, an imbalance in the level of oxidants and antioxidants in the body [ 7 ]. In PCOS, this imbalance occurs due to a combination of metabolic disturbances in the body, including hyperinsulinemia, dyslipidemia, hyperglycemia, and obesity (which has a prevalence of 30–40% in women with PCOS) [ 7 ]. Each of the above-mentioned conditions leads to a buildup of reactive oxidative species (ROS), causing an imbalance in their concentrations and resulting in dysregulation of cell growth, differentiation, and apoptosis. ROS also stimulate the production of inflammatory markers such as tumor necrosis factor alpha (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells, both of which cause an increase in androgen production and reinforce the development of symptoms caused by hyperandrogenism [ 7 ]. Additionally, TNF-α plays a role in stimulating insulin resistance, exacerbating the underlying metabolic irregularities that may augment the progression of PCOS [ 7 ]. An increase in lipids in the endometrium of obese women with PCOS has also been found to have an additive inflammatory effect due to disruption of homeostasis in the endometrial endoplasmic reticulum (ER) [ 9 ]. This leads to an ER stress response, impacting the normal physiological function of endometrial cells and increasing the risk of PCOS pathogenesis progression [ 10 ].
PCOS patients have distinct changes in gene expression in their ovarian tissues [
11
]. One study reported 573 upregulated and 430 downregulated genes in the ovaries of women with PCOS [
11
]. The dysregulated genes were notably involved in the metabolism and biosynthesis of lipids, cholesterol, and steroids [
11
]. However, it is still unclear whether these dysregulated genes are directly associated with the pathogenesis of PCOS [
11
] as gaps remain in the current understanding of the pathophysiological mechanisms underlying PCOS. Due to the uncertainty about the etiology of this condition, a standardized treatment approach has yet to be agreed upon. One current area of interest is the role of HSPs in the pathogenesis of PCOS and their potential as therapeutic targets for the treatment of PCOS.
2. Biology of Heat Shock Proteins
Heat shock proteins (HSPs) are a group of proteins discovered in 1962 whose expression is triggered by heat shock or other stressors [ 12 ]. HSPs are classified and named based upon their size and molecular mass [ 13 ]. They range from 10 to 150 kDa and are expressed in all major cellular compartments [ 13 ]. HSPs are a ubiquitous group of molecular chaperones that bind to polypeptide chains to prevent protein misfolding [ 13 ]. They are expressed at low levels when the cell is in its normal physiological state but become elevated once a cell faces a stress stimulus [ 14 ]. Figure 2 illustrates how stress conditions cause HSPs to be activated and synthesized. HSPs function mainly to protect against cellular stress [ 15 ]. HSPs are found in endothelial cells and play an essential role in cell function modulation and protein homeostasis [ 14 , 15 ]. They are also involved in protein homeostasis functions such as protein folding, degradation, and assembly [ 16 ].
Figure 2. The molecular mechanism for the synthesis of heat shock proteins (HSPs). Under physiological conditions, an HSP and a heat shock factor (HSF) are a complex found in the cytosol in an inactive state. However, stressors such as UV radiation, viral infection, heavy metal exposure, oxidative stress, hypothermia, hyperthermia, and cancer cause HSFs to become detached from HSPs. HSFs undergo phosphorylation and trimerization. Once inside the nucleus, they bind to heat shock elements (HSEs), initiating transcription. The HSP mRNAs then leave the nucleus and are translated, synthesizing new HSPs. These HSPs then act as molecular chaperones and bind to polypeptide chains to prevent misfolding of proteins. To protect cells, HSPs also repair and refold damaged proteins under stressful conditions.
In metabolic disorders, cells undergo various stresses, among which genotoxic, oxidative, and metabolic stresses are well documented; however, emerging evidence has revealed proteotoxic stress (perturbations of protein synthesis, misfolding of proteins) to be a common feature of metabolic syndrome [ 17 ], features of which are very common in PCOS, and hence, changes in HSPs are not unexpected [ 18 ]. Proteostasis (or proteome homeostasis) is a process by which cells balance the processes of protein biosynthesis, folding, and degradation, which are vital to cellular fitness. To counter proteomic perturbations and preserve proteostasis, cells activate the protective response (termed the heat shock response (HSR)) by mobilizing the evolutionarily conserved transcriptional program that is orchestrated in eukaryotic cells by heat shock factor 1 (HSF1) [ 19 ]. The HSR is a cellular tool to cope with different stressors, including heat, cold, and metabolic stresses [ 20 ], and is mediated by HSF1-dependent heat shock proteins (HSPs). HSPs function as molecular chaperones that recognize and bind to other proteins when these other proteins are in non-native conformations. HSPs function as a facilitator of native protein stabilization, translocation, re-folding, and degradation when they are under proteotoxic stress due to protein denaturation or because the peptides that comprise them have not yet been fully synthesized, folded, assembled, or localized to an appropriate cellular compartment [ 21 ].
HSPs have been classified into six major families according to their molecular size: HSP100, HSP90, HSP70, HSP60, HSP40, and small heat shock proteins. The HSP70 family consists of two sub-classes; one is constitutively expressed (HSC70, 73-KDa) and the other is stress-inducible HSP 70 (HSP 72-KDa). Under normal physiological conditions, HSP72 is expressed at low levels; however, following stress stimuli, intracellular synthesis and release of HSP72 increases markedly to function as both an intracellular and extracellular chaperone in cytoprotection [ 22 ]. Likewise, the 90-KDa HSP (HSP90) consists of two isoforms, namely inducible HSP90α and constitutively expressed HSP90β [ 23 ]. Other large HSPs include the HSP40s or J-proteins, which interact with HSP70 through their J domain and serve as regulatory co-chaperones [ 24 ]. Among many aspects of dealing with misfolded proteins, HSPs function in the proteolysis of substrates by the proteasomes. HSP70 and/or HSP90 and related co-chaperones are required for the recognition of misfolded or mislocalized proteins that are subsequently degraded by the proteasome [ 25 , 26 ]. The exact mechanism linking the chaperone and proteasomal systems is still under investigation; however, in different cellular models, HSP70 and its co-chaperone DNAJ were also found to be required for proteasomal degradation of misfolded proteins [ 25 , 26 ].
While classically elevated due to heat shock, HSPs can also be produced in excess under other stressful conditions such as UV radiation, viral infections, oxidative stress, and heavy metal exposure [ 27 , 28 ]. Under certain conditions, a cell can prioritize the HSP response over autophagy and the HSP system can prioritize itself over autophagy if both systems are activated [ 27 , 28 ]. Since most HSPs are expressed under stress, they are considered highly sensitive disease biomarkers [ 16 ].
Recent reports have linked HSPs to a variety of pathological conditions. For example, they are overexpressed in many cancers [ 29 ]. They are involved in cancer cell development because HSPs inhibit programmed cell death, which is an essential component of the normal cell cycle [ 30 ]. HSPs do this by suppressing p53, a protein commonly inactivated in cancers [ 28 ]. HSP90B1 has also been reported to play a crucial role in suppressing autophagy and cell apoptosis [ 11 , 30 ]. In addition, high levels of bacterial HSPs, such as HSP60 and HSP70, are involved in many diseases, including type 1 diabetes, Crohn’s disease, atherosclerosis, and juvenile chronic arthritis [ 13 ]. HSPs have been reported to be expressed as autoantigens in atherosclerosis development and expressed in cardiovascular diseases where they induce inflammation [ 31 ].
Similarly, recent evidence indicates that HSPs play a role in the pathogenesis of PCOS. For example, HSP70 is an essential family of molecular chaperones with multiple functions that include regulating cell-mediated immunity, apoptosis, and cellular stress responses [ 17 , 32 ]. Elevated HSP70 levels have been found in non-obese PCOS patients [ 33 ]. HSP70 expression is also correlated with insulin resistance and is involved in the ovarian stress response [ 33 ]. Increased levels of HSP70, together with insulin resistance, oxidative stress, and low-grade chronic inflammation, have been found in PCOS patients [ 10 ]. HSPs and reproductive hormones closely correlate, which indicates in part how HSPs are involved in PCOS pathogenesis [ 33 ].
This review aims to put into context the existing evidence on the association between HSPs and PCOS, particularly their role in the pathogenesis of PCOS and its related conditions, and discusses the potential use of HSPs as therapeutic agents for the treatment of PCOS.
3. The Effects of Heat Shock Proteins on the Pathogenesis of Polycystic Ovarian Syndrome
Expression levels of HSPs are altered in the ovarian tissues of women with PCOS and can affect PCOS pathology via different mechanisms ( Figure 3 ). Their expression has been particularly associated with apoptosis and cell viability. A study in 2016 found an increase in HSP90B1 of at least 2-fold in the ovarian tissues of women with PCOS in comparison to normal subjects [ 11 ]. HSP90 isoforms have been associated with epithelial ovarian cancer, cancer cell survival, apoptosis, and circadian clock gene expression [ 34 , 35 ]. Reduced HSP90 levels may also affect cell survival; for example, decreased expression of HSP90 was found to be associated with reduced zona pellucida thickness and oocyte growth in mouse zygotes [ 36 ]. On this basis, the 2016 study investigated the role of HSP90B1 in the pathogenesis of PCOS. Knockdown of HSP90B1 levels was found to decrease cell viability and increase apoptosis in ovarian cells of women with PCOS [ 36 ]. On the contrary, cell survival was increased, and apoptosis of ovarian cells was decreased by at least 50%, in ovarian cells overexpressing HSP90B1 [ 36 ]. PCOS has been linked to an increase in granulosa cell proliferation [ 37 ]. This study suggested that HSP90B1 may play a role in granulosa cell proliferation and ovarian cell survival and is, consequently, highly likely to be involved in the pathogenesis of PCOS.
Figure 3.
The effect of heat-shock proteins (HSPs) on the pathogenesis of polycystic ovary syndrome (PCOS). (
Left panel
) The stages of oogenesis in the ovary and the structure of a mature follicle. HSPs function at different stages of oogenesis in PCOS. HSP27 negatively regulates oocyte maturation and was downregulated in women with PCOS. (
Right panel
) Intracellular mechanisms of action of HSPs in a granulosa cell (shown in a small green square) of a mature follicle. HSP70 binds to the cell surface toll-like receptor 4 (TLR4) and co-receptor myeloid differentiation protein 2 (MD2). HSP90 binds to the cell surface low-density lipoprotein (LDL)-related protein-1 (LRP-1) in association with clusterin (CLU). Downstream signaling of both HSP70 and HSP90 (phosphorylation of protein kinase B, AKT) leads to the activation of NF-ĸB, a novel transcription factor that regulates the transcription of genes related to cell survival and protection. HSP90 and its co-chaperone DJ2 (HSDJ/hdj-2/rdj1) inhibit mitochondrial proapoptotic Bcl-2 associated X-protein (BAX). HSP90, in association with HSP70, potentiates the mitochondrial antiapoptotic protein B-cell lymphoma 2 (BCL2). HSP10 regulates the transcription of multiple proteins related to cellular apoptosis. Cas-3, caspase-3; Cas-9, caspase-9; p-ERK, phosphorylated extracellular signal associated kinase; Ki67, marker of proliferation Ki-67. Downward orange arrows labeled “PCOS” indicate the HSPs that were found to be downregulated in PCOS in previous publications. This illustration was created using biorender.com (with publication license).
HSP70, the most conserved protein, is also increased in ovarian tissue in women with PCOS and was associated with a decrease in apoptosis of ovarian follicular cells. Velázquez et al. found the most intense HSP70 immunostaining in the granulosa and theca cells of cystic follicles of rats with induced PCOS compared to other follicular cell types [
38
]. In a study in a dehydro-epiandrosterone (DHEA)-induced PCOS rat model, HSP70 was found to be significantly increased in ovarian tissues of the PCOS versus the control group, but also significantly reduced in serum [
33
]. This increase in HSP70 may contribute to apoptosis in the ovarian tissues of women with PCOS because HSP70 and its co-chaperone, dj2, can affect apoptosis by preventing the Bcl-2 family protein, Bax, from translocating from the cytosol to the mitochondria [
39
].
The imbalance between apoptosis and antiapoptosis in the ovaries of patients with PCOS has also been demonstrated in studies focused upon HSP10. Downregulation in HSP10 expression in human granulosa cells of PCOS versus normal ovaries has been reported [ 40 ]. In a recent study, mouse granulosa cells demonstrated low levels of HSP10 when injected with testosterone and displayed poor viability, suggesting that HSP10 is a downstream factor in ovarian granulosa cell apoptosis [ 41 ]. Lower expression of HSP10 was associated with the upregulation of proapoptotic factors such as Bax, caspase-9, and caspase-3 [ 41 ]. Reduced expression of HSP10 was associated with the downregulation of the antiapoptotic factors Bcl-2, phosphorylated-ERK, and Ki67 [ 41 ]. Overexpression of HSP10 demonstrated opposite effects [ 42 ]. Hyperandrogenic conditions lowered HSP10 expression and consequently induced apoptosis in mouse granulosa cells [ 41 ].
Similarly, proteomic analysis has shown that small HSPs, such as HSP27, an antiapoptotic protein, are downregulated in the oocytes of women with PCOS [ 40 ]. In a study on mouse oocytes, downregulation of HSP27 improved oocyte maturation and led to early-stage apoptosis, thus countering the atretic follicles found in PCOS [ 43 ]. To further elucidate the role of HSP27 in oocyte development, a study employing overexpression of HSP27 found a reduced oocyte maturation rate and reduced expression of apoptotic-related factors in women with PCOS [ 44 ]. This scenario can lead to the development of multiple small antral follicles [ 44 ]. These HSP27-induced mechanisms can play a role in the altered fertility of patients with PCOS as lower expression of HSP27 can lead to abnormal oocyte development, characteristic of PCOS. Other small HSPs, for example α-crystallin, have also been found to be associated with endocrine disorders in women. Elevated levels of anti-α-crystallin antibodies were found in patients with PCOS, due to the overproduction of α-crystallin in response to oxidative stress and chronic inflammation in PCOS [ 45 ].
Taken together, these findings indicate that the rate of granulosa cell proliferation and apoptosis is affected in women with PCOS and can lead directly to the development of PCOS. Das et al. observed fewer apoptotic granulosa cells and increased proliferation rates in the PCOS anovulatory follicles versus normal ovulatory follicles [ 37 ]. Furthermore, activated caspase-3, a functionally required protein for granulosa cell apoptosis, was found to be significantly reduced [ 37 ]. In addition, increased gene expression of inhibitors of apoptotic proteins (IAP) and Bcl-X Long (an antiapoptotic factor) and downregulated expression of Bax (proapoptotic) were reported [ 37 ]. By contrast, lower proliferation rates were reported in granulosa follicles of rats with induced ovarian cysts [ 46 ]. These results are consistent with other animal studies [ 42 , 47 ]. However, an increase in proliferation can be attributed to the high levels of androgens that occur in human PCOS, but not in induced animal models. The evidence is also conflicting, since other studies on DHEA-induced PCOS rats found apoptosis of granulosa cells to be increased and an imbalance of Bcl-2 family members [ 48 ]. Moreover, it should be noted that the unknown nutritional conditions and other stress factors of the animal models used in the studies could also influence the expression of HSPs and thus affect the results. Regardless, there is strong evidence that an imbalance between apoptosis and proliferation can serve as a mechanism to impact follicle development and lead to polycystic ovaries. HSPs appear to play a role in this aberrant folliculogenesis in women with PCOS.
HSPs can also lead to immunological abnormalities in PCOS. This is of significance since the breakdown of immune homeostasis has been linked to the pathogenesis of PCOS [
5
]. In a cross-sectional study, the significantly higher levels of HSP70 in the PCOS cohort were correlated with the regulatory T cell (Treg)/T helper cell 17 (Th17) ratio [
32
]. Th17 cells produce an inflammatory autoimmune response, whereas Treg cells inhibit this inflammatory phenomenon. In this way, these two cells balance each other functionally and maintain homeostasis of the immune system. Serum HSP70 levels were negatively correlated with the Treg/Th17 ratio, indicating that high levels of HSP70 promote the expression of the Th17 gene [
32
]. This may be because of HSP70’s ability to enhance the immune response under stress. Blocking the function of HSP70 can lead to a reduction in the inflammatory response in women with PCOS [
32
]. This demonstrates that HSPs may not only change their expression profiles in PCOS and affect the rates of proliferation and apoptosis, but also affect the immunological pathogenesis.
The factors regulating the HSPs in PCOS have not been fully elucidated. However, emerging evidence suggests that non-coding RNAs (ncRNAs) may play an important role in heat responses and the regulatory mechanisms of HSPs. The ncRNAs (which do not encode a protein) are a class of regulatory RNAs including microRNAs (miRNAs), small interfering RNAs (siRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Among ncRNAs, lncRNAs have been reported to be involved in the regulation of the heat stress (HS) response in some species [ 49 , 50 , 51 , 52 ]. The “non-coding” part of the lncRNA may be involved in the rapid and coordinated reshaping of protein-coding gene expression [ 53 ]. The mechanism of lncRNA actions in regulating HS may involve interaction with the transcription factor heat shock transcription factor 1 (HSF1) [ 54 ] or feedback regulation of key stress response proteins encoded by the pseudo-gene of HSP70 [ 55 , 56 ]. In a well-established HS-rat model, potential functions of lncRNA as transcriptional regulators of the HS response have been found in the liver and adrenal glands [ 57 ], indicating the involvement of lncRNAs in regulating HSPs in a wide variety of tissues. Previous research has demonstrated the significant differential expression of small ncRNAs (sncRNAs) in serum, granulosa cells (GCs), follicular fluid (FF), and other tissues between women with PCOS and healthy control women [ 58 , 59 ]. Moreover, the dysregulation of lncRNAs in PCOS and the potential influence of lncRNAs in the pathogenesis of PCOS have also been reported [ 60 ]. Taken together, it is tempting to speculate that, in PCOS, the molecular mechanisms of heat stress responses (mediated by HSPs) involve non-coding RNAs (ncRNAs).
The evidence for the role of HSPs in the pathogenesis of PCOS is summarized in Table 1 . Moreover, HSPs may also play a part in the pathogenesis of conditions associated with PCOS, such as diabetes and obesity.
Table 1. A summary of the evidence relating to the role of HSPs in the pathogenesis of PCOS.
4. The Role of Heat Shock Proteins in Type 2 Diabetes
The risk of T2D is significantly increased in women with PCOS [ 61 ], to the extent that PCOS has been identified as a significant non-modifiable risk factor associated with T2D by the International Diabetes Federation [ 62 ] and by the American Diabetes Association [ 63 ]. Literature regarding the involvement of HSPs in the mechanism of PCOS and diabetes exists but is limited. For example, HSP70 serum levels were increased in women with PCOS, and this was associated with insulin resistance (IR), low-grade chronic inflammation, and oxidative stress, indicating that HSP70 could potentially serve as an independent marker for PCOS [ 14 ]. HSP70 levels were higher in patients with diabetes versus controls, especially in patients who had diabetes for longer than 5 years [ 64 ]. HSP70 leads to IR and may lead to diabetes, but this relationship seems to be bidirectional; IR can also facilitate the accumulation of HSP70 in the body [ 65 ]. This provides evidence for a link between HSP70 and IR. However, conversely, a study of Caucasian subjects with T2D found reduced expression of the HSP70 gene [ 66 ]. A study on mice also found increased expression of the related HSP72 that protects against insulin resistance by preventing the phosphorylation of inflammatory signaling proteins [ 67 ].
Other HSPs have been implicated in the pathogenesis of diabetes. HSP40/DNAJB3 was significantly decreased in obese and diabetic subjects, and this expression was upregulated with a regular exercise protocol [
68
]. Diabetic mice had reduced expression of HSP60 in the brain, which was suggested to cause mitochondrial dysfunction and IR in the hypothalamus [
69
]. The expression of heat shock factor protein 1 was also altered in the islets of rat models of spontaneous T2D [
70
]. These results indicate that HSPs are involved in insulin resistance, but there are minimal studies on the direct involvement of HSPs in the pathogenesis of PCOS women with diabetes.
Similarly, gaps in the literature exist for the role of HSP72 in the development of diabetes. The expression of intramuscular HSP72 was reduced in patients with T2D [ 71 ], and this decreased expression has been inversely correlated with IR [ 66 ]. The low expression can contribute to a higher risk of IR and, consequently, diabetes.
Furthermore, reduced HSP72 expression during endoplasmic reticulum stress can lead to beta cell dysfunction and reduced insulin secretion [ 72 ]. This is of concern since HSP72 is reduced in women with obesity, and obesity is common in women with PCOS [ 67 ]. Mice lacking HSP72 were phenotypically obese and had insulin resistance in skeletal muscle and glucose intolerance [ 73 ]. Even in healthy individuals, reduced levels of HSP72 in skeletal muscle were associated with decreased insulin sensitivity and increased adiposity [ 74 ]. However, a recent study on T2D mice and humans did not find HSP72 to be reduced in T2D, nor did it find reduced HSP72 to be associated with IR in T2D [ 75 ]. This conflicting evidence warrants further research with regard to the role of HSPs in T2D and PCOS.
5. The Role of Heat Shock Proteins in Obesity
Obesity is another common finding in women with PCOS. Anywhere from 38 to 88% of women with PCOS are overweight or obese [ 76 ]. Even moderate weight loss can result in clinically beneficial improvements in the metabolic features of PCOS [ 76 ]. In women with PCOS, saturated fat ingestion can stimulate a proatherogenic inflammatory response, even in non-obese women with PCOS [ 77 ]. This response is enhanced by the combination of PCOS and obesity [ 78 ]. In a study on women with PCOS, ingestion of saturated fat led to a more significant increase in serum HSP70 levels in lean women with PCOS compared to lean controls and in obese women with PCOS compared to obese controls [ 78 ]. HSP70 was one of the proatherogenic inflammatory markers identified in this study; however, the inflammatory response was more significant in the setting of PCOS and obesity combined versus obesity alone [ 78 ]. In addition, HSP70 was inversely correlated with insulin sensitivity [ 78 ]. This suggests a mechanism through which women with PCOS are susceptible to atherogenesis [ 78 ].
Other studies have also linked HSPs to obesity, but research using PCOS samples is limited. HSP72 can reduce inflammation and prevent insulin resistance induced by diet or obesity [ 67 ]. However, obesity was linked with the reduced expression of HSP72 and increased JNK phosphorylation in skeletal muscle [ 67 ]. Intracellular HSP70 and HSP27 miRNA expression levels were significantly reduced in obese subjects with metabolic syndrome compared with obese subjects without metabolic syndrome [ 77 ], a finding applicable to PCOS since metabolic syndrome is present in 33% of women with PCOS [ 79 ]. Serum HSP60 levels were higher in obese versus lean subjects, and bariatric surgery reduced circulating HSP60 [ 80 ]. These studies provide evidence that HSPs may play a role in the pathogenesis of obesity, but further studies are necessary to investigate its role in women with PCOS with stratification of lean, overweight, or obese body mass indices.
6. Therapeutic Interventions
Due to the complex and largely unknown pathogenesis of PCOS, researchers have not yet been able to pinpoint an exact cause, nor have they found a definitive treatment for the condition. However, HSPs play a significant role in the progression of this multifactorial disorder. Abnormal levels of HSPs are a common finding in women with PCOS, and it has been established that they are involved in many aspects of the condition, making them suitable targets for possible treatments. Nevertheless, in searching for an effective way to modify HSPs, the reported evidence is contradictory. This suggests that HSPs cannot broadly be labeled as “good” or “bad”, but simply integral factors in the mechanism of PCOS that, once disrupted, contribute to its pathogenesis and can potentially be modulated to alleviate the condition. In the following sections, we explore the various evidence-based therapies for PCOS and their association with HSPs.
6.1. Induction of Heat Shock Proteins through Exercise
Following diagnosis, exercise and lifestyle are first-line therapies advised for women with PCOS. This approach is mainly associated with increased HSPs in the body in response to stressors such as exercise. PCOS is an inflammatory disorder, and HSPs are known to be induced following stressors such as inflammation and oxidative stress [
81
]. HSP70 and HSP72 can block heat-induced apoptosis, which occurs through SAPK/JNK stimulation [
82
]. These proteins inhibit steps that occur upstream and play a role in minimizing the cleavage of poly (ADP-ribose) polymerase, a common death substrate protein [
82
]. Exercise induces the expression of HSPs, which would increase the inhibition of apoptosis and molecular damage as a result of disturbances in cell homeostasis in inflammatory states [
83
].
In one study, an 8-week moderate-intensity exercise program was performed to explore the effects of exercise on inducing the expression of HSPs and determine if this process is efficient in women with PCOS versus controls [
15
]. By the completion of the experiment, both groups showed some improvement in VO
2
max, waist–hip ratio, BMI, and systolic blood pressure; however, these results were seen to a much lesser extent in the PCOS cohort. As for HSP72 expression in monocytes and lymphocytes, the control group showed a significant increase, while the increased trend in the PCOS cohort was not significant [
15
]. Thus, it was concluded that the HSP response to exercise was impaired in women with PCOS compared to the control group, and it was suggested that high-intensity exercise could have more favorable effects in inducing HSP activity [
15
]. It is, however, important to note that the small sample size, inability to evaluate the influence of obesity, and failure to measure serum HSP levels could have affected the outcomes of this study.
Further research into alternative methods to effectively induce HSPs, such as high-intensity interval training and resistance training, could have therapeutic implications for women with PCOS. Weightlifting has also been shown to be suitable for women with PCOS because it decreases testosterone levels, lowers IR, and, most importantly, increases metabolic rate [ 84 ]. More extensive studies are needed on this treatment approach as the exact association of these approaches with HSPs has not been adequately investigated.
6.2. Heat Shock Therapy
The role of heat shock therapy could be promising for patients with PCOS. A study has shown that heat therapy decreases sympathetic activity and enhances cardiovascular health in obese women with PCOS [
85
]. Heat therapy comprises several approaches, such as using a sauna, hot tub, and combined exercise heat stress [
86
]. This could be a promising approach since it has been clinically proven to improve cardiometabolic health in obese people [
85
]. Since obesity and PCOS both have potential cardiovascular risks, exploring and comparing heat shock therapy in both pathological conditions would be of interest.
It is important to note that there are not many pharmaceutical or lifestyle interventions that would decrease the cardiovascular risk for women with PCOS [ 85 ]. Most research and treatment options aimed at decreasing cardiovascular risk target men, thus it is crucial to further explore options and therapeutic interventions that can help women who have cardiovascular risk factors, including women with PCOS.
One study has found that, through a program of 30 one-hour heat therapy sessions conducted on obese women with PCOS, there were improvements in carotid and femoral artery wall thickness and decreased total cholesterol and fasting glucose [ 85 ]. Heat therapy clinically improved indicators of PCOS, such as lowering serum testosterone and normalizing menstrual cycles [ 87 ]. This emphasizes the role of heat therapy in metabolic and ovarian function in women with PCOS [ 87 ]. Another study showed that heat therapy in obese women with PCOS improved PCOS symptoms, systemic insulin sensitivity, whole-body glucose uptake, and insulin signaling in subcutaneous adipose tissue [ 87 ]. A single heat treatment lasting 20 min increased HSP72 levels maximally in all depots of white adipose tissue and also improved insulin signaling [ 88 ]. The beneficial improvements due to heat therapy can be attributed to increased levels of HSPs which act to inhibit inflammatory factors such as JNK [ 88 ]. Low levels of HSPs were found in adipose tissue of T2D patients, further supporting the association between increased levels of HSPs and metabolic health [ 89 ].
Nonetheless, these studies have limitations as they only included obese women with PCOS. Future research regarding heat therapy in non-obese women with PCOS remains to be explored. Further studies are also needed to analyze the effects of chronic heat treatment on the activity of HSPs.
6.3. Induction of HSPs to Treat Insulin Resistance
Although limited research has been conducted on the direct use of HSPs as therapy for PCOS, HSPs have been proven to combat insulin resistance. Patients with T2D were shown to have reduced gene expression of HSP72 [
67
]. According to a model proposed by Hooper and Hooper (2009), this decrease in HSPs is due to insulin resistance stimulated by inflammation in obesity [
15
]. When fatty acid levels are elevated in muscle fibers, this stimulates the formation of diacylglycerol and the activation of protein kinase C [
90
]. This leads to the phosphorylation of a critical residue on insulin receptor substrate-1 by IKK-beta and JNK, preventing the substrate from effectively interacting with the active insulin receptor [
90
]. HSP27 and HSP72 can prevent the activation of IKK-beta and JNK, thus allowing IRS-1 to appropriately bind to the receptor.
The use of bimoclomol and lipoic acid, inducers/co-inducers of HSPs, in obese rodents with insulin resistance was proven to improve insulin sensitivity [
90
]. BPG-15, another co-inducer of HSPs, was tested on insulin-resistant patients versus placebo and resulted in a notable increase in insulin sensitivity and glucose utilization [
91
]. This hypothesis was also tested on human subjects using heat shock therapy, transgenic overexpression in rodent models, and pharmacological drugs to induce HSP72 locally in skeletal muscle (as JNK phosphorylation was thought to be increased in skeletal muscle) [
67
]. Data showed that the increased expression of HSP72 prevented the phosphorylation of JNK and thus decreased diet/obesity-induced hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance [
67
].
Another study further tested the effects of HSPs using mild electrical stimulation (MES) in combination with heat shock [
92
]. Different doses and durations were tested in vivo and in vitro. This combined treatment for 10 min, twice weekly, could lower insulin resistance, insulin levels, and fasting blood glucose. In mice, this treatment stimulated the insulin signaling pathway and thus improved fat metabolism [
92
]. HSP70 was also shown to protect against oxidative stress injury in diabetes and insulin resistance. This action is stimulated by the reduced release of nitric oxide, which leads to inflammation and simultaneously induces HSP70 in an attempt to reduce it [
93
]. Considering that insulin resistance is a major symptom of PCOS, treating this aspect alone would undeniably improve patient quality of life. However, additional research exploring the effects of HSP induction on women with insulin resistance and PCOS is needed to ensure that these findings have therapeutic relevance.
6.4. Repression of Heat Shock Proteins through miRNAs
Although HSPs are generally believed to have a protective role, there is evidence suggesting that HSPs play a role in exacerbating the progression of PCOS [ 94 ]. MicroRNAs play a significant role in various diseases, such as cancers, metabolic disorders, and PCOS. HSP function is regulated by differing miRNAs, and hence, they have been a common target for experimental cancer therapies [ 95 ]. Researchers have applied the same methodology to PCOS because of the known involvement of miRNAs in the condition. The presence of miRNAs in follicular fluid allows them to influence follicular development and regulate dysfunction in granulosa cells that could otherwise lead to abnormalities such as PCOS [ 94 ]. An experiment conducted on DHT-induced rats revealed that 24% of potential miRNAs were differentially expressed in the PCOS group versus controls [ 94 , 96 ]. Another study used an RNase III enzyme necessary for the biogenesis of miRNAs, Dicer 1, to showcase their effects on ovarian function [ 5 ]. Knockout of Dicer 1 in mice led to infertility, decreased ovarian weight, decreased ovulation, disrupted the formation of the corpus luteum, and increased synthesis of cysts on the oviducts [ 5 ].
Due to the prevalence of miRNAs in ovarian function and their ability to influence heat shock activity, a study investigated the use of miR-144-3p to reduce HSP activity and whether that would yield favorable results in women with PCOS [
94
]. Initially, decreased expression of miR-144-3p and increased HSP70 expression were found in women with PCOS [
94
]. The miRNA was then upregulated/downregulated to measure its effects on HSPs. Upregulation of miR-144-3p led to stimulation of granulosa cell survival/proliferation and repressed cell apoptosis. Furthermore, an inhibitory effect on serum testosterone, estrogen, and LH levels was observed, and FSH was increased. Downregulation of the protein had opposite effects and contributed to the progression of endocrine disorders and ovarian weight. HSP70 was also confirmed as a direct target, as its expression was reduced by miR-144-3p mimics and induced by inhibitors. Decreased HSP70 levels improved granulosa cell proliferation, reduced apoptosis, decreased abnormal ovarian weight, and benefited endocrine disorders.
Anti-miR-144-3p applied in vivo increased serum testosterone, estradiol, and LH, but knockdown of HSP70 was able to minimize this increase [ 94 ]. Hence, targeting miRNAs could be a promising avenue for treating PCOS, but further research is necessary to increase knowledge about this therapeutic approach.
Besides miR-144-3p, using other microRNAs to modulate HSP activity might yield useful results as a treatment option for PCOS. Table 2 summarizes the roles of different microRNAs in regulating the activity of HSPs. However, it should be noted that limited research is available on the effect of microRNAs on the activity of HSPs in the context of PCOS.
Table 2. A list of possible microRNAs and their role in the regulation of HSPs. These microRNAs may act as potential treatment options for modulating the activity of HSPs to yield favorable results in women with PCOS.
Despite these promising findings, there are some obstacles to using HSPs therapeutically. It is challenging to ensure that the specific HSP is upregulated in the intended tissue, at the correct level/specificity, and at a suitable time together with all the necessary co-chaperones present to yield the desired results [ 101 ]. It is likely that pharmaceutical inducers may not be able to reach the desired cells or bring about the intended effects. Moreover, research combining heat therapy and exercise has still not been explored, which could potentially be promising for considering the additive benefits of both therapeutic interventions.
7. Future Directions
Research to date on the role of HSPs in the pathogenesis of PCOS is limited.
Further research is warranted in the following areas:
Studies to elucidate the detailed molecular mechanisms underlying the function of HSPs in human ovarian cells, as modulating the activity of HSPs may lead to novel strategies for treating PCOS.
Further studies focusing upon on the expression profiles and mutations of the different HSPs in ovarian cell function, as current information is limited.
Studies need to be conducted on the therapeutic and prognostic relevance of expression profiles of HSPs. There is limited research on the involvement of HSPs in the pathogenesis of diabetes for example using PCOS as a model.
Studies of the effects of HSPs on PCOS pathophysiology using human samples, as a key limitation is the dearth of information in this area and studies on mouse oocyte models in vitro may not simulate PCOS oocyte development.
Adequately powered studies are needed to address the influence of HSPs on lean, overweight, and obese cohorts with and without PCOS.
Studies in PCOS populations of differing ethnicity are needed to determine the generalizability of findings across ethnic groups.
Studies employing targeted manipulation of HSPs to determine their potential clinical utility for treating PCOS and its related conditions.
8. Conclusions
The available data suggest that HSPs play a role in the pathogenesis of PCOS and its sequelae. The differing expression levels of HSPs in ovarian tissues of women with PCOS can affect cell apoptosis and proliferation, as well as follicle development. High levels of HSP70 can also increase the expression of Th17 genes, which may disrupt immune homeostasis and increase inflammation. Abnormal expression of HSPs is also found in T2D patients, and there is evidence for an association between HSPs and IR. HSPs may also play a role in the pathogenesis of obesity through inflammatory mechanisms that are amplified by the combination of PCOS and obesity. Research on therapeutic interventions for PCOS indicates that the HSP response to moderate-intensity exercise may be impaired in women with PCOS. Heat therapy, as a therapeutic intervention, increased HSP levels in PCOS subjects and improved metabolic health through HSP-mediated inhibition of inflammatory factors. Furthermore, the modulation of the activity of HSPs for the reduction of insulin resistance and the repression of HSPs through miRNAs were also shown to alleviate symptoms of PCOS. Despite this promising research, more studies using human samples are needed to define in detail the mechanisms by which HSPs impact ovarian cells, their role in the pathogenesis of PCOS and its related conditions, and their potential use as therapeutic interventions. The contradictory evidence concerning the levels of different HSPs and their specific roles in ovarian tissue most definitely requires further study.
Funding
Institutional Review Board Statement
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Figure 1. The clinical manifestations of PCOS in women.
Figure 2. The molecular mechanism for the synthesis of heat shock proteins (HSPs). Under physiological conditions, an HSP and a heat shock factor (HSF) are a complex found in the cytosol in an inactive state. However, stressors such as UV radiation, viral infection, heavy metal exposure, oxidative stress, hypothermia, hyperthermia, and cancer cause HSFs to become detached from HSPs. HSFs undergo phosphorylation and trimerization. Once inside the nucleus, they bind to heat shock elements (HSEs), initiating transcription. The HSP mRNAs then leave the nucleus and are translated, synthesizing new HSPs. These HSPs then act as molecular chaperones and bind to polypeptide chains to prevent misfolding of proteins. To protect cells, HSPs also repair and refold damaged proteins under stressful conditions.
Figure 3. The effect of heat-shock proteins (HSPs) on the pathogenesis of polycystic ovary syndrome (PCOS). ( Left panel ) The stages of oogenesis in the ovary and the structure of a mature follicle. HSPs function at different stages of oogenesis in PCOS. HSP27 negatively regulates oocyte maturation and was downregulated in women with PCOS. ( Right panel ) Intracellular mechanisms of action of HSPs in a granulosa cell (shown in a small green square) of a mature follicle. HSP70 binds to the cell surface toll-like receptor 4 (TLR4) and co-receptor myeloid differentiation protein 2 (MD2). HSP90 binds to the cell surface low-density lipoprotein (LDL)-related protein-1 (LRP-1) in association with clusterin (CLU). Downstream signaling of both HSP70 and HSP90 (phosphorylation of protein kinase B, AKT) leads to the activation of NF-ĸB, a novel transcription factor that regulates the transcription of genes related to cell survival and protection. HSP90 and its co-chaperone DJ2 (HSDJ/hdj-2/rdj1) inhibit mitochondrial proapoptotic Bcl-2 associated X-protein (BAX). HSP90, in association with HSP70, potentiates the mitochondrial antiapoptotic protein B-cell lymphoma 2 (BCL2). HSP10 regulates the transcription of multiple proteins related to cellular apoptosis. Cas-3, caspase-3; Cas-9, caspase-9; p-ERK, phosphorylated extracellular signal associated kinase; Ki67, marker of proliferation Ki-67. Downward orange arrows labeled “PCOS” indicate the HSPs that were found to be downregulated in PCOS in previous publications. This illustration was created using biorender.com (with publication license).
Table 1. A summary of the evidence relating to the role of HSPs in the pathogenesis of PCOS.
Authors Year HSPs Aim of the Study Main Findings Li L et al. [ 11 ] 2016 90B1 To analyze protein expression profiles in the ovarian tissues of subjects with PCOS HSP90B1’s expression was increased by at least 2-fold and associated with the proliferation and survival of ovarian cells Velázquez MML et al. [ 38 ] 2013 27 and 60 To analyze HSP expression changes in bovine ovaries with cystic ovarian disease (COD) (induced by ACTH) Induced COD caused differences in HSP protein expression Wu G et al. [ 33 ] 2016 70 To study the correlation between HSP70 and hormones and inflammatory factors and investigate the role of HSP70 in the pathogenesis of PCOS HSP70 showed abnormal expression in PCOS, which correlated with testosterone and inflammatory factors Zhao K-K et al. [ 41 ] 2013 10 To determine the effect of HSP10 on apoptosis induced by testosterone in granulosa cells of mouse ovaries Testosterone may reduce HSP10 expression in granulosa cells causing reduced Bcl-2 expression and increased Bax expression Liu J-J et al. [ 43 ] 2010 27 To investigate the effects of HSP27 downregulation on oocyte development Reduction in HSP27 levels improved the maturation of mouse oocytes and increased the early stage of apoptosis in oocytes Cai L et al. [ 44 ] 2013 27 To investigate the effects of upregulation of HSP27 on oocyte development and maturation in PCOS Upregulation of HSP27 led to inhibition of oocyte maturation in women with PCOS Yang Y et al. [ 32 ] 2021 70 To study the correlation between HSP70 and Treg/Th17 ratio Abnormal levels of HSP70 were correlated with Treg/Th17 imbalance, indicating that HSP70 plays a role in PCOS immunological pathogenesis
| https://www.mdpi.com/1422-0067/24/3/1838/xml |
To James Madison from the Citizens of Columbia, South Carolina …
To James Madison from the Citizens of Columbia, South Carolina, 30 June 1812 (Abstract)
To James Madison from the Citizens of Columbia, South Carolina, 30 June 1812 (Abstract)
§ From the Citizens of Columbia, South Carolina
“It was impossible to forget that the protection of the national arm is due by the social compact to those who make the Mountain wave their home, as well as to the Cultivators of the Earth.
“The Injuries perpetrated on our Commerce, and the violations of the personal freedom of our Fellow Citizens have therefore been keenly resented as national injuries by every Man who had the sense to discern, and the patriotism to feel, that his individual happiness is bound up in the National prosperity.
“Still however as War and Conquest form no part of the Code of our Country, as Peace and justice form the standing policy of our National Institutions, we have approved the cautious conduct of our Government, which exhausted every source of Negociation before it would resort to the horrors of war. But forbearance ceases to be a virtue, when the hope of redress has vanished, such a spirit would necessarily lead to submission; to the resignation of our dearest rights, and to the prostration of the national Character. This could not be endured. Our Government has at last taken its stand, and proclaimed war against that Belligerent which pressed most heavily on our rights, whilst the wrongs of the other Belligerent are not forgotten.
“In this awful appeal to arms we are entirely satisfied that the Government of our Country is well warranted; for we conscientiously believe that the outrages of Great Britain as well as France had long since furnished just cause of war. And though divisions have heretofore prevailed among our Fellow Citizens on many measures of Government; we trust that the sound of war will be the signal of Union, that Party Spirit will cease, and that every Man who is sincerely attached to our inestimable Constitution, and to the Principles of Republican Government secured by it, will rally around the Constituted authorities.
“The Maintenance of our National Union, the Agis of our safety required this determination, and the justice of our cause sanctifies this resolution.
“We do therefore solemnly pledge ourselves to support with our lives and fortunes the Government of the United States in all proper Measures calculated to ensure a vigorous prosecution of the just war in which it is at present engaged, until it shall obtain through a safe and honorable Peace, the firm establishment of the rights which are the object of the war.
“And we humbly trust that the God of our Fathers who led us to this goodly Land, and established us therein, and supported us in our struggle for Independence, will be pleased to strengthen our Arms, and fortify our hearts, to maintain this contest with the resolution becoming Freemen.”
RC( DNA: RG59, ML). 4 pp. Signed by Henry William Desaussure and four others.
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To James Madison from the Citizens of Columbia, South Carolina, 30 June 1812 (Abstract)
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30 June 1812
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“To James Madison from the Citizens of Columbia, South Carolina, 30 June 1812 (Abstract),” Founders Online, National Archives, https://founders.archives.gov/documents/Madison/03-04-02-0560. [Original source: The Papers of James Madison , Presidential Series, vol. 4, 5 November 1811–9 July 1812 and Supplement 5 March 1809 – 19 October 1811 , ed. J. C. A. Stagg, Jeanne Kerr Cross, Jewel L. Spangler, Ellen J. Barber, Martha J. King, Anne Mandeville Colony, and Susan Holbrook Perdue. Charlottesville: University Press of Virginia, 1999, pp. 523–524.]
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BIDEN AMENDMENT NOS. 1972 THROUGH 1974
BIDEN AMENDMENT NOS. 1972 THROUGH 1974
(Senate - June 06, 1990)
[Page: S7502]
(Ordered to lie on the table.)
Mr. BIDEN submitted three amendments intended to be proposed by him to the bill S. 1970, supra, as follows:
Amendment No. 1972
At the appropriate place in the bill, add the following:
SECTION . RAILROAD POLICE AUTHORITY.
A railroad police officer who is employed by a rail carrier and certified or commissioned as a police officer under the laws of any State shall, in accordance with regulations issued by the Secretary of Transportation, be authorized to enforce the laws of any jurisdiction in which the rail carrier owns property, for the purpose of protecting--
(1) the employees, passengers, or patrons of the rail carrier;
(2) the property, equipment, and facilities owned, leased, operated, or maintained by the rail carrier;
(3) property moving in interstate or foreign commerce in the possesson of the rail carrier; and
(4) personnel, equipment, and materials moving via railroad that are vital to the national defense,to the extent of the authority of a police officer properly certified or commissioned under the laws of that jurisdiction.
Amendment No. 1973
In lieu of the matter proposed to be inserted, insert the following:
TITLE I--DEATH PENALTY
SEC. 101. SHORT TITLE.This title may be cited as the `Federal Death Penalty Act of 1989'.
SEC. 102. CONSTITUTIONAL PROCEDURES FOR THE IMPOSITION OF THE SENTENCE OF DEATH.(a)In General: Part II of title 18 of the United States Code is amended by adding the following new chapter after chapter 227:
`CHAPTER 228--DEATH SENTENCE
`Sec.
`3591. Sentence of death.
`3592. Factors to be considered in determining whether a sentence of death is justified.
`3593. Special hearing to determine whether a sentence of death is justified.
`3594. Imposition of a sentence of death.
`3595. Review of a sentence of death.
`3596. Implementation of a sentence of death.
`3597. Use of State facilities.
`3591. Sentence of death`A defendant who has been found guilty of--
`(a) an offense described in section 794 or section 2381 of this title;
`(b) an offense described in section 1751(c) of this title, if the offense, as determined beyond a reasonable doubt at the hearing under section 3593, constitutes an attempt to kill the President of the United States and results in bodily injury to the President or comes dangerously close to causing the death of the President; or
`(c) any other offense for which a sentence of death is provided, if the defendant, as determined beyond a reasonable doubt at the hearing under section 3593--
`(1) intentionally killed the victim;
`(2) intentionally inflicted serious bodily injury that resulted in the death of the victim;
`(3) intentionally participated in an act, contemplating that the life of a person would be taken or intending that lethal force would be used in connection with a person, other than one of the participants in the offense, and the victim died as a direct result of the act; or
`(4) intentionally and specifically engaged in an act, knowing that the act created a grave risk of death to a person, other than one of the participants in the offense, such that participation in the act constituted a reckless disregard for human life and the victim died as a direct result of the act,shall be sentenced to death if, after consideration of the factors set forth in section 3592 in the course of a hearing held pursuant to section 3593, it is determined that imposition of a sentence of death is justified; provided that no person may be sentenced to death who was less than 17 years of age at the time of the offense.
`3592. Factors to be considered in determining whether a sentence of death is justified`(a)Mitigating Factors:In determining whether a sentence of death is to be imposed on a defendant, the finder of fact shall consider mitigating factors, including the following:
`(1) The defendant's capacity to appreciate the wrongfulness of the defendant's conduct or to conform conduct to the requirements of law was significantly impaired, regardless of whether the capacity was so impaired as to constitute a defense to the charge.
`(2) The defendant was under unusual and substantial duress, regardless of whether the duress was of such a degree as to constitute a defense to the charge.
`(3) The defendant is punishable as a principal (as defined in section 2 of title 18 of the United States Code) in the offense, which was committed by another, but the defendant's participation was relatively minor, regardless of whether the participation was so minor as to constitute a defense to the charge.
`(4) The defendant could not reasonably have foreseen that the defendant's conduct in the course of the commission of murder, or other offense resulting in death for which the defendant was convicted, would cause, or would create a grave risk of causing, death to any person.
`(5) The defendant did not have a significant prior criminal record.
`(6) The defendant committed the offense under severe mental or emotional disturbance.
`(7) The victim consented to the criminal conduct that resulted in the victim's death.
`(8) That other factors in the defendant's background or character mitigate against imposition of the death sentence.`(b)Aggravating Factors for Espionage and Treason:In determining whether a sentence of death is justified for an offense described in section 3591(a), the jury, or if there is no jury, the court, shall consider each of the following aggravating factors and determine which, if any, exist:
`(1) the defendant has previously been convicted of another offense involving espionage or treason for which either a sentence of life imprisonment or death was authorized by statute;
`(2) in the commission of the offense the defendant knowingly created a grave risk of substantial danger to the national security; and
`(3) in the commission of the offense the defendant knowingly created a grave risk of death to another person.The jury, or if there is no jury, the court, may consider whether any other aggravating factor exists.`(c)Aggravating Factors for Homicide and for Attempted Murder of the President:In determining whether a sentence of death is justified for an offense described in section 3591 (b) or (c), the jury, or if there is no jury, the court, shall consider each of the following aggravating factors and determine which, if any, exist:
`(1) the death, or injury resulting in death, occurred during the commission or attempted commission of, or during the immediate flight from the commission of, an offense under section 751 (prisoners in custody of institution or officer), section 794 (gathering or delivering defense information to aid foreign government), section 844(d) (transportation of explosives in interstate commerce for certain purposes), section 844(f) (destruction of Government property in interstate commerce by explosives), section 1118 (prisoners serving life term), section 1201 (kidnaping), or section 2381 (treason) of this title, or section 902 (i) or (n) of the Federal Aviation Act of 1958, as amended (49 U.S.C. 1472 (i) or (n)) (aircraft piracy);
`(2) the defendant has previously been convicted of another Federal or State offense resulting in the death of a person, for which a sentence of life imprisonment or a sentence of death was authorized by statute;
`(3) the defendant has previously been convicted of two or more Federal or State offenses, punishable by a term of imprisonment of more than one year, committed on different occasions, involving the infliction of, or attempted infliction of, serious bodily injury or death upon another person;
`(4) the defendant, in the commission of the offense, or in escaping apprehension for the violation of the offense, knowingly created a grave risk of death to one or more persons in addition to the victim of the offense;
`(5) the defendant committed the offense in an especially heinous, cruel, or depraved manner;
`(6) the defendant procured the commission of the offense by payment, or promise of payment, of anything of pecuniary value;
`(7) the defendant committed the offense as consideration for the receipt, or in the expectation of the receipt, of anything of pecuniary value;
`(8) the defendant committed the offense after planning and premeditation to cause the death of a person or commit an act of terrorism;
`(9) the defendant has previously been convicted of two or more State or Federal offenses punishable by a term of imprisonment of more than one year, committed on different occasions, involving the distribution of a controlled substance;
`(10) the victim was particularly vulnerable due to old age, youth, or infirmity;
`(11) the defendant had previously been convicted of violating title II or title III of the Controlled Substances Act for which a sentence of 5 or more years may be imposed or had previously been convicted of engaging in a continuing criminal enterprise;
`(12) the defendant violated section 408(c) of the Controlled Substances Act to the extent that the conduct described in section 408(c) of such Act was a violation of section 405 of such Act; or
`(13) the defendant committed the offense against--
`(A) the President of the United States, the President-elect, the Vice President, the Vice-President-elect, the Vice-President-designate, or, if there is no Vice President, the officer next in order of succession to the office of the President of the United States, or any person who is acting as President under the Constitution and laws of the United States;
`(B) a chief of state, head of government, or the political equivalent, of a foreign nation;
`(C) a foreign official listed in section 1116(b)(3)(A) of this title, if he is in the United States on official business; or
`(D) a Federal public servant who is a judge, a law enforcement officer, or an employee of a United States penal or correctional institution--
`(i) while he is engaged in the performance of his official duties;
`(ii) because of the performance of his official duties; or
`(iii) because of his status as a public servant.
For purposes of this subparagraph, a `law enforcement officer' is a public servant authorized by law or by a Government agency or Congress to conduct or engage in the prevention, investigation, or prosecution of an offense.The jury, or if there is no jury, the court, may consider whether any other aggravating factor exists.
[Page: S7503]
`3593. Special hearing to determine whether a sentence of death is justified`(a)Notice by the Government:If, in a case involving an offense described in section 3591, the attorney for the government believes that the circumstances of the offense are such that a sentence of death is justified under this chapter, he shall, a reasonable time before the trial, or before acceptance by the court of a plea of guilty, or at such time thereafter as the court may permit upon a showing of good cause, sign and file with the court, and serve on the defendant, a notice--
`(1) stating that the government believes that the circumstances of the offense are such that, if the defendant is convicted, a sentence of death is justified under this chapter and that the government will seek the sentence of death; and
`(2) setting forth the aggravating factor or factors that the government, if the defendant is convicted, proposes to prove as justifying a sentence of death.The court may permit the attorney for the government to amend the notice upon a showing of good cause.`(b)Hearing Before a Court or Jury:If the attorney for the government has filed a notice as required under subsection (a) and the defendant is found guilty of or pleads guilty to an offense described in section 3591, the judge who presided at the trial or before whom the guilty plea was entered, or another judge if that judge is unavailable, shall conduct a separate sentencing hearing to determine the punishment to be imposed. The hearing shall be conducted--
`(1) before the jury that determined the defendant's guilt;
`(2) before a jury impaneled for the purpose of the hearing if--
`(A) the defendant was convicted upon a plea of guilty;
`(B) the defendant was convicted after a trial before the court sitting without a jury;
`(C) the jury that determined the defendant's guilt was discharged for good cause; or
`(D) after initial imposition of a sentence under this section, reconsideration of the sentence under this section is necessary; or
`(3) before the court alone, upon the motion of the defendant and with the approval of the attorney for the government.A jury impaneled pursuant to paragraph (2) shall consist of twelve members, unless, at any time before the conclusion of the hearing, the parties stipulate, with the approval of the court, that it shall consist of a lesser number.
`(c)Proof of Mitigating and Aggravating Factors:Notwithstanding rule 32(c) of the Federal Rules of Criminal Procedure, when a defendant is found guilty or pleads guilty to an offense under section 3591, no presentence report shall be prepared. At the sentencing hearing, information may be presented as to any matter relevant to the sentence, including any mitigating or aggravating factor permitted or required to be considered under section 3592. Information presented may include the trial transcript and exhibits if the hearing is held before a jury or judge not present during the trial. Any other information relevant to a mitigating or aggravating factor may be presented by either the attorney for the government or the defendant, regardless of its admissibility under the rules governing admission of evidence at criminal trials, except that information may be excluded if its probative value is substantially outweighed by the danger of creating unfair prejudice, confusing the issues, or misleading the jury. The government and the defendant shall be permitted to rebut any information received at the hearing, and shall be given fair opportunity to present argument as to the adequacy of the information to establish the existence of any aggravating or mitigating factor, and as to the appropriateness in the case of imposing a sentence of death. The government shall open the argument. The defendant shall be permitted to reply. The government shall then be permitted to reply in rebuttal. The burden of establishing the existence of any aggravating factor is on the government, and is not satisfied unless the existence of such a factor is established beyond a reasonable doubt. The burden of establishing the existence of any mitigating factor is on the defendant, and is not satisfied unless the existence of such a factor is established by a preponderance of the information.`(d)Return of Special Findings:The jury, or if there is no jury, the court, shall consider all the information received during the hearing. It shall return special findings identifying any aggravating factor or factors set forth in section 3592 found to exist and any other aggravating factor for which notice has been provided under subsection (a) found to exist. A finding with respect to a mitigating factor may be made by one or more members of the jury, and any member of the jury who finds the existence of a mitigating factor may consider such factor established for purposes of this section regardless of the number of jurors who concur with the factor has been established. A finding with respect to any aggravating factor must be unanimous. If no aggravating factor set forth in section 3592 is found to exist, the court shall impose a sentence other than death authorized by law.
`(e)Return of a Finding Concerning a Sentence of Death:If, in the case of--
`(1) an offense described in section 3591(a), an aggravating factor required to be considered under section 3592(b) is found to exist; or
`(2) an offense described in section 3591 (b) or (c), an aggravating factor required to be considered under section 3592(c) is found to exist;the jury, or if there is no jury, the court, shall then consider whether all the aggravating factor or factors found to exist sufficiently outweigh all the mitigating factor or factors found to exist to justify a sentence of death, or, in the absence of a mitigating factor, whether the aggravating factor or factors alone are sufficient to justify a sentence of death. Based upon this consideration, the jury by unanimous vote, or if there is no jury, the court, shall recommend whether a sentence of death shall be imposed rather than some other lesser sentence. The jury or the court, if there is no jury, regardless of its findings with respect to aggravating and mitigating factors, is never required to impose a death sentence, and the jury shall be so instructed.`(f)Special Precaution To Assure Against Discrimination:In a hearing held before a jury, the court, prior to the return of a finding under subsection (e), shall instruct the jury that, in considering whether a sentence of death is justified, it shall not consider the race, color, religious beliefs, national origin, or sex of the defendant or of any victim and that the jury is not to recommend a sentence of death unless it has concluded that it would recommend a sentence of death for the crime in question no matter what the race, color, religious beliefs, national origin, or sex of the defendant or of any victim may be. The jury, upon return of a finding under subsection (e), shall also return to the court a certificate, signed by each juror, that consideration of the race, color, religious beliefs, national origin, or sex of the defendant or any victim was not involved in reaching his or her individual decision and that the individual juror would have made the same recommendation regarding a sentence for the crime in question no matter what the race, color, religious beliefs, national origin, or sex of the defendant or any victim may be.
`3594. Imposition of a sentence of death`Upon a finding under section 3593(e) that a sentence of death is justified, the court shall sentence the defendant to death. Upon a finding under section 3593(e) that a sentence of death is not justified, or under section 3593(d) that no aggravating factor required to be found exists, the court shall impose any sentence other than death that is authorized by law. Notwithstanding any other provision of law, if the maximum term of imprisonment for the offense is life imprisonment, the court may impose a sentence of life imprisonment without parole.
`3595. Review of a sentence of death`(a)Appeal:In a case in which a sentence of death is imposed, the sentence shall be subject to review by the court of appeals upon appeal by the defendant. Notice of appeal must be filed within the time specified for the filing of a notice of appeal. An appeal under this section may be consolidated with an appeal of the judgment of conviction and shall have priority over all other cases.`(b)Review:The court of appeals shall review the entire record in the case, including--
`(1) the evidence submitted during the trial;
`(2) the information submitted during the sentencing hearing;
`(3) the procedures employed in the sentencing hearing; and
`(4) the special findings returned under section 3593(d).`(c)Decision and Disposition:
`(1) If the court of appeals determines that--
`(A) the sentence of death was not imposed under the influence of passion, prejudice, or any other arbitrary factor; and
`(B) the information supports the special finding of the existence of an aggravating factor required to be considered under section 3592;
it shall affirm the sentence.
`(2) In any other case, the court of appeals shall remand the case for reconsideration under section 3593.
`(3) The court of appeals shall state in writing the reasons for its disposition of an appeal of a sentence of death under this section.
[Page: S7504]
`3596. Implementation of a sentence of death`(a) A person who has been sentenced to death pursuant to the provisions of this chapter shall be committed to the custody of the Attorney General until exhaustion of the procedures for appeal of the judgment of conviction and for review of the sentence. When the sentence is to be implemented, the Attorney General shall release the person sentenced to death to the custody of a United States marshal, who shall supervise implementation of the sentence in the manner prescribed by the law of the State in which the sentence is imposed. If the law of such State does not provide for implementation of a sentence of death, the court shall designate another State, the law of which does so provide, and the sentence shall be implemented in the latter State in the manner prescribed by such law.`(b) A sentence of death shall not be carried out upon a woman while she is pregnant.`(c) A sentence of death shall not be carried out upon a person who is mentally retarded. A sentence of death shall not be carried out upon a person who, as a result of mental disability--
`(1) cannot understand the nature of the pending proceedings, what such person was tried for, the reason for the punishment, or the nature of the punishment; or
`(2) lacks the capacity to recognize or understand facts which would make the punishment unjust or unlawful, or lacks the ability to convey such information to counsel or to the court.
`3597. Use of State facilities`(a)In General: A United States marshal charged with supervising the implementation of a sentence of death may use appropriate State or local facilities for the purpose, may use the services of an appropriate State or local official or of a person such an official employs for the purpose, and shall pay the costs thereof in an amount approved by the Attorney General.`(b)Excuse of an Employee on Moral or Religious Grounds: No employee of any State department of corrections or the Federal Bureau of Prisons and no employee providing services to that department or bureau under contract shall be required, as a condition of that employment, or contractual obligation to be in attendance at or to participate in any execution carried out under this section if such participation is contrary to the moral or religious convictions of the employee. For purposes of this subsection, the term `participation in executions' includes personal preparation of the condemned individual and the apparatus used for execution and supervision of the activities of other personnel in carrying out such activities.'.(b)Repeal: Sections 3566 and 3567 of title 18, United States Code, are hereby repealed.(c)Amendments to Chapter Analysis: (1) The chapter analysis of part II of title 18, United States Code, is amended by adding the following new item after the item relating to chapter 227:
`228. Death sentence
3591'.(2) The section analysis of chapter 227 of title 18, United States Code, is amended by amending the items relating to sections 3566 and 3567 to read as follows:
`3566. Repealed.
`3567. Repealed.'.
SEC. 103. CONFORMING CHANGES IN TITLE 18.(a)Aircrafts and Motor Vehicles: Section 34 of title 18, United States Code, is amended by striking the comma after `imprisonment for life' and inserting a period and striking the remainder of the section.(b)Espionage: Section 794(a) of title 18, United States Code, is amended by striking the period at the end of the section and inserting `, except that the sentence of death shall not be imposed unless the jury or, if there is no jury, the court, further finds that the offense directly concerned nuclear weaponry, military spacecraft or satellites, early warning systems, or other means of defense or retaliation against large-scale attack; war plans; communications intelligence or cryptographic information; or any other major weapons system or major element of defense strategy.'.
(c)Explosive Materials: (1) Section 844(d) of title 18, United States Code, is amended by striking `as provided in section 34 of this title'.(2) Section 844(f) of title 18, United States Code, is amended by striking `as provided in section 34 of this title'.(3) Section 844(i) of title 18, United States Code, is amended by striking the words `as provided in section 34 of this title'.(d)Murder: (1) The second undesignated paragraph of section 1111(b) of title 18, United States Code, is amended to read as follows:`Whoever is guilty of murder in the first degree shall be punished by death or by imprisonment for life;'.(2) Section 1116(a) of title 18, United States Code, is amended by striking `any such person who is found guilty of murder in the first degree shall be sentenced to imprisonment for life, and'.(e)Kidnapping: Section 1201(a) of title 18, United States Code, is amended by inserting after `or for life' the following: `and, if the death of any person results, shall be punished by death or life imprisonment'.(f)Nonmailable Injurious Articles: The last paragraph of section 1716 of title 18, United States Code, is amended by striking the comma after `imprisonment for life' and inserting a period and striking the remainder of the paragraph.(g)Presidential Assassinations: Subsection (c) of section 1751 of title 18, United States Code, is amended to read as follows:`(c) Whoever attempts to kill or kidnap any individual designated in subsection (a) of this section shall be punished (1) by imprisonment for any term of years or for life, or (2) by death or imprisonment for any term of years or for life, if the conduct constitutes an attempt to kill the President of the United States and results in bodily injury to the President or otherwise comes dangerously close to causing the death of the President.'.(h)Wrecking Trains: The second to the last undesignated paragraph of section 1992 of title 18, United States Code, is amended by striking the comma after `imprisonment for life' and inserting a period and striking the remainder of the section.(i)Bank Robbery: Section 2113(e) of title 18, United States Code, is amended by striking `or punished by death if the verdict of the jury shall so direct' and inserting `or if death results shall be punished by death or life imprisonment'.(j)Hostage Taking: Section 1203(a) of title 18, United States Code, is amended by inserting after `or for life' the following: `and, if the death of any person results, shall be punished by death or life imprisonment'.(k)Racketeering: (1) Section 1958 of title 18, United States Code, is amended by striking `and if death results, shall be subject to imprisonment for any term of years or for life, or shall be fined not more than $50,000, or both' and inserting `and if death results, shall be punished by death or life imprisonment, or shall be fined not more than $250,000, or both'.(2) Section 1959(a)(1) of title 18, United States Code, is amended to read as follows:
`(1) for murder, by death or life imprisonment, or a fine of not more than $250,000, or both; and for kidnapping, by imprisonment for any term of years or for life, or a fine of not more than $250,000, or both;'.(l)Genocide:Section 1091(b)(1) of title 18, United States Code, is amended by striking `a fine of not more than $1,000,000 or imprisonment for life,' and inserting `, where death results, a fine of not more than $1,000,000, or imprisonment for life or a sentence of death,'.
SEC. 104. CONFORMING AMENDMENT TO FEDERAL AVIATION ACT OF 1954.Section 903 of the Federal Aviation Act of 1958, as amended (49 U.S.C. 1473), is amended by striking subsection (c).
SEC. 105. APPLICABILITY TO UNIFORM CODE OF MILITARY JUSTICE.The provisions of chapter 228 of title 18, United States Code, as added by this Act, shall not apply to prosecutions under the Uniform Code of Military Justice (10 U.S.C. 801).
SEC. 106. MURDER BY A FEDERAL PRISONER.(a)In General: Chapter 51 of title 18, United States Code, is amended by adding at the end thereof the following:
`1118. Murder by a Federal prisoner`(a) Whoever, while confined in a Federal correctional institution under a sentence for a term of life imprisonment, murders another shall be punished by death or by life imprisonment without the possibility of parole.`(b) For the purposes of this section--
`(1) the term `Federal correctional institution' means any Federal prison, Federal correctional facility, Federal community program center, or Federal halfway house;
`(2) the term `term of life imprisonment' means a sentence for the term of natural life, a sentence commuted to natural life, an indeterminate term of a minimum of at least fifteen years and a maximum of life, or an unexecuted sentence of death; and
`(3) the term `murders' means committing first degree or second degree murder as defined by section 1111 of this title.'.(b)Amendment to Chapter Analysis: The chapter analysis for chapter 51 of title 18, United States Code, is amended by adding at the end thereof the following:
`1118. Murder by a Federal prisoner.'.
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TITLE II--EXCLUSIONARY RULE
SEC. 201. SEARCHES AND SEIZURES PURSUANT TO AN INVALID WARRANT.(a)In General:Chapter 109 of title 18, United States Code, is amended by adding at the end thereof the following new section:
`2237. Evidence obtained by invalid warrant`Evidence which is obtained as a result of search or seizure shall not be excluded in a proceeding in a court of the United States on the ground that the search or seizure was in violation of the Fourth Amendment to the Constitution of the United States, if the search or seizure was carried out in reasonable reliance on a warrant issued by a detached and neutral magistrate ultimately found to be invalid, unless--
`(1) the judicial officer in issuing the warrant was materially misled by information in an affidavit that the affiant knew was false or would have known was false except for his reckless disregard of the truth;
`(2) the judicial officer provided approval of the warrant without exercising a neutral and detached review of the application for the warrant;
`(3) the warrant was based on an affidavit so lacking in indicia of probable cause as to render official belief in its existence entirely unreasonable; or
`(4) the warrant is so facially deficient that the executing officers could not reasonably presume it to be valid.'.(b)Amendment to Chapter Analysis:The chapter analysis for chapter 109 of title 18, United States Code, is amended by adding at the end thereof the following:
`2237. Evidence obtained by invalid warrant.'.
TITLE III--INTERNATIONAL MONEY LAUNDERING
SEC. 301. REPORTS ON USES MADE OF CURRENCY TRANSACTION REPORTS.(a)Report to Congress on Use of Transaction Reports:Not later than 180 days after the effective date of this section, and annually thereafter for 3 years, the Secretary of the Treasury shall report to the Congress the following:
(1) the number of each type of report filed pursuant to subchapter II of chapter 53 of title 31, United States Code (or regulations promulgated thereunder) in the previous fiscal year;
(2) the number of reports filed pursuant to section 6050I of the Internal Revenue Code of 1986 (regarding transactions involving currency) in the previous fiscal year;
(3) an estimate of the rate of compliance with the reporting requirements by persons required to file the reports referred to in paragraphs (1) and (2);
(4) the manner in which the Department of the Treasury and other agencies of the United States collect, organize, analyze and use the reports referred to in paragraphs (1) and (2) to support investigations and prosecutions of (A) violations of the criminal laws of the United States, (B) violations of the laws of foreign countries, and (C) civil enforcement of the laws of the United States including the provisions regarding asset forfeiture;
(5) a summary of sanctions imposed in the previous fiscal year against persons who failed to comply with the reporting requirements referred to paragraphs (1) and (2), and other steps taken to ensure maximum compliance;
(6) a summary of criminal indictments filed in the previous fiscal year which resulted, in large part, from investigations initiated by analysis of the reports referred to in paragraphs (1) and (2); and
(7) a summary of criminal indictments filed in the previous fiscal year which resulted, in large part, from investigations initiated by information regarding suspicious financial transactions provided voluntarily by financial institutions.(b)Advisory Group on Reporting Requirements:Not later than 90 days after the effective date of this section, the Secretary shall establish an Advisory Group on Reports on Monetary Instruments Transactions consisting of representatives of the Department of the Treasury and of financial institutions and other persons subject to the reporting requirements referred to in paragraphs (1) and (2) of subsection (a). The Advisory Group shall provide a means by which the Secretary--
(1) informs private sector representatives, on a regular basis, of the ways in which the reports referred to in subsections (a) (1) and (2) have been used for the purposes described in subsection (a)(4);
(2) informs private sector representatives, on a regular basis, of how information regarding suspicious financial transactions provided voluntarily by financial institutions has been used for the purposes described in subsection (a)(4); and
(3) receives advice on the manner in which the reporting requirements referred to in subsections (a) (1) and (2) should be modified to enhance the ability of law enforcement agencies to use the information provided for law enforcement purposes.
SEC. 402. ELECTRONIC SCANNING OF CERTAIN UNITED STATES CURRENCY NOTES.(a)Electronic Scanning Task Force:(1) Not more than thirty days after the date of enactment of this section, the Secretary of the Treasury (hereafter in this section referred to as the `Secretary') shall appoint an Electronic Scanning Task Force (hereafter in this section referred to as the `Task Force') to--
(A) study methods of printing on United States currency notes issued under section 51115 of title 31, United States Code, in denominations of $10 or more a serial number on each such United States currency note that may be read by electronic scanning;
(B) make an assessment of the cost of implementing such electronic scanning of such United States currency notes; and
(C) make recommendations about the amount of time needed to implement such electronic scanning.(2) In appointing members to the Task Force described in subsection (a), the Secretary shall appoint such number of members as the Secretary determines to be appropriate. The Secretary, shall, at a minimum appoint to the Task Force--
(A) the Assistant Secretary for Enforcement in the Department of the Treasury (who shall serve as a nonvoting, ex officio member); and
(B) at least one recognized expert from each of the following fields relating to electronic scanning technology:
(i) coding,
(ii) symbology,
(iii) scanning systems,
(iv) computer data compilation, and
(v) printing technology.(3) Except as provided in paragraph (2)(A), no individual who is a full-time employee of the Federal Government may serve as a member of the Task Force.(4) The provisions of the Federal Advisory Committee Act shall not apply with respect to the Task Force.(5) Members of the Task Force shall, while attending meetings and conferences of the Task Force or otherwise engaging in the business of the Task Force (including travel time), be entitled to receive compensation at a rate fixed by the Secretary, but not exceeding the rate specified at the time of such service under GS-18 of the General Schedule established under section 5332 of title 5, United States Code.(6) While away from their homes or regular places of business on the business of the Task Force, such members may be allowed travel expenses, including per diem in lieu of subsistence, as authorized by section 5703 of title 5, United States Code, for persons employed intermittently in the Government service.(7) Upon the issuance of the report by the Secretary under subsection (b), the Task Force shall cease to exist.(b)Report to the Congress:Not later than one hundred and eighty days after the date of enactment of this section, the Secretary shall issue a report to the appropriate committees of the Congress that summarizes the findings and recommendations of the Task Force under subsection (a)(1), and includes any additional recommendations by the Secretary.(c)Authorization of Appropriations:There are authorized to be appropriated such sums as may be necessary to carry out the purposes of this section.
SEC. 303. CONFORMING AMENDMENT OF PROVISION RELATING TO THE EQUITABLE TRANSFER TO A PARTICIPATING FOREIGN NATION OF FORFEITED PROPERTY OR PROCEEDS.Section 981(i) of title 18, United States Code, is amended--
(1) by striking `In the case of property subject to forfeiture under subsection (a)(1)(B), the following additional provisions shall, to the extent provided by treaty, apply:';
(2) in paragraph (1), by striking the first two sentences and inserting the following: `Whenever property is civilly or criminally forfeited under this chapter, the Attorney General may transfer the forfeited personal property or the proceeds of the sale of any forfeited personal or real property to any foreign country which participated directly or indirectly in the seizure or forfeiture of the property, if such a transfer (i) has been agreed to by the Secretary of State and the Secretary of the Treasury, (ii) is authorized in an international agreement between the United States and the foreign country, and (iii) is made to a country that, if applicable, has been certified under section 481(h) of the Foreign Assistance Act of 1961.'; and
(3) in paragraph (1), by striking the last sentence.
SEC. 304. ADDITION OF CONFORMING PREDICATE MONEY LAUNDERING REFERENCES TO `INSIDER' EXEMPTION FROM THE RIGHT TO FINANCIAL PRIVACY ACT.Section 1113(l)(2) of the Right to Financial Privacy Act of 1978 (12 U.S.C. 3413(l)(2)) is amended by inserting `or of section 1956 or 1957 of title 18, United States Code' after `any provision of subchapter II of chapter 53 of title 31, United States Code'.
SEC. 305. CLARIFICATION OF DEFINITION OF `MONETARY INSTRUMENTS'.Section 1956(c)(5) of title 18, United States Code, is amended to read as follows:
`(5) the term `monetary instruments' means (i) coin or currency of the United States or of any other country, travelers' checks, personal checks, bank checks, and money orders, or (ii) investment securities or negotiable instruments, in bearer form or otherwise in such form that title thereto passes upon delivery;'.
SEC. 306. MONEY LAUNDERING AMENDMENTS.Section 1956(c)(1) is amended by striking `State or Federal' and inserting `State, Federal, or foreign'.
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SEC. 307. DEFINITION OF `SPECIFIED UNLAWFUL ACTIVITY' FOR MONEY LAUNDERING STATUTE.Section 1956(c)(7)(D) of title 18, United States Code, is amended--
(1) by inserting `sections 1005-07 (relating to false statements by an employee of a financial institution), section 1014 (relating to false statements in connection with loan and credit applications),' after `section 875 (relating to interstate communications),'; and
(2) by striking `section 1344 (relating to bank fraud),'.
SEC. 308. RIGHT TO FINANCIAL PRIVACY ACT AMENDMENT.Section 1103(c) of the Right to Financial Privacy Act (12 U.S.C. 3403(c)) is amended in the last sentence--
(1) by striking `or' after `such disclosure' and inserting a comma; and
(2) by inserting before the period the following:
`, or for a refusal to do business with that customer after having made such disclosure'.
SEC. 309. CORRECTION OF ERRONEOUS PREDICATE OFFENSE REFERENCE UNDER 18 U.S.C. 1956.Section 1956(c)(7)(D) of title 18, United States Code, is amended by striking out `section 310 of the Controlled Substances Act (21 U.S.C. 830) (relating to precursor and essential chemicals)' and inserting in lieu thereof `a felony violation of the Chemical Diversion and Trafficking Act of 1988 (relating to precursor and essential chemicals)'.
SEC. 310. KNOWLEDGE REQUIREMENT FOR INTERNATIONAL MONEY LAUNDERING.Section 1956(a) of title 18, United States Code, is amended--
(1) in paragraph (2) by inserting at the end the following: `For the purpose of the offense described in subparagraph (B), the defendant's knowledge may be established by proof that a law enforcement officer represented the matter specified in subparagraph (B) as true, and the defendant's subsequent statements or actions indicate that the defendant believed such representations to be true.'; and
(2) in paragraph (3) by striking `For purposes of this paragraph' and inserting `For purposes of this paragraph and paragraph (2)'.
SEC. 311. MONEY LAUNDERING FORFEITURES.Section 982(b)(2) of title 18, United States Code, is amended by inserting before the period the following: `unless the defendant, in committing the offense or the offenses giving rise to the forfeiture, conducted 3 or more separate transactions involving a total of $100,000 or more in any 12 month period'.
SEC. 312. MONEY LAUNDERING CONSPIRACIES.Section 1956 of title 18, United States Code, is amended by adding at the end thereof the following new subsection:`(g) Any person who attempts or conspires to commit any offense defined in this section or in section 1957 of this title shall be subject to the same penalties as those prescribed for the offense, the commission of which was the object of the attempt or conspiracy.'.
Amendment No. 1974
In lieu of the matter proposed to be inserted, insert the following:
TITLE I--DEATH PENALTY
SEC. 101. SHORT TITLE.This title may be cited as the `Federal Death Penalty Act of 1989'.
SEC. 102. CONSTITUTIONAL PROCEDURES FOR THE IMPOSITION OF THE SENTENCE OF DEATH.(a)In General: Part II of title 18 of the United States Code is amended by adding the following new chapter after chapter 227:
`CHAPTER 228--DEATH SENTENCE
`Sec.
`3591. Sentence of death.
`3592. Factors to be considered in determining whether a sentence of death is justified.
`3593. Special hearing to determine whether a sentence of death is justified.
`3594. Imposition of a sentence of death.
`3595. Review of a sentence of death.
`3596. Implementation of a sentence of death.
`3597. Use of State facilities.
`3591. Sentence of death`A defendant who has been found guilty of--
`(a) an offense described in section 794 or section 2381 of this title;
`(b) an offense described in section 1751(c) of this title, if the offense, as determined beyond a reasonable doubt at the hearing under section 3593, constitutes an attempt to kill the President of the United States and results in bodily injury to the President or comes dangerously close to causing the death of the President; or
`(c) any other offense for which a sentence of death is provided, if the defendant, as determined beyond a reasonable doubt at the hearing under section 3593--
`(1) intentionally killed the victim;
`(2) intentionally inflicted serious bodily injury that resulted in the death of the victim;
`(3) intentionally participated in an act, contemplating that the life of a person would be taken or intending that lethal force would be used in connection with a person, other than one of the participants in the offense, and the victim died as a direct result of the act; or
`(4) intentionally and specifically engaged in an act, knowing that the act created a grave risk of death to a person, other than one of the participants in the offense, such that participation in the act constituted a reckless disregard for human life and the victim died as a direct result of the act,shall be sentenced to death if, after consideration of the factors set forth in section 3592 in the course of a hearing held pursuant to section 3593, it is determined that imposition of a sentence of death is justified; provided that no person may be sentenced to death who was less than 17 years of age at the time of the offense.
`3592. Factors to be considered in determining whether a sentence of death is justified`(a)Mitigating Factors:In determining whether a sentence of death is to be imposed on a defendant, the finder of fact shall consider mitigating factors, including the following:
`(1) The defendant's capacity to appreciate the wrongfulness of the defendant's conduct or to conform conduct to the requirements of law was significantly impaired, regardless of whether the capacity was so impaired as to constitute a defense to the charge.
`(2) The defendant was under unusual and substantial duress, regardless of whether the duress was of such a degree as to constitute a defense to the charge.
`(3) The defendant is punishable as a principal (as defined in section 2 of title 18 of the United States Code) in the offense, which was committed by another, but the defendant's participation was relatively minor, regardless of whether the participation was so minor as to constitute a defense to the charge.
`(4) The defendant could not reasonably have foreseen that the defendant's conduct in the course of the commission of murder, or other offense resulting in death for which the defendant was convicted, would cause, or would create a grave risk of causing, death to any person.
`(5) The defendant did not have a significant prior criminal record.
`(6) The defendant committed the offense under severe mental or emotional disturbance.
`(7) The victim consented to the criminal conduct that resulted in the victim's death.
`(8) That other factors in the defendant's background or character mitigate against imposition of the death sentence.`(b)Aggravating Factors for Espionage and Treason:In determining whether a sentence of death is justified for an offense described in section 3591(a), the jury, or if there is no jury, the court, shall consider each of the following aggravating factors and determine which, if any, exist:
`(1) the defendant has previously been convicted of another offense involving espionage or treason for which either a sentence of life imprisonment or death was authorized by statute;
`(2) in the commission of the offense the defendant knowingly created a grave risk of substantial danger to the national security; and
`(3) in the commission of the offense the defendant knowingly created a grave risk of death to another person.The jury, or if there is no jury, the court, may consider whether any other aggravating factor exists.`(c)Aggravating Factors for Homicide and for Attempted Murder of the President:In determining whether a sentence of death is justified for an offense described in section 3591 (b) or (c), the jury, or if there is no jury, the court, shall consider each of the following aggravating factors and determine which, if any, exist:
`(1) the death, or injury resulting in death, occurred during the commission or attempted commission of, or during the immediate flight from the commission of, an offense under section 751 (prisoners in custody of institution or officer), section 794 (gathering or delivering defense information to aid foreign government), section 844(d) (transportation of explosives in interstate commerce for certain purposes), section 844(f) (destruction of Government property in interstate commerce by explosives), section 1118 (prisoners serving life term), section 1201 (kidnaping), or section 2381 (treason) of this title, or section 902 (i) or (n) of the Federal Aviation Act of 1958, as amended (49 U.S.C. 1472 (i) or (n)) (aircraft piracy);
`(2) the defendant has previously been convicted of another Federal or State offense resulting in the death of a person, for which a sentence of life imprisonment or a sentence of death was authorized by statute;
`(3) the defendant has previously been convicted of two or more Federal or State offenses, punishable by a term of imprisonment of more than one year, committed on different occasions, involving the infliction of, or attempted infliction of, serious bodily injury or death upon another person;
`(4) the defendant, in the commission of the offense, or in escaping apprehension for the violation of the offense, knowingly created a grave risk of death to one or more persons in addition to the victim of the offense;
`(5) the defendant committed the offense in an especially heinous, cruel, or depraved manner;
`(6) the defendant procured the commission of the offense by payment, or promise of payment, of anything of pecuniary value;
`(7) the defendant committed the offense as consideration for the receipt, or in the expectation of the receipt, of anything of pecuniary value;
`(8) the defendant committed the offense after planning and premeditation to cause the death of a person or commit an act of terrorism;
`(9) the defendant has previously been convicted of two or more State or Federal offenses punishable by a term of imprisonment of more than one year, committed on different occasions, involving the distribution of a controlled substance;
`(10) the victim was particularly vulnerable due to old age, youth, or infirmity;
`(11) the defendant had previously been convicted of violating title II or title III of the Controlled Substances Act for which a sentence of 5 or more years may be imposed or had previously been convicted of engaging in a continuing criminal enterprise;
`(12) the defendant violated section 408(c) of the Controlled Substances Act to the extent that the conduct described in section 408(c) of such Act was a violation of section 405 of such Act; or
`(13) the defendant committed the offense against--
`(A) the President of the United States, the President-elect, the Vice President, the Vice-President-elect, the Vice-President-designate, or, if there is no Vice President, the officer next in order of succession to the office of the President of the United States, or any person who is acting as President under the Constitution and laws of the United States;
`(B) a chief of state, head of government, or the political equivalent, of a foreign nation;
`(C) a foreign official listed in section 1116(b)(3)(A) of this title, if he is in the United States on official business; or
`(D) a Federal public servant who is a judge, a law enforcement officer, or an employee of a United States penal or correctional institution--
`(i) while he is engaged in the performance of his official duties;
`(ii) because of the performance of his official duties; or
`(iii) because of his status as a public servant.
For purposes of this subparagraph, a `law enforcement officer' is a public servant authorized by law or by a Government agency or Congress to conduct or engage in the prevention, investigation, or prosecution of an offense.The jury, or if there is no jury, the court, may consider whether any other aggravating factor exists.
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`3593. Special hearing to determine whether a sentence of death is justified`(a)Notice by the Government:If, in a case involving an offense described in section 3591, the attorney for the government believes that the circumstances of the offense are such that a sentence of death is justified under this chapter, he shall, a reasonable time before the trial, or before acceptance by the court of a plea of guilty, or at such time thereafter as the court may permit upon a showing of good cause, sign and file with the court, and serve on the defendant, a notice--
`(1) stating that the government believes that the circumstances of the offense are such that, if the defendant is convicted, a sentence of death is justified under this chapter and that the government will seek the sentence of death; and
`(2) setting forth the aggravating factor or factors that the government, if the defendant is convicted, proposes to prove as justifying a sentence of death.The court may permit the attorney for the government to amend the notice upon a showing of good cause.`(b)Hearing Before a Court or Jury:If the attorney for the government has filed a notice as required under subsection (a) and the defendant is found guilty of or pleads guilty to an offense described in section 3591, the judge who presided at the trial or before whom the guilty plea was entered, or another judge if that judge is unavailable, shall conduct a separate sentencing hearing to determine the punishment to be imposed. The hearing shall be conducted--
`(1) before the jury that determined the defendant's guilt;
`(2) before a jury impaneled for the purpose of the hearing if--
`(A) the defendant was convicted upon a plea of guilty;
`(B) the defendant was convicted after a trial before the court sitting without a jury;
`(C) the jury that determined the defendant's guilt was discharged for good cause; or
`(D) after initial imposition of a sentence under this section, reconsideration of the sentence under this section is necessary; or
`(3) before the court alone, upon the motion of the defendant and with the approval of the attorney for the government.A jury impaneled pursuant to paragraph (2) shall consist of twelve members, unless, at any time before the conclusion of the hearing, the parties stipulate, with the approval of the court, that it shall consist of a lesser number.
`(c)Proof of Mitigating and Aggravating Factors:Notwithstanding rule 32(c) of the Federal Rules of Criminal Procedure, when a defendant is found guilty or pleads guilty to an offense under section 3591, no presentence report shall be prepared. At the sentencing hearing, information may be presented as to any matter relevant to the sentence, including any mitigating or aggravating factor permitted or required to be considered under section 3592. Information presented may include the trial transcript and exhibits if the hearing is held before a jury or judge not present during the trial. Any other information relevant to a mitigating or aggravating factor may be presented by either the attorney for the government or the defendant, regardless of its admissibility under the rules governing admission of evidence at criminal trials, except that information may be excluded if its probative value is substantially outweighed by the danger of creating unfair prejudice, confusing the issues, or misleading the jury. The government and the defendant shall be permitted to rebut any information received at the hearing, and shall be given fair opportunity to present argument as to the adequacy of the information to establish the existence of any aggravating or mitigating factor, and as to the appropriateness in the case of imposing a sentence of death. The government shall open the argument. The defendant shall be permitted to reply. The government shall then be permitted to reply in rebuttal. The burden of establishing the existence of any aggravating factor is on the government, and is not satisfied unless the existence of such a factor is established beyond a reasonable doubt. The burden of establishing the existence of any mitigating factor is on the defendant, and is not satisfied unless the existence of such a factor is established by a preponderance of the information.`(d)Return of Special Findings:The jury, or if there is no jury, the court, shall consider all the information received during the hearing. It shall return special findings identifying any aggravating factor or factors set forth in section 3592 found to exist and any other aggravating factor for which notice has been provided under subsection (a) found to exist. A finding with respect to a mitigating factor may be made by one or more members of the jury, and any member of the jury who finds the existence of a mitigating factor may consider such factor established for purposes of this section regardless of the number of jurors who concur with the factor has been established. A finding with respect to any aggravating factor must be unanimous. If no aggravating factor set forth in section 3592 is found to exist, the court shall impose a sentence other than death authorized by law.
`(e)Return of a Finding Concerning a Sentence of Death:If, in the case of--
`(1) an offense described in section 3591(a), an aggravating factor required to be considered under section 3592(b) is found to exist; or
`(2) an offense described in section 3591 (b) or (c), an aggravating factor required to be considered under section 3592(c) is found to exist;the jury, or if there is no jury, the court, shall then consider whether all the aggravating factor or factors found to exist sufficiently outweigh all the mitigating factor or factors found to exist to justify a sentence of death, or, in the absence of a mitigating factor, whether the aggravating factor or factors alone are sufficient to justify a sentence of death. Based upon this consideration, the jury by unanimous vote, or if there is no jury, the court, shall recommend whether a sentence of death shall be imposed rather than some other lesser sentence. The jury or the court, if there is no jury, regardless of its findings with respect to aggravating and mitigating factors, is never required to impose a death sentence, and the jury shall be so instructed.`(f)Special Precaution To Assure Against Discrimination:In a hearing held before a jury, the court, prior to the return of a finding under subsection (e), shall instruct the jury that, in considering whether a sentence of death is justified, it shall not consider the race, color, religious beliefs, national origin, or sex of the defendant or of any victim and that the jury is not to recommend a sentence of death unless it has concluded that it would recommend a sentence of death for the crime in question no matter what the race, color, religious beliefs, national origin, or sex of the defendant or of any victim may be. The jury, upon return of a finding under subsection (e), shall also return to the court a certificate, signed by each juror, that consideration of the race, color, religious beliefs, national origin, or sex of the defendant or any victim was not involved in reaching his or her individual decision and that the individual juror would have made the same recommendation regarding a sentence for the crime in question no matter what the race, color, religious beliefs, national origin, or sex of the defendant or any victim may be.
`3594. Imposition of a sentence of death`Upon a finding under section 3593(e) that a sentence of death is justified, the court shall sentence the defendant to death. Upon a finding under section 3593(e) that a sentence of death is not justified, or under section 3593(d) that no aggravating factor required to be found exists, the court shall impose any sentence other than death that is authorized by law. Notwithstanding any other provision of law, if the maximum term of imprisonment for the offense is life imprisonment, the court may impose a sentence of life imprisonment without parole.
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`3595. Review of a sentence of death`(a)Appeal:In a case in which a sentence of death is imposed, the sentence shall be subject to review by the court of appeals upon appeal by the defendant. Notice of appeal must be filed within the time specified for the filing of a notice of appeal. An appeal under this section may be consolidated with an appeal of the judgment of conviction and shall have priority over all other cases.`(b)Review:The court of appeals shall review the entire record in the case, including--
`(1) the evidence submitted during the trial;
`(2) the information submitted during the sentencing hearing;
`(3) the procedures employed in the sentencing hearing; and
`(4) the special findings returned under section 3593(d).`(c)Decision and Disposition:
`(1) If the court of appeals determines that--
`(A) the sentence of death was not imposed under the influence of passion, prejudice, or any other arbitrary factor; and
`(B) the information supports the special finding of the existence of an aggravating factor required to be considered under section 3592;
it shall affirm the sentence.
`(2) In any other case, the court of appeals shall remand the case for reconsideration under section 3593.
`(3) The court of appeals shall state in writing the reasons for its disposition of an appeal of a sentence of death under this section.
`3596. Implementation of a sentence of death`(a) A person who has been sentenced to death pursuant to the provisions of this chapter shall be committed to the custody of the Attorney General until exhaustion of the procedures for appeal of the judgment of conviction and for review of the sentence. When the sentence is to be implemented, the Attorney General shall release the person sentenced to death to the custody of a United States marshal, who shall supervise implementation of the sentence in the manner prescribed by the law of the State in which the sentence is imposed. If the law of such State does not provide for implementation of a sentence of death, the court shall designate another State, the law of which does so provide, and the sentence shall be implemented in the latter State in the manner prescribed by such law.`(b) A sentence of death shall not be carried out upon a woman while she is pregnant.`(c) A sentence of death shall not be carried out upon a person who is mentally retarded. A sentence of death shall not be carried out upon a person who, as a result of mental disability--
`(1) cannot understand the nature of the pending proceedings, what such person was tried for, the reason for the punishment, or the nature of the punishment; or
`(2) lacks the capacity to recognize or understand facts which would make the punishment unjust or unlawful, or lacks the ability to convey such information to counsel or to the court.
`3597. Use of State facilities`(a)In General: A United States marshal charged with supervising the implementation of a sentence of death may use appropriate State or local facilities for the purpose, may use the services of an appropriate State or local official or of a person such an official employs for the purpose, and shall pay the costs thereof in an amount approved by the Attorney General.`(b)Excuse of an Employee on Moral or Religious Grounds: No employee of any State department of corrections or the Federal Bureau of Prisons and no employee providing services to that department or bureau under contract shall be required, as a condition of that employment, or contractual obligation to be in attendance at or to participate in any execution carried out under this section if such participation is contrary to the moral or religious convictions of the employee. For purposes of this subsection, the term `participation in executions' includes personal preparation of the condemned individual and the apparatus used for execution and supervision of the activities of other personnel in carrying out such activities.'.(b)Repeal: Sections 3566 and 3567 of title 18, United States Code, are hereby repealed.(c)Amendments to Chapter Analysis: (1) The chapter analysis of part II of title 18, United States Code, is amended by adding the following new item after the item relating to chapter 227:
`228. Death sentence
3591'.(2) The section analysis of chapter 227 of title 18, United States Code, is amended by amending the items relating to sections 3566 and 3567 to read as follows:
`3566. Repealed.
`3567. Repealed.'.
SEC. 103. CONFORMING CHANGES IN TITLE 18.(a)Aircrafts and Motor Vehicles: Section 34 of title 18, United States Code, is amended by striking the comma after `imprisonment for life' and inserting a period and striking the remainder of the section.(b)Espionage: Section 794(a) of title 18, United States Code, is amended by striking the period at the end of the section and inserting `, except that the sentence of death shall not be imposed unless the jury or, if there is no jury, the court, further finds that the offense directly concerned nuclear weaponry, military spacecraft or satellites, early warning systems, or other means of defense or retaliation against large-scale attack; war plans; communications intelligence or cryptographic information; or any other major weapons system or major element of defense strategy.'.(c)Explosive Materials: (1) Section 844(d) of title 18, United States Code, is amended by striking `as provided in section 34 of this title'.(2) Section 844(f) of title 18, United States Code, is amended by striking `as provided in section 34 of this title'.(3) Section 844(i) of title 18, United States Code, is amended by striking the words `as provided in section 34 of this title'.(d)Murder: (1) The second undesignated paragraph of section 1111(b) of title 18, United States Code, is amended to read as follows:`Whoever is guilty of murder in the first degree shall be punished by death or by imprisonment for life;'.(2) Section 1116(a) of title 18, United States Code, is amended by striking `any such person who is found guilty of murder in the first degree shall be sentenced to imprisonment for life, and'.(e)Kidnapping: Section 1201(a) of title 18, United States Code, is amended by inserting after `or for life' the following: `and, if the death of any person results, shall be punished by death or life imprisonment'.(f)Nonmailable Injurious Articles: The last paragraph of section 1716 of title 18, United States Code, is amended by striking the comma after `imprisonment for life' and inserting a period and striking the remainder of the paragraph.(g)Presidential Assassinations: Subsection (c) of section 1751 of title 18, United States Code, is amended to read as follows:`(c) Whoever attempts to kill or kidnap any individual designated in subsection (a) of this section shall be punished (1) by imprisonment for any term of years or for life, or (2) by death or imprisonment for any term of years or for life, if the conduct constitutes an attempt to kill the President of the United States and results in bodily injury to the President or otherwise comes dangerously close to causing the death of the President.'.(h)Wrecking Trains: The second to the last undesignated paragraph of section 1992 of title 18, United States Code, is amended by striking the comma after `imprisonment for life' and inserting a period and striking the remainder of the section.(i)Bank Robbery: Section 2113(e) of title 18, United States Code, is amended by striking `or punished by death if the verdict of the jury shall so direct' and inserting `or if death results shall be punished by death or life imprisonment'.(j)Hostage Taking: Section 1203(a) of title 18, United States Code, is amended by inserting after `or for life' the following: `and, if the death of any person results, shall be punished by death or life imprisonment'.(k)Racketeering: (1) Section 1958 of title 18, United States Code, is amended by striking `and if death results, shall be subject to imprisonment for any term of years or for life, or shall be fined not more than $50,000, or both' and inserting `and if death results, shall be punished by death or life imprisonment, or shall be fined not more than $250,000, or both'.(2) Section 1959(a)(1) of title 18, United States Code, is amended to read as follows:
`(1) for murder, by death or life imprisonment, or a fine of not more than $250,000, or both; and for kidnapping, by imprisonment for any term of years or for life, or a fine of not more than $250,000, or both;'.(l)Genocide:Section 1091(b)(1) of title 18, United States Code, is amended by striking `a fine of not more than $1,000,000 or imprisonment for life,' and inserting `, where death results, a fine of not more than $1,000,000, or imprisonment for life or a sentence of death,'.
SEC. 104. CONFORMING AMENDMENT TO FEDERAL AVIATION ACT OF 1954.Section 903 of the Federal Aviation Act of 1958, as amended (49 U.S.C. 1473), is amended by striking subsection (c).
SEC. 105. APPLICABILITY TO UNIFORM CODE OF MILITARY JUSTICE.The provisions of chapter 228 of title 18, United States Code, as added by this Act, shall not apply to prosecutions under the Uniform Code of Military Justice (10 U.S.C. 801).
SEC. 106. MURDER BY A FEDERAL PRISONER.(a)In General: Chapter 51 of title 18, United States Code, is amended by adding at the end thereof the following:
`1118. Murder by a Federal prisoner`(a) Whoever, while confined in a Federal correctional institution under a sentence for a term of life imprisonment, murders another shall be punished by death or by life imprisonment without the possibility of parole.`(b) For the purposes of this section--
`(1) the term `Federal correctional institution' means any Federal prison, Federal correctional facility, Federal community program center, or Federal halfway house;
`(2) the term `term of life imprisonment' means a sentence for the term of natural life, a sentence commuted to natural life, an indeterminate term of a minimum of at least fifteen years and a maximum of life, or an unexecuted sentence of death; and
`(3) the term `murders' means committing first degree or second degree murder as defined by section 1111 of this title.'.(b)Amendment to Chapter Analysis: The chapter analysis for chapter 51 of title 18, United States Code, is amended by adding at the end thereof the following:
`1118. Murder by a Federal prisoner.'.
[Page: S7509]
TITLE II--EXCLUSIONARY RULE
SEC. 301. SEARCHES AND SEIZURES PURSUANT TO AN INVALID WARRANT.(a)In General:Chapter 109 of title 18, United States Code, is amended by adding at the end thereof the following new section:
`2237. Evidence obtained by invalid warrant`Evidence which is obtained as a result of search or seizure shall not be excluded in a proceeding in a court of the United States on the ground that the search or seizure was in violation of the Fourth Amendment to the Constitution of the United States, if the search or seizure was carried out in reasonable reliance on a warrant issued by a detached and neutral magistrate ultimately found to be invalid, unless--
`(1) the judicial officer in issuing the warrant was materially misled by information in an affidavit that the affiant knew was false or would have known was false except for his reckless disregard of the truth;
`(2) the judicial officer provided approval of the warrant without exercising a neutral and detached review of the application for the warrant;
`(3) the warrant was based on an affidavit so lacking in indicia of probable cause as to render official belief in its existence entirely unreasonable; or
`(4) the warrant is so facially deficient that the executing officers could not reasonably presume it to be valid.'.(b)Amendment to Chapter Analysis:The chapter analysis for chapter 109 of title 18, United States Code, is amended by adding at the end thereof the following:
`2237. Evidence obtained by invalid warrant.'.
TITLE III--INTERNATIONAL MONEY LAUNDERING
SEC. 401. REPORTS ON USES MADE OF CURRENCY TRANSACTION REPORTS.(a)Report to Congress on Use of Transaction Reports:Not later than 180 days after the effective date of this section, and annually thereafter for 3 years, the Secretary of the Treasury shall report to the Congress the following:
(1) the number of each type of report filed pursuant to subchapter II of chapter 53 of title 31, United States Code (or regulations promulgated thereunder) in the previous fiscal year;
(2) the number of reports filed pursuant to section 6050I of the Internal Revenue Code of 1986 (regarding transactions involving currency) in the previous fiscal year;
(3) an estimate of the rate of compliance with the reporting requirements by persons required to file the reports referred to in paragraphs (1) and (2);
(4) the manner in which the Department of the Treasury and other agencies of the United States collect, organize, analyze and use the reports referred to in paragraphs (1) and (2) to support investigations and prosecutions of (A) violations of the criminal laws of the United States, (B) violations of the laws of foreign countries, and (C) civil enforcement of the laws of the United States including the provisions regarding asset forfeiture;
(5) a summary of sanctions imposed in the previous fiscal year against persons who failed to comply with the reporting requirements referred to paragraphs (1) and (2), and other steps taken to ensure maximum compliance;
(6) a summary of criminal indictments filed in the previous fiscal year which resulted, in large part, from investigations initiated by analysis of the reports referred to in paragraphs (1) and (2); and
(7) a summary of criminal indictments filed in the previous fiscal year which resulted, in large part, from investigations initiated by information regarding suspicious financial transactions provided voluntarily by financial institutions.(b)Advisory Group on Reporting Requirements:Not later than 90 days after the effective date of this section, the Secretary shall establish an Advisory Group on Reports on Monetary Instruments Transactions consisting of representatives of the Department of the Treasury and of financial institutions and other persons subject to the reporting requirements referred to in paragraphs (1) and (2) of subsection (a). The Advisory Group shall provide a means by which the Secretary--
(1) informs private sector representatives, on a regular basis, of the ways in which the reports referred to in subsections (a) (1) and (2) have been used for the purposes described in subsection (a)(4);
(2) informs private sector representatives, on a regular basis, of how information regarding suspicious financial transactions provided voluntarily by financial institutions has been used for the purposes described in subsection (a)(4); and
(3) receives advice on the manner in which the reporting requirements referred to in subsections (a) (1) and (2) should be modified to enhance the ability of law enforcement agencies to use the information provided for law enforcement purposes.
SEC. 402. ELECTRONIC SCANNING OF CERTAIN UNITED STATES CURRENCY NOTES.(a)Electronic Scanning Task Force:(1) Not more than thirty days after the date of enactment of this section, the Secretary of the Treasury (hereafter in this section referred to as the `Secretary') shall appoint an Electronic Scanning Task Force (hereafter in this section referred to as the `Task Force') to--
(A) study methods of printing on United States currency notes issued under section 51115 of title 31, United States Code, in denominations of $10 or more a serial number on each such United States currency note that may be read by electronic scanning;
(B) make an assessment of the cost of implementing such electronic scanning of such United States currency notes; and
(C) make recommendations about the amount of time needed to implement such electronic scanning.(2) In appointing members to the Task Force described in subsection (a), the Secretary shall appoint such number of members as the Secretary determines to be appropriate. The Secretary, shall, at a minimum appoint to the Task Force--
(A) the Assistant Secretary for Enforcement in the Department of the Treasury (who shall serve as a nonvoting, ex officio member); and
(B) at least one recognized expert from each of the following fields relating to electronic scanning technology:
(i) coding,
(ii) symbology,
(iii) scanning systems,
(iv) computer data compilation, and
(v) printing technology.(3) Except as provided in paragraph (2)(A), no individual who is a full-time employee of the Federal Government may serve as a member of the Task Force.(4) The provisions of the Federal Advisory Committee Act shall not apply with respect to the Task Force.(5) Members of the Task Force shall, while attending meetings and conferences of the Task Force or otherwise engaging in the business of the Task Force (including travel time), be entitled to receive compensation at a rate fixed by the Secretary, but not exceeding the rate specified at the time of such service under GS-18 of the General Schedule established under section 5332 of title 5, United States Code.(6) While away from their homes or regular places of business on the business of the Task Force, such members may be allowed travel expenses, including per diem in lieu of subsistence, as authorized by section 5703 of title 5, United States Code, for persons employed intermittently in the Government service.(7) Upon the issuance of the report by the Secretary under subsection (b), the Task Force shall cease to exist.(b)Report to the Congress:Not later than one hundred and eighty days after the date of enactment of this section, the Secretary shall issue a report to the appropriate committees of the Congress that summarizes the findings and recommendations of the Task Force under subsection (a)(1), and includes any additional recommendations by the Secretary.(c)Authorization of Appropriations:There are authorized to be appropriated such sums as may be necessary to carry out the purposes of this section.
SEC. 403. CONFORMING AMENDMENT OF PROVISION RELATING TO THE EQUITABLE TRANSFER TO A PARTICIPATING FOREIGN NATION OF FORFEITED PROPERTY OR PROCEEDS.Section 981(i) of title 18, United States Code, is amended--
(1) by striking `In the case of property subject to forfeiture under subsection (a)(1)(B), the following additional provisions shall, to the extent provided by treaty, apply:';
(2) in paragraph (1), by striking the first two sentences and inserting the following: `Whenever property is civilly or criminally forfeited under this chapter, the Attorney General may transfer the forfeited personal property or the proceeds of the sale of any forfeited personal or real property to any foreign country which participated directly or indirectly in the seizure or forfeiture of the property, if such a transfer (i) has been agreed to by the Secretary of State and the Secretary of the Treasury, (ii) is authorized in an international agreement between the United States and the foreign country, and (iii) is made to a country that, if applicable, has been certified under section 481(h) of the Foreign Assistance Act of 1961.'; and
(3) in paragraph (1), by striking the last sentence.
SEC. 404. ADDITION OF CONFORMING PREDICATE MONEY LAUNDERING REFERENCES TO `INSIDER' EXEMPTION FROM THE RIGHT TO FINANCIAL PRIVACY ACT.Section 1113(l)(2) of the Right to Financial Privacy Act of 1978 (12 U.S.C. 3413(l)(2)) is amended by inserting `or of section 1956 or 1957 of title 18, United States Code' after `any provision of subchapter II of chapter 53 of title 31, United States Code'.
[Page: S7510]
SEC. 405. CLARIFICATION OF DEFINITION OF `MONETARY INSTRUMENTS'.Section 1956(c)(5) of title 18, United States Code, is amended to read as follows:
`(5) the term `monetary instruments' means (i) coin or currency of the United States or of any other country, travelers' checks, personal checks, bank checks, and money orders, or (ii) investment securities or negotiable instruments, in bearer form or otherwise in such form that title thereto passes upon delivery;'.
SEC. 406. MONEY LAUNDERING AMENDMENTS.Section 1956(c)(1) is amended by striking `State or Federal' and inserting `State, Federal, or foreign'.
SEC. 407. DEFINITION OF `SPECIFIED UNLAWFUL ACTIVITY' FOR MONEY LAUNDERING STATUTE.Section 1956(c)(7)(D) of title 18, United States Code, is amended--
(1) by inserting `sections 1005-07 (relating to false statements by an employee of a financial institution), section 1014 (relating to false statements in connection with loan and credit applications),' after `section 875 (relating to interstate communications),'; and
(2) by striking `section 1344 (relating to bank fraud),'.
SEC. 408. RIGHT TO FINANCIAL PRIVACY ACT AMENDMENT.Section 1103(c) of the Right to Financial Privacy Act (12 U.S.C. 3403(c)) is amended in the last sentence--
(1) by striking `or' after `such disclosure' and inserting a comma; and
(2) by inserting before the period the following:
`, or for a refusal to do business with that customer after having made such disclosure'.
SEC. 409. CORRECTION OF ERRONEOUS PREDICATE OFFENSE REFERENCE UNDER 18 U.S.C. 1956.Section 1956(c)(7)(D) of title 18, United States Code, is amended by striking out `section 310 of the Controlled Substances Act (21 U.S.C. 830) (relating to precursor and essential chemicals)' and inserting in lieu thereof `a felony violation of the Chemical Diversion and Trafficking Act of 1988 (relating to precursor and essential chemicals)'.
SEC. 410. KNOWLEDGE REQUIREMENT FOR INTERNATIONAL MONEY LAUNDERING.Section 1956(a) of title 18, United States Code, is amended--
(1) in paragraph (2) by inserting at the end the following: `For the purpose of the offense described in subparagraph (B), the defendant's knowledge may be established by proof that a law enforcement officer represented the matter specified in subparagraph (B) as true, and the defendant's subsequent statements or actions indicate that the defendant believed such representations to be true.'; and
(2) in paragraph (3) by striking `For purposes of this paragraph' and inserting `For purposes of this paragraph and paragraph (2)'.
SEC. 411. MONEY LAUNDERING FORFEITURES.Section 982(b)(2) of title 18, United States Code, is amended by inserting before the period the following: `unless the defendant, in committing the offense or the offenses giving rise to the forfeiture, conducted 3 or more separate transactions involving a total of $100,000 or more in any 12 month period'.
SEC. 412. MONEY LAUNDERING CONSPIRACIES.Section 1956 of title 18, United States Code, is amended by adding at the end thereof the following new subsection:`(g) Any person who attempts or conspires to commit any offense defined in this section or in section 1957 of this title shall be subject to the same penalties as those prescribed for the offense, the commission of which was the object of the attempt or conspiracy.'.
| https://www.globalsecurity.org/intell/library/congress/1990_cr/s900606-amend3.htm |
Psyonix have announced what is replacing Rocket League loot boxes and it sounds reasonable | GamingOnLinux
One change I am particularly happy about is Rocket League removing all loot box gambling and Psyonix have now announced it's happening in December along with what will replace it.
Psyonix have announced what is replacing Rocket League loot boxes and it sounds reasonable
One change I am particularly happy about is Rocket League removing all loot box gambling and Psyonix have nowannouncedit's happening in December along with what will replace it.
When writing about their original announcementback in August, I suggested they might replace loot boxes with a still randomized system but you would see the contents and an item shop. Guess what? I was right.
Instead of loot boxes, they will have a Blueprint system. It will be a random drop and possibly have special attributes but you know exactly what it is. There will also be a dedicated rotating item shop to buy items from, with a new Credits premium currency that will be used for basically everything including making items from Blueprints, upgrading to the Premium Rocket Pass and buying from the shop.
<here is a image cf0680566fe96051-8c30ee8943a8e366>
When the big change goes live in December, with the exact date to be confirmed, any keys you have left over will be converted into these Credits and your current loot crates will turn into a Blueprint of the same series.
Trading is also going to change. You will not be able to trade-in anything purchased, only free item drops it seems. They've not confirmed if you will be able to trade Blueprints though. An updated inventory interface is also coming, with some new features like archiving items so you could keep around stuff you use regularly and basically hide the rest.
Additionally, they're still keeping the Esports stuff separated from the rest. See the full announcementhere.
It's sounding more and more like they're eventually going to announce a free to play release. It would make sense with systems like this, otherwise it feels a bit greedy. Until then you can find Rocket League onHumble StoreandSteam.
Tags:Sports,Steam,Upcoming, Update
Quoting: pbWhat I'm more interested in is: will it stay playable through steam and on Linux.
Yes. Why wouldn't it? They've said nothing about leaving Steam or Linux.
Quoting: kaimanAnyone else that read Psygnosisin the headline? :-)
I did with another article a while ago about this company. I was getting flashbacks to Lemmings, but unfortunately it was about a game that combined my two most hated/least favourite genres: vehicles and sports.
Quoting: Patola@Liam why did you ignore my question? Since you're the most direct line with these developers, have you even asked them about their regional pricing changes? This is quite related to this news topic, their monetization policy. I believe there are many gamingonlinux readers which are affected by this decision, not everyone is fortunate enough to live in developed countries.
You
can
email them yourself. Have you tried?
Quoting: Patola@Liam why did you ignore my question? Since you're the most direct line with these developers, have you even asked them about their regional pricing changes? This is quite related to this news topic, their monetization policy. I believe there are many gamingonlinux readers which are affected by this decision, not everyone is fortunate enough to live in developed countries.
You were not being ignored, I just have nothing to say about it at this time. I am waiting on a reply from the developer.
So it's has even more free to play game business mechanics....without actually being free to play.
Cool cool.
Last edited by Dribbleondo on 2 October 2019 at 10:07 am UTC
Quoting: Liam Dawe
Quoting: pbWhat I'm more interested in is: will it stay playable through steam and on Linux.
Yes. Why wouldn't it? They've said nothing about leaving Steam or Linux.
They didn't say the inverse, too... the game becoming Epic Games exclusive, there's no guarantee anymore that they will keep supporting Linux next year, for example, because no Linux gamers will be able to buy the game anymore, so keeping it updated will be only a big waste of money from the developers.
I wanna be wrong, though.
Quoting: DribbleondoSo it's has even more free to play game business mechanics....without actually being free to play.
Cool cool.
Quoting: GuestNobody would forgive this if the devs were EA or Ubisoft, selling a game and then using microtransactions bullshit like it was a F2P game.
But it's Epic so let's just ignore this bullshit.
Do you both post the same sort of thing about Valve with Counter-Strike: Global Offensive loot boxes? You can't pick and choose.
Quoting: Patola@Liam why did you ignore my question? Since you're the most direct line with these developers, have you even asked them about their regional pricing changes? This is quite related to this news topic, their monetization policy. I believe there are many gamingonlinux readers which are affected by this decision, not everyone is fortunate enough to live in developed countries.
Psyonix finally replied today about my regional pricing query, they said this:
QuoteHey Liam,
Thank you for being a Rocket League fan!
I appreciate that you have taken the time to bring the game pricing to attention. Though we currently don't have information to share, rest assured that we have taken your report into account.
Keep having fun in the field!
That was all, they're not talking about it.
| https://www.gamingonlinux.com/articles/psyonix-have-announced-what-is-replacing-rocket-league-loot-boxes-and-it-sounds-reasonable.15128/ |
(PDF) The Influence of Blending Different Molecular Weights of Cellulose Acetate Butyrate for CO2/N2 Separation
PDF | On Aug 25, 2020, Dick Shion Chong and others published The Influence of Blending Different Molecular Weights of Cellulose Acetate Butyrate for CO2/N2 Separation | Find, read and cite all the research you need on ResearchGate
The Influence of Blending Different Molecular Weights of Cellulose Acetate Butyrate for CO2/N2 Separation
August 2020
Journal of Physical Science 31(2):91-112
DOI: 10.21315/jps2020.31.2.7
Authors:
University of Technology-Iraq
Figures
Schematic diagram of the experiment test rig. …
Contact angle of CAB membrane fabricated from various ratios of CAB of Mn 12000 and 70000, M1 (2:1), M2 (1:1) and M3 (1:2), with the 250 mm casting thickness, 5 min solvent evaporation time, 4 wt% polymer concentration and 60 min 2-isopropyl alcohol exchange drying time, followed by 60 min n-hexane drying time. …
N 2 permeance of CAB membrane fabricated from various ratio of CAB of Mn 12000 and 70000, M1 (2:1), M2 (1:1), M3 (1:2) and M4 (1:3), with the 250 µm casting thickness, 5 min solvent evaporation time, 4 wt% polymer concentration and 60 min 2-isopropyl alcohol exchange drying time, followed by 60 min n-hexane drying time. …
CO 2 /N 2 selectivity of CAB membrane fabricated from various ratios of CAB of Mn 12000 and 70000, M1 (2:1), M2 (1:1), M3 (1:2) and M4 (1:3) with the 250 µm casting thickness, 5 min solvent evaporation time, 4 wt% polymer concentration and 60 min 2-isopropyl alcohol exchange drying time, followed by 60 min n-hexane drying time. …
CO 2 permeance and N 2 permeance (left) and selectivity of CO 2 /N 2 (right) CAB membrane fabricated from various ratio of CAB Mn (12000 and 70000) M1 (2:1), M2 (1:1), M3 (1:2) and M4 (1:3) with 250 µm casting thickness, 5 min solvent evaporation time, 4 wt% polymer concentration and 60 min 2-isopropyl alcohol exchange drying time, followed by 60 min n-hexane drying time. …
Figures - uploaded by
Mayyadah Abed
Author content
2 /N 2
Dick Shion Chong, 1 Zeinab Abbas Jawad, 1* Peng Chee Tan 2
and Mayyadah Shanan Abed Al-Fatlawi 3
1 School of Engineering and Science, Department of Chemical Engineering,
Curtin University Malaysia, CDT 250, Miri 98009, Sarawak, Malaysia
2 School of Energy and Chemical Engineering, Xiamen University Malaysia,
Jalan Sunsuria, Bandar Sunsuria, 43900 Sepang, Selangor, Malaysia
3 Department of Materials Engineering, University of Technology, Baghdad, Iraq
* Corresponding author: zeinab.aj@curtin.edu.my
Published online: 25 August 2020
weights of cellulose acetate butyrate for CO 2 /N 2 separation. J. Phys. Sci. , 31(2), 91–112.
https://doi.org/10.21315/jps2020.31.2.7
To link to this article: https://doi.org/10.21315/jps2020.31.2.7
Public awareness of the environment and legislation has promoted
intensive studies on the reduction of greenhouse gases (GHGs) emission. One of the
promising breakthroughs discovered was the polymer blend membrane that demonstrated
signicant carbon dioxide (CO 2 ) /nitrogen (N 2 ) separation performance. Instead of
other polymers, cellulose acetate butyrate (CAB) polymer was chosen due to its high
CO 2 sorption ability. This membrane was prepared by optimising the ratios of the CAB
molecular weights (Mn) of 12000, 70000 and 30000 to enhance the CO 2 /N 2 separation.
The single gas permeation test results showed that the CO 2 /N 2 separation performance
had increased from 0.7396 ± 0.0396 (M3) to 1.8986 ± 0.0195 (M6) due to the presence
of the hydroxyl (OH) group in the membrane. In this study, the newly fabricated polymer
blend membrane demonstrated an improvement in the CO 2 /N 2 separation performance.
Therefore, this membrane qualies to be applied in the industry.
Gas separation, polymer blending, solvent exchange drying, polymer molecular
weight, cellulose acetate butyrate membrane
CAB for CO 2 /N 2 Separation 92
1.
The effects of global warming caused by the emission of greenhouse gases (GHGs)
have been categorised as one of the most important issues since the Industrial
Revolution. 1 It is widely known that the application of alternative energy sources
such as renewable energy and nuclear power is an option for reducing GHGs.
However, until sufcient research studies prove that these methods are able to
generate signicant amount of energy, conventional combustion of fossil fuels is
likely to continue. 2 In order to reduce the global warming effects, it is necessary to
perform carbon dioxide (CO 2 ) separation from ue gas since CO 2 dominates 77%
of the total emission of GHGs. 3
In recent years, membrane technology has drawn much attention because of high
performance and high selectivity. 4 The technology inherits numerous benets
like low energy, low capital costs, environmental friendly materials and modular
designs that allow further expansion effortlessly. 5 One of the materials utilised is
cellulose acetate butyrate (CAB). 6 It has been tested and proven to be an excellent
material for CO 2 separation because of its high tolerance to chemicals. 7 Moreover,
it is easy to modify its structure for high selectivity characteristics. 8 In addition,
Shanbhag et al. reported that the CAB membrane surpassed the results when
compared to the standard CA membrane for membrane stability and drying time
requirements. 9
However, one of the most important limitations of the polymeric membrane is
the challenge in achieving high permeability and high selectivity at the same time
due to the morphology of the fabricated membrane. 10 Therefore, it has become
relatively important to control its morphology and one of the methods employed
is by controlling the polymer molecular weight (Mn) when preparing the casting
solution. 11 According to Kee and Idris, the pore diameter, the effective surface
porosity and permeability of the membrane exhibits an equal increment when the
Mn of the polymer in the casting solution increases. 12 In addition, when a higher
Mn polymer is present in the casting solution, it promotes a lower diffusion rate,
which encourages the establishment of a thinner membrane with lower resistance to
gas permeation. 13 A major drawback of a polymer blend membrane is the difculty
in establishing an optimum ratio when its hydrophilic characteristic is modied. 14
Based on this, the aim of this study is to fabricate a polymer blend membrane by
optimising the polymer’s Mn. Over the decades, numerous studies and researches
have been undertaken to demonstrate the advantages of the CAB membrane in
the gas separation eld as well as separation of CO 2 from ue gas due to its high
emission since the industrial revolution. 15 Nevertheless, no studies have been
conducted to evaluate the effect of blending different ratios of the CAB polymer
Journal of Physical Science, Vol. 31(2), 91–112, 2020 93
with Mn of 12000, 70000 and 30000 with the polar acetyl group of 16–19 wt%,
12–15 wt% and 12–15 wt%, respectively, on the separation of the non-polar
CO 2 /N 2 . It is believed that this work will contribute signicantly towards the
environment with its high permeation rate, high selectivity, energy efcient and
low-cost characteristics.
2.
2.1
CAB of different Mn of 12000, 70000 and 30000 was acquired from Sigma-
Aldrich (Malaysia). The solvent chloroforms (≥99.7%) of 2-isopropyl alcohol and
n-hexane were purchased from Merck (Malaysia).
2.2
The CAB membrane (M1) was fabricated by preparing the casting solution from
4 wt% of the CAB polymer of different Mn of 12000 and 70000 at a ratio of
1:2 and 96% of chloroform. The solution was then stirred for 24 h. After the
stirring process, the mixture was sonicated for 20 min to remove any bubble
present in the solution in order to develop a neat membrane with smooth surface. 16
The methodology continued with the membrane casting process by controlling
the casting thickness at 250 μm with the assistance of a casting machine. 17
Next, solvent evaporation was performed on the membrane for 5 min under
room temperature conditions. Subsequently, the cast membrane was immersed
in distilled water at room temperature for 24 h. 18 The goal was to eliminate all
the residual solvent. With regards to the membrane drying process, the solvent
exchange drying method was applied by using 2-isopropyl alcohol as the rst
solvent for 30 min followed by n-hexane as the second solvent for 60 min. Lastly,
the fabricated membrane was left to dry for 24 h by evaporation under room
temperature to remove any volatile liquid. 19
2.3
In this research study, the casting solution was prepared by using different ratios
for Mn 12000 and 70000 and thus, obtaining the best solvent exchange time.
This is tabulated in Table 1.
CAB for CO 2 /N 2 Separation 94
2.4
The polymer of Mn 30000 was added to the polymer matrix M3 of Mn 12000 and
70000 at a ratio of 1:2, as tabulated in Table 1.
Table 1. The composition prepared for membrane fabrication with various polymer
concentration.
Membrane
samples
CAB (wt%)
(Mn) Chloroform
solvent
concentration
(wt%)
2-isopropyl
alcohol
exchange
time
(min)
n-hexane
exchange
time
(min)
Membrane
casting
thickness
(mm)
Evaporation
time
(min)
12000 70000 30000
M1 2 1 0 96 60 60 250 4
M2 1 1 0 96 60 60 250 4
M3 1 2 0 96 60 60 250 4
M4 1 3 0 96 60 60 250 4
M5 1 2 1 96 60 60 250 4
M6 1 2 2 96 60 60 250 4
2.5
The gas permeation test of the membrane was carried out with puried CO 2 and
N 2 gases at room temperature conditions. The ow rate of the feed (CO 2 or N 2 )
was controlled in order to release at a rate of 100 ml min −1 from a compressed gas
cylinder with the aid of a mass ow controller (Aalborg AFC 26, United States).
At the same time, the controller was linked to a two-channel digital set point/
readout unit device (Aalborg 0–200 ml min −1 , United States). The appointed gas
was thereafter injected into the stainless-steel membrane cell with pressure ranging
from 1 bar to 3 bars.
To ensure that the results were precise and accurate, several steps were taken
during preparation and membrane testing. This included cutting the membrane into
the shape of a disc and subsequently, placing it on top of the membrane cell and
covering it tightly. In addition, leak detection analysis was carried out to ensure that
no circumstance of leakage occurred during the test. The procedure of measuring
the ow rate of permeation and retentate was conducted by the assistance of a
soap bubble ow meter that measures each volume displacement individually.
Figure 1 shows the schematic diagram of an experimental rig set-up.
Journal of Physical Science, Vol. 31(2), 91–112, 2020 95
Pressure regulator
Mass ow controller Pressure gauge
Retentate stream
Needle valve Needle valve
membrane
Membrane
permeation cell
Permeate stream
Porous stainless steel disc
Bubble gas ow meter
Rubber O-ring
Feed
N 2
CO 2
Oven
Figure 1: Schematic diagram of the experiment test rig.
The performance of gas separation in terms of gas permeability and selectivity
were determined by the application of various dedicated formulas as shown in the
subsequent discussion.
The membrane presence ( P / l ) expressed in GPU was determined by applying
Equation 1 below into the calculation. 20
P = Q (1)
l A Δ p
where:
l = The membrane thickness (cm)
A = Effective membrane area (cm 2 )
Q = The volumetric ow rate at standard condition (cm 3 /s)
Δ p = The pressure drop across the membrane (cmHg)
1 GPU = [1 × 10 −6 (cm 3 (STP))/(cm 2 scmHg)]
Secondly, the calculation of the ratio of permeability for CO 2 /N 2 was obtained by
the application of Equation 2. 21
α CO 2 / N 2 = P CO 2 = ( P / l ) CO 2 (2)
l N 2 ( P / l ) N 2
CAB for CO 2 /N 2 Separation 96
2.6
2.6.1
The Attenuated Total Reectance Fourier Transform Infrared Spectroscopy
(ATR-FTIR) was utilised in this study with the aid of the NicoletIS10 (United
States) spectrometer having specications that ranged from 400 cm −1 to 4000 cm −1
across the diamond crystal. The information on background room condition was
recorded in advance before collecting the wavelengths of the samples. The process
was repeated three times to obtain the average for each sample.
2.6.2
To obtain the wettability of each membrane sample, the Rame-Hart Model 3000
Advanced Goniometer was utilised in this study. The recorded angles were
employed to analyse the membrane properties pertaining to liquid interaction and
repulsion forces among its interfacial properties. Ten measurements were obtained
from each sample to ensure preciseness of data.
2.6.3
The scanning electron microscope (SEM, Hitachi TM30000, Tokyo, Japan)
was used to obtain the morphology of the CAB membrane. At the beginning
of the process, the CAB membrane specimen was fractured into smaller pieces
followed by freezing at a temperature of −80°C in the cryogenic freezer for
24 h. This was to ensure that the consistency and clean crack of the membrane
could be achieved. This process was continued by coating the cracked specimen
with platinum in order to generate high contrast images. The minimum number of
samples required to produce genuine consistent results was decided at ve.
3.
3.1
According to Chakarabarty et al., the morphology of a membrane is highly
dependent on the Mn available in the casting solution due to variation in the
diffusion rate that affects the membrane thickness. 11 Therefore, it is relatively
important to obtain the optimum ratio of different Mn of the CAB polymer in order
to fabricate a high CO 2 /N 2 permeance and selectivity membrane. Thus, the CAB of
Mn 12000 was rst optimised, followed by optimisation of the CAB of Mn 70000
with solvent exchange time of 60 min for 2-isopropyl and 60 min for n-hexane.
Journal of Physical Science, Vol. 31(2), 91–112, 2020 97
3.1.1
Both the surface and cross-sectional morphologies of the fabricated CAB
membrane of Mn 12000 and 70000 at ratios of 2:1 (M1), 1:1 (M2), 1:2 (M3)
and 1:3 (M4) are demonstrated in Figure 2. Based on Figures 2(a, c, e), the
surface structure of the membrane was rough when the Mn of the CAB was at
12000 but smooth and defect-free when the Mn of the CAB was higher, i.e., at
70000. The rough surfaces formed on M1 and M2 were due to the increase in
the hydrophobicity of the membranes, as displayed in Figure 3. The hydrophobic
membrane surface reduces the ability of hydrogen to bond to form water, which
affects the surface morphology. Based on Figure 3, the contact angle increased
from 68.0° (M2) to 69.2° (M1) when the ratio of Mn 12000 was increased
from 1 to 2.
On the other hand, the cross-sectional morphology of the membranes was exhibited
in Figures 2(b, d, f and h). As indicated in Figures 2(b and d), the membrane
thickness increased from 21.75 ± 0.0216 µm (M2) to 31.49 ± 0.0542 µm (M1)
when the ratio of Mn 12000 increased from 1 (M2) to 2 (M1) in the casting
solution. This was because the membrane cast with the lower Mn of 12000 had
a low propensity of shrinking. 12 However, the membrane displayed a signicant
reduction in thickness from 31.49 ± 0.0542 µm (M1), 21.75 ± 0.0216 µm (M2) to
9.80 ± 0.0399 µm (M3) when the ratio of the higher Mn of 70000 was increased
from 1 (M2) to 2 (M3). The higher Mn of 70000 had a lower diffusion rate as
compared to the lower Mn of 12000. Therefore, when the cast membrane was
in contact with water, the lower Mn of 12000 with higher diffusion rate owed
out from the matrix rapidly causing the higher Mn of 70000 to aggregate. 13
As a result, a thinner membrane was formed, shown in Figure 2(f). Additionally,
the higher Mn of 70000 (M4) had the propensity of shrinking during fabrication
due to its higher compact structure. 12 Thus, M4 had a thickness of 13.39 ±
0.2098 µm.
3.1.2
3.1.2.1 Single gas permeation test of CO 2
The fabricated membranes M1, M2, M3 and M4 were tested using the single
gas permeation test of CO 2 . Based on Figure 4, when the ratio of the lower
Mn of CAB at 12000 increased from 1 (M2) to 2 (M1), the CO 2 permeance
of the membranes decreased signicantly from 29.81 ± 1.3203 GPU (M2)
to 17.32 ± 1.1039 GPU (M1). However, the thickness increased from 21.75
± 0.0216 µm (M2) to 31.49 ± 0.0542 µm (M1). This is shown in Figure 2.
CAB for CO 2 /N 2 Separation 98
(b)
(d)
(f) (e)
(g) (h)
(a)
(c)
Figure 2: SEM images of CAB membrane surface and cross sectional structure fabricated
from various ratio of CAB of Mn 12000 and 70000; (a, b) 2:1 (M1), (c, d) 1:1
(M2), (e, f) 1:2 (M3) and (g, h) 1:3 (M4) with the 250 µm casting thickness,
5 min solvent evaporation time, 4 wt% polymer concentration and 60 min
2-isopropyl alcohol exchange drying time, followed by 60 min n-hexane drying
time.
Journal of Physical Science, Vol. 31(2), 91–112, 2020 99
On the other hand, when the ratio of the higher Mn of CAB at 70000 increased
from 1 (M2) to 2 (M3) the CO 2 permeance increased dramatically from 29.81 ±
1.3203 GPU (M2) to 61.04 ± 1.0288 GPU. The high permeance of CO 2 for M3
was due to the higher surface hydrophilicity. This is demonstrated in Figure 3.
Based on this gure, when the Mn of 70000 was increased to the ratio of 2 (M3),
a more hydrophilic membrane was formed where M3 displayed the lowest contact
angle with a value of 67.8° when compared to M2 and M1, which had higher
contact angles of 68.0° and 69.2°, respectively. The reason for the reduction in
the value of the contact angle when the ratio of the CAB of Mn 70000 increased
was due to the extra hydroxyl (-OH) present in the polymer. This is shown in the
higher stretching vibrations of the FTIR in Figure 5 where the hydrophilicity of
the membrane surface is enhanced. 22 According to a study, the -OH functional
group increases the hydrophilicity of the membrane surface. 12 Thus, the CO 2
permeance of M3 increased. The increase was attributed mainly to the availability
of the polar functional groups (-OH), which have the potential to react with the
non-polar CO 2 gas. 23 On the contrary, when the ratio of the CAB of Mn 70000
was increased to 3 (M4), the CO 2 permeance decreased dramatically to 19.15
± 1.6949 GPU resulting in the increase of the membrane thickness from 9.80 ±
0.0399 µm (M3) to 13.39 ± 0.2098 µm (M4), as shown in Figure 2. This is because
the permeance of a membrane is inversely proportional to its cross-sectional
thickness. 24
Membrane
M1
Mean contact angle
M2
70
69
69
68
68
67
M3
Figure 3: Contact angle of CAB membrane fabricated from various ratios of CAB of Mn
12000 and 70000, M1 (2:1), M2 (1:1) and M3 (1:2), with the 250 mm casting
thickness, 5 min solvent evaporation time, 4 wt% polymer concentration
and 60 min 2-isopropyl alcohol exchange drying time, followed by 60 min
n-hexane drying time.
CAB for CO 2 /N 2 Separation 100
Pressure (bar)
2.5 1.5 3 2 1
M1
CO 2 permeance (GPU)
M2
70
60
50
40
30
20
0
10
M3
M4
Figure 4: CO 2 permeance of CAB membrane fabricated from various ratio of CAB of
Mn 12000 and 70000, M1 (2:1), M2(1:1), M3 (1:2) and M4 (1:3) with the
250 µm casting thickness, 5 min solvent evaporation time, 4 wt% polymer
concentration and 60 min 2-isopropyl alcohol exchange drying time, followed
by 60 min n-hexane drying time.
Wavenumbers (cm −1 )
Transmittance (%)
70
80
100
95
90
85
3300 2800 2300 1800
M3
M2
1300 800
75 (C-O-C)
(C-O)
(-OH)
(C=O)
(C-H)
Figure 5: ATR-FTIR spectra of selected CAB membrane M3 (1:2) and M2 (1:1)
fabricated from CAB of Mn of 12000 and 70000, with the 250 µm casting
thickness, 5 min solvent evaporation time, 4 wt% polymer concentration and
60 min 2-isopropyl alcohol exchange drying time, followed by 60 min n-hexane
drying time.
Journal of Physical Science, Vol. 31(2), 91–112, 2020 101
3.1.2.2 Single gas permeation test of N 2
Similarly, the membranes were evaluated using the single gas permeation test of
N 2 . Based on Figure 6, the N 2 permeance decreased from 38.36 ± 0.6954 GPU to
23.99 ± 0.7500 GPU when the ratio of the Mn of 12000 increased from 1 (M2) to
2 (M1) causing the membrane thickness to increase from 21.75 ± 0.0216 µm (M2)
to 31.49 ± 0.0542 µm (M1). This is presented in Figure 2.
Pressure (bar)
2.5 1.5 3 2 1
M1
N 2 permeance (GPU)
M2
70
80
60
50
40
30
20
0
10
M3
M4
Figure 6: N 2 permeance of CAB membrane fabricated from various ratio of CAB of
Mn 12000 and 70000, M1 (2:1), M2 (1:1), M3 (1:2) and M4 (1:3), with the
250 µm casting thickness, 5 min solvent evaporation time, 4 wt% polymer
concentration and 60 min 2-isopropyl alcohol exchange drying time, followed
by 60 min n-hexane drying time.
On the other hand, when the ratio of the Mn of 70000 was increased from
1 (M2) to 2 (M3), the N 2 permeance showed a notable increase from 38.36 ±
0.6954 GPU to 66.49 ± 0.8172 GPU. The high N 2 gas permeance achieved
for M3 was due principally to the occurrence of blending of the higher Mn of
CAB at 70000 into the casting solution resulting in the formation of a thinner
membrane. This is discussed in Figures 2(b, d, f and h). These results agreed with
Du et al., who stated that the permeance of a membrane is inversely proportional
to its cross-sectional thickness. 24 Therefore, thinner membrane promotes an
easier pathway as well as lower resistance for the gases to go through more
rapidly. 25 Thus, when the ratio of the Mn of 70000 increased to 3 (M4), the N 2
permeance signicantly reduced to 25.70 ± 0.9598 GPU. This was due to the
formation of a thicker membrane of 13.39 ± 0.2098 µm (M4) as compared to
9.80 ± 0.0399 µm (M3).
CAB for CO 2 /N 2 Separation 102
3.1.2.3 Separation performance of CO 2 /N 2
Figure 7 demonstrates the CO 2 /N 2 separation performance for the membranes M1,
M2, M3 and M4. According to this gure, the selectivity of CO 2 /N 2 across the
membrane increased from 0.8447 ± 0.0110 to 0.9186 ± 0.0113 when the ratio
of Mn 70000 was increased from 1 (M2) to 2 (M3). The high CO 2 /N 2 selectivity
obtained for M3 was due to the presence of the polar functional group (-OH) at
the ratio of 1:2 for Mn 12000 and 70000, respectively. Based on Figure 5, M3 had
a higher polar functional group (-OH) compared with M2. With the presence of
this functional group, the CO 2 /N 2 selectivity was enhanced. Further, Zhang et al.
proved that the functional groups demonstrated in the CAB polymer were highly
interactive toward CO 2 because it was one of the gas-responsive polymers. 26
Pressure (bar)
2.5 1.5 3 2 1
M1
Selectivity (−)
M2
0.40
0.50
0.60
0.70
1.00
0.90
0.80
M3 M4 Linear (M3)
Linear line M3
Figure 7: CO 2 /N 2 selectivity of CAB membrane fabricated from various ratios of CAB
of Mn 12000 and 70000, M1 (2:1), M2 (1:1), M3 (1:2) and M4 (1:3) with
the 250 µm casting thickness, 5 min solvent evaporation time, 4 wt% polymer
concentration and 60 min 2-isopropyl alcohol exchange drying time, followed
by 60 min n-hexane drying time.
As illustrated in Figure 8, when M3 was prepared with Mn of 12000 and 70000
at a ratio of 1:2, it proved in having the best CO 2 /N 2 selectivity (0.9186 ± 0.0113)
compared with the other membranes (M1, M2 and M4). Figure 5 shows the high
CO 2 /N 2 selectivity attributed to the Mn of 70000, which contained a higher OH
group. The OH group increased the membrane surface hydrophilicity from 69.2°
(M1) to 67.8° (M3) that were more favourable to the non-polar molecules of CO 2 . 27
Thus, the permeance of CO 2 and the CO 2 /N 2 selectivity were further enhanced.
Journal of Physical Science, Vol. 31(2), 91–112, 2020 103
Permeance (GPU)
Selectivity (−)
M1 (2:1)
CO 2 /N 2 selectivity
Membrane (Mw = 120000 and Mw = 700000
CO 2
M2 (1:1)
70
80
60
50
40
30
20
0
10
M3 (1:2) M4 (1:3)
1.2
1.0
0.8
0.6
0.4
0.2
0.0
N 2
Figure 8: CO 2 permeance and N 2 permeance (left) and selectivity of CO 2 /N 2 (right)
CAB membrane fabricated from various ratio of CAB Mn (12000 and 70000)
M1 (2:1), M2 (1:1), M3 (1:2) and M4 (1:3) with 250 µm casting thickness,
5 min solvent evaporation time, 4 wt% polymer concentration and 60 min
2-isopropyl alcohol exchange drying time, followed by 60 min n-hexane drying
time.
3.2
In order to enhance the performance of the CAB membrane, the best membrane
(M3) was fabricated at the ratio of 1:2 and the Mn of 12000 and 70000 was further
optimised with additional CAB of Mn 30000 at various ratios of 1:2:1 (M5) and
1:2:2 (M6) of Mn 12000, 70000 and 30000, respectively.
3.2.1
The surface and cross-sectional morphologies of the cast membranes M5 (1:2:1)
and M6 (1:2:2) are demonstrated in Figure 9. According to Figures 9(a, c), a rough
surface formed when the ratio of Mn 30000 increased from 1 (M5) to 2 (M6)
resulting in the increase of the membrane hydrophilicity when synthesised with
Mn of 30000. This is displayed in Figure 10. As seen from this Figure, the contact
angle reduced from 80.1° (M5) to 70.0° ± 0.0200 (M6). Du et al. proved that as
the hydrophilicity of the membrane increased, a rougher membrane surface was
formed because of higher surface tension and the ability of forming hydrogen bond
with water. As a result, this affected the surface morphology. 28
CAB for CO 2 /N 2 Separation 104
On the other hand, Figures 9(b and d) show that the membrane thickness
decreased from 9.21 ± 0.0428 µm (M5) to 8.23 ± 0.0245 µm (M6) when the ratio
of Mn 30000 increased from 1 (M5) to 2 (M6) in the casting solution. This result
was due to the varying diffusion rates between Mn 12000, 70000 and 30000. 29
The higher ratios of Mn 30000 and 70000 had a relatively lower diffusion rate
when compared to the lower ratio of Mn 12000. Therefore, during immersion
in water the lower Mn of 12000 owed out rst due to the higher diffusion rate
instead of the higher CAB of Mn 30000 and 70000. 13 In addition, the higher
Mn of 70000 and 30000 had a higher propensity of shrinking when fabricated. 12
Thus, membrane M6, which was fabricated at a higher concentration of Mn 70000
and 30000 formed a thinner membrane (8.23 ± 0.0245 µm) in comparison to M5
(9.21 ± 0.0428 µm) and M3 (9.80 ± 0.0399 µm).
(a)
(b)
(c)
(d)
Figure 9: SEM images of CAB membrane surface and cross sectional structure fabricated
from various ratios of CAB Mn (12000, 70000 and 30000), M5 (1:2:1), M6
(1:2:2) with the 250 µm casting thickness, 5 min solvent evaporation time,
4 wt% polymer concentration and 60 min 2-isopropyl alcohol exchange drying
time, followed by 60 min n-hexane drying time.
Journal of Physical Science, Vol. 31(2), 91–112, 2020 105
Membrane
Mean Contact Angle
70
72
82
80
78
76
74
64
66
68
M5 M6
Figure 10: Contact angle of CAB membrane fabricated at Mn of 12000, 70000 and
30000 for (a) 1:2:1 (M5) and (b) 1:2:2 (M6) with the 250 µm casting thickness,
5 min solvent evaporation time, 4 wt% polymer concentration and 60 min
2-isopropyl alcohol exchange drying time, followed by 60 min n-hexane drying
time.
3.2.2
3.2.2.1 Single gas permeation test of CO 2
The results obtained from the single gas permeance test of CO 2 for M5 (1:2:1)
and M6 (1:2:2) were then compared with M3. This is demonstrated in Figure 11.
Based on this gure, the CO 2 permeance increased with the addition of Mn 30000
into the polymer matrix of M3. Figure 11 also shows that the highest CO 2 permeance
was 262.58 ± 1.2138 GPU for M6 (1:2:2), which was 5 times higher than the CO 2
permeance of M3 (61.04 ± 1.0288 GPU). The increase was due to reduction in the
membrane thickness from 9.80 ± 0.0399 µm (M3, Figure 2(d)) to 8.23 ± 0.0254
µm (M6, Figure 9(f )) when the ratio of Mn 30000 increased to 2 (M6). Further,
when the ratio of Mn 30000 increased from 0 (M3) to 2 (M6), the stretching of the
polar groups (-OH) increased, as presented in the ATR-FTIR spectroscopy (Figure
12). Hence, the CO 2 permeance increased because of the high interaction between
the polar group (-OH) and the non-polar CO 2 .
CAB for CO 2 /N 2 Separation 106
Pressure (bar)
2.5 1.5 3 2 1
CO 2 permeance (GPU)
M5
300
250
200
150
100
0
50
M3
M6
Figure 11: CO 2 permeance of CAB membrane fabricated at Mn of 12000, 70000 and
30000, 1:2:1 (M5), 1:2:2 (M6) and M3 (1:2) with the 250 µm casting thickness,
5 min solvent evaporation time, 4 wt% polymer concentration and 60 min
2-isopropyl alcohol exchange drying time, followed by 60 min n-hexane drying
time.
Wavenumbers (cm −1 )
Transmittance (%)
70
80
100
95
90
85
3300 2800 2300 1800
M3
M6
1300 800
75
(C-O-C)
(C-O)
(-OH)
(C=O)
(C-H)
Figure 12: ATR-FTIR spectra of CAB membrane fabricated at Mn of 12000, 70000 and
30000, 1:2:2 (M6) and M3 (1:2), with the 250 µm casting thickness, 5 min
solvent evaporation time, 4 wt% polymer concentration and 60 min 2-isopropyl
alcohol exchanges drying time, followed by 60 min n-hexane drying time.
Journal of Physical Science, Vol. 31(2), 91–112, 2020 107
3.2.2.2 Single gas permeation test of N 2
As displayed in Figure 13, the N2 permeance increased from 66.49 ± 1.3390 GPU
to 178.25 ± 3.6033 GPU when the ratio of Mn 30000 increased from 0 (M3) to
1 (M5). This was due to the formation of a thinner membrane that resulted in
lower resistance to gas permeation. On the contrary, when the ratio of Mn 30000
was increased to 2 (M6) the N 2 permeance showed gradual reduction to 138.36 ±
1.5479 GPU. This is presented in Figure 13. In addition, this reduction might
be attributed to the increase in the carbonyl (C=O) groups as demonstrated in
Figure 14, that are competent to interact with the N 2 molecules by its π-electron
system. 16 Thus, this strengthened the intermolecular interactive force between
N 2 molecules and C=O group that indicate a greater mass transfer resistant that
reduced the N 2 gas permeance through the membrane. 16
Pressure (bar)
2.5 1.5 3 2 1
N 2 permeance (GPU)
M5
250
200
150
100
0
50
M3
M6
Figure 13: N 2 permeance of CAB membrane fabricated at Mn of 12000, 70000 and
30000, 1:2:1 (M5), 1:2:2 (M6) and M3 (1:2), with the 250 µm casting thickness,
5 min solvent evaporation time, 4 wt% polymer concentration and 60 min
2-isopropyl alcohol exchange drying time, followed by 60 min n-hexane drying
time.
CAB for CO 2 /N 2 Separation 108
Wavenumbers (cm −1 )
Transmittance (%)
70
80
100
95
90
85
3300 2800 2300 1800
M5
M6
1300 800
75
(C-O-C)
(C-O)
(-OH)
(C=O)
(C-H)
Figure 14: ATR-FTIR spectra of CAB membrane fabricated at Mn of 12000, 70000 and
30000, 1:2:1 (M5) and 1:2:2 (M6), with the 250 µm casting thickness, 5 min
solvent evaporation time, 4 wt% polymer concentration and 60 min 2-isopropyl
alcohol exchanges drying time, followed by 60 min n-hexane drying time.
3.2.2.3 Separation performance of CO 2 /N 2
The optimisation of the blended ratios of CAB of Mn 30000 into the best
membrane that was obtained upon the optimisation of CAB of Mn 12000 and
70000 proved that the separation performance successfully improved. The CO 2
permeance of the membrane upon increasing the Mn of CAB to 30000 in the
polymer blend, dramatically increased from 61.04 ± 1.0288 GPU (M3) to 262.58
± 1.2138 GPU (M6). As exhibited in Figure 15, this resulted in the enhancement
of CO 2 /N 2 selectivity from 0.9186 ± 0.0113 (M3) to 1.8986 ± 0.0195 (M6). This
was due to the increase in the surface hydrophilicity of M6 that attracted the
non-polar molecules of CO 2 , as proven by the contact angle results (Figure 10),
which reduced from 80.1° (M5) to 70.0° ± 0.0200 (M6). In addition, the CO 2 /N 2
selectivity further improved when the ratio of Mn 30000 increased from 0 (M3)
to 2 (M6) thereby, increasing the polar functional group (-OH) of the membrane
(Figure 12). Eventually, the attraction between CO 2 and the membrane improved.
Noticeably, the blending of Mn 30000 within CAB membrane structure had
improved the CO 2 permeance of the present work as compared to other research
works with the same casting conditions (Table 2). According to this table, the
Journal of Physical Science, Vol. 31(2), 91–112, 2020 109
membrane fabricated with CAB of Mn 30000 at ratio of 2 showed the highest
permeance of CO 2 . This might be due to the enhanced surface hydrophilicity that
attracted non-polar molecules CO 2 , as discussed previously in Figure 10.
Permeance (GPU)
Selectivity (−)
CO 2 /N 2 selectivity
Membrane CAB of Mn (120000; 70000; 12000)
CO 2
M3 (1:2) M5 (1:2:1) M6 (1:2:2)
2.5000
2.0000
1.5000
1.0000
0.5000
0.0000
N 2
300.0000
250.0000
150.0000
100.0000
50.0000
0.0000
200.0000
Figure 15: CO 2 permeance and N 2 permeance (left) and selectivity of CO 2 /N 2 (right) of
CAB membrane fabricated at Mn of 12000, 70000 and 30000 1:2:1 (M5),
1:2:2 (M6) and M3 (1:2), with the 250 µm casting thickness, 5 min solvent
evaporation time, 4 wt% polymer concentration and 60 min 2-isopropyl alcohol
exchange drying time, followed by 60 min n-hexane drying time.
Table 2: A comparison between current study gas separation performance results and
other literature works.
References CAB (wt%) (Mn) Permeability (GPU) Selectivity
12000 70000 65000 30000 CO 2 N 2 CO 2 /N 2
Present work 1 2 0 0 61.04
(−76.75%)
66.49
(−51.95%)
0.7396
(−51.62%)
1 2 0 1 223.38
(265.95%)
178.25
(168.09%)
1.2529
(36.39%)
1 2 0 2 262.58
(330.16%)
138.36
(108.10%)
1.8986
(106.68%)
Cha et al. 16 1 0 1 0 106.87 15.31 6.982
Lee et al. 19 1 1 1 0 205.09 249.34 0.84
Lee et al. 30 0 1 0 0 40.51 119.20 2.94
CAB for CO 2 /N 2 Separation 110
4.
In this study, the CAB membranes with different molecular weights (Mn) were
successfully fabricated by optimising the CAB polymer blends with Mn of
12000, 70000 and 30000. The results showed that the Mn of CAB signicantly
affected the CO 2 /N 2 selectivity of the membrane. When the CAB blend ratio of
Mn 70000:12000 increased from 2:1 (M1) to 1:2 (M3), the CO 2 /N 2 selectivity
enhanced from 0.7396 ± 0.0396 (M1) to 0.9186 ± 0.0113 (M3) due to the presence
of the higher hydroxyl group (-OH) that attracted the non-polar CO 2 . However,
on further increasing the ratio to 1:3 (M4) the separation performance showed
insignicant changes due to long plugging effect by the long chain polymer. To
enhance the separation performance, M3 (1:2) was optimised by adding CAB
of Mn 30000 into the polymer blend. When CAB of Mn 30000 was increased
from the ratio of 0 (M3) to 2 (M6), the CO 2 /N 2 selectivity increased signicantly
from 0.9186 ± 0.0113 (M3) to 1.8986 ± 0.0195 (M6), resulting in a higher
CO 2 permeance of 262.58 ± 1.2138 GPU as compared to 61.04 ± 1.0288 GPU
(M3). This was mainly due to the thinner membrane fabricated for M6 (8.23 ±
0.0245 µm) and M3 (9.80 ± 0.0399 µm). In summary, different molecular weights
of CAB inuences the CO 2 /N 2 selectivity and permeance of the membrane
signicantly.
5.
1. Weissburg, M. & Draper, A. M. (2019). Impacts of global warming and elevated
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... Furthermore, higher PEG content in the casting solution results in an increase of rubbery segments that leads to a higher dominance of gas separation through adsorption [184]. Further, the pore-forming and pore-reducing effects of PEG of different molecular weights must also be considered due to the relationship between CO 2 /N 2 selectivity and CO 2 permeance [118,
185]
. PEG with low molecular weights results in higher gas permeation with the cost of selectivity, while the PEG with high molecular weights results in the opposite effect [186]. In order to synthesise a membrane with optimum selectivity and permeability, it is necessary to decide the optimum concentration of the polymer in the casting solution. ...
The prospect of synthesis of PES/PEG blend membranes using blend NMP/DMF for CO2/N2 separation
Carbon dioxide (CO 2 ) emissions have been the root cause for anthropogenic climate change. Decarbonisation strategies, particularly carbon capture and storage (CCS) are crucial for mitigating the risk of global warming. Among all current CO 2 separation technologies, membrane separation has the biggest potential for CCS as it is inexpensive, highly efficient, and simple to operate. Polymeric membranes are the preferred choice for the gas separation industry due to simpler methods of fabrication and lower costs compared to inorganic or mixed matrix membranes (MMMs). However, plasticisation and upper-bound trade-off between selectivity and permeability has limited the gas separation performance of polymeric membranes. Recently, researchers have found that the blending of glassy and rubbery polymers can effectively minimise trade-off between selectivity and permeability. Glassy poly(ethersulfone) (PES) and rubbery poly(ethylene) glycol (PEG) are polymers that are known to have a high affinity towards CO 2 . In this paper, PEG and PES are reviewed as potential polymer blend that can yield a final membrane with high CO 2 permeance and CO 2 /nitrogen (N 2 ) selectivity. Gas separation properties can be enhanced by using different solvents in the phase-inversion process. N-Methyl-2-Pyrrolidone (NMP) and Dimethylformamide (DMF) are common industrial solvents used for membrane fabrication. Both NMP and DMF are reviewed as prospective solvent blend that can improve the morphology and separation properties of PES/PEG blend membranes due to their effects on the membrane structure which increases permeation as well as selectivity. Thus, a PES/PEG blend polymeric membrane fabricated using NMP and DMF solvents is believed to be a major prospect for CO 2 /N 2 gas separation.
Investigation of the effect of pristine and functionalized carbon nanotubes in cellulose acetate butyrate for mixed-gas separation: A molecular simulation study
| https://www.researchgate.net/publication/343860033_The_Influence_of_Blending_Different_Molecular_Weights_of_Cellulose_Acetate_Butyrate_for_CO2N2_Separation |
The role of melatonin in acute myocardial infarction | Request PDF
Request PDF | On Jan 1, 2012, Alberto Dominguez-Rodriguez published The role of melatonin in acute myocardial infarction | Find, read and cite all the research you need on ResearchGate
The role of melatonin in acute myocardial infarction
DOI: 10.2741/4063
To read the full-text of this research, you can request a copy directly from the author.
... Sci. 2020, 21, 1804 2 of 16 with a peak in the morning hours [2]
[3]
[4][5][6][7][8]. Preservation of circadian oscillations from the level of intracellular organelles to the integrated cardiovascular system appears to be essential for maintaining health and preventing diseases [8][9][10][11][12]. ...
... The administration of high pharmacological doses of melatonin protects against oxidative and nitroxidative stress, arrhythmias, and inflammation, reduces blood pressure, and attenuates metabolic syndrome [15][16][17]. A cardioprotective role of physiological levels of melatonin has been observed in the clinical scenario, and it has been tested under experimental conditions using pinealectomy
[3,
5,6,13,14,18]. ...
Reperfusion Arrhythmias Increase after Superior Cervical Ganglionectomy Due to Conduction Disorders and Changes in Repolarization
Mar 2020
Luz ESTEFANIA Farias Altamirano
Pharmacological concentrations of melatonin reduce reperfusion arrhythmias, but less is known about the antiarrhythmic protection of the physiological circadian rhythm of melatonin. Bilateral surgical removal of the superior cervical ganglia irreversibly suppresses melatonin rhythmicity. This study aimed to analyze the cardiac electrophysiological effects of the loss of melatonin circadian oscillation and the role played by myocardial melatonin membrane receptors, SERCA2A, TNFα, nitrotyrosine, TGFβ, KATP channels, and connexin 43. Three weeks after bilateral removal of the superior cervical ganglia or sham surgery, the hearts were isolated and submitted to ten minutes of regional ischemia followed by ten minutes of reperfusion. Arrhythmias, mainly ventricular tachycardia, increased during reperfusion in the ganglionectomy group. These hearts also suffered an epicardial electrical activation delay that increased during ischemia, action potential alternants, triggered activity, and dispersion of action potential duration. Hearts from ganglionectomized rats showed a reduction of the cardioprotective MT2 receptors, the MT1 receptors, and SERCA2A. Markers of nitroxidative stress (nitrotyrosine), inflammation (TNFα), and fibrosis (TGFβ and vimentin) did not change between groups. Connexin 43 lateralization and the pore-forming subunit (Kir6.1) of KATP channels increased in the experimental group. We conclude that the loss of the circadian rhythm of melatonin predisposes the heart to suffer cardiac arrhythmias, mainly ventricular tachycardia, due to conduction disorders and changes in repolarization.
... Acute coronary syndrome (ACS) contains three types of coronary artery disease: ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina. Reasons for the use of melatonin in acute coronary syndrome have been reviewed by Dominguez-Rodriguez et al.
[9,
10]. Stipulated mechanisms for benefic effects melatonin in this pathology include vasodilatory effects of vascular melatoninergic receptors, antioxidative and anti-inflammatory actions, and influence on circadian cardiovascular rhythms [9,10]. ...
... Reasons for the use of melatonin in acute coronary syndrome have been reviewed by Dominguez-Rodriguez et al. [9,10]. Stipulated mechanisms for benefic effects melatonin in this pathology include vasodilatory effects of vascular melatoninergic receptors, antioxidative and anti-inflammatory actions, and influence on circadian cardiovascular rhythms
[9,
10]. Through these mechanisms, several preclinical studies have suggested melatonin as effective in reducing ischemia-reperfusion injury, including injury in the heart (reviewed by Reiter and Tan, [11]). ...
Cardioprotective Melatonin: Translating from Proof-of-Concept Studies to Therapeutic Use
Jose Cipolla-Neto
In this review we summarized the actual clinical data for a cardioprotective therapeutic role of melatonin, listed melatonin and its agonists in different stages of development, and evaluated the melatonin cardiovascular target tractability and prediction using machine learning on ChEMBL. To date, most clinical trials investigating a cardioprotective therapeutic role of melatonin are in phase 2a. Selective melatonin receptor agonists Tasimelteon, Ramelteon, and combined melatonergic-serotonin Agomelatine, and other agonists with registered structures in CHEMBL were not yet investigated as cardioprotective or cardiovascular drugs. As drug-able for these therapeutic targets, melatonin receptor agonists have the benefit over melatonin of well-characterized pharmacologic profiles and extensive safety data. Recent reports of the X-ray crystal structures of MT1 and MT2 receptors shall lead to the development of highly selective melatonin receptor agonists. Predictive models using machine learning could help to identify cardiovascular targets for melatonin. Selecting ChEMBL scores > 4.5 in cardiovascular assays, and melatonin scores > 4, we obtained 284 records from 162 cardiovascular assays carried out with 80 molecules with predicted or measured melatonin activity. Melatonin activities (agonistic or antagonistic) found in these experimental cardiovascular assays and models include arrhythmias, coronary and large vessel contractility, and hypertension. Preclinical proof-of-concept and early clinical studies (phase 2a) suggest a cardioprotective benefit from melatonin in various heart diseases. However, larger phase 3 randomized interventional studies are necessary to establish melatonin and its agonists’ actions as cardioprotective therapeutic agents.
... Evidence has shown that MT has a clear protective effect against cell death
[26]
. In this study, the effects of MT on the survival of RGCs were assessed by counting the number of specific stain (Tuj-1 and RBPMS)-positive cells in retinal flat mounts. ...
Melatonin Alleviates Retinal Ischemia–Reperfusion Injury by Inhibiting p53–Mediated Ferroptosis
Retinal ischemia–reperfusion (RIR) injury caused by high intraocular pressure (IOP) is an important risk factor contributing to retinal ganglion cell (RGC) death, eventually causing blindness. A key progressive pathological process in the development of RIR is the death of RGCs. However, the detailed mechanisms underlying RGC death caused by RIR have not yet been clearly elucidated, and effective treatments are lacking. Ferroptosis is a recently defined form of programmed cell death that is closely related to organ injury. Melatonin (MT) is a promising neuroprotective agent, but its effects on RIR injury remain unclear. In this study, murine models of acute ocular hypertension and oxygen and glucose deprivation/reoxygenation (OGD/R) model were adopted to simulate retinal ischemia. MT alleviated retinal damage and RGC death in RIR mice, significantly attenuating RIR–induced ferroptosis. Furthermore, MT reduced the expression of p53, a master regulator of ferroptosis pathways, and the upregulation of p53 promoted ferroptosis and largely abolished the neuroprotective effects of MT. Mechanistically, the overexpression (OE) of p53 suppressed the expression of the solute carrier family 7 member 11 (Slc7a11), which was accompanied by increased 12–lipoxygenase (Alox12) expression, triggering retinal ferroptosis. Moreover, MT–ameliorated apoptosis, neuroinflammation and microglial activation were observed. In summary, MT conferred neuroprotection against RIR injury by inhibiting p53–mediated ferroptosis. These findings indicate that MT is a retina–specific ferroptosis inhibitor and a promising therapeutic agent for retinal neuroprotection.
... Solid evidence exists that melatonin influences the cardiovascular system [4]
[5]
[6][7]. A post hoc analysis investigated whether the melatonin effect is time dependent, i.e., from symptom onset to artery opening in patients with AMI treated with primary angioplasty [8]. ...
Early Treatment of Acute Myocardial Infarction with Melatonin: Effects on MMP-9 and Adverse Cardiac Events
Background:
Matrix metalloproteinase-9 (MMP-9) is crucial in tissue remodeling after an adverse cardiac event. In experimental studies, melatonin has been found to attenuate MMP-9 activation. The present study assessed the effects of systemic melatonin administration on the prognosis of patients with acute myocardial infarction (AMI) successfully treated with primary percutaneous coronary intervention, and to examine the effects on MMP-9 levels.
Methods:
We conducted a randomized controlled trial, enrolling patients who underwent primary percutaneous coronary intervention due to AMI. They were assigned to two groups for melatonin or placebo. The primary endpoint was a combined event of mortality and heart failure readmission at 2 years. The secondary endpoint was the levels of MMP-9 after the percutaneous coronary intervention.
Results:
Ninety-four patients were enrolled, 45 in the melatonin group and 49 in the control group. At 2 years of follow-up, 13 (13.8%) patients suffered the primary endpoint (3 deaths and 10 readmissions due to heart failure), 3 patients in the melatonin group and 10 in the placebo group. The difference in the restricted mean survival time was 87.5 days (p = 0.02); HR = 0.3 (95% CI 0.08-1.08; p = 0.06); Log-rank test 0.04. After controlling for confounding variables, melatonin administration reduced MMP-9 levels to 90 ng/mL (95% CI 77.3-102.6).
Conclusions:
This pilot study demonstrated that compared to placebo, melatonin administration was associated with better outcomes in AMI patients undergoing primary percutaneous coronary intervention.
... In this study, melatonin was suggested to modulate OPA1 by up-regulating the AMPactivated protein kinase (AMPK) signaling pathway [137]. Human investigation reported that low circulating melatonin levels were associated with aggravated heart dysfunction in patients with post-acute MI
[138]
. Therefore, melatonin supplementation may represent a promising approach against various cardiovascular pathologies. ...
Molecular Sciences Tryptophan: From Diet to Cardiovascular Diseases Academic Editors: Ida Daniela
Cardiovascular disease (CVD) is one of the major causes of mortality worldwide. Inflammation is the underlying common mechanism involved in CVD. It has been recently related to amino acid metabolism, which acts as a critical regulator of innate and adaptive immune responses. Among different metabolites that have emerged as important regulators of immune and inflammatory responses, tryptophan (Trp) metabolites have been shown to play a pivotal role in CVD. Here, we provide an overview of the fundamental aspects of Trp metabolism and the interplay between the dysregulation of the main actors involved in Trp metabolism such as indoleamine 2, 3-dioxygenase 1 (IDO) and CVD, including atherosclerosis and myocardial infarction. IDO has a prominent and complex role. Its activity, impacting on several biological pathways, complicates our understanding of its function, particularly in CVD, where it is still under debate. The discrepancy of the observed IDO effects could be potentially explained by its specific cell and tissue contribution, encouraging further investigations regarding the role of this enzyme. Thus, improving our understanding of the function of Trp as well as its derived metabolites will help to move one step closer towards tailored therapies aiming to treat CVD.
... Melatonin originally identified in the bovine pineal gland in 1958 (6) has multiple beneficial actions in various cardiac pathologies (7)
(8)
(9)(10). Melatonin is a pleiotropic molecule with several functions that protect the heart against IR injury. ...
Melatonin and Cardioprotection in Humans: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Myocardial ischemia/reperfusion (IR) injury represents a critical problem associated with interventional approaches for coronary reperfusion. Pharmacological cardioprotective interventions are advocated to ameliorate IR injury. Melatonin is an anti-inflammatory and antioxidant agent with a wide range of therapeutic properties that may contribute to its cardioprotective effects. No systematic review or meta-analysis has compared melatonin vs. placebo as a cardioprotective agent in humans. The present study, based on a systematic review and meta-analysis, was carried out to assess melatonin's efficacy as a cardioprotective treatment. We performed a systematic review of the available literature. Randomized controlled trials (RCTs) were identified and information was extracted using predefined data extraction forms. The primary outcomes were (a) left ventricular ejection fraction (LVEF) and (b) blood troponin levels in patients who underwent myocardial revascularization and were randomized to melatonin or placebo. The inverse-variance random-effects method was used to pool the estimates. Heterogeneity and publication bias were assessed. Weighted mean differences or standardized mean differences were calculated. A total of 283 records were screened and seven RCTs met all the inclusion criteria. After the pooled analysis, the results on LVEF were consistent across all studies, and a significant heterogeneity was found in the results on troponin levels. The melatonin-treated patients had on average higher LVEF than the placebo-treated individuals with a weighted mean difference = 3.1% (95% CI 0.6–5.5, p = 0.01). Five works compared the levels of troponin after melatonin or placebo treatment. The melatonin-treated patients had lower levels of troponin with a standardized mean difference = −1.76 (95% CI −2.85 to −0.67, p = 0.002). The findings of this meta-analysis revealed that melatonin administration in humans as a cardioprotective agent attenuated heart dysfunction with a favorable effect on the LVEF.
... Specifically, animal studies revealed that melatonin exerted protective effect against ischemic heart disease [9,10]. Interestingly, patients with coronary heart disease have a low plasma melatonin level, especially those with higher risk of cardiac infarction and/or sudden death [36,
37]
. So, administering melatonin to patients with ischemic heart diseases might be a novel treatment strategy in clinical application, and this assumption is also supported by the low toxicity and high safety of melatonin. ...
Membrane receptor-dependent Notch1/Hes1 activation by melatonin protects against myocardial ischemia-reperfusion injury: In vivo and in vitro studies
Zhihong Lu
Melatonin confers profound protective effect against myocardial ischemia reperfusion injury (MI/RI). Activation of Notch1/ Hairy and enhancer of split 1 (Hes1) signaling also ameliorates MI/RI. We hypothesize that melatonin attenuates MI/RI-induced oxidative damage by activating Notch1/Hes1 signaling pathway with phosphatase and tensin homolog deleted on chromosome ten (Pten)/Akt acting as the down-stream signaling pathway in a melatonin membrane receptor dependent manner. Male Sprague-Dawley rats were treated with melatonin (10 mg/kg/d) for 4 weeks and then subjected to MI/R surgery. Melatonin significantly improved cardiac function, decreased myocardial apoptosis and oxidative damage. Furthermore, in cultured H9C2 cardiomyocytes, melatonin (100 μmol/L) attenuated simulated ischemia/reperfusion (SIR)-induced myocardial apoptosis and oxidative damage. Both in vivo and in vitro study demonstrated that melatonin treatment increased Notch1, Notch1 intracellular domain (NICD), Hes1, Bcl-2 expressions and p-Akt/Akt ratio, decreased Pten, Bax and caspase-3 expressions. However, these protective effects conferred by melatonin were blocked by DAPT (the specific inhibitor of Notch1 signaling), Luzindole (the antagonist of melatonin membrane receptors), Notch1 siRNA or Hes1 siRNA administration. In summary, our study demonstrates that melatonin treatment protects against MI/RI by modulating Notch1/Hes1 signaling in a receptor-dependent manner and Pten/Akt signaling pathways are key down-stream mediators. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Melatonin - Recent Updates
Use of Melatonin as a Feed Additive
Melatonin is a molecule that plays an active role in reducing many stress factors in plants and has important functions in the growth, development and reproduction of plants. It has many physiological functions that directly affect feed consumption, feed efficiency, energy metabolism and immune system in animal organisms. In addition, its anti-inflammatory, antioxidant, anticancer and antiapoptotic effects are also known. While melatonin has an antioxidative effect at low doses, it can exert a prooxidant effect at high doses. It has been suggested that when melatonin is used as a silage additive, it increases the total acid content of the silage and significantly improves the silage fermentation quality by lowering the pH level and butyric acid. Although it has positive effects on mammary gland involution and general health in ruminants, its effects on yield parameters have not been proven. Broilers and layers are expected high productivity and performance, in this regard, they are faced with stress factors such as intensive feeding and housing conditions. Considering its positive effects on stress factors, health and productivity, melatonin is a promising feed additive. Effects of melatonin additive or supplements on animal productivity and health should be revealed in further studies.
Antioxidants effects in health: The bright and the dark sides
Chapter
As a double-edge knife, oxidative stress (OS) has shown paradoxical behaviors toward beneficial/harmful responses on human health. In this regard, while the high levels and long-lasting exposure to OS is associated with disease development, low/moderate levels of OS could be a natural defense system in the human body. From the mechanistic point, resilience pathways and related signaling mediators (e.g., Nrf2, catalase, glutathione, heme oxygenase, etc.) are responsible for the final outcome of OS which could be modulated by enzymatic and nonenzymatic approaches. Additionally, natural compounds are promising compounds in modulating OS. Altogether, providing a balance between OS and antioxidants could be a critical step forward in a healthy system.
Melatonin ameliorates myocardial injury by reducing apoptosis and autophagy of cardiomyocytes in a rat cardiopulmonary bypass model
Background
Myocardial injury is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to test the hypothesis that melatonin could attenuate myocardial injury in a rat CPB model.
Methods
Eighteen male Sprague-Dawley rats were randomly divided into three groups, n = 6 for each group: the sham operation (SO) group, CPB group and melatonin group. Rats in the SO group underwent cannulation without CPB, rats in CPB group intraperitoneal injected an equal volume of vehicle daily for 7 days before being subjected to CPB and rats in melatonin group intraperitoneal injected 20 mg/kg of melatonin solution daily for 7 days before being subjected to CPB. After 120 min for CPB, the expression levels of plasma interleukin (IL) -6, IL-1β, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), creatine kinase (CK) -MB and cardiac troponin T (cTnT) were measured. Reactive oxygen species (ROS) were detected by dihydroethidium (DHE). Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Mitochondrial damage and autophagosomes were detected by electron microscopy. Apoptosis inducing factor (AIF) was detected by immunofluorescence. The expression of B cell lymphoma/leukemia2 associated X (Bax), B cell lymphoma/leukemia 2 (Bcl-2), cytochrome C (Cyto-C), cleaved caspase-9, AKT, p-AKT, signal transducer and activator of transcription 3 (STAT3), p-STAT3, LC3, P62, mechanistic target of rapamycin kinase (mTOR), p-mTOR and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined using western blotting.
Results
Melatonin significantly decreased the levels of IL-1β, IL-6, MDA, CK-MB and cTnT and increased the levels of SOD and GSH-Px, all of which were altered by CPB. Melatonin reduced cardiomyocyte superoxide production, the apoptosis index and autophagy in cardiomyocytes induced by CPB. The AKT, STAT3 and mTOR signaling pathways were activated by melatonin during CPB.
Conclusion
Melatonin may serve as a cardioprotective factor in CPB by inhibiting oxidative damage, apoptosis and autophagy. The AKT, STAT3 and mTOR signaling pathways were involved in this process.
Worldwide melatonin research: a bibliometric analysis of the published literature between 2015 and 2019
Aidi Ahmi
This study presents a bibliometric analysis of the publications on melatonin research from the Scopus database during the period 2015–2019. Based on the keywords used, which are related to melatonin in the article title, the study retrieved 4411 documents for further analysis using various tools. We used Microsoft Excel to conduct the frequency analysis, VOSviewer for data visualization, and Harzing’s Publish or Perish for citation metrics and analysis. This study reports the results using standard bibliometric indicators such as the growth of publications, authorship patterns, collaboration, and prolific authors, country contribution, most active institutions, preferred journals, and top-cited articles. Based on our findings, there is a continuous growth of publications on melatonin research for 5 years since 2015. China was the largest contributor to melatonin research, followed by the United States. The Journal of Pineal Research published the most number of publications related to melatonin research. Our findings suggest that the role of melatonin in plant and food sciences, as well as in cancer, may in later years take over the clusters that earlier dominated melatonin research.
Effect of time of day of recreational and household physical activity on prostate and breast cancer risk (MCC-Spain Study)
Experimental evidence indicates that exercise performed at different times of the day may affect circadian rhythms and circadian disruption has been linked to breast and prostate cancer. We examined in a population-based case-control study (MCC-Spain) if the time-of-day when physical activity is done affects prostate and breast cancer risk. Lifetime recreational and household physical activity was assessed by in-person interviews. Information on time-of-day of activity (assessed approximately 3 years after the assessment of lifetime physical activity and confounders) was available for 781 breast cancer cases, 865 population female controls, 504 prostate cases and 645 population male controls from 10 Spanish regions, 2008-2013. We estimated odds ratios (ORs) and 95% confidence intervals (95% CI) for different activity timings compared to inactive subjects using unconditional logistic regression adjusting for confounders. Early morning (8-10 am) activity was associated with a protective effect compared to no physical activity for both breast (OR = 0.74, 95% CI = 0.48-1.15) and prostate cancer (OR = 0.73, 95% CI = 0.44-1.20); meta-OR for the two cancers combined 0.74 (95%CI = 0.53-1.02). There was no effect observed for breast or prostate cancer for late morning to afternoon activity while a protective effect was also observed for evening activity only for prostate cancer (OR = 0.75, 95% CI = 0.45-1.24). Protective effects of early morning activity were more pronounced for intermediate/evening chronotypes for both cancers. This is the first population-based investigation identifying a differential effect of timing of physical activity on cancer risk with more pronounced effects for morning hour activity. Our results, if confirmed, may improve current physical activity recommendations for cancer prevention.
Diabetes and atherothrombosis: The circadian rhythm and role of melatonin in vascular protection
Anastasia Otamas
Peter J Grant
Obesity-related euglycaemic insulin resistance clusters with cardiometabolic risk factors, contributing to the development of both type 2 diabetes and cardiovascular disease. An increased thrombotic tendency in diabetes stems from platelet hyperactivity, enhanced activity of prothrombotic coagulation factors and impaired fibrinolysis. Furthermore, a low-grade inflammatory response and increased oxidative stress accelerate the atherosclerotic process and, together with an enhanced thrombotic environment, result in premature and more severe cardiovascular disease. The disruption of circadian cycles in man secondary to chronic obesity and loss of circadian cues is implicated in the increased risk of developing diabetes and cardiovascular disease. Levels of melatonin, the endogenous synchronizer of circadian rhythm, are reduced in individuals with vascular disease and those with deranged glucose metabolism. The anti-inflammatory, antihypertensive, antioxidative and antithrombotic activities of melatonin make it a potential therapeutic agent to reduce the risk of vascular occlusive disease in diabetes. The mechanisms behind melatonin-associated reduction in procoagulant response are not fully known. Current evidence suggests that melatonin inhibits platelet aggregation and might affect the coagulation cascade, altering fibrin clot structure and/or resistance to fibrinolysis. Large-scale clinical trials are warranted to investigate the effects of modulating the circadian clock on insulin resistance, glycaemia and cardiovascular outcome.
Melatonin and Nicotinamide Mononucleotide Attenuate Myocardial Ischemia/Reperfusion Injury via Modulation of Mitochondrial Function and Hemodynamic Parameters in Aged Rats
Ischemic heart diseases are the major reasons for disability and mortality in elderly individuals. In this study, we tried to examine the combined effects of nicotinamide mononucleotide (NMN) preconditioning and melatonin postconditioning on cardioprotection and mitochondrial function in ischemia/reperfusion (I/R) injury of aged male rats. Sixty aged Wistar rats were randomly allocated to 5 groups, including sham, control, NMN-receiving, melatonin-receiving, and combined therapy (NMN+melatonin). Isolated hearts were mounted on Langendorff apparatus and then underwent 30-minue ligation of left anterior descending coronary artery to induce regional ischemic insult, followed by 60 minutes of reperfusion. Nicotinamide mononucleotide (100 mg/kg/d intraperitoneally) was administered for every other day for 28 days before I/R. Melatonin added to perfusion solution, 5 minutes prior to the reperfusion up to 15 minutes early reperfusion. Myocardial hemodynamic and infarct size (IS) were measured, and the left ventricles samples were obtained to evaluate cardiac mitochondrial function and oxidative stress markers. Melatonin postconditioning and NMN had significant cardioprotective effects in aged rats; they could improve hemodynamic parameters and reduce IS and lactate dehydrogenase release compared to those of control group. Moreover, pretreatment with NMN increased the cardioprotection by melatonin. All treatments reduced oxidative stress and mitochondrial reactive oxygen species (ROS) levels and improved mitochondrial membrane potential and restored NAD ⁺ /NADH ratio. The effects of combined therapy on reduction of mitochondrial ROS and oxidative status and improvement of mitochondrial membrane potential were greater than those of alone treatments. Combination of melatonin and NMN can be a promising strategy to attenuate myocardial I/R damages in aged hearts. Restoration of mitochondrial function may substantially contribute to this cardioprotection.
Pharmacological approaches to the prevention of myocardial ischemia-reperfusion injury in experimental study and clinical practice
Pharmacological approaches to the prevention of myocardial ischemia-reperfusion injury in experimental study and clinical practice
Article
Early reperfusion of the infarct related coronary artery is essential for the preservation of myocardial tissue and improve clinical outcome. The establishment of pharmacological and mechanical reperfusion treatment was a major improvement in the management of patients with myocardial infarction. However, this therapy is often complicated by reperfusion injury including ventricular arrhythmias, myocardial stunning and micro-vascular dysfunction, in addition to significant cardiomyocyte death. The ГУ «Национальный научный центр «Институт кардиологии имени академика Н. Д. Стражеско НАМН Украины», г. Киев A-концепция и дизайн исследования; B-сбор данных; C-анализ и интерпретация данных; D-написание статьи; E-редактирование статьи; F-окончательное утверждение статьи Ранняя реперфузия инфаркт-зависимой коронарной артерии способствует ограничению зоны некроза, улучшает насо-сную функцию сердца и положительно влияет на исход заболевания. Внедрение фармакологической и механической реперфузии (тромболитической терапии и перкутанных вмешательств) в клиническую практику значительно улучшило лечение пациентов с острым инфарктом миокарда. Однако эта терапия часто осложняется реперфузионным повреждением (феномен no reflow), которое в дополнение к значительной гибели кардиомиоцитов включает желудочковые нарушения ритма сердца, оглушение миокарда, микрососудистую дисфункцию, а также другими нарушениями. Наиболее важные составляющие реперфузионного повреждения: избыточная продукция реактивных форм кислорода, внутриклеточная перегрузка кальцием, воспалительная клеточная инфильтрация и др. Некоторые из этих механизмов взаимосвязаны. Исходя из этой концепции, существуют теоретические предпосылки использования фармакологических вмешательств для предупреждения осложнений реперфузии. Эту гипотезу в основном изучали в экспериментальных исследованиях, получены убедительные данные по защите миокарда. Цель работы-рассмотреть различные фармакологические вмешательства для лечения реперфузионного повреждения миокарда, включая антиоксидантные флавоноиды, терапию глюкозо-инсулин-калиевой смесью, аденозином, мелато-нином, метопрололом, никорандилом, фосфокреатином, триметазидином, циклоспорином А и др. Выводы. Влияя на процессы, связанные с реперфузионным повреждением, можно улучшить результаты лечения инфаркта миокарда. К сожалению, до сих пор эта цель не достигнута в реальной клинической практике. Тем не менее, при изучении в экспериментальных и клинических исследованиях новых молекул получены важные данные, которые могут быть положены в основу новых исследований и внедрение кардиопротекции в клиническую практику. Можливості фармакологічного захисту міокарда при синдромі ішемії-реперфузії в експерименті та клінічній практиці С. М. Кожухов, О. М. Пархоменко Рання реперфузія інфаркт-залежної коронарної артерії сприяє обмеженню зони некрозу, поліпшує насосну функцію серця та позитивно впливає на наслідки захворювання. Впровадження фармакологічної та механічної реперфузії (тромболітичної терапії та перкутанних втручань) у клінічну практику суттєво поліпшило лікування пацієнтів із гострим інфарктом міокарда. Однак ця терапія часто ускладнюється реперфузійним пошкодженням (феномен no reflow), що на додаток до чималої загибелі кардіоміоцитів включає шлуночкові порушення ритму серця, оглушення міокарда, мікросудинну дисфункцію, а також інші порушення. Найважливіші складові реперфузійного пошкодження: надлишкова продукція реактивних форм кисню, внутрішньоклітинне перевантаження кальцієм, запальна клітинна інфільтрація тощо. Деякі з цих механізмів взаємопов'язані. Виходячи з цієї концепції, наявні теоретичні передумови використання фармакологічних втручань для запобігання ускладненням реперфузії. Цю гіпотезу в основному вивчали в експериментальних дослідженнях, отримали переконливі дані щодо захисту міокарда. Мета роботи-розглянути різні фармакологічні втручання для лікування реперфузійного пошкодження міокарда, включаючи антиоксидантні флавоноїди, терапію глюкозо-інсулін-калієвою сумішшю, аденозином, мелатоніном, метопрололом, нікорандилом, фосфокреатином, триметазидином, циклоспорином А тощо. Висновки. Впливаючи на процеси, що пов'язані з реперфузійним пошкодженням, можна поліпшити результати ліку-вання інфаркту міокарда. На жаль, досі ця ціль не досягнута в реальній клінічній практиці. Але під час вивчення в експериментальних і клінічних дослідженнях нових молекул отримали важливі дані, які можуть бути покладені в основу нових досліджень і впровадження кардіопротекції у клінічну практику. Ключові слова: інфаркт міокарда, реперфузія, фармакологічні втручання. Запорізький медичний журнал.-2019.-Т. 21, № 4(115).-С. 528-537 Ключевые слова: инфаркт миокарда, реперфузия, фармакологические вмешательства.
The effects of melatonin on neurohormonal regulation in cardiac cachexia: A mechanistic review
Heart failure (HF) is one of the prominent health concerns and its morbidity is comparable to many malignancies. Cardiac cachexia (CC), characterized by significant weight loss and muscle wasting, frequently occurs in progressive stage of HF. The pathophysiology of CC is multifactorial including nutritional and gastrointestinal alterations, immunological and neurohormonal activation, and anabolic/catabolic imbalance. Neurohormones are critically involved in the development of both HF and CC. Melatonin is known as an anti-inflammatory and antioxidant hormone. It seems that melatonin possibly regulates the neurohormonal signaling pathway related to muscle wasting in CC, but limited comprehensive data is available on the mechanistic aspects of its activity. In this, we reviewed the reports regarding the role of neurohormones in CC occurrence and possible activity of melatonin in modulation of HF and subsequently CC via neurohormonal regulation. In addition, we have discussed proposed mechanisms of action for melatonin considering its possible interactions with neurohormones. In conclusion, melatonin likely regulates the signaling pathways related to muscle wasting in CC by reducing tumor necrosis factor α levels and activating the gene expression of insulin-like growth factor-1. Also, this hormone inhibits the proteolytic pathway by inhibiting nuclear factor-κB (NF-κB), renin-angiotensin system and forkhead box protein O1 pathways and could increase protein synthesis by activating Akt and mammalian target of rapamycin. To elucidate the positive role of melatonin in CC and exact mechanisms related to muscle wasting more cellular and clinical trial studies are needed.
Complexities in Cardiovascular Rhythmicity - Perspectives on Circadian Normality, Aging and Disease
Edward G. Lakatta
"And the rhythm of life is a powerful beat Puts a tingle in your fingers and a tingle in your feet Rhythm in your bedroom, rhythm in the street Yes, the rhythm of life is a powerful beat" - Sammy Davis Jr, Rhythm of Life 1969 Biological rhythms exist in organisms at all levels of complexity, in most organs and at myriad time scales. Our own biological rhythms are driven by solar energy emitted by the sun, interacting via our retinas with brain stem centers, which then send out complex messages designed to synchronize the behavior of peripheral non-light sensing organs, to ensure optimal physiological responsiveness and performance of the organism based on the time of day. Peripheral organs themselves have autonomous rhythmic behaviors that can act independently from central nervous system control but is entrainable. Dysregulation of biological rhythms either through environment or disease has far reaching consequences on health that we are only now beginning to appreciate. In this review we focus on cardiovascular rhythms in health, with aging and under disease conditions.
Plasma levels of melatonin in dilated cardiomyopathy
Background
Melatonin is a multifunctional indolamine, and has a cardioprotective role in a variety of cardiovascular processes via antioxidant, anti‐inflammatory, anti‐hypertensive, anti‐thrombotic and anti‐lipemic effects. It has been reported that lower levels of circulating melatonin are significantly associated with a higher risk of acute myocardial infarction (AMI) and later cardiac remodeling. However, levels of melatonin in patients with dilated cardiomyopathy (DCM) and associations between melatonin levels and cardiac function remain unclear.
Methods and Results
We measured and compared plasma levels of melatonin in 61 control subjects, 81 AMI patients, and 77 DCM patients. Plasma levels of melatonin were progressively decreased from 71.9 pg/ml in the control group to 52.6 pg/ml in the DCM group and 21.9 pg/ml in the AMI group. Next, we examined associations of melatonin levels with parameters of laboratory data, echocardiography and right‐heart catheterization. In the DCM patients, circulating melatonin showed significant correlations with both high‐sensitivity troponin T (R=‐0.422, P<0.001) and cardiac output (R=0.431, P=0.003), but not with B‐type natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), pulmonary artery wedge pressure or pulmonary artery pressure.
Conclusion
Patients with not only AMI but also DCM had lower circulating melatonin levels. Circulating melatonin levels appear to correlate with myocardial injury and cardiac output in DCM patients.
This article is protected by copyright. All rights reserved.
Future strategies for acute cardioprotection: 'melatonin as promising therapy'
Melatonin, a toll-like receptor inhibitor: Current status and future perspectives: TAMTAJI et al.
Article
Full-text available
Moein Mobini
Zatollah Asemi
Toll‐like receptors (TLRs) are crucial activators of inflammatory responses, they are considered immune receptors. TLRs are of fundamental importance in the pathophysiology of disorders related to inflammation including neurodegenerative diseases and cancer. Melatonin is a beneficial agent in the treatment of inflammatory and immune disorders. Melatonin is potent anti‐inflammatory hormone that regulates various molecular pathways. Withal, limited studies have evaluated the inhibitory role of melatonin on TLRs. This review summarizes the current knowledge related to the effects of melatonin on TLRs in some common inflammatory and immunity disorders.
Melatonin Use in Psychiatry—Quo Vadis?
Melatonin use in clinical psychiatry is currently rife, and the trend of utilization is on the rise. Efficacy coupled with safety and lack of abuse potential render melatonin an attractive therapeutic option. Data from neuroscience accrue speaking to the idea of a pluripotent molecule beyond a mere sleeping aid. Here, authors would shed some light on melatonin use in psychiatry while examining the extant evidence
Melatonin and age‐related cardiovascular diseases
Jiayu Zhong
The pineal gland is a neuroendocrine gland closely related to human aging. Melatonin is a kind of indole neuroendocrine hormone secreted by the pineal gland, which is essential for maintaining physiological function. Many researches found that melatonin plays a key role in anti‐aging‐related cardiovascular diseases. In this paper, the latest advances in the study of melatonin and aging‐related cardiovascular diseases are reviewed, and their related physiological functions and mechanisms are discussed.
Radiolabeling of melatonin using different oxidizing agents for immunoassay purpose
Kh. M. Sallam
A. S. A. El-Bayoumy
N. Farouk
An efficient method was developed for radioiodination of melatonin with ¹²⁵I. Chloramine-T and iodogen were used as oxidizing agents. The radioiodination was carried out via electrophilic substitution of the H atom with the I⁺ cation. Indirect iodination using Bolton–Hunter reagent was also performed. The influence exerted on the radiochemical yield by the melatonin concentration, pH of the reaction mixture, type of oxidizing agent, and reaction time was studied. The shelf life and specific activity of the product were determined. The radiochemical yield and product purity were determined by HPLC and paper electrophoresis. The immunoreactivity of the tracer was checked using its specific antibody. Specific and sensitive polyclonal antimelatonin was prepared using two New Zealand rabbits, which were injected with 5-methoxy-N-acetyltryptamine–bovine serum albumin conjugate as immunogen. The tracer prepared by the indirect method with iodogen had high specific activity, high yield, and long shelf life; it was also more selective in the melatonin assessment using radioimmunoassay technique.
Circadian Clock-Mediated Regulation of Blood Pressure
FREE RADICAL BIO MED
Lauren Grace Douma
Most bodily functions vary over the course of a 24 hour day. Circadian rhythms in body temperature, sleep-wake cycles, metabolism, and blood pressure (BP) are just a few examples. These circadian rhythms are controlled by the central clock in the suprachiasmatic nucleus (SCN) of the hypothalamus and peripheral clocks located throughout the body. Light and food cues entrain these clocks to the time of day and this synchronicity contributes to the regulation of a variety of physiological processes with effects on overall health. The kidney, brain, nervous system, vasculature, and heart have been identified through the use of mouse models and clinical trials as peripheral clock regulators of BP. The dysregulation of this circadian pattern of BP, with or without hypertension, is associated with increased risk for cardiovascular disease. The mechanism of this dysregulation is unknown and is a growing area of research. In this review, we highlight research of human and mouse circadian models that has provided insight into the roles of these molecular clocks and their effects on physiological functions. Additional tissue-specific studies of the molecular clock mechanism are needed, as well as clinical studies including more diverse populations (different races, female patients, etc.), which will be critical to fully understand the mechanism of circadian regulation of BP. Understanding how these molecular clocks regulate the circadian rhythm of BP is critical in the treatment of circadian BP dysregulation and hypertension.
Mitochondrial bioenergetics decay in aging: beneficial effect of melatonin
Giuseppe Petrosillo
Aging is a biological process characterized by progressive decline in physiological functions, increased oxidative stress, reduced capacity to respond to stresses, and increased risk of contracting age-associated disorders. Mitochondria are referred to as the powerhouse of the cell through their role in the oxidative phosphorylation to generate ATP. These organelles contribute to the aging process, mainly through impairment of electron transport chain activity, opening of the mitochondrial permeability transition pore and increased oxidative stress. These events lead to damage to proteins, lipids and mitochondrial DNA. Cardiolipin, a phospholipid of the inner mitochondrial membrane, plays a pivotal role in several mitochondrial bioenergetic processes as well as in mitochondrial-dependent steps of apoptosis and in mitochondrial membrane stability and dynamics. Cardiolipin alterations are associated with mitochondrial bienergetics decline in multiple tissues in a variety of physiopathological conditions, as well as in the aging process. Melatonin, the major product of the pineal gland, is considered an effective protector of mitochondrial bioenergetic function. Melatonin preserves mitochondrial function by preventing cardiolipin oxidation and this may explain, at least in part, the protective role of this compound in mitochondrial physiopathology and aging. Here, mechanisms through which melatonin exerts its protective role against mitochondrial dysfunction associated with aging and age-associated disorders are discussed.
Melatonin as an Agent for Cardioprotection in Patients with ST-Elevation Myocardial Infarction and Short Ischaemic Time
Circadian Dysregulation and Melatonin Rhythm Suppression in the Context of Aging
R.J. Russel
Du-Xian Tan
Fifty years ago, little was known of the role of the prevailing light:dark environment in terms of its impact on the circadian pathophysiology of organisms. In the intervening years the field of photoperiodic regulation of the master circadian oscillator, i.e., the suprachiasmatic nucleus (SCN), has advanced at a rapid pace. The importance of the regulatory actions of the light:dark cycle, and particularly of perturbed light:dark cycles, not only on the SCN but also on the circadian production of pineal melatonin as well as the cyclic metabolism of cells throughout the body are by no means trivial. When the regular cyclic information generated and dispensed by the SCN is dysregulated, the negative consequences in terms of cellular and organismal physiology can be dire to the extent that the rate of aging and the onset and progression of a variety of age-related diseases have now been at least provisionally linked to circadian disruption and/or melatonin suppression. While the findings are not definitive, there is certainly credible data to warrant the conclusion that regular circadian rhythms at multiple levels, including a stable day:night melatonin cycle, enhance life quality and potentially delay senescence and forestall diseases normally associated with advanced age. As a result, the prolonged health span may also predispose to a longer life span. In view of the critical role of an abnormal or unusual light environment in terms of perturbing essential circadian physiological events, serious consideration should be given to rational thought about the misuse of artificial light and the consequences thereof.
Melatonin for cardioprotection in ST elevation myocardial infarction: Are we ready for the challenge?
Russel J Reiter
Melatonin, an endocrine product of the pineal gland, is formed predominantly during the nighttime. Light has an inhibitory effect on pineal melatonin secretion. Pineal melatonin release is synchronised by this daily light-dark cycle via a multisynaptic pathway between the eyes and the pineal gland. Light stimulates the retina to modulate the activity of the suprachiasmatic nucleus, the master biological clock.1 The suprachiasmatic nucleus controls pineal melatonin synthesis and the concentrations of melatonin in the sera of healthy subjects, which reach values of 10−10 to 10−9 mol/L during the night, with much lower concentrations being present during the day. Many publications have shown that melatonin has an important role in a variety of cardiovascular pathophysiologic processes: the indoleamine has anti-inflammatory, antioxidant, antihypertensive, antithrombotic and antilipaemic properties1 (figure 1).
Figure 1
The properties of melatonin and the effects on multiple organs.
In their Heart manuscript, McMullan et al 2 report their findings when analysing data from the Nurses's Health Study I (NHS I) and NHS II to investigate the independent association of nocturnal melatonin secretion with the incidence of myocardial infarction (MI). In accordance with the authors, the NHS I began in 1976, with 121 701 registered nurses aged 30–55 years returning an initial questionnaire; the NHS II began in 1989 with 116 430 female registered nurses. In the initial and subsequent biennial questionnaires, health status, medications, dietary intake and lifestyle factors, including smoking history, physical activity and sleeping patterns, were ascertained. In addition to completing questionnaires, blood and urine samples were provided by 18 743 women between 1999 and 2000 in NHS I …
Melatonin: Protection against Age-related Cardiac Pathology
Gaia Favero
Lorenzo Franceschetti
Barbara Buffoli
Rita Rezzani
Aging is a complex and progressive process that involves physiological and metabolic deterioration in every organ and system. Cardiovascular diseases are one of the most common causes of mortality and morbidity among elderly subjects worldwide. Most age-related cardiovascular disorders can be influenced by modifiable behaviours such as a healthy diet rich in fruit and vegetables, avoidance of smoking, increased physical activity and reduced stress. The role of diet in prevention of various disorders is a well-established factor, which has an even more important role in the geriatric population. Melatonin, an indoleamine with multiple actions including antioxidant properties, has been identified in a very large number of plant species, including edible plant products and medical herbs. Among products where melatonin has been identified include wine, olive oil, tomato, beer, and others. Interestingly, consumed melatonin in plant foods or melatonin supplementation may promote health benefits by virtue of its multiple properties and it may counteract pathological conditions also related to cardiovascular disorders, carcinogenesis, neurological diseases and aging. In the present review, we summarized melatonin effects against age-related cardiac alteration and abnormalities with a special focus on heart ischemia/reperfusion (IR) injury and myocardial infarction.
Effect of intravenous and intracoronary melatonin as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: results of the Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty (MARIA
Article
Oct 2016
J PINEAL RES
Jose M de la Torre Hernandez
Alberto Dominguez-Rodriguez
Pedro Abreu González
Russel J Reiter
The MARIA randomized trial evaluated the efficacy and safety of melatonin for the reduction of reperfusion injury in patients undergoing revascularization for ST-elevation myocardial infarction (STEMI). This was a prespecified interim analysis. A total of 146 patients presenting with STEMI within 6 hours of chest pain onset were randomized to receive intravenous and intracoronary melatonin (n=73) or placebo (n=73) during primary pecutaneous coronary intervention (PPCI). Primary endpoint was myocardial infarct size as assessed by magnetic resonance imaging (MRI) at 6±2 days. Secondary endpoints were changes in left ventricular volumes and ejection fraction (LVEF) at 130±10 days post-PPCI and adverse events during the first year. No significant differences in baseline characteristics were observed between groups. MRI was performed in 108 patients(86.4%). Myocardial infarct size by MRI evaluated 6±2 days post-PPCI, did not differ between melatonin and placebo groups (P=0.63). Infarct size assessed by MRI at 130±10 days post-PPCI, performed in 91 patients(72.8%), did not show statistically significant differences between groups(P=0.27). The recovery of LVEF from 6±2 to 130±10 days post-PPCI was greater in the placebo group (60.0±10.4% vs 53.1±12.5%,P=0.008). Both left ventricular end-diastolic and end-systolic volumes were lower in the placebo group (P=0.01). The incidence of adverse events at 1 year was comparable in both groups (P=0.150). Thus, in a non-restricted STEMI population, intravenous and intracoronary melatonin was not associated with a reduction in infarct size and has an unfavourable effect on the ventricular volumes and LVEF evolution. Likewise, there is lack of toxicity of melatonin with the doses used. This article is protected by copyright. All rights reserved.
Association between concentration of melatonin, and lipoproteins, LPO, hsCRP, NTproBNP in chronic heart failure patients
Article
Full-text available
Sep 2014
Kimak Elzbieta
Grzegorz Dzida
Dariusz Duma
Kowalska Agnieszka
The aim of the study was to examine concentrations and relationships between melatonin levels assessed at 0:200 hrs and 0:700 hrs, lipid hydroperoxide (LPO) assessed at 0:200 hrs and 0:700 hrs, and apolipoprotein (apo)AI, apoAII, apoB, high sensitivity C-reactive protein (hsCRP) and NT-proBNP, in 27 patients with chronic heart failure (CHF) (17 patients - with NYHA class II and 10 - with NYHA class III). In the study, Lipoproteins apoAI, apoAII, apoB, high sensitivity C-reactive protein (hsCRP) levels were determined by way of immunonephelometric methods, serum melatonin concentration was measured by using a competitive enzyme immunoassay technique, while serum LPO concentration was measured by using Cayman’s Lipid Hydroperoxide Assay Kit. In the study, CHF patients without acute inflammatory response demonstrated a decreased concentration of high density lipoprotein cholesterol (HDL-C), apoAI, apoAII levels, but an increased concentration of NT-proBNP, hsCRP and LPO at night, and LPO at daytime; however, the concentration of LPO at 0:700 was lower than at 0:200. Pearson’s correlation test and multiple ridge stepwise regression showed that melatonin administered at night exerts an effect on the composition of apoAI and apoAII of HDL particles, and induces decreased LPO at 0:700, but has no effect upon NT-proBNP levels in patients with NYHA class II. However, in patients with NYHA class III, melatonin administered at night induces an increase in the content of apoAII and apoAI, which further decreases hsCRP, and this, together with the administered melatonin, brings about daytime decreases in NT-proBNP and hsCRP levels. The results indicated that the content of apoAII and apoAI in HDL particles and melatonin demonstrate an anti-oxidative and anti-inflammatory effect, and together, have a cardio-protective effect on patients with advanced CHF. Hence, the results support melatonin being a cardio-protective agent. These relationships, however, need to be confirmed in further studies.
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Melatonin as an Antioxidant: Under Promises but Over Delivers
Article
Full-text available
Aug 2016
J PINEAL RES
Juan Carlos Mayo
Lilian Qin
Russel J Reiter
Du-Xian Tan
Melatonin is uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances. It achieves this action via a variety of means: direct detoxification of reactive oxygen and reactive nitrogen species and indirectly by stimulating antioxidant enzymes while suppressing the activity of pro-oxidant enzymes. In addition to these well-described actions, melatonin also reportedly chelates transition metals which are involved in the Fenton/Haber-Weiss reactions; in doing so, melatonin reduces the formation of the devastatingly toxic hydroxyl radical resulting in the reduction of oxidative stress. Melatonin's ubiquitous but unequal intracellular distribution, including its high concentrations in mitochondria, likely aid in its capacity to resist oxidative stress and cellular apoptosis. There is credible evidence to suggest that melatonin should be classified as a mitochondria-targeted antioxidant. Melatonin's capacity to prevent oxidative damage and the associated physiological debilitation is well documented in numerous experimental ischemia/reperfusion (hypoxia/reoxygenation) studies especially in the brain (stroke) and in the heart (heart attack). Melatonin, via its anti-radical mechanisms, also reduces the toxicity of noxious prescription drugs and of methamphetamine, a drug of abuse. Experimental findings also indicate that melatonin renders treatment-resistant cancers sensitive to various therapeutic agents and may be useful, due to its multiple antioxidant actions, in especially delaying and perhaps treating a variety of age-related diseases and dehumanizing conditions. Melatonin has been effectively used to combat oxidative stress, inflammation and cellular apoptosis and to restore tissue function in a number of human trials; its efficacy supports its more extensive use in a wider variety of human studies. The uncommonly high safety profile of melatonin also bolsters this conclusion. It is the current feeling of the authors that, in view of the widely-diverse beneficial functions that have been reported for melatonin, these may be merely epiphenomena of the more fundamental, yet-to-be identified basic action(s) of this ancient molecule. This article is protected by copyright. All rights reserved.
Melatonin is associated with reverse remodeling after cardiac resynchronization therapy in patients with heart failure and ventricular dyssynchrony
Article
Jul 2016
Raffaele Piccolo
Alberto Dominguez-Rodriguez
Pedro Abreu González
Russel J Reiter
Background:
Cardiac resynchronization therapy (CRT) is an effective treatment for left ventricular reverse remodeling (LVRR) in patients with congestive heart failure (HF) and ventricular dyssynchrony. Melatonin is a secretory product of the pineal gland with highly beneficial effects from any tissues including the heart. Herein, we investigated whether the response to CRT is associated with levels of melatonin before CRT implantation in patients with HF and ventricular dyssynchrony.
Methods:
Diurnal melatonin levels were performed in serum from 93 patients with HF and ventricular dyssynchrony before CRT implantation. Moreover, we calculated the MADIT-CRT score. Evaluation of patients at 1-year follow-up included an echocardiographic study since the patients were categorized as responders if they presented both a reduction in left ventricular end-systolic volume index >10% and an increase in left ventricular ejection fraction >10%.
Results:
At 1-year, 34 patients (36.5%) were considered responders to CRT according to the predefined criteria. The diurnal melatonin levels were significantly lower in the non-responder group (9.9±2.84 vs 14.7±2.32pg/mL). After adjustment by multivariate analysis, diurnal serum melatonin levels (P<0.001) and diabetes mellitus (P=0.03) were predictors of LVRR. On Cox regression analysis, diurnal serum melatonin levels (P<0.001) and left atrial volume<40mL/m(2) (P=0.04) remained independent predictors of the adverse clinical events. The area under of curve for the prediction LVRR of melatonin (0.91, 95%CI 0.85-0.97; P<0.001) was significantly higher compared to MADIT-CRT score (0.69, 95%CI 0.58-0.80; P=0.002).
Conclusion:
Diurnal levels of melatonin before CRT implantation are associated with LVRR at 12month follow-up.
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Show abstract
Elevated heart rate and non-dipping heart rate as potential targets for melatonin: a review
Article
Full-text available
Jun 2016
J PINEAL RES
Fedor Simko
Tomas Baka
Ludovit Paulis
Russel J Reiter
Elevated heart rate is a risk factor for cardiovascular and all-cause mortalities in the general population and various cardiovascular pathologies. Insufficient heart rate decline during the night, that is, nondipping heart rate, also increases cardiovascular risk. Abnormal heart rate reflects an autonomic nervous system imbalance in terms of relative dominance of sympathetic tone. There are only a few prospective studies concerning the effect of heart rate reduction in coronary heart disease and heart failure. In hypertensive patients, retrospective analyses show no additional benefit of slowing down the heart rate by beta-blockade to blood pressure reduction. Melatonin, a secretory product of the pineal gland, has several attributes, which predict melatonin to be a promising candidate in the struggle against elevated heart rate and its consequences in the hypertensive population. First, melatonin production depends on the sympathetic stimulation of the pineal gland. On the other hand, melatonin inhibits the sympathetic system in several ways representing potentially the counter-regulatory mechanism to normalize excessive sympathetic drive. Second, administration of melatonin reduces heart rate in animals and humans. Third, the chronobiological action of melatonin may normalize the insufficient nocturnal decline of heart rate. Moreover, melatonin reduces the development of endothelial dysfunction and atherosclerosis, which are considered a crucial pathophysiological disorder of increased heart rate and pulsatile blood flow. The antihypertensive and antiremodeling action of melatonin along with its beneficial effects on lipid profile and insulin resistance may be of additional benefit. A clinical trial investigating melatonin actions in hypertensive patients with increased heart rate is warranted. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Circadian rhythms in blood pressure, heart rate, hormones, and on polysomnographic parameters in severe OSAS patients: Effect of continuous positive airway pressure (CPAP)
Article
Jun 2016
Blood Pres Monit
Björn Lemmer
Joachim Scholtze
Judith Schmitt
Introduction:
Seventeen male patients with severe obstructive sleep apnea syndrome (OSAS; apnea-hypopnea index>30/h) were monitored by polysomnography in the sleep lab before and after about 8 weeks of continuous positive airway pressure (CPAP). Twelve of the patients were hypertensive, but treated by antihypertensive drugs. The circadian rhythms in blood pressure (BP) and heart rate were determined by ambulatory BP monitoring and motor activity was monitored by a motion logger. As the sympathetic tone is reported to be increased in sleep apnea, the circadian rhythm in plasma norepinephrine was studied in parallel and as a marker rhythm of the biological clock plasma melatonin was determined around the clock by radioimmunoassay.
Results:
Level and rhythm in BP and heart rate were not significantly affected by CPAP in this group of patients, but the number of dippers increased after CPAP intervention. The high 24 h plasma values of norepinephrine were lowered by CPAP therapy. In contrast, melatonin values were disturbed in OSAS patients with a loss in nocturnal increase; this pattern was not corrected by CPAP. Sleep functions (deep sleep, slow wave sleep, rapid eye movement sleep, arousal index, apnea-hypopnea index, desaturation index) were disturbed in OSAS patients as monitored by polysomnography and were significantly improved by CPAP therapy.
Conclusion:
The study indicates that BP-controlled hypertensive patients with OSAS can additionally benefit from CPAP therapy by increasing the number of dippers. This treatment significantly improved sleep functions and OSAS symptoms. In addition, arousal movements at night were also reduced and the high sympathetic tone during early morning hours was also decreased. However, there is still an indication of a disturbed function of the biological clock as the loss in the rhythm in plasma melatonin was not corrected by CPAP.
Role of melatonin, melatonin receptors and STAT3 in the cardioprotective effect of chronic and moderate consumption of red wine
Article
Full-text available
Aug 2015
Kim Lamont
Frederic Nduhirabandi
Tasneem Adam
Sandrine Lecour
We have recently discovered that melatonin, given acutely and directly to the isolated heart at the concentration found in wine, confers cardioprotection against ischemia-reperfusion (I/R). However, whether the presence of melatonin in wine contributes to the cardioprotective effect of chronic and moderate consumption of wine and its signalling mechanisms of protection are unknown. We therefore used both in vivo and in vitro models of I/R to investigate whether the presence of melatonin in red wine may contribute to the cardioprotective effect of chronic and moderate consumption of red wine. Wistar rats and C57black6 mice (WT) received drinking water supplemented daily with a moderate amount of red wine or melatonin given at the concentration found in the red wine. Rats were also pretreated with luzindole, a specific inhibitor of melatonin receptors 1 and 2 (2.3 mg/kg/day, intraperitoneally) or prazosin, a specific inhibitor of melatonin receptor type 3 (2.5mg/kg/day, intraperitoneally). After 14 days, hearts were subjected to I/R in vivo or ex vivo. Red wine reduced the infarct size in both rats and WT mice (p<0.001). Luzindole did not affect wine-induced cardioprotection, while prazosin reduced the infarct sparing effect of red wine (p<0.05). Furthermore, red wine or melatonin failed to protect tumor necrosis factor alpha (TNF) receptor 2 knockout or cardiomyocyte specific signal transducer and activator of transcription 3 (STAT3) deficient mice (n.s. vs control). Our novel findings suggest that the presence of melatonin in red wine contributes to the cardioprotective effect of chronic and moderate consumption of red wine against lethal I/R injuries. This effect is most likely mediated, at least in part, via melatonin receptor 3 and the activation of TNF and STAT3, both key players of the prosurvival and well described SAFE pathway.
Copyright © 2015. Published by Elsevier Inc.
Subthreshold Concentrations of Melatonin and Galantamine Improves Pathological AD-Hallmarks in Hippocampal Organotypic Cultures
Article
Full-text available
Feb 2016
MOL NEUROBIOL
Izaskun Buendia
Esther Parada
Elisa Navarro
Manuela G López
Melatonin is a neurohormone whose levels are significantly reduced or absent in Alzheimer's disease (AD) patients. In these patients, acetylcholinesterase inhibitors (AChEI) are the major drug class used for their treatment; however, they present unwanted cholinergic side effects and have provided limited efficacy in clinic. Because combination therapy is being extensively used to treat different pathological diseases such as cancer or acquired immune deficiency syndrome, we posed this study to evaluate if melatonin in combination with an AChEI, galantamine, could provide beneficial properties in a novel in vitro model of AD. Thus, we subjected organotypic hippocampal cultures (OHCs) to subtoxic concentrations of β-amyloid (0.5 μM βA) plus okadaic acid (1 nM OA), for 4 days. This treatment increased by 95 % cell death, which was mainly apoptotic as shown by positive TUNEL staining. In addition, the combination of βA/OA increased Thioflavin S aggregates, hyperphosphorylation of Tau, oxidative stress (increased DCFDA fluorescence), and neuroinflammation (increased IL-1β and TNFα). Under these experimental conditions, melatonin (1-1000 nM) and galantamine (10-1000 nM), co-incubated with the toxic stimuli, caused a concentration-dependent neuroprotection; maximal neuroprotective effect was achieved at 1 μM of melatonin and galantamine. Most effective was the finding that combination of sub-effective concentrations of melatonin (1 nM) and galantamine (10 nM) provided a synergic anti-apoptotic effect and reduction of most of the AD-related pathological hallmarks observed in the βA/OA model. Therefore, we suggest that supplementation of melatonin in combination with lower doses of AChEIs could be an interesting strategy for AD patients.
Protective role of melatonin in mitochondrial dysfunction and related disorders
The aim of this study was to investigate the effective role of silymarin either alone or in combination with chlorogenic acid and/or melatonin against the toxic impact of carbon tetrachloride (CCl4) induced cardiac infarction. CCl4 (l.2 ml/kg body weight) was administered as a single dose intraperitoneally. The results revealed that the administration of silymarin alone or in combination with chlorogenic acid (CGA) and/or melatonin for 21 consecutive days, 24 h after CCl4 injection to rats, markedly ameliorated the increases in serum markers of cardiac infarction, including troponin T and creatine kinase-MB (CK-MB), as well as increases in the pro-inflammatory biomarkers, including interleukin-6 (IL-6), interferon-γ (IFN-γ) in serum and tumor necrosis factor-α (TNF-α) and C-reactive protein in cardiac tissue compared to CCl4 intoxicated rats. The used agents also successfully modulated the alteration in vascular endothelial growth factor (VEGF) in serum and the oxidative DNA damage and the increase in the apoptosis marker caspase 3 in cardiac tissue in response to CCl4 toxicity. The present biochemical results are supported by histo-pathological examination. The current results proved that treatment with silymarin in combination with CGA and melatonin was the most effective one in ameliorating the toxicity of CCl4 induced cardiac damage and this may support the use of this combination as an effective drug to treat cardiac damage induced by toxic agents.
The Expression of Inflammatory Cytokines on the Aorta Endothelia Are Up-regulated in Pinealectomized Rats
This study was designed to investigate the effect of melatonin on the expression of aortic inflammatory cytokines and its underlying mechanisms in rats. Melatonin deficiency rats (Px, N = 16) were created by pinealectomy and were fed with normal diet for 16 weeks after the surgery, and compared with sham-operated rats (Con, N = 14). Serum lipid profile, glucose metabolism parameters, serum oxidative stress and inflammatory biomarkers were evaluated. The expression of inflammatory cytokines in the aorta endothelia was analyzed. To evaluate the signal transduction pathways of melatonin on the expression of cytokines, rat aortic endothelial cell lines (RAECs) were treated with melatonin, and their protein expressions of inflammatory cytokines and phosphorylation levels of relevant signal pathways were detected. At the 16th week after surgery in Px rats, their serum triglyceride, very low density lipoprotein cholesterol, free fatty acid and glucose levels were prominently elevated (all P < 0.05); serum oxidative stress biomarker malondialdehyde, serum inflammatory biomarkers oxidized low-density lipoprotein, tumor necrosis factor-α, interleukin-6 and C reactive protein were also significantly increased. Meanwhile, the expression of inflammatory cytokines: monocyte chemotactic protein-1 (MCP-1), vascular adhesion molecule 1 (VCAM-1) and matrix metalloproteinase-9 (MMP-9) of the aorta endothelia in Px rats were significantly up-regulated (all P < 0.05). In vitro, melatonin significantly decreased the expression of MCP-1, VCAM-1 and MMP-9 proteins, along with the suppression of phosphorylation levels of nuclear factor κB (NF-κB)/P65 and p38 mitogen-activated protein kinase (P38-MAPK) in RAECs. Melatonin deficiency elevates the serum inflammatory biomarkers and increases aortic inflammatory responses. Melatonin regulates these inflammatory responses by NF-κB and P38-MAPK involved pathways.
Our knowledge and understanding of the pathophysiology of coronary atherosclerosis has increased enormously over the last 20 years. Reperfusion through thrombolysis or percutaneous coronary angioplasty is the standard treatment for preventing acute myocardial infarction. Early reperfusion is an absolute prerequisite for survival of the ischemic myocardium, but reperfusion itself may lead to accelerated and additional myocardial injury beyond that generated by ischemia alone. These outcomes, in a range of reperfusion-associated pathologies, are collectively termed "reperfusion injuries". Reactive oxygen species are known to be produced in large quantities in the first few minutes of the post-ischemia reperfusion process. Similarly, scientific evidence from the last 15 years has suggested that melatonin has beneficial effects on the cardiovascular system. The presence of vascular melatoninergic receptor binding sites has been demonstrated; these receptors are functionally linked to vasoconstrictor or vasodilatory effects of melatonin. It has been shown that patients with coronary heart disease have a low melatonin production rate, especially those with higher risk of cardiac infarction and/or sudden death. Melatonin attenuates molecular and cellular damage resulting from cardiac ischemia-reperfusion in which destructive free radicals are involved.
Melatonin: An Established Antioxidant Worthy of Use in Clinical Trials
Oxidative stress plays a key role in the pathogenesis of aging and many metabolic diseases; therefore, an effective antioxidant therapy would be of great importance in these circumstances. Nutritional, environmental, and chemical factors can induce the overproduction of the superoxide anion radical in both the cytosol and mitochondria. This is the first and key event that leads to the activation of pathways involved in the development of several metabolic diseases that are related to oxidative stress. As oxidation of essential molecules continues, it turns to nitrooxidative stress because of the involvement of nitric oxide in pathogenic processes. Once peroxynitrite forms, it damages via two distinctive mechanisms. First, it has direct toxic effects leading to lipid peroxidation, protein oxidation, and DNA damage. This mechanism involves the induction of several transcription factors leading to cytokine-induced chronic inflammation. Classic antioxidants, including vitamins A, C, and E, have often failed to exhibit beneficial effects in metabolic diseases and aging. Melatonin is a multifunctional indolamine that counteracts virtually all pathophysiologic steps and displays significant beneficial actions against peroxynitrite-induced cellular toxicity. This protection is related to melatonin's antioxidative and antiinflammatory properties. Melatonin has the capability of scavenging both oxygen- and nitrogen-based reactants, including those formed from peroxynitrite, and blocking transcriptional factors, which induce proinflammatory cytokines. Accumulating evidence suggests that this nontoxic indolamine may be useful either as a sole treatment or in conjunction with other treatments for inhibiting the biohazardous actions of nitrooxidative stress.
Effect of angiotensin-(1–7) on reperfusion arrhythmias in isolated rat hearts
There is increasing evidence that angiotensin-(1-7)(Ang-(1-7)) is an endogenous biologically active component of the renin-angiotensin system(RAS). In the present study, we investigated the effects of Ang-(1-7) on reperfusion arrhythmias in isolated rat hearts. Isolated rat hearts were perfused with two different media, i.e., Krebs-Ringer (2.52 mM CaCl2) and low-Ca2+ Krebs-Ringer (1.12 mM CaCl2). In hearts perfused with Krebs-Ringer, Ang-(1-7) produced a concentration-dependent (27-210 nM) reduction in coronary flow (25% reduction at highest concentration), while only slight and variable changes in contraction force and heart rate were observed. Under the same conditions, angiotensin II (Ang II; 27 and 70 nM) produced a significant reduction in coronary flow (39% and 48%, respectively) associated with a significant increase in force. A decrease in heart rate was also observed. In low-Ca2+ Krebs-Ringer solution, perfusion with Ang-(1-7) or Ang II at 27 nM concentration produced similar changes in coronary flow, contraction force and heart rate. In isolated hearts perfused with normal Krebs-Ringer, Ang-(1-7) produced a significant enhancement of reperfusion arrhythmias revealed by an increase in the incidence and duration of ventricular tachycardia and ventricular fibrillation (more than 30-min duration). The facilitation of reperfusion arrhythmias by Ang-(1-7) was associated with an increase in the magnitude of the decreased force usually observed during the postischemic period. The effects of Ang-(1-7) were abolished in isolated rat hearts perfused with low-Ca2+ Krebs-Ringer. The effect of Ang II (27 nM) was similar but less pronounced than that of Ang-(1-7) at the same concentration. These results indicate that the heart is a site of action for Ang-(1-7) and suggest that this heptapeptide may be involved in the mediation of the cardiac effects of the RAS.
Halestrap, AP, Clarke, SJ and Javadov, SA. Mitochondrial permeability transition pore opening during myocardial reperfusion-a target for cardioprotection. Cardiovasc Res 61: 372-385
Reperfusion of the heart after a period of ischaemia leads to the opening of a nonspecific pore in the inner mitochondrial membrane, known as the mitochondrial permeability transition pore (MPTP). This transition causes mitochondria to become uncoupled and capable of hydrolysing rather than synthesising ATP. Unrestrained, this will lead to the loss of ionic homeostasis and ultimately necrotic cell death. The functional recovery of the Langendorff-perfused heart from ischaemia inversely correlates with the extent of pore opening, and inhibition of the MPTP provides protection against reperfusion injury. This may be mediated either by a direct interaction with the MPTP [e.g., by Cyclosporin A (CsA) and Sanglifehrin A (SfA)], or indirectly by decreasing calcium loading and reactive oxygen species (ROS; key inducers of pore opening) or lowering intracellular pH. Agents working in this way may include pyruvate, propofol, Na+/H+ antiporter inhibitors, and ischaemic preconditioning (IPC). Mitochondrial KATP channels have been implicated in preconditioning, but our own data suggest that the channel openers and blockers used in these studies work through alternative mechanisms. In addition to its role in necrosis, transient opening of the MPTP may occur and lead to the release of cytochrome c and other proapoptotic molecules that initiate the apoptotic cascade. However, only if subsequent MPTP closure occurs will ATP levels be maintained, ensuring that cell death continues down an apoptotic, rather than a necrotic, pathway.
Melatonin, the chief secretory product of the pineal gland, has been shown to protect the heart against ischemia-reperfusion injury. This was attributed to its free radical scavenging and broad-spectrum antioxidant properties. The possibility that melatonin may act via its receptor and intracellular signaling, has not yet been addressed in this regard. In all previous studies, only the acute effects of melatonin on the heart, were evaluated. The aims of the present study were to: (i) compare the acute and long-term effects of melatonin on infarct size and functional recovery of the ischemic heart, and (ii) evaluate the role of the melatonin receptor in cardioprotection. For evaluation of the short-term effects of melatonin on contractile recovery and infarct size, the isolated perfused working rat heart was subjected to 20 min global ischemia or 35 min regional ischemia respectively, and melatonin (25-50 microm) administered either before and during reperfusion, or before ischemia or during reperfusion after ischemia. The melatonin receptor was manipulated using luzindole and N-acetyltryptamine. The long-term effects of melatonin were evaluated 24 hr after melatonin administration (2.5 or 5.0 mg/kg, i.p.) or after oral administration for 7 days (20 or 40 microg/mL). Infarct size and mechanical recovery during reperfusion of the working heart were used as endpoints. Melatonin (50 microm), when administered either before and during reperfusion after ischemia or during reperfusion only, significantly improved cardiac output and work performance and reduced infarct size compared with untreated controls. Luzindole (5 microm), a melatonin receptor antagonist, abolished these cardioprotective effects. Long-term administration of melatonin (i.p. or orally for 7 days) caused a significant reduction in infarct size of hearts subjected to 35 min regional ischemia. The cardioprotection persisted for 2-4 days after discontinuation of treatment. In summary, the results obtained suggest that melatonin induces short- as well as long-term protection and that the melatonin receptor is also involved in its cardioprotective actions.
24h variation in the expression of the mt(1) melatonin receptor subtype in coronary arteries derived from patients with coronary heart disease
Previous studies presented evidence for impaired nocturnal secretion and synthesis of melatonin in patients with coronary heart disease (CHD). This study aimed to investigate whether the melatonin receptor subtype mt1 is differentially expressed in coronary arteries derived from patients with CHD (n = 9) compared to patients with dilative cardiomyopathy (CMP; n = 10) who served as controls. Expression of the mt1 receptor was studied in sections of isolated coronary arteries by a reverse transcriptase–polymerase chain reaction (RT-PCR) and a Western immunoblot technique. In addition, the data from the Western blotting of 15 patients were interpolated against the exact time of aortic clamp to study the 24h expression of the mt1 receptor. The analyses of the results from both methods indicated the presence of the mt1 receptor in all of the individuals. No statistically significant difference was observed in the receptor expression between patients with CHD and those with CMP (in arbitrary units: 3.39 ± 3.08 versus 3.91 ± 2.78). Expression of the melatonin receptor in the coronary arteries of the whole patient group presented a 24h variation, with the lowest values detectable after 02:00 up to the late morning hours and a progressive increase beginning after 13:00 until 00:00 (mesor = 3.66, amplitude = 3.23, acrophase = 20.45, P =. 0003). When studying the 24h variation in patients with CHD and CMP separately, a nearly similar circadian course was observed. In conclusion, we demonstrated for the first time a 24h variation of a melatonin receptor subtype in human vessels. Furthermore, in relation to our results, we suggest that the expression of the mt1 melatonin receptor in the coronary arteries is probably not impaired in patients with CHD. (Chronobiology International, 18(6), 973–985, 2001)
| https://www.researchgate.net/publication/277384847_The_role_of_melatonin_in_acute_myocardial_infarction |
UNIPROT:Q13451 - FACTA Search
Query: UNIPROT:Q13451 (
peptidyl prolyl cis-trans isomerase
)
136
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Structure-reactivity relationships of human peptidyl prolyl cis-trans isomerase ( PPI ) toward the two slow folding reactions of yeast iso-2 cytochrome c have been used to characterize the structure of folding intermediates in the vicinity of critical prolines. We propose that the relative catalytic efficiency of PPI for the protein substrate relative to a peptide substrate, (kcat/Km)rel, is a measure of structure in folding intermediates. The structural stability of slow-folding intermediates as detected by changes in (kcat/Km)rel was investigated using two structural perturbants: guanidine hydrochloride and site-directed mutagenesis. Neither of the two slow folding reactions for wild-type cytochrome c is catalyzed at low denaturant concentrations. However, both phases are catalyzed at moderate concentrations of guanidine hydrochloride. A mutation in cytochrome c enhances catalysis of the fluorescence-detected slow folding phase. For protein substrates destabilized by denaturants or mutation, we suggest that increases in (kcat/Km)rel result from a loosening of the substrate structure, providing better access of peptidyl prolyl isomerase to critical proline(s).
...
PMID:Characterization of folding intermediates using prolyl isomerase. 829 95
Wheat FKBP73 (wFKBP73) belongs to the FK506-binding protein (FKBP) family which, in common with the cyclophilin and parvulin families, possesses peptidyl prolyl cis-trans isomerase ( PPIase ) activity. Wheat FKBP73 has been shown to contain three FKBP12-like domains, a tetratricopeptide repeat (TPR) via which it binds heat shock protein 90 and a calmodulin-binding domain (CaMbd). In this study we investigated: (1) the contribution of the N-terminal and C-terminal moieties of wFKBP73 to its biological activity by over-expression of the prolyl isomerase domains in transgenic rice, and (2) the biochemical characteristics of the C-terminal moiety. The recombinant wFKBP73 was found to bind calmodulin via the CaMbd and to be present mainly as a dimer in solution. The dimerization was abrogated when 138 amino acids from the C-terminal half were deleted. Expression of the full-length FKBP73 produced fertile rice plants, whereas the expression of the peptidyl prolyl cis-trans isomerase domains in transgenic rice resulted in male-sterile plants. The male sterility was expressed at various stages of anther development with arrest of normal pollen development occurring after separation of the microspores from the tetrads. Although the direct cause of the dominant male sterility is not yet defined, we suggest that it is associated with a novel interaction of the prolyl isomerase domains with anther specific target proteins.
...
PMID:Deletion of the C-terminal 138 amino acids of the wheat FKBP73 abrogates calmodulin binding, dimerization and male fertility in transgenic rice. 1190 64
Proline is unique in the realm of amino acids in its ability to adopt completely distinct cis and trans conformations, which allows it to act as a backbone switch that is controlled by prolyl cis-trans isomerization. This intrinsically slow interconversion can be catalyzed by the evolutionarily conserved group of peptidyl prolyl cis-trans isomerase enzymes. These enzymes include cyclophilins and FK506-binding proteins, which are well known for their isomerization-independent role as cellular targets for immunosuppressive drugs. The significance of enzyme-catalyzed prolyl cis-trans isomerization as an important regulatory mechanism in human physiology and pathology was not recognized until the discovery of the phosphorylation-specific prolyl isomerase Pin1. Recent studies indicate that both phosphorylation-dependent and phosphorylation-independent prolyl cis-trans isomerization can act as a novel molecular timer to help control the amplitude and duration of a cellular process, and prolyl cis-trans isomerization might be a new target for therapeutic interventions.
...
PMID:Prolyl cis-trans isomerization as a molecular timer. 1787 19
Pin1 is a peptidyl prolyl cis-trans isomerase that only binds to and isomerizes phosphorylated serine/threonine-proline motifs, inducing conformational changes that alter target protein function and phosphorylation. We have shown previously that deficiency of another peptidyl prolyl isomerase , FK506 binding protein 12/12.6, alters endothelial NO synthase phosphorylation and causes endothelial dysfunction and hypertension. Endothelial NO synthase contains the Pin1 binding sequence at (p)serine 116-proline 117 and phosphorylation of endothelial NO synthase serine 116 inhibits NO production; however, whether Pin1 deficiency alters vascular function and blood pressure is unknown. We hypothesized that Pin1 isomerizes p-endothelial NO synthase serine 116, which enables dephosphorylation and stimulates NO production. Immunoprecipitation of endothelial NO synthase and probing for Pin1 in rat aortic endothelial cells confirmed the interaction between the two. Pin1 knockdown via small interfering RNA or inhibition by juglone increased endothelial NO synthase serine 116 phosphorylation and prevented vascular endothelial growth factor-induced serine 116 dephosphorylation in endothelial cells. Acute treatment of isolated mouse aortas with juglone increased endothelial NO synthase serine 116 phosphorylation and decreased NO production and relaxation responses. Mice treated with juglone for 2 weeks, as well as Pin1 knockout mice, exhibited increased aortic endothelial NO synthase serine 116 phosphorylation, endothelial dysfunction, and hypertension. These data demonstrate that Pin1 binds endothelial NO synthase and enables dephosphorylation of serine 116, which increases NO production and endothelium-dependent dilation, leading to blood pressure maintenance.
...
PMID:Pin1 deficiency causes endothelial dysfunction and hypertension. 2215 42
| http://www.nactem.ac.uk/facta/cgi-bin/facta3.cgi?query=UNIPROT%3AQ13451%7C111111%7C0%7C0%7C2044%7C0%7C10 |
5 Programmer-Defined Datatypes
On this page:
5 Programmer-Defined Datatypes
StructuresinThe Racket Referencealso documents structure types.
New datatypes are normally created with the structform, which is the topic of this chapter. The class-based object
system, which we defer toClasses and Objects, offers an alternate
mechanism for creating new datatypes, but even classes and objects are
implemented in terms of structure types.
5.1 Simple Structure Types: struct
Defining Structure Types: structinThe Racket Referencealso documents struct.
To a first approximation, the syntax of structis
( struct struct-id ( field-id ... ) )
Examples:
( struct posn ( x y ) )
The structform binds struct-idand a number of
identifiers that are built from struct-idand the field-ids:
struct-id: a constructorfunction that
takes as many arguments as the number of field-ids,
and returns an instance of the structure type.
Example:
> ( posn 1 2 ) #<posn>
struct-id ?: a predicatefunction that takes a single argument and returns #tif it is an instance of the structure type, #fotherwise.
Examples:
> ( posn? 3 ) #f > ( posn? ( posn 1 2 ) ) #t
struct-id - field-id: for
each field-id, an accessorthat extracts
the value of the corresponding field from an instance of the
structure type.
Examples:
> ( posn-x ( posn 1 2 ) ) 1 > ( posn-y ( posn 1 2 ) ) 2
struct: struct-id: a structure type descriptor, which is a value that
represents the structure type as a first-class value (with #:super, as discussed later inMore Structure Type Options).
A structform places no constraints on the kinds of
values that can appear for fields in an instance of the structure
type. For example, ( posn "apple" #f )produces an
instance of posn, even though "apple"and #fare not valid coordinates for the obvious uses of posninstances. Enforcing constraints on field values, such
as requiring them to be numbers, is normally the job of a contract, as
discussed later inContracts.
5.2 Copying and Update
The struct-copyform clones a structure and optionally
updates specified fields in the clone. This process is sometimes
called a functional update, because the result is a
structure with updated field values. but the original structure is not
modified.
( struct-copy struct-id struct-expr [ field-id expr ] ... )
The struct-idthat appears after struct-copymust
be a structure type name bound by struct(i.e., the
name that cannot be used directly as an expression). The struct-exprmust produce an instance of the structure type.
The result is a new instance of the structure type that is like the old
one, except that the field indicated by each field-idgets
the value of the corresponding expr.
Examples:
> ( define p1 ( posn 1 2 ) ) > ( define p2 ( struct-copy posn p1 [ x 3 ] ) ) > ( list ( posn-x p2 ) ( posn-y p2 ) ) '(3 2) > ( list ( posn-x p1 ) ( posn-y p1 ) ) '(1 2)
5.3 Structure Subtypes
An extended form of structcan be used to define a structure subtype, which is a structure type that extends an
existing structure type:
( struct struct-id super-id ( field-id ... ) )
The super-idmust be a structure type name bound by struct(i.e., the name that cannot be used directly as
an expression).
Examples:
( struct posn ( x y ) ) ( struct 3d-posn posn ( z ) )
A structure subtype inherits the fields of its supertype, and the
subtype constructor accepts the values for the subtype fields after
values for the supertype fields. An instance of a structure subtype
can be used with the predicate and accessors of the
supertype.
Examples:
> ( define p ( 3d-posn 1 2 3 ) ) > p #<3d-posn> > ( posn? p ) #t > ( 3d-posn-z p ) 3 ; a 3d-posn has an x field, but there is no 3d-posn-x selector: > ( 3d-posn-x p ) 3d-posn-x: undefined; cannot reference an identifier before its definition in module: top-level ; use the supertype's posn-x selector to access the x field: > ( posn-x p ) 1
5.4 Opaque versus Transparent Structure Types
With a structure type definition like
( struct posn ( x y ) )
an instance of the structure type prints in a way that does not show
any information about the fields’ values. That is, structure types by
default are opaque. If the accessors and mutators of a
structure type are kept private to a module, then no other module can
rely on the representation of the type’s instances.
To make a structure type transparent, use the #:transparentkeyword after the field-name sequence:
( struct posn ( x y ) #:transparent ) > ( posn 1 2 ) (posn 1 2)
An instance of a transparent structure type prints like a call to the
constructor, so that it shows the structures field values. A
transparent structure type also allows reflective operations, such as struct?and struct-info, to be used on its instances
(seeReflection and Dynamic Evaluation).
Structure types are opaque by default, because opaque structure
instances provide more encapsulation guarantees. That is, a library
can use an opaque structure to encapsulate data, and clients of the
library cannot manipulate the data in the structure except as allowed
by the library.
5.5 Structure Comparisons
A generic equal?comparison automatically recurs on the
fields of a transparent structure type, but equal?defaults
to mere instance identity for opaque structure types:
( struct glass ( width height ) #:transparent ) > ( equal? ( glass 1 2 ) ( glass 1 2 ) ) #t
( struct lead ( width height ) ) > ( define slab ( lead 1 2 ) ) > ( equal? slab slab ) #t > ( equal? slab ( lead 1 2 ) ) #f
To support instances comparisons via equal?without making
the structure type transparent, you can use the #:methodskeyword, gen:equal+hash, and implement three methods:
( struct lead ( width height ) #:methods gen:equal+hash [ ( define ( equal-proc a b equal?-recur ) ; compare a and b ( and ( equal?-recur ( lead-width a ) ( lead-width b ) ) ( equal?-recur ( lead-height a ) ( lead-height b ) ) ) ) ( define ( hash-proc a hash-recur ) ; compute primary hash code of a ( + ( hash-recur ( lead-width a ) ) ( * 3 ( hash-recur ( lead-height a ) ) ) ) ) ( define ( hash2-proc a hash2-recur ) ; compute secondary hash code of a ( + ( hash2-recur ( lead-width a ) ) ( hash2-recur ( lead-height a ) ) ) ) ] ) > ( equal? ( lead 1 2 ) ( lead 1 2 ) ) #t
The first function in the list implements the equal?test on
two leads; the third argument to the function is used instead
of equal?for recursive equality testing, so that data cycles
can be handled correctly. The other two functions compute primary and
secondary hash codes for use with hash tables:
> ( define h ( make-hash ) ) > ( hash-set! h ( lead 1 2 ) 3 ) > ( hash-ref h ( lead 1 2 ) ) 3 > ( hash-ref h ( lead 2 1 ) ) hash-ref: no value found for key key: #<lead>
The first function provided with gen:equal+hashis not
required to recursively compare the fields of the structure. For
example, a structure type representing a set might implement equality
by checking that the members of the set are the same, independent of
the order of elements in the internal representation. Just take care
that the hash functions produce the same value for any two structure
types that are supposed to be equivalent.
5.6 Structure Type Generativity
Each time that a structform is evaluated, it
generates a structure type that is distinct from all existing
structure types, even if some other structure type has the same name
and fields.
This generativity is useful for enforcing abstractions and
implementing programs such as interpreters, but beware of placing a structform in positions that are evaluated multiple
times.
Examples:
( define ( add-bigger-fish lst ) ( struct fish ( size ) #:transparent ) ; new every time ( cond [ ( null? lst ) ( list ( fish 1 ) ) ] [ else ( cons ( fish ( * 2 ( fish-size ( car lst ) ) ) ) lst ) ] ) ) > ( add-bigger-fish null ) (list (fish 1)) > ( add-bigger-fish ( add-bigger-fish null ) ) fish-size: contract violation expected: fish? given: (fish 1)
( struct fish ( size ) #:transparent ) ( define ( add-bigger-fish lst ) ( cond [ ( null? lst ) ( list ( fish 1 ) ) ] [ else ( cons ( fish ( * 2 ( fish-size ( car lst ) ) ) ) lst ) ] ) ) > ( add-bigger-fish ( add-bigger-fish null ) ) (list (fish 2) (fish 1))
5.7 Prefab Structure Types
Although a transparentstructure type prints in a way that
shows its content, the printed form of the structure cannot be used in
an expression to get the structure back, unlike the printed form of a
number, string, symbol, or list.
A prefab(“previously fabricated”) structure type is a
built-in type that is known to the Racket printer and expression
reader. Infinitely many such types exist, and they are indexed by
name, field count, supertype, and other such details. The printed form
of a prefab structure is similar to a vector, but it starts #sinstead of just #, and the first element in the
printed form is the prefab structure type’s name.
The following examples show instances of the sproutprefab structure type that has one field. The first instance has a
field value ' bean, and the second has field value ' alfalfa:
> ' #s ( sprout bean ) '#s(sprout bean) > ' #s ( sprout alfalfa ) '#s(sprout alfalfa)
Like numbers and strings, prefab structures are “self-quoting,” so
the quotes above are optional:
> #s ( sprout bean ) '#s(sprout bean)
When you use the #:prefabkeyword with struct, instead of generating a new structure type,
you obtain bindings that work with the existing prefab structure type:
> ( define lunch ' #s ( sprout bean ) ) > ( struct sprout ( kind ) #:prefab ) > ( sprout? lunch ) #t > ( sprout-kind lunch ) 'bean > ( sprout ' garlic ) '#s(sprout garlic)
The field name kindabove does not matter for finding
the prefab structure type; only the name sproutand the
number of fields matters. At the same time, the prefab structure type sproutwith three fields is a different structure type
than the one with a single field:
> ( sprout? #s ( sprout bean #f 17 ) ) #f > ( struct sprout ( kind yummy? count ) #:prefab ) ; redefine > ( sprout? #s ( sprout bean #f 17 ) ) #t > ( sprout? lunch ) #f
A prefab structure type can have another prefab structure type as its
supertype, it can have mutable fields, and it can have auto
fields. Variations in any of these dimensions correspond to different
prefab structure types, and the printed form of the structure type’s
name encodes all of the relevant details.
> ( struct building ( rooms [ location #:mutable ] ) #:prefab ) > ( struct house building ( [ occupied #:auto ] ) #:prefab #:auto-value ' no ) > ( house 5 ' factory ) '#s((house (1 no) building 2 #(1)) 5 factory no)
Every prefabstructure type is transparent—but even
less abstract than a transparenttype, because instances can be
created without any access to a particular structure-type declaration
or existing examples. Overall, the different options for structure
types offer a spectrum of possibilities from more abstract to more
convenient:
Opaque(the default) : Instances cannot be inspected or
forged without access to the structure-type declaration. As
discussed in the next section, constructor guardsand propertiescan be attached to the structure type to
further protect or to specialize the behavior of its
instances.
Transparent: Anyone can inspect or create an instance
without access to the structure-type declaration, which means
that the value printer can show the content of an instance. All
instance creation passes through a constructor guard,
however, so that the content of an instance can be controlled,
and the behavior of instances can be specialized through properties. Since the structure type is generated by its
definition, instances cannot be manufactured simply through the
name of the structure type, and therefore cannot be generated
automatically by the expression reader.
Prefab: Anyone can inspect or create an instance at any
time, without prior access to a structure-type declaration or
an example instance. Consequently, the expression reader can
manufacture instances directly. The instance cannot have a constructor guardor properties.
Since the expression reader can generate prefabinstances, they
are useful when convenient serializationis more important than
abstraction. Opaqueand transparentstructures also can
be serialized, however, if they are defined with serializable-structas described inDatatypes and Serialization.
5.8 More Structure Type Options
The full syntax of structsupports many options, both
at the structure-type level and at the level of individual fields:
( struct struct-id maybe-super ( field ... ) struct-option ... ) maybe-super = | super-id field = field-id | [ field-id field-option ... ]
A struct-optionalways starts with a keyword:
#:mutable
Causes all fields of the structure to be mutable, and introduces
for each field-ida mutator set- struct-id - field-id !that sets the value of the corresponding field in an instance of
the structure type.
Examples:
> ( struct dot ( x y ) #:mutable ) ( define d ( dot 1 2 ) ) > ( dot-x d ) 1 > ( set-dot-x! d 10 ) > ( dot-x d ) 10
The #:mutableoption can also be used as a field-option, in which case it makes an individual field
mutable.
Examples:
> ( struct person ( name [ age #:mutable ] ) ) ( define friend ( person "Barney" 5 ) ) > ( set-person-age! friend 6 ) > ( set-person-name! friend "Mary" ) set-person-name!: undefined; cannot reference an identifier before its definition in module: top-level
#:transparent
Controls reflective access to structure instances, as discussed
in a previous section,Opaque versus Transparent Structure Types.
#:inspector inspector-expr
Generalizes #:transparentto support more controlled access
to reflective operations.
#:prefab
Accesses a built-in structure type, as discussed
in a previous section,Prefab Structure Types.
#:auto-value auto-expr
Specifies a value to be used for all automatic fields in the
structure type, where an automatic field is indicated by the #:autofield option. The constructor procedure does not
accept arguments for automatic fields. Automatic fields are
implicitly mutable (via reflective operations), but mutator
functions are bound only if #:mutableis also specified.
Examples:
> ( struct posn ( x y [ z #:auto ] ) #:transparent #:auto-value 0 ) > ( posn 1 2 ) (posn 1 2 0)
#:guard guard-expr
Specifies a constructor guardprocedure to be called whenever an
instance of the structure type is created. The guard takes as many
arguments as non-automatic fields in the structure type, plus one
more for the name of the instantiated type (in case a sub-type is
instantiated, in which case it’s best to report an error using the
sub-type’s name). The guard should return the same number of values
as given, minus the name argument. The guard can raise an exception
if one of the given arguments is unacceptable, or it can convert an
argument.
Examples:
> ( struct thing ( name ) #:transparent #:guard ( lambda ( name type-name ) ( cond [ ( string? name ) name ] [ ( symbol? name ) ( symbol->string name ) ] [ else ( error type-name "bad name: ~e" name ) ] ) ) ) > ( thing "apple" ) (thing "apple") > ( thing ' apple ) (thing "apple") > ( thing 1/2 ) thing: bad name: 1/2
The guard is called even when subtype instances are created. In that
case, only the fields accepted by the constructor are provided to
the guard (but the subtype’s guard gets both the original fields and
fields added by the subtype).
Examples:
> ( struct person thing ( age ) #:transparent #:guard ( lambda ( name age type-name ) ( if ( negative? age ) ( error type-name "bad age: ~e" age ) ( values name age ) ) ) ) > ( person "John" 10 ) (person "John" 10) > ( person "Mary" -1 ) person: bad age: -1 > ( person 10 10 ) person: bad name: 10
#:methods interface-expr [ body ... ]
Associates method definitions for the structure type that correspond
to a generic interface. For example, implementing the
methods for gen:dictallows instances of a structure
type to be used as dictionaries. Implementing
the methods for gen:custom-writeallows the customization
of how an instance of a structure type is displayed.
Examples:
> ( struct cake ( candles ) #:methods gen:custom-write [ ( define ( write-proc cake port mode ) ( define n ( cake-candles cake ) ) ( show " ~a ~n" n #\. port ) ( show " .-~a-. ~n" n #\| port ) ( show " | ~a | ~n" n #\space port ) ( show "---~a---~n" n #\- port ) ) ( define ( show fmt n ch port ) ( fprintf port fmt ( make-string n ch ) ) ) ] ) > ( display ( cake 5 ) ) ..... .-|||||-. | | -----------
#:property prop-expr val-expr
Associates a propertyand value with the structure type.
For example, the prop:procedureproperty allows a
structure instance to be used as a function; the property value
determines how a call is implemented when using the structure as a
function.
Examples:
> ( struct greeter ( name ) #:property prop:procedure ( lambda ( self other ) ( string-append "Hi " other ", I'm " ( greeter-name self ) ) ) ) ( define joe-greet ( greeter "Joe" ) ) > ( greeter-name joe-greet ) "Joe" > ( joe-greet "Mary" ) "Hi Mary, I'm Joe" > ( joe-greet "John" ) "Hi John, I'm Joe"
#:super super-expr
An alternative to supplying a super-idnext to struct-id. Instead of the name of a structure type (which is
not an expression), super-exprshould produce a structure type descriptorvalue. An advantage of #:superis that structure type descriptors are values, so
they can be passed to procedures.
Examples:
( define ( raven-constructor super-type ) ( struct raven ( ) #:super super-type #:transparent #:property prop:procedure ( lambda ( self ) ' nevermore ) ) raven ) > ( let ( [ r ( ( raven-constructor struct:posn ) 1 2 ) ] ) ( list r ( r ) ) ) (list (raven 1 2) 'nevermore) > ( let ( [ r ( ( raven-constructor struct:thing ) "apple" ) ] ) ( list r ( r ) ) ) (list (raven "apple") 'nevermore)
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Speakers | Development Of PE Device By Submicron Resolution R2R Printing Process | Electric Vehicles: Everything is Changing. USA 2018
E-mobility Reinvented. Conference and Exhibition. Part of the IDTechEx Show. 3500+ Attendees · 270+ Exhibitors · 250+ Presentations - Click here to buy conference proceedings
Speakers from the world's largest organizations will share their needs and experiences with many world first announcements. Register now!
Mr Yuta Matsubayashi
Researcher-Corporate Production Technology
Presentation Title
Development Of PE Device By Submicron Resolution R2R Printing Process
Santa Clara Convention Center, CA, USA
Exhibition Theater Presentations: Day 2
15 November 2018
14:30 - 14:50
Presentation Summary
We are developing Roll to Roll process for PE to manufacture huge amounts of the sensors at low cost.
The most important technology is Seamless Roller Mold (SRM), which have sub-micron Resolution.
We would like to introduce the fabrication process of SRM,some PE products fabricated by using SRM, and AsahiKaseifs Roadmap.
Speaker Biography
Yuta Matsubayashi joined Asahi Kasei Corporation in 2001, and He is engaged in the development of SRM manufacturing technology.
From 2017 , he has been joinning a project of patterning technology development for printed electronics and he completed the R2R submicron patterning process.
Company Profile
Founded in 1922, the Asahi Kasei Group is a diversified manufacturer centered on chemistry. Throughout more than nine decades of growth, we have continued to proactively diversify and adapt our operating portfolio to changes in the economy, changes in society, and changes in the environment. We are now a major global enterprise with operations in the four business sectors of Chemicals & Fibers, Housing & Construction Materials, Electronics, and Health Care and having consolidated annual sales of some $18 billion with 29 thousand employees and 130 consolidated subsidiaries.
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Wuerth Elektronik eiSos GmbH & Co. KG Mr Lorandt Foelkel Business Development Manager & FAE The Reality About Energy Harvesting
3D Sensing and Perception
<here is a image 79538db1c60d4946-aad3ca2d60d1ae78 United States >
Quanergy Dr Louay Eldada CEO, Co-Founder Unparalleled Situational Awareness: The Cross-Industry Applications Of LiDAR
<here is a image 0706d93becef815b-975e659e8e49f65a United States >
FocalSpec, Inc. Mr Juha Saily Sales & Marketing Manager New High-Speed 3D Imaging Technology In Printed Electronics Metrology Applications
<here is a image 4596924893a67238-3d24f8621d3fab21 United States >
Cepton Technologies, Inc Dr Jun Pei CEO & Co-Founder Driving Forward: Enabling Smart Machines Of Tomorrow
<here is a image abd7b551a89b821e-70a2d2d668094918 United States >
Velodyne LiDAR Prof Stephen Nestinger Director of Mechanical Engineering Illuminating The Perception Horizon With Multi-Modality 3D Lidar
New Products: Exhibition Theater Presentations
<here is a image b6d42022dec39262-1be619a90887fa14 Germany >
Elantas Europe GmbH Dr Fabian Gyger R&D Electronics Inks Inks For Smart Surfaces
<here is a image e70f268405ff7503-c2d7a020c3d1574b United States >
ZSK Dr Topher Anderson Project Manager/Product Development Embroidery And Electronics - How Does That Fit Together?
More Speakers
This conference is co-located with other relevant conferences at the IDTechEx Show! Your conference pass allows you to access any conference sessions.
3D Printing Keynotes
<here is a image fb9f02ec90111326-910e5acc9ea56e7c United Kingdom >
IDTechEx Dr Bryony Core Technology Analyst Unlocking The Potential Of Additive Manufacturing
<here is a image 54514bab5d081877-15a830ac088128f6 United States >
Dassault Systemes Rachel Fu Senior Manager, Aerospace & Defense Initiatives Print To Perform: Validated And Deployed Solutions For Additive Manufacturing
<here is a image 643e7cd6b28409c3-b22ef8c19096b8ac United States >
BASF Oleksandra Korotchuk New Market Development BASF's Ever-Evolving 3D Printing Material Portfolio And Services For Open-Source Systems
<here is a image a1be8bd15afbcefe-84c3f892a6b711c6 Netherlands >
Ultimaker B.V. Peter Brier System Architect Multi-Material 3D Printing: Consider The Whole Workflow!
3D Printing Electronics
<here is a image c45d023a32d379c7-c905bec3fe503af0 Canada >
Voltera Mr Alroy Almeida CEO/Co-Founder Printed Electronics' Missing Link
<here is a image b860172f9c160928-682dd52059e9d38a United States >
BotFactory Inc Mr Carlos Ospina Co-Founder & CTO 3D Printed Electronics - Rapid Prototyping Of PCBs
<here is a image 5906fc31133f667c-01e413abc7fbc1a6 United States >
Team NEO Mr Timothy Fahey VP-Innovation & Industry Asset Roadmaps: Key Lessons For Growth In Additive Manufacturing And Printed Electronics
<here is a image 6dc333226bb6af91-adc29390cea93723 Germany >
Neotech AMT GmbH Dr Martin Hedges Managing Director Scalable 3D Printed Electronics - From Fully Additive To High Volume Manufacture
<here is a image 831c326a0f97be3e-5a229a2859a574af United States >
ChemCubed Dr Daniel Slep Chief Technology Officer Digital Printing Technique Of Conductive Inks And New Method Of Increasing Line Height
3D Printing with Metals
<here is a image 8983aa79b603d567-bfed5c3bbf075c75 Switzerland >
Cytosurge AG Mr Edgar Hepp 3D Business Development Manager Micro 3D Metal Printing - For Science And Industrial Application
<here is a image 2f475cd3314dbe8c-0ee7d017cd023bc8 United States >
Velo3D Tatjana Dzambazova Director of Product Management Breaking The Boundaries Of Metal Additive
<here is a image 320a992e726bcd7d-13e03c6bed65d061 France >
Z3DLAB SAS Dr Jean-Jacques Fouchet VP/Business Development Advanced Titanium For Additive Manufacturing
<here is a image d9338b1880d45ee0-5b13c0557ff91521 United States >
Star Rapid Zak Smith Global Sales Director 3D Metal Printing: When To Use It And Design Pitfalls
3D Printing of Polymers
<here is a image 7aa2a4bf14cfa06f-9d72001a52397435 United States >
Voxel8 Mr Travis Busbee CEO/CTO/Co-Founder Digital Footwear Manufacturing And Reactive Elastomer Printing
<here is a image e4ba5edb00cf2b2b-bb638f01b5f817f8 Netherlands >
Maastricht University Mr Jules Harings Assistant Professor Aligning Molecular And Structural Dynamics In Fused Deposition Modelling Of Polylactides For Enhanced Biomedical Performance
<here is a image b0c48a64b6c184ce-9e09cbbf9b71c475 United States >
FORECAST 3D Mr Ken Burns Technical Sales Director HP Multi Jet Fusion vs. Traditional Mass Production Methods
<here is a image eae7a7b7043a2a36-ffcd83f45787377a United States >
SHAP3D Prof Joey Mead Professor of Plastics Engineering Heterogeneous Additive Printing Of 3D Materials
<here is a image 7816689d25ab4711-827e259ed459e74f United States >
Vision Miner Robert Lent 3D Printing PEEK, ULTEM, And Other Engineering Thermoplastics With Open-Material Systems
<here is a image 7816689d25ab4711-827e259ed459e74f United States >
Vision Miner Patrick Smith 3D Printing PEEK, ULTEM, And Other Engineering Thermoplastics With Open-Material Systems
3D Printing of Composites
<here is a image 794786ff9cf32783-fffc4166f6d74905 United States >
Markforged Andrew de Geofroy VP of Application Engineering Carbon-Fiber Footprint Puts Markforged Step Ahead Of The Competition
<here is a image fee1c80cbe1c4893-31c8695250b18338 United States >
Vartega Andrew Maxey Founder & CEO Sustainable 3D Printing With Recycled Carbon Fiber
<here is a image b5fdea271a817674-4a966c25956c1787 United States >
Arevo Labs Wiener Mondesir Co-Founder A Revolution In Composite Manufacturing - Introducing Digital Additive Manufacturing Of Thermoplastic Composites
<here is a image 0dfff356f77c1bfd-c7f7aff89ebd9b93 Netherlands >
Studio Michiel Van der Kley Mr Michiel Van der Kley A 29 Meters Concrete 3D Printed Bridge In The Netherlands
Medical 3D Printing
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Anatomics, Inc. Josh Mikulich Senior Product Specialist Additive Manufacturing For Surgical Tools And Implants
<here is a image 9eb50186bb0d465c-767ab74722fda809 United States >
University of the Pacific School of Dentistry Nabeel Cajee A Bite Of The Future: Dentistry's Digital Revolution
<here is a image 0b97a13a41a72eb9-c9cd0a249d193686 United Kingdom >
Sutrue Alex Berry Managing Director Rapid Prototyping: How Using 3D Printing And 'Multi-Typing' Can Reduce Costs, Time And Waste When Engineering Medical Device Prototypes
<here is a image 0b97a13a41a72eb9-c9cd0a249d193686 United Kingdom >
Sutrue Ltd Thea Partridge Communications Director Rapid Prototyping: How Using 3D Printing And 'Multi-Typing' Can Reduce Costs, Time And Waste When Engineering Medical Device Prototypes
<here is a image e53b1dc3fdf5a727-f8ae62eed310c83f United States >
Advanced Solutions Mr Michael Golway Chairman and CEO BioAssemblyBot® Agile Manufacturing Processes
<here is a image 1e22b1338cf321b2-6ac6c03d3837c034 Korea >
Medicalip Co. Ltd. Dr Sang Joon Park CEO AI-Based Workflow Software For Medical 3D Printing: Examples Of Clinical Trial And Application
Enabling Technologies for 3D Printing
<here is a image 08422eeaa9142938-d8b8cd5409ad7bc9 United States >
Tempo Industries Dr Michael Bremser Executive Vice President of R&D Manufacturing LED Lighting Products Employing FDM 3D Printing Technology
<here is a image e54985297274432d-ea7d2eba2df5ee91 China >
Huafeng Dr Thomas Schmidt Director of Innovation & RSL Graphene/GO Doped HAPTIC 3D Coatings For Textile Applications
<here is a image f892e273cb516127-40f9e7d4f4f48357 United States >
HoneyPoint 3D Liza Wallach-Kloski Co-Founder & President, 3D Services Division Process And Examples Of Product Development Using 3D CAD, 3D Scanning And 3D printing
<here is a image f892e273cb516127-40f9e7d4f4f48357 United States >
HoneyPoint 3D Mr Nick Kloski Co-Founder & President, Education & Events Division Process And Examples Of Product Development Using 3D CAD, 3D Scanning And 3D printing
<here is a image d626846727e16137-042940d5b09ea7ac United States >
Elkem Silicones Dr Remi Thiria Science & Technology Leader Enhanced Additive Manufacturing Solutions For Personalized Health Care Applications With Silicones Elastomers'
Battery Manufacturing
<here is a image 9fda8d0e51ceac95-22808c60a77b710d United States >
Dürr MEGTEC Mr David Ventola Director Business Development - Engineered Products Reduce Electrode Manufacturing Cost; Transition From Batch To Continuous Production
<here is a image aa591c5d0b34cb67-7addd562dbb04bfd United States >
Soteria Battery Innovation Group Dr Brian Morin CEO Metallized Film Lithium Battery Current Collectors Reduce Weight & Cost & Improve Safety
<here is a image ce60c1ec330cf162-f2fc73db4a39ced4 United States >
EnerDel Dr Mary Patterson Senior Manager, Cell Engineering Passenger Cars And Commercial Vehicles: Different Approaches, Requirements And Challenges For Advanced Energy Storage Systems
<here is a image b60337d17e7531da-77936772cf734668 United States >
Imprint Energy Dr Christine Ho CEO & Co-Founder Printed Batteries: Progress On Scale And Cost, Driving Real Deployments
<here is a image b60337d17e7531da-77936772cf734668 United States >
Imprint Energy Dr Konstantin Tikhonov VP of R&D Printed Batteries: Progress On Scale And Cost, Driving Real Deployments
<here is a image 8a6a16243b76dafa-dd2386ec9420ded6 China >
Microvast Weifeng Fang Batteries And Battery Materials For Electric Buses
Fuel Cells
<here is a image fb9f02ec90111326-910e5acc9ea56e7c United Kingdom >
IDTechEx Mr Luke Gear Technology Analyst 'Fuel Cells For Marine Vessels
Internet of Things Applications Keynotes
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IDTechEx Dr Luyun Jiang Technology Analyst IoT Innovations And Trends
<here is a image 5f0809ee2a68cb70-cfe1c49734f9c6bf United Kingdom >
Arm Mr Andrew Frame Director Business Development, IoT Device IP Line of Business Removing The Barriers To Building Secure Solutions For IoT Systems
<here is a image 95dafbe4d056d54a-780c1ac751d5248c United States >
Microsoft Tony Shakib IoT/AI Business Acceleration Executive - Microsoft Azure IoT Driving Value From IoT And The Intelligent Edge
<here is a image 5e68629c162a24f6-f65b6f1a78e51d46 United States >
Intel Industrial & Energy Solutions Division, IOT Group Dr Irene Petrick Director of Industrial Innovation Toward Autonomy: The People, Process And Technology Challenges
Connectivity, Big Data, AI
<here is a image 11b815fd73a811a2-3a65e97fda326d96 China >
Liu Shen & Associates Ms Jian Zhang Attorney AI And IoT Related Intellectual Property Protection In China
<here is a image c07b572b6c4044ee-531c3595859570e3 United States >
Semtech Corporation Mr Vivek Mohan Director IoT - Wireless & Sensing Product Group LoRa Technology For The IoT
<here is a image 95e057a289b7d32c-4fcf5135ab5f4c72 United States >
Flex Mahsa Nakhjiri Sr. Director, Connectivity 5G & Industry 4.0
<here is a image 1ab54cbdc284f67e-94839b492a9768ea United States >
Wiliot Mr Steve Statler SVP Marketing & Business Development Scaling IoT With Passive Bluetooth And Connected Products
<here is a image 762564af290849a7-6459dfd1cffb9f65 United States >
Orange Silicon Valley Mr Michael Vladimer Co-Founder, IoT Studio How To Extract Value From The Internet Of Things
IoT Applications
<here is a image 9272c0a93de3c32f-d93e6c7f9fa6089c United States >
PassivDom Corp Max Gerbut CEO Internet Of Houses - Next Generation Prefabricated Housing Solutions
<here is a image 63780596e30865e1-4dfdf9a00d1d87ea United States >
Behr Technologies Inc. Mr Michel Hepp VP of Global Sales Providing Enhanced Industrial And Commercial Worker Safety Using Innovative IoT Wireless Solutions
<here is a image 52d720252941d249-8ceb1d7009b21aac United States >
U.S. State Department Landon C. Van Dyke Senior Advisor - Energy, Environment & Sustainability Making Smart-Cities With IoT Buildings & Blocks
<here is a image 47664df949d65a49-dadada5b943a0a21 United States >
ON Semiconductor Mr Douglas Seitz Product Marketing Manager, Power Solutions Group Agricultural Sensors: Facilitating Deployment
Realizing Digital Twinning and Predictive Maintenance
<here is a image d01307143e86bd08-c7c22aa95ba185c8 United States >
Thermo Fisher Scientific Larry S. Newman Sr. Manager - Asset Management & Metrology, Global Facilities & EHS Using PdM Temperature Monitoring To Reduce Costs And Risk For Refrigerated Storage In A Life Science Company
<here is a image 138e5fb52d41d22e-732cdf03db5ec69f United States >
Software Design Solutions, Inc. Ed Kuzemchak CTO and Director of IoT Industrial IoT Systems - The Promise And The Practice
<here is a image ce21e7c74d4a8579-b7f8fecef49afc03 United States >
Veritas Technologies LLC Mr Jayant Thomas Director/Head of AI and Machine Learning Predicting Reliability Of Industrial Machines Using Machine Learning
<here is a image a9a92669082e441a-34a899de6125e15c United States >
Jabil Mr Geoff Mulligan CTO for IIoT Opportunities With The IIoT And Micro-services To Make Money At The Edge
Industry 4.0: Smart Manufacturing
<here is a image 281f27ca64c696f5-75f6bf307e2f3ac5 United States >
Software AG, Cumulocity IoT Mr Mighael Bhota CTO North America AI Application In Manufacturing: Hear How Machine Learning Is Revolutionizing Predictive Maintenance In Manufacturing
<here is a image 681f51c779916bb0-fdc70d3f9544da89 United States >
Instrumental Inc. Anna-Katrina Shedletsky CEO Founder Five Factors That Are Putting Pressure On Manufacturing To Do Better And How AI Will Help
<here is a image 33f7538c12ef3688-1926afe354919a23 United States >
Porex Dr Gene Kim Global Business Development DIrector Custom Porous Plastic Solutions: Unique Value For Unique Applications
<here is a image 74a17f69ca320d97-4d1e41a2386bca0e United States >
Benchmark Electronics Inc. Mr Dave Higgins Vice President, IoT Design Center Using Advances In Ultra-Wideband Radio And Localized Sensor Networks To Develop Customizable IoT Edge Platforms
<here is a image 493471013572da55-a161899a92a2be88 United States >
King & Spalding LLP Mr Scott Ferber Partner Arrested Development: Legal & Policy Considerations
RFID
<here is a image fac95640ebb851f4-7166a2b599929176 United States >
RAIN RFID Mr Steve Halliday President RAIN RFID Introduction
<here is a image 87ac79ae1a3d603d-8d57292d3ed40585 United States >
Murata Electronics NA Inc Mr Gerry Hubers Market Segment Manager Brand Protection Using Ultra-Small Embeddable RAIN RFID Tags
<here is a image 5771bfed63e1ed85-f7bee5ff2bca6ee0 Canada >
Teslonix Inc. Dr C Paul Slaby CEO Describe How RAIN Technology Is Being Used For IoT And Sensors
<here is a image 5e494af4a344d1f0-525b0c9abcc2966e United States >
Aware Innovations Bart Ivy Director AIDC/RFID Solutions Rain RFID - Giving The IOT A Voice
<here is a image 01ba62c18ce645ae-5568be4f1e3685e5 United States >
Voyantic Mr Donald E Ray Director, North America Printed Antennas In Distributed Manufacturing Of RAIN RFID Tags And Labels
<here is a image 763800e0a6763be7-412f5ea17c5853b3 United Kingdom >
Silent Sensors Limited Mr Marcus Taylor CEO Development Of Energy Harvesting Material For TPMS Sensors
Connectivity and Security
<here is a image 37c044d9a6b360bf-772ca92d4ba297d7 United States >
Sigfox USA Richard Han Director of Business Development Why Connectivity Matters And What You Need To Know
<here is a image a116e98697a674a2-57e68d80459c3ed2 United States >
Rambus Nisha Amthul Product Marketing Keeping IoT Secure: Preempting Emerging Cyber Attacks Of Tomorrow
<here is a image cc6d9a00427af671-f6d4109c7f441ccc United States >
Ericsson Mr Zsolt G. Parnaki Head of Robotics Innovation Open Data Exchange For Connected And Autonomous Vehicles
<here is a image 66eef88342b07f52-7252b48de233b737 United States >
BSAC: Berkeley Sensor & Actuator Center Prof Kristofer Pister Co-Director Autonomous Microsystem Connectivity
Printed Electronics Keynotes
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IDTechEx Mr Raghu Das CEO Printed, Hybrid And Flexible Electronics - Status, Forecast, Innovation And Opportunities
<here is a image 022ed367ee123e82-4a6066e82a42b27d United States >
United Technologies Research Center Dr Sameh Dardona Associate Director, Research & Innovation Printed And Embedded Advanced Asset Monitoring Sensors
<here is a image bac60f39428d1306-c4a3ee356421c467 United Kingdom >
PolyPhotonix Mr Richard Kirk Chief Executive Saving Sight With Light
<here is a image 5eff062c53d08cce-454c98a7d76989f0 Japan >
JOLED Inc. Dr Toshiaki Arai Chief Technologist-SID Fellow The World's First Commercial Printed OLED Display
Printed and Flexible Electronics in Healthcare
<here is a image 52ed3582d82cf87c-379e20a4d89b1ca8 Germany >
Siemens Healthineers Dr Sandro Francesco Tedde Senior Key Expert Research Scientist Flat Panel X-Ray Detectors Based On Organometallic Perovskites
<here is a image b9e925c958d72a53-3951d2f7158fe4c1 Ireland >
Boston Scientific Corporation Mr Graham Lonergan Principal R&D Engineer Cardiac And Neuromodulation Medical Devices - Boston Scientific
<here is a image e901fe9cc7a76d4b-2a607ea0eb92f21c United States >
Nissha Si-Cal Inc Mr Jaye Tyler President / CEO Design Considerations And Manufacturing Process Tradeoff For The Creation Of Printed Electronics Healthcare Devices
<here is a image 32e01243dc29380f-805cd91e8285fc4f United States >
Blue Spark Technologies Mr Matthew Ream EVP Marketing and Innovations TempTraq: A commercial Evolution Of Printed And Flexible Electronics
OLED Display Innovations
<here is a image e2fefc76e8f78436-e5dbae43e482b997 China >
Visionox Dr Wang Chenggong Project Director,Display Research Ubiquitous Display, The Golden Age Of OLED
<here is a image 7b0a03dec84545ba-9b87b6c23046d168 United States >
Royole Corporation Dr Ze Yuan R&D Director-Flexible Display Business Group Mass Manufacturing Of Flexible OLED Displays
<here is a image 3694150762acca5b-48858e8fe4f88bc5 Korea >
Korea Institute of Industrial Technology Dr Kwan Hyun Cho Senior Researcher-Micro/Nano Scale Mfg. Intense Pulsed Light Transfer Printing For Solution Processed OLEDs
<here is a image 39a2035c6ccea510-44da98917934f263 Canada >
OTI Lumionics Inc Mr Jacky Qiu Vice President & Co-Founder Unlocking New Markets For OLEDs With Novel Cathode Materials
<here is a image fb5128465fc834da-d6a3df06ec173c83 United States >
Atom Nanoelectronics Dr Huaping Li Chief Scientist Fully Printed Carbon Nanotube Electronics
Display and Lighting Innovations
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Nth Degree Technologies Dr William J Ray Chief Scientist Integrating Printed Electronic Elements
<here is a image 727257953ca28eb1-f60dfd3862e041e7 United States >
CLEARink Mr Sri Peruvemba CMO Retro-Reflective eTIR Technology
<here is a image 5e9095b77979a729-1f45897ccbb9ea2b Portugal >
Ynvisible Mr Jani-Mikael Kuusisto CEO Expanding Fields Of Application For Printed Electrochromics: From Smart Labels And IoT To Ambient Intelligence
<here is a image 9cd5fb81c23caf61-68d33c6447ed17ba United States >
EMD Performance Materials Dr Rebekah Miller Technology Scout Chemistry Of Novel Displays: EMD Performance Materials For Next Generation Interfaces.
<here is a image b4c0c2f6896ccd03-f79f251d101f4df6 United States >
Kent Displays, Inc. Dr Mauricio Echeverri Senior Scientist Design And Development Of Flexible eWriters With Novel Functionalities
Haptics and HMI
<here is a image cc65e8eabf3634f9-1619b007457a20cf United Kingdom >
Cambridge Mechatronics Ltd. Mr Marc Scholz Technical Lead - Haptics Haptics Transformation Through SMA For A More Accurate Feeling
<here is a image 06dc21b61661f09c-286dd144f0104c6b United States >
Ultrahaptics Mr Alex Driskill-Smith VP North America Using Ultrasound To Enable Touch In The Digital World
<here is a image defdb559a0cd35d9-3f97b870d79dca9f Canada >
Tangio Printed Electronics Mr Mark Westgarth-Graham Product Development The Fusion Of Printed Technologies For Enhanced User Experience In HMI Applications
<here is a image d6f8e7f97dbc632a-0f0e85fd0f7e4d37 United States >
NOVASENTIS, INC. Dr Michael Vestel CTO It Aint Virtual Anymore
Structural Electronics and Advanced Materials
<here is a image 027da5e0baaca684-88cb5f410f04e0b3 United States >
DuPont Dr Dave Hui Marketing & Business Development Manager In Mold Electronics - New Solutions With Next Generation Materials
<here is a image a7b91cc7b3e6aa55-a984d58e51d04be4 United States >
Optomec Inc Mr Mike O'Reilly Director, Aerosol Jet Product Management Aerosol Jet®, An Evolutionary Electronic Material Dispense Solution
<here is a image f705dec96072105e-f8d29f5361318241 Netherlands >
Holst Centre Dr Daniel Tordera Senior Scientist Printed Organic Fingerprint Scanners For User Authentication
<here is a image e839014ebca166be-0758f50219226101 Finland >
TactoTek Dr Antti Keranen CTO, Co-Founder Designing And Making Parts Using Injection Molded Structural Electronics (IMSE™)
Printed Electronics Material Advances
<here is a image ac1c9214e89a3038-c0bfac59fa0ef4aa Belgium >
Agfa-Gevaert Mr Peter Willaert Global Marketing Manager Printed Electronics Nanosilver: Turning Features Into Benefits
<here is a image 446d1074b1398088-4043d4e45a6f4ff5 China >
Suzhou Nano-Tech and Nano-Bionics Prof Zheng Cui Director of PE Research Centre Progress On Hybrid Printed Metal-Mesh And New Applications
<here is a image 34a10546ad8c4bb2-076333f6312041a8 Korea >
DUKSAN Hi-Metal Co., Ltd. Dr Young Yoo Director, R&D Center Recent Progress On Silver Nano-Wire Based Electrode: An Atomically Flat Transparent Conductive Outcoupling Electrode For Flexible Electronics
<here is a image bd5f585fd0454292-71f0ab808029e4f1 Norway >
CondAlign AS Mr Morten Lindberget VP-Business Development & Sales Anisotropic Particle-Filled Polymer Films Structured By Electric Fields - Technology, Applications And Markets
<here is a image 0b63e62657edb35a-21349e3214ea97ca Germany >
Heraeus Deutschland GmbH & Co. KG Mr Franz Vollmann Project Manager/Product Development A Novelty: The First Integrated Solution Platform For Digitally Printed Electronics
Smart Packaging and Printed IoT
<here is a image f25ada9625c27035-516dd11066e82c6e Canada >
Ahead Of The Curve Christine Di Fabio A Good Idea Is A Good Idea. A Good Idea In Market Is Great Idea
<here is a image 34d1d92c8deb36ce-608c37beb9b92d3f United Kingdom >
PragmatIC Mr Scott White CEO To Trillions Of Smart Objects And Beyond
<here is a image a70d2b0f9110f5a0-5350753df6ae6d4d Norway >
Thin Film Electronics ASA Dr Davor Sutija CEO From Stand-Alone Memory to Printed Systems
<here is a image 1e8ec06fa7345c53-b4e73c97d4997089 Japan >
Toray Industries, Inc Dr Junji Wakita Senior Research Engineer-R&D Planning Dept. Printed Thin Film Transistors Using Semi-Conductive Single-Wall Carbon Nanotube-Polymer Complexes
<here is a image 80a045eb620d5ebd-59c62e80e8db5e7b United States >
PARC, a Xerox company Mr Mike Kuniavsky Project Manager/Product Development How PARC's Innovation Services Group Rapidly Explores New Applications For Printed Electronics
Hybrid Electronics
<here is a image a798e2192445850b-48cb167dabc00bc5 United States >
Hewlett Packard Labs Dr Jim Huang Research Scientist Process Design Kit (PDK) For Flexible Electronics
<here is a image 462a67db3ec4d2d1-7cf89c3318276595 United States >
American Semiconductor, Inc. Mr Douglas R. Hackler President/CEO Advanced Flexible Hybrid Electronic (FHE) Demonstrators
<here is a image a8b37b4f71259b03-6ee48da72286e32f United States >
US Army ARDEC Mr James Zunino ARDEC Project Officer / Materials Engineer Operationalizing Printed Electronics & Additive Manufacturing To Enhance Warfighter Capabilities And Strengthen The Organic Industrial Base
<here is a image 4495be0f8c1a84b5-fff503bfbbf4278e United States >
Muhlbauer Inc Mr Gerald Steinwasser General Manager Multicomponent Assembly On Flexible Material In Reel To Reel Process
<here is a image abf37ad1cde3a50b-a9fb569a810d8741 Canada >
Xerox Research Centre Canada Dr Sarah Vella Research Scientist From Materials To Integrated Electronic Devices: The Road To Printed Intelligence
Printed Electronics Manufacturing
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NovaCentrix Dr Vahid Akhavan Senior Applications Engineer Merging Design And Function Through Conductive Inks And Photonic Curing
<here is a image 033bf6b08e920257-0f1aea7e5c50d8b3 United States >
Applied Materials Mr Daniel Hada Director, Sales, North America & Southeast Asia High Volume R2R And S2S Manufacturing Technologies For Flexible Electronics
<here is a image 436a0388f12d29a7-db8ffea732142869 France >
CERADROP Mr Tim H. Luong Sales & Marketing Manager Digital Printing for Multi-Material Functional Components Manufacturing: Printed Electronics And Smart 3D Printing Applications
<here is a image 0bfc9bd4f81cad19-beb52d743cfea906 United States >
ACI Materials, Inc. Dr Damon D. Brink VP Business Development Stretchable Component Attach Strategies For FHE
Graphene Keynotes
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IDTechEx Dr Richard Collins Senior Technology Analyst Graphene And Carbon Nanotubes: Existing And Future Markets
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Global Graphene Group Dr Bor Jang CEO Industrial-scale Production of Graphene: Challenges and Opportunities
<here is a image c25bd7b76b165f0e-0a5e5409bcfa03d2 United States >
XG Sciences Dr Percy Chinoy Sr. Director, Business Development Graphene Reinforced Rubber Composite For Golf Ball Application
<here is a image 7e55c5c6513ff390-79c286b13dd8ad1d United States >
Callaway Mr Dave Bartels Sr. Director, Golf Ball, R&D Graphene Reinforced Rubber Composite For Golf Ball Application
<here is a image 666591e17fd2bbef-7ceeb1c73149d01d Canada >
NanoXplore Inc. Dr Soroush Nazarpour President and CEO Large-Scale, Commercially Viable Graphene
Commercial Applications of Graphene and 2D Materials
<here is a image 9cfef4721274f837-fd61871a0fad91c2 United States >
The Graphene Council Mr Terrance Barkan Executive Director Graphene Enhanced Composites And Plastics
<here is a image 6bcb2a92d5f60542-969b5abfd9d2253d Sweden >
GraphMaTech AB Bjorn Lindh Engineering Of Thermal Interface Materials By Aros Graphene® Technology
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Fibronectin Stimulates Endothelial Cell 18F-FDG Uptake Through Focal Adhesion Kinase–Mediated Phosphatidylinositol 3-Kinase/Akt Signaling | Journal of Nuclear Medicine
Fibronectin Stimulates Endothelial Cell 18 F-FDG Uptake Through Focal Adhesion Kinase–Mediated Phosphatidylinositol 3-Kinase/Akt Signaling
Jin-Young Paik , Bong-Ho Ko , Kyung-Ho Jung and Kyung-Han Lee
Journal of Nuclear Medicine April 2009, 50 (4) 618-624; DOI: https://doi.org/10.2967/jnumed.108.059386
Abstract
There has been recent interest in the relationship between 18F-FDG uptake and the angiogenic activity of endothelial cells (ECs). The angiogenic process is strongly dependent on the interaction of ECs with matrix fibronectin (FN), a key regulator of EC survival, migration, and proliferation. Therefore, we investigated how FN influences EC glucose uptake and elucidated the signaling pathways that mediate this effect.Methods:Human umbilical vein ECs were allowed to adhere to FN-coated plates and were compared with control cells for 18F-FDG uptake, membrane GLUT1 levels, and hexokinase activity. The roles of focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3K), and Akt were evaluated with Western blotting, small interfering RNA (siRNA), and specific inhibitors.Results:FN adhesion significantly enhanced the protein-corrected 18F-FDG uptake in HUVEC, to 2.1-, 2.7-, and 4.3-fold that in control cells by 2, 3, and 5 d, respectively. This effect was mediated by the upregulation of both membrane GLUT1 expression and hexokinase activity and was accompanied by FAK activation. Silencing of FAK signaling by siRNA completely abrogated both FN-induced FAK phosphorylation and 18F-FDG uptake. FN also activated PI3K and Akt, well-known angiogenesis mediators, and the inhibition of either pathway totally abolished the effect of FN on 18F-FDG uptake. Nitric oxide, a downstream Akt effector that stimulates glucose uptake, was not involved in the metabolic effect of FN.Conclusion:The results of this study demonstrated that an EC–FN interaction induces strong enhancement of 18F-FDG uptake through the upregulation of GLUT1 expression and hexokinase activity. The findings also showed that the response occurs through FAK-mediated activation of PI3K and Akt, indicating a role for this pathway in modulating EC glucose metabolism.
endothelial cell
fibronectin
18 F-FDG, angiogenesis
focal adhesion kinase
Endothelial cells (ECs) have recently gained attention as an important nontumor cellular component of significant glucose use and 18F-FDG uptake ( 1 – 5). ECs take up 18F-FDG avidly in magnitudes comparable to or even greater than those of tumor cells and macrophages ( 2) and cause high levels of 18F-FDG uptake in tumors of vascular endothelial origin ( 6 , 7). An issue of particular interest in EC 18F-FDG uptake is its relationship to angiogenic activity, a fundamental step in tumor growth and ischemic injury healing. Observations in patients with cancer have shown tumors to have 18F-FDG kinetics that are modulated by angiogenesis-related gene expression ( 8), and in some instances 18F-FDG uptake has been correlated with histologic markers of angiogenesis ( 9 , 10). These findings likely reflect the increased metabolic activity of tumor cells but may also be partly attributable to the augmented 18F-FDG uptake in activated endothelia in angiogenic vessels. Indeed, a positive influence on 18F-FDG uptake was suggested in studies in which ECs were treated with angiogenic stimuli such as vascular endothelial growth factor ( 2), nitric oxide (NO) ( 4), and hypoxia ( 5).
Crucial for activation of the angiogenic process, however, are EC attachment to and interaction with the extracellular matrix (ECM); the latter, in turn, transmits signal cascades that mediate major angiogenic responses, including EC proliferation and migration ( 11). Because the performance of these functions requires increased energy expenditure ( 4 , 12 , 13) and EC energy is predominantly generated by glycolysis ( 12 , 14), it is plausible that an interaction with the ECM induces intracellular signals that augment glucose use and 18F-FDG uptake.
Fibronectin (FN), a high-molecular-weight glycoprotein abundant in the matrix, is the foremost angiogenesis-associated ECM component promoting EC adhesion, proliferation, migration, and survival ( 11 , 15 – 17). The attachment of EC surface receptors to FN results in the transmission of intracellular signals through the activation of focal adhesion kinase (FAK), a nonreceptor tyrosine kinase that localizes to regions of focal adhesion ( 18 , 19). Activated FAK, in turn, triggers several signaling pathways that regulate EC functions such as cell cycle progression, spreading, and survival. The autophosphorylation of FAK creates a binding site for the regulatory p85 subunit of phosphatidylinositol 3-kinase (PI3K), which can activate the catalytic p110 subunit and the PI3K/Akt signaling cascade ( 20 , 21). This pathway is a highly plausible candidate for mediating the enhancement of 18F-FDG uptake in activated ECs because, although it is a well-recognized regulator of cell growth, survival, and angiogenesis, it also plays an important role in promoting glucose metabolism ( 22 – 25).
Elucidation of how an interaction with FN regulates EC glucose metabolism could provide insight into the contribution of angiogenic activity to 18F-FDG uptake and how ECs are guaranteed a sufficient supply of energy to execute angiogenic processes. In this study, we investigated the influence of FN on EC 18F-FDG uptake and explored the potential roles of FAK and downstream PI3K and Akt pathways in mediating this metabolic response.
MATERIALS AND METHODS
Cell Culture
Human umbilical vein ECs (HUVEC) were obtained from the American Type Culture Collection and maintained in EC basal medium (Clonetics) supplemented with epidermal growth factors, 12% fetal bovine serum, glucose at 2 g/L, and penicillin–streptomycin at 100 U/mL. Cells were cultured in a humidified atmosphere of 5% CO 2at 37°C, the medium was changed every 3 d, and only cells from passages 4 and 5 were used.
For FN coating, the surface of standard polystyrene-treated culture plates (Corning Inc.) was covered with phosphate-buffered saline (PBS, pH 7.4) containing FN (10 μg/mL; Sigma Chemical Co.), and the plates were incubated at 37°C for 24 h. HUVEC were used to seed FN-coated or uncoated 12-well culture plates at 10 5cells per well for experiments.
Evaluation of Cell Proliferation and 18 F-FDG Uptake
Cell morphology was inspected with hematoxylin–eosin staining, and cell proliferation was assessed by Bradford protein assays and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays.
18F-FDG uptake was measured 48 h after seeding, when cell confluence reached 80%. The use of culture medium rather than PBS enabled 18F-FDG uptake to be measured at 37°C, thereby providing information more relevant to in vivo conditions than measuring uptake at 4°C. Thus, cells were incubated with 370 kBq (10 μCi) of 18F-FDG added to the culture medium at 37°C for 40 min in 5% CO 2, rapidly washed twice with cold PBS, and lysed in 1 mL of distilled water. Cell-associated radioactivity was measured with a high-energy γ-counter (Wallac), and protein-corrected 18F-FDG uptake levels expressed as a percentage of the level in control cells were calculated.
Measurements of Hexokinase Activity and NO Concentration
Total cellular hexokinase activity was measured by the method of Vinuela et al. as modified by Waki et al. ( 26). In brief, cells were homogenized in a buffer containing 50 mM triethanolamine and 5 mM MgCl 2(pH 7.6), and a supernatant was obtained after centrifugation at 1,000 gfor 5 min at 4°C. The same type of buffer containing 0.5 mM glucose, 5 mM adenosine triphosphate, 0.25 mM reduced nicotinamide adenine dinucleotide phosphate, and 6 U of glucose 6-phosphate dehydrogenase was preincubated at 20°C for 15 min. Cell lysate samples were added, and the absorbance of the reaction mixture was measured. Hexokinase activity was determined from a standard curve, with 1 U being defined as enzyme activity that phosphorylated 1 μmol of glucose per minute at 20°C. Aliquots were removed to measure the protein content, and enzyme activity was expressed as a percentage of that in control cells.
For measurement of the concentration of NO released, 100 μL of medium was taken from culture plates 48 h after seeding. The medium was mixed with an equal volume of Griess reagent, which contained 1% sulfanilamide, 0.1% N-(1-naphthyl)ethylenediamine dihydrochloride, and 2.5% phosphoric acid. After incubation for 10 min, the absorbance at 540 nm was measured with a spectrophotometer, and the results were expressed as the NO concentration relative to that in control cells. The effect of exogenous NO was evaluated by adding 10–100 μM of sodium nitroprusside (SNP) (Sigma Chemical Co.) to the cell medium and incubating the mixture in a humidified atmosphere of 5% CO 2at 37°C for 24 h.
Western Blotting of Membrane GLUT1
For the analysis of membrane GLUT1 expression, two 150-mm plates of 80% confluent HUVEC were washed twice with PBS. The cells were solubilized with 500 μL of a lysis buffer containing sucrose (0.0856 g/mL), N-2-hydroxyethylpiperazine- N′-2-ethanesulfonic acid (HEPES) (10 mmol/mL), ethylenediaminetetraacetic acid (EDTA) (25 μmol/mL), aprotinin (10 μg/mL), leupeptin (10 μg/mL), and phenylmethylsulfonyl fluoride (1 mM). After centrifugation at 1,000 gfor 20 min, the supernatant was collected and incubated with 1.5 mL of a lysis buffer containing sucrose (0.0856 g/mL), HEPES (10 mmol/mL), and MgCl 2(10 mmol/mL) at 4°C for 1 h. The mixture was centrifuged at 45,000 rpm for 60 min, and the pellet was dissolved in a minimum volume of PBS. Membrane proteins were separated on a 10% polyacrylamide gel, electroblotted to a Hybond enhanced chemiluminescence nitrocellulose membrane (Amersham), and reacted with a polyclonal antibody against human GLUT1 (1:1,000 dilution; Calbiochem). GLUT1 protein was visualized by incubation with a horseradish peroxidase–conjugated secondary antirabbit IgG antibody (1:1,000 dilution; Caltag), 1 min of soaking in Amersham ECL Western Blotting Detection Reagent (GE Healthcare), and detection of signals on a high-performance chemiluminescence film. Protein band intensities on the film were measured with a GS-800 calibrated densitometer and Quantity One software (both from Bio-Rad Laboratories).
Western Blotting of Phosphorylated FAK (p-FAK), Phosphorylated PI3K (p-PI3K), and Phosphorylated Akt (p-Akt)
For the analysis of p-FAK protein, cells from 100-mm culture plates were washed, lysed, and sonicated for 10–15 s to reduce sample viscosity. After the lysate was heated to 95°C for 5 min and centrifuged at 15,000 gfor 5 min, the proteins were separated on a 10% polyacrylamide gel, electroblotted, and visualized as described earlier after reaction with a polyclonal antibody against human p-FAK (pY397; BD Biosciences) at a 1:1,000 dilution and a horseradish peroxidase–conjugated secondary sheep antimouse IgG antibody (GE Healthcare) at a 1:1,000 dilution. For p-FAK and GLUT1 immunoblots, 20-μg samples were loaded in each lane after protein assays, and the similarity of protein loading among lanes was confirmed by Ponceau S staining of the membranes without the use of a loading control protein.
For the analysis of p-PI3K and p-Akt proteins, cells from 100-mm culture plates (after 24 h of adhesion) were washed and solubilized at room temperature with 1 mL of a radioimmunoprecipitation buffer containing Tris base (0.079 g/mL), NaCl (0.09 g/mL), NP-40 (10%; Sigma-Aldrich), EDTA (10 μmol/L), aprotinin (10 μg/mL), leupeptin (10 μg/mL), and phenylmethylsulfonyl fluoride (1 mM). After centrifugation at 14,000 gfor 15 min, supernatants were incubated with 100 μL of precleared protein A–Sepharose beads (Sigma-Aldrich) at 4°C for 10 min to reduce nonspecific binding. The beads were then removed by centrifugation, and total cell protein was diluted to 1 mg/mL with PBS to reduce the concentrations of detergents. The collected protein was mixed with an antibody against p-PI3K (500:1; Santa Cruz Biotechnology) or p-Akt (200:1; Cell Signaling Technology), and the mixture was incubated at 4°C for 2 h on a shaker. The immunocomplex was captured by adding 50 μL of a protein A–Sepharose bead slurry and gently rocking the mixture on a shaker overnight at 4°C. The immunoprecipitate was collected by centrifugation and 2–4 washes of the pellet with 1.0 mL of the radioimmunoprecipitation buffer. After the final wash, the pellet was suspended in 50 μL of 2× electrophoresis sample buffer, and the mixture was boiled for 4 min. The proteins were separated on a 10% polyacrylamide gel, electroblotted, and incubated with the same polyclonal antibody against human p-PI3K (1:500 dilution) or human p-Akt (1:200 dilution) as that used for immunoprecipitation. p-PI3K and p-Akt bands were visualized with horseradish peroxidase–conjugated secondary antigoat and antirabbit IgG antibodies (both at a 1:1,000 dilution; Santa Cruz Biotechnology), respectively.
Silencing of FAK Signaling by Small Interfering RNA (siRNA) Transfection
For the silencing of FAK signaling, cells were transfected with target-specific 20- to 25-nucleotide siRNA designed to decrease FAK gene expression in human cells (SC-29310; Santa Cruz Biotechnology). Transfection was accomplished with a SignalSilence kit (Cell Signaling Technology) according to the recommended protocol. In brief, 2 μL of transfection reagent was added to 100 μL of serum-free medium in a sterile tube, and the mixture was incubated at room temperature for 5 min. FAK-inactivating siRNA was added to a final concentration of 100 nM, and the mixture was incubated for another 5 min. This final mixture was added to the culture medium of 60% confluent cells that had been used to seed 12-well plates 24 h earlier. After vigorous agitation to allow the even dispersion of siRNA, cells were incubated in a humidified atmosphere of 5% CO 2at 37°C. The medium was replaced with fresh medium 3 d later, and 18F-FDG uptake was measured the next day.
Inhibition of Kinases and NO Synthase
Candidate signaling pathways were evaluated by adding specific kinase inhibitors to the medium 48 h before 18F-FDG uptake experiments. PI3K was blocked by 10 μM LY294002 or 200 nM wortmannin, and Akt was blocked by a 1 μM concentration of a cell-permeating benzimidazole compound (Akt inhibitor IV; molecular formula, C 31H 27IN 4S; Calbiochem) that inhibits Akt phosphorylation without affecting PI3K activity.
Blocking of NO release was achieved by adding N G-nitro- l-arginine methyl ester (L-NAME; RBI) at a concentration of 0.05–1 mM to the medium 48 h before 18F-FDG uptake measurements.
Statistical Analysis
All 18F-FDG uptake data and hexokinase assay data are the summed results of 2 or 3 independent experiments performed in triplicate. All values shown represent the mean ± SD. Student's test was used to evaluate statistical significance between groups, and Pvalues of <0.05 were considered significant.
RESULTS
FN Interaction Augments HUVEC 18 F-FDG Uptake
Microscopic inspection revealed little alteration in HUVEC morphology by FN. MTT and protein assays revealed a proliferative effect after 3 d of FN treatment (protein contents were 149.0% ± 8.1% and 249.0% ± 3.2% those in control cells at days 3 and 5, respectively). FN significantly enhanced 18F-FDG uptake in a manner that preceded and surpassed its proliferative effect. Hence, even after correction for protein content, the 18F-FDG uptake in FN-treated cells was increased to 210%, 268%, and 431% that in control cells at 2, 3, and 5 d, respectively. On the basis of these findings, the remaining 18F-FDG uptake experiments were performed 48 h after seeding to exclude effects from cell proliferation.
The specificity of the effect of FN was evaluated by using FN with graded degrees of degradation through repeated use. With fresh FN, there was a significant increase in 18F-FDG uptake, which reached 198.6% ± 7.2% that in control cells (Fig. 1A). However, FN reused once and twice had proportionally attenuated stimulatory effects on 18F-FDG uptake—153.2% ± 6.6% and 111.7% ± 8.3% that of control cells, respectively—indicating that the effect was specific for intact FN protein (Fig. 1A).
FIGURE 1.
Effects of FN on 18F-FDG uptake, GLUT1 expression, and hexokinase activity. (A) 18F-FDG uptake in HUVEC treated with fresh or reused FN relative to that in nontreated control cells. Data are mean ± SD of 3 independent experiments. (B) Representative Western blot of plasma membrane GLUT1 protein in FN-treated (FN+) and non–FN-treated (FN−) cells. (C) Total cellular hexokinase activity relative to that in control cells. Data are mean ± SD of 2 independent experiments.
FN Enhances Membrane GLUT1 Expression and Hexokinase Activity
Western blotting of HUVEC treated with FN for 2 d revealed an increase in the expression of membrane GLUT1 protein, the main glucose transporter in ECs, compared with that in control cells (Fig. 1B). Furthermore, FN treatment for 2 d induced a significantly higher level of total cellular hexokinase activity, which reached 1.6 ± 0.0-fold that in control cells (Fig. 1C).
FAK Silencing Completely Abrogates FN-Stimulated 18 F-FDG Uptake
p-FAK protein band densities were significantly increased by FN treatment, to 189.2% ± 7.2% that in control cells (Fig. 2A). However, silencing of FAK signaling by siRNA transfection completely blocked this effect, with p-FAK protein being reduced to a level lower than that in control cells (44.0% ± 2.6%) (Fig. 2A). Blocking of FAK signaling by siRNA also completely abolished FN-stimulated 18F-FDG uptake, from 200.7% ± 11.4% to 86.6% ± 19.4% that in control cells (Fig. 2B).
FIGURE 2.
Effect of FAK silencing by siRNA transfection on p-FAK levels (A) and 18F-FDG uptake (B). 18F-FDG uptake data are mean ± SD of 2 independent experiments.
FN-Stimulated 18 F-FDG Uptake Is Mediated Through PI3K/Akt Pathway
FN significantly increased HUVEC p-PI3K (Fig. 3A) and p-Akt (Fig. 3B) protein levels. Furthermore, FN-stimulated 18F-FDG uptake was effectively blocked by the specific PI3K inhibitors wortmannin and LY294002 and by Akt inhibitor IV to 58.5% ± 12.1%, 52.0% ± 7.9%, and 53.0% ± 1.8% uninhibited levels, respectively (Figs. 4A and 4B). These results indicated that FN-stimulated 18F-FDG uptake occurs through the PI3K/Akt pathway.
FIGURE 3.
Western blot and band intensity of p-PI3K (A) and p-Akt (B) in FN-treated (FN+) and non–FN-treated (FN−) cells. Data are mean ± SD of band densities relative to that in control cells in triplicate samples. * P< 0.05 compared with control cell values. † P< 0.001 compared with control cell values.
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FIGURE 4.
Effects of specific PI3K inhibitors (A) and Akt inhibitor (B) on FN-stimulated 18F-FDG uptake. Data are mean ± SD of 3 independent experiments. AKT Inh, 1 μM Akt inhibitor IV; Ly294002, 10 μM LY294002; WM, 200 nM wortmannin.
NO Signaling Is Not Involved in FN-Stimulated 18 F-FDG Uptake
The possible involvement of NO was evaluated because it is a major downstream effector of Akt signaling and is capable of stimulating EC 18F-FDG uptake. Exogenous donation of NO by the addition of 10 and 100 μM SNP indeed increased 18F-FDG uptake in non–FN-treated cells to 213.3% ± 9.0% and 238.3% ± 8.3% that in nonstimulated control cells, respectively, and in FN-treated cells from 225.7% ± 38.0% to 230.4% ± 33.7% and 254.% ± 17.4% that in nonstimulated control cells, respectively (Fig. 5A). However, NO release was not increased by FN treatment, regardless of whether or not SNP was added (Fig. 5B). Furthermore, blocking of NO synthase with various doses of L-NAME had no effect on FN-stimulated 18F-FDG uptake (Fig. 5C).
FIGURE 5.
Role of NO in FN-stimulated 18F-FDG uptake. (A) Effect of 10 and 100 μM SNP on 18F-FDG uptake in FN-treated (FN+) and non–FN-treated (FN−) cells. (B) Concentration of released NO in culture medium with or without addition of SNP. (C) Effect of inhibition of NO synthase by L-NAME on 18F-FDG uptake. 18F-FDG uptake data are mean ± SD of 2 independent experiments. ‡ P< 0.0001 compared with control cell values.
DISCUSSION
ECs are the primary effector cells for new vessel formation, a process critical for tumor growth and ischemic injury healing. The execution of angiogenic responses requires an increase in energy supply, which in ECs is predominantly met with adenosine triphosphate generated from glycolysis ( 13 , 14). Thus, the molecular mechanisms that regulate EC glucose metabolism are of significant interest, particularly in relation to the influence of major angiogenic stimuli.
In the present study, we investigated the effect of an interaction with FN, a highly specialized glycoprotein that mediates a variety of ECM–cell interactions and that plays a pivotal role in angiogenesis ( 11 , 15 , 16), on HUVEC 18F-FDG uptake. We found that FN stimulates significant enhancement of 18F-FDG uptake and that this effect is mediated by the upregulation of both the expression of membrane GLUT1, the predominant EC glucose transporter ( 27), and the activity of hexokinase, the rate-limiting enzyme in glycolysis. Further exploration of the molecular mechanisms revealed the involvement of FAK and downstream PI3K/Akt signaling in the FN-induced metabolic effect.
We also found that attachment to FN led to an increase in the number of HUVEC compared with the number of control cells after 3 d. A similar proliferative effect of FN on ECs was previously observed ( 28 , 29). However, our findings demonstrated that FN-stimulated 18F-FDG uptake clearly precedes and surpasses the increase in cell numbers, suggesting that the metabolic effect of FN is distinct from its proliferative effect.
To identify the signaling mechanism that mediated this metabolic effect, we explored the involvement of FAK, a cytoplasmic kinase that resides at focal adhesion sites and that links ECM-derived signals to the cell interior ( 18 , 19). Significant activation of FAK was observed in FN-treated HUVEC, and perturbation of FAK signaling by RNA interference completely abolished the augmentation of cellular 18F-FDG uptake as well as FAK phosphorylation. FAK is a well-recognized mediator of growth factor signaling, cell proliferation, and migration in cancer cells ( 18) and has been implicated in EC functions that promote angiogenesis ( 19). Our findings indicated that FAK is involved in modulating EC glucose metabolism as well. A similar effect of FAK levels in regulating glucose uptake in C2C12 skeletal muscle cells was recently observed by Bisht et al. ( 30).
In the study of Bisht et al., the effect of FAK on skeletal myocyte glucose metabolism appeared to be mediated mainly through PI3K and protein kinase C rather than Akt ( 30). In the present study, however, the FN-induced phosphorylation of FAK in HUVEC was accompanied by the activation of both PI3K and Akt. Furthermore, the inhibition of PI3K by wortmannin or LY294002 and the blocking of Akt activity by a specific inhibitor completely abrogated the stimulatory effect of FN on 18F-FDG uptake. Given the known instability of wortmannin in culture medium ( 31), it is possible that the actual inhibitory effect of this agent was even greater than that observed. In ECs, the PI3K/Akt signaling axis is activated by many angiogenic growth factors and critically regulates cell survival and angiogenesis ( 22 – 25). The PI3K/Akt pathway is also a well-recognized regulator of cellular glucose uptake and metabolism. The serine/threonine kinase Akt is activated in response to insulin and growth factors in a PI3K-dependent fashion and stimulates glucose uptake through the upregulation of glucose transporters and increased hexokinase activity ( 25). Our results implied a mechanism in ECs that is induced by FN-activated FAK signaling, similar to that induced by growth factor receptor activation in tumor cells, through which glucose uptake is promoted via activation of the PI3K/Akt pathway.
Because neovascularization plays a key role in the ability of malignant cells to grow and metastasize, many studies have focused on evaluating novel agents that inhibit angiogenesis as a method for controlling tumor growth. Elucidating the relationship among FN, EC glucose metabolism, and the FAK/PI3K/Akt signaling pathway may provide valuable insights into prospective targets for angiogenesis inhibition and mechanisms for assessing the efficacy of new potential therapeutic agents. A difficulty in the use of cultured EC models, however, is that the behaviors of cells derived from different organs or species as well as of cells originating from microvascular and large vessels can differ. Indeed, ECs from different origins have been described to vary with regard to glucose metabolism and transporter-related responses ( 14). Therefore, the results that we observed in the present study are limited to HUVEC.
We also evaluated whether NO signaling was involved in the FN-induced metabolic effect because Akt is known to stimulate NO release through NO synthase activation in ECs ( 32) and we had previously found NO to be a powerful simulator of 18F-FDG uptake in ECs ( 4). However, our results showed that although NO could indeed stimulate 18F-FDG uptake, FN-stimulated 18F-FDG uptake was neither accompanied by elevated NO release nor attenuated by the inhibition of NO synthase, indicating that the metabolic effect of FN was independent of NO signaling.
CONCLUSION
The results of the present study demonstrated that FN enhances EC glucose uptake through the upregulation of membrane GLUT1 expression and hexokinase activity. Furthermore, the FN-induced metabolic response is mediated by FAK and downstream PI3K/Akt activation, indicating a role for this pathway in modulating EC glucose metabolism.
Acknowledgments
This work was supported by a Korean Science and Engineering Foundation (KOSEF) grant funded by the Korea Government (M20702010003-08N0201-00312). This work was presented in part at the Joint Molecular Imaging Conference, September 8–11, 2007, Providence, RI.
Footnotes
COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.
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DR. MICHAEL S. RUSSO DPT, NPI 1619948973 - Physical Therapist in Hoboken, NJ
Michael Russo a provider in 10 Church Towers Hoboken, Nj 07030. Taxonomy code 225100000X with license number 40QA00991200 (NJ). Accepted Insurance: Medicaid and Medicare
DR. MICHAEL S. RUSSO DPT NPI 1619948973
Physical Therapist in Hoboken, NJ
Table of Contents
NPI Profile Information
Primary Taxonomy
Accepted Insurance
Clinician Utilization
NPI Validation
About DR. MICHAEL S. RUSSO DPT
Michael Russois a provider established inHoboken, New Jerseyand his medical specialization isPhysical Therapist. The NPI number of this provider is1619948973and was assigned on January 2006. The practitioner's primary taxonomy code is225100000Xwith license number 40QA00991200 (NJ). The provider is registered as an individual and his NPI record was last updated 3 years ago.
NPI 1619948973
Provider Name DR. MICHAEL S. RUSSO DPT
Location Address 10 CHURCH TOWERS HOBOKEN, NJ 07030
Location Phone (201) 401-9687
Mailing Address 864 BROADWAY BAYONNE, NJ 07002
Gender Male
NPI Entity Type Individual
Is Sole Proprietor? Yes
Enumeration Date 01-26-2006
Last Update Date 08-05-2020
Primary Taxonomy
The primary taxonomy code defines the provider type, classification, and specialization. There could be only one primary taxonomy code per NPI record. For individual NPIs the license data is associated to the taxonomy code.
Taxonomy Code 225100000X
Classification Physical Therapist
Type Respiratory, Developmental, Rehabilitative and Restorative Service Providers
License No. 40QA00991200
License State NJ
Taxonomy Description
Physical therapists (PTs) are licensed health care professionals who diagnose and treat individuals of all ages, from newborns to the very oldest, who have medical problems or other health-related conditions that limit their abilities to move and perform functional activities in their daily lives. PTs examine each individual and develop a plan using treatment techniques to promote the ability to move, reduce pain, restore function, and prevent disability. In addition, PTs work with individuals to prevent the loss of mobility before it occurs by developing fitness- and wellness-oriented programs for healthier and more active lifestyles. PTs:
Diagnose and manage movement dysfunction and enhance physical and functional abilities.
Restore, maintain, and promote not only optimal physical function but optimal wellness and fitness and optimal quality of life as it relates to movement and health.
Prevent the onset, symptoms, and progression of impairments, functional limitations, and disabilities that may result from diseases, disorders, conditions, or injuries.
Treat conditions of the musculoskeletal, neuromuscular, cardiovascular, pulmonary, and/or integumentary systems.
Address the negative effects attributable to unique personal and environmental factors as they relate to human performance.
PTs provide care for people in a variety of settings, including hospitals, private practices, outpatient clinics, home health agencies, schools, sports and fitness facilities, work settings, and nursing homes. State licensure is required in each state in which a PT practices.
Accepted Insurance
The NPI profile data indicates this provider might be enrolled and accepting health plans from the following insurance companies or healthcare programs:
Medicaid
Medicare
*Please verify directly with this provider to make sure your insurance plan is currently accepted.
Business Address
10 CHURCH TOWERS
HOBOKEN, NJ
ZIP 07030
Phone: (201) 401-9687
Mailing Address
864 BROADWAY
BAYONNE, NJ
ZIP 07002
Phone: (201) 339-1109
Fax: (908) 353-1505
Location Map
Clinician Utilization
The following Healthcare Common Procedure Coding System (HCPCS) codes were publicly reported as the top services rendered by this provider under the Medicare program for the year 2017. The reported codes are based on the top 5 codes for each available Medicare specialty, excluding evaluation and management codes.
1071Therapeutic activities to improve function, with one-on-one contact between patient and provider, each 15 minutes (HCPCS:97530)
668Therapeutic procedure to re-educate brain-to-nerve-to-muscle function, each 15 minutes (HCPCS:97112)
17Physical therapy evaluation (HCPCS:97001)
Additional Identifiers
Additional identifier(s) currently or formerly used as an identifier for the provider. The codes may include UPIN, NSC, OSCAR, DEA, Medicaid State or PIN identification numbers.
<table><tr><th> Identifier</th><th> Type / Code</th><th> Identifier State</th><th> Identifier Issuer</th></tr><tbody><tr><td> 1619948973</td><td> OTHER (01)</td><td> NJ</td><td> NPI #</td></tr></tbody></table>
NPI Validation Check Digit Calculation
The following table explains the step by step NPI number validation process using the ISO standard Luhn algorithm.
Start with the original NPI number, the last digit is the check digit and is not used in the calculation.
1 6 1 9 9 4 8 9 7 3
Step 1: Double the value of the alternate digits, beginning with the rightmost digit.
2 6 2 9 18 4 16 9 14
Step 2: Add all the doubled and unaffected individual digits from step 1 plus the constant number 24.
2 + 6 + 2 + 9 + 1 + 8 + 4 + 1 + 6 + 9 + 1 + 4 + 24= 77
Step 3: Subtract the total obtained in step 2 from the next higher number ending in zero, the result is the check digit.
80 - 77 = 3 3
The NPI number 1619948973 is valid because the calculatedcheck digit 3using the Luhn validation algorithm matches the last digit of the original NPI number.
Frequently Asked Questions
What is Dr. Michael Russo DPT NPI number?
The NPI number assigned to this healthcare provider is 1619948973, registered as an "individual" on January 26, 2006
Where is Dr. Michael Russo DPT located?
The provider is located at 10 Church Towers Hoboken, Nj 07030 and the phone number is (201) 401-9687
Which is Dr. Michael Russo DPT specialty?
The provider's speciality is Physical Therapist
What insurance does Dr. Michael Russo DPT accept?
The provider might be accepting Medicaid and Medicare. Please consult your insurance carrier or call the provider to make sure your health plan is currently accepted.
What are some of the services provided by Dr. Michael Russo DPT?
The most common procedures or services performed by this practitioner are: Therapeutic activities to improve function, with one-on-one contact between patient and provider, each 15 minutes, Therapeutic procedure to re-educate brain-to-nerve-to-muscle function, each 15 minutes and Physical therapy evaluation.
How do I update my NPI information?
The NPI record of Dr. Michael Russo DPT was last updated on January 26, 2006. To officially update your NPI information contact the National Plan and Provider Enumeration System (NPPES) at 1-800-465-3203 (NPI Toll-Free) or by email atcustomerservice@npienumerator.com.
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Applied Sciences | Free Full-Text | A Wi-Fi FTM-Based Indoor Positioning Method with LOS/NLOS Identification
In recent years, many new technologies have been used in indoor positioning. In 2016, IEEE 802.11-2016 created a Wi-Fi fine timing measurement (FTM) protocol, making Wi-Fi ranging more robust and accurate, and providing meter-level positioning accuracy. However, the accuracy of positioning methods based on the new ranging technology is influenced by non-line-of-sight (NLOS) errors. To enhance the accuracy, a positioning method with LOS (line-of-sight)/NLOS identification is proposed in this paper. A Gaussian model has been established to identify NLOS signals. After identifying and discarding NLOS signals, the least square (LS) algorithm is used to calculate the location. The results of the numerical experiments indicate that our algorithm can identify and discard NLOS signals with a precision of 83.01% and a recall of 74.97%. Moreover, compared with the traditional algorithms, by all ranging results, the proposed method features more accurate and stable results for indoor positioning.
A Wi-Fi FTM-Based Indoor Positioning Method with LOS/NLOS Identification
by Minghao Si 1,2 , Yunjia Wang 1,2,* , Shenglei Xu 2 , Meng Sun 2 and Hongji Cao 2
Author to whom correspondence should be addressed.
Appl. Sci. 2020 , 10 (3), 956; https://doi.org/10.3390/app10030956
Received: 30 December 2019 / Revised: 27 January 2020 / Accepted: 28 January 2020 / Published: 2 February 2020
Abstract
:
In recent years, many new technologies have been used in indoor positioning. In 2016, IEEE 802.11-2016 created a Wi-Fi fine timing measurement (FTM) protocol, making Wi-Fi ranging more robust and accurate, and providing meter-level positioning accuracy. However, the accuracy of positioning methods based on the new ranging technology is influenced by non-line-of-sight (NLOS) errors. To enhance the accuracy, a positioning method with LOS (line-of-sight)/NLOS identification is proposed in this paper. A Gaussian model has been established to identify NLOS signals. After identifying and discarding NLOS signals, the least square (LS) algorithm is used to calculate the location. The results of the numerical experiments indicate that our algorithm can identify and discard NLOS signals with a precision of 83.01% and a recall of 74.97%. Moreover, compared with the traditional algorithms, by all ranging results, the proposed method features more accurate and stable results for indoor positioning.
Keywords:
indoor positioning
;
Wi-Fi fine timing measurement
;
NLOS identification
;
Gaussian model
1. Introduction
Among these methods, methods based on Wi-Fi have attracted much attention due to their wide distribution. They can be defined as fingerprint-based methods [
16
] and distance-based methods. The former can reach an accuracy of about 2 m and needs to construct a fingerprint database at the offline stage, which costs more labor and time. The latter can calculate the distance between the transceivers according to the received signal strength indicator (RSSI), then use the least square (LS), trilateral positioning, or other algorithms to derive the location. However, the RSSI, when collected at a fixed place, could be influenced by device heterogeneity and non-line-of-sight (NLOS) errors, so it is difficult to use widely.
This phenomenon did not change until 2016. The fine timing measurement (FTM) protocol has been standardized by the Institute of Electrical and Electronics Engineers (IEEE) 802.11-2016 and can provide meter-level positioning accuracy [ 17 ] through time of flight (TOF) echo technology [ 18 ]. However, just like many other ranging measurements, such as UWB [ 19 , 20 ] and Global Positioning System (GPS) [ 21 , 22 ], one of the major challenges for positioning is the mitigation of NLOS effects. If the direct path between a fixed terminal (FT) and a mobile terminal (MT) is obstructed, the time of arrival (TOA) of the signal to the FT will be delayed, which will introduce a positive bias. The use of such TOA estimates may significantly degrade accuracy during the positioning process. Hence, it is necessary to identify NLOS signals.
NLOS identification has been extensively discussed for UWB signals [ 23 ], while it has rarely been discussed for Wi-Fi signals, as only RSSIs rather than more detailed channel state information (CSI) data can be collected from Wi-Fi devices with mobile phones. Therefore, elucidating how to identify NLOS signals using RSSI has become one of the major difficulties of this work. Joan Borras [ 24 ] formulated a theoretical framework where various theoretical tests were developed for known and unknown models of NLOS errors. Ke Han [ 25 ] calculated the distance between the coordinates of the FT and that of MT, which were obtained via pedestrian dead reckoning (PDR). Then, the obtained values were used to build two Gaussian models to identify line-of-sight (LOS) signals and NLOS signals, respectively. Considering that RSSIs will attenuate as they pass through different materials, this method may perform poorly in some environments. Jo [ 26 ] determined LOS signals according to the difference of RSSI between a 2.4 GHz signal and that of a 5 GHz signal. However, the new FTM protocol that supports Wi-Fi devices can only send single-frequency signals, so this method is not suitable. Except for identification methods based on received multipath signals, some methods have been designed using the overall mobile network as their basis. Chen [ 27 ] used various combinations of ranging results to evaluate the positioning and residual of an MT. The combination with a smaller residual has a larger chance of obtaining a higher accuracy. Some other NLOS error mitigation methods using the mobile network have been reported in [ 28 , 29 , 30 , 31 , 32 , 33 , 34 ].
This study proposes a Wi-Fi FTM-based indoor positioning method that uses LOS/NLOS identification. A Gaussian model has been built in order to identify NLOS signals. LOS signals are used to calculate the locations of an MT with an LS algorithm. Based on the newest Wi-Fi technology, this method is suitable for future Wi-Fi devices. Moreover, the identification model built by this method is more suitable for complex indoor environments.
The contributions of this work are summarized as follows:
(1)
In order to discard the NLOS error, an identification model is proposed. Differing from other Gaussian-based models, which have established two models for LOS and NLOS, the model presented here only needs to establish one model in order to adapt to the complex indoor environment.
(2)
To solve the difficulty of setting parameters, we have researched and fit the relation between RSSI and ranging results, achieving adaptive settings.
The remainder of this paper is organized as follows: Section 2 introduces the theoretical framework, including the round-trip time (RTT)-based ranging model and the propagation and attenuation of Wi-Fi signals. Section 3 introduces the proposed method, including the construction of the Gaussian model for identification and the iterative least squares algorithm. Section 4 describes the experimental results by the proposed method. Section 5 presents a conclusion and points out areas for future work.
2. Theoretical Framework
2.1. RTT-Based Ranging Model
Here, TOF echo technology is used in the Wi-Fi FTM protocol and makes the RTT based ranging more convenient [
18
]. This new technology determines the distance according to the RTT of a Wi-Fi FTM pulse from an MT to an FT. Accordingly, it can eliminate the time synchronization errors in the time of arrival (TOA)/time difference of arrival (TDOA)-based ranging, with no need to synchronize the times of the FT and MT. The whole procedure of ranging is shown in
Figure 1
. It shows that a mobile phone is used as an MT to send an FTM request to FTs supporting the FTM protocol. After an FT receives the request, an Acknowledgement (ACK) signal is sent from the FT to the MT. After that, several FTM feedback signals are sent from the FT to the MT, where the mean RTT can then be calculated. The time information can be expressed as follows:
where
are the times for when the request was sent from the MT and when the ACK signal arrives at MT;
is the location of the MT when the FTM request is sent;
is the location of the FT when the MT receives the FTM request;
is standard time deviation between the MT and the FT;
is the time delay error caused by the NLOS effect; and c is the speed of light. Hence, the distance can be calculated by Equation (2):
T
−
p
F
T
‖
2
=
d
R
T
T
−
d
D
−
d
N
L
O
S
(2)
where
d
R
T
T
is the ranging result;
d
D
is the ranging error caused by standard time deviation, as shown in Equation (3); and
d
N
L
O
S
is the ranging error caused by the NLOS effect. The ranging error
d
D
not only includes a fixed time delay error, a device error, and a start error, but also is influenced by the distance of pulse propagation and other environmental factors [
35
], which can be expressed as follows:
d
D
=
e
n
+
φ
(
s
)
+
ε
(3)
where
e
n
is the constant error caused by the fixed time delay error, the device error, and the start error;
φ
(
s
)
is the error formed by different ranging results, which can be seen as a polynomial function related to the ranging results; and
ε
is the system noise. It can be seen that the standard time deviation error of the equipment needs to be determined and calibrated to provide more precise ranging results.
2.2. Propagation of Wi-Fi Signals
With wave-particle duality, electromagnetic waves are the method of Wi-Fi propagation, which exhibit both particle properties and wave properties during propagation [
36
,
37
]. In a wide space, electromagnetic waves are only transmitted directly without obstacles. While in an indoor environment, the propagation characteristics will change due to the existence of various objects, causing reflection and diffraction, etc. In addition, electromagnetic waves have a certain penetration ability and can spread across walls. As a result, the actual propagation process of electromagnetic waves is varied and complex.
The propagation of electromagnetic waves follows the ‘skin effect’ [
38
]. That is, when there is an alternating current or alternating electromagnetic field in a conductor, the current distributes unevenly and concentrates in the ‘skin’ part of the conductor, that is, the current is concentrated on the thin layer of the outer surface of the conductor. As a result, the resistance of the conductor is increased, and its power loss is also increased. When an electromagnetic wave carrying a signal passes through some media, it is restricted by the skin effect, such that a part of the electromagnetic wave stays on the surface of the media and cannot completely pass through the media. The better the conductivity of the medium, the more obvious the effect of blocking in the electromagnetic wave is, and the more obvious the attenuation of the signal intensity is.
Table 1
presents the signal attenuation of electromagnetic waves with a frequency of 2.4 GHz when crossing various common obstacles in indoor buildings. It can be obtained through observation that the better the conductivity of an obstacle is, the more obvious signal attenuation will be.
Electromagnetic waves will wear out when propagating in air. The loss in free space is mainly caused by the air’s own propagation and the scattering and refraction of fine dust particles. In the case of no obstacles in the air, the propagation of electromagnetic waves can be expressed as per Equation (4) [
39
], where d is the distance from the MT to the FT;
d
0
is the reference distance;
L
(
d
)
is the received power of the MT when the distance from the FT is d;
L
(
d
0
)
is the received power when the distance from the FT to the MT is 1 m;
η
is the attenuation coefficient; and k is the shadowing factor, obeying a Gaussian distribution with a mean of 0. Since the model is in the case of LOS, k is 0.
L
(
d
)
=
L
(
d
0
)
+
10
⋅
η
⋅
l
g
d
)
3. The Proposed Indoor Localization Method
3.1. Overall Structure of the Proposed Method
Figure 2 shows the procedures of the proposed positioning method. The ranging results and RSSIs are collected from the FTs and then input into the LOS/NLOS identification model. Then, the model identifies NLOS signals and only outputs the LOS ranging results. If the number of LOS ranging results is greater than the minimum number required for positioning, the LOS ranging results are used as the input of the single point positioning to calculate the location of the MT. If the number of LOS ranging results is less than the minimum number, all the ranging results, including LOS and NLOS, will be used as the input of the single point positioning to derive the location.
3.2. The Identification Model of LOS/NLOS
Figure 3
shows the ranging results (the red solid line and the dotted line) and RSSIs (the blue solid line and the dotted line) collected at different distances from FTs under both NLOS and LOS conditions. Here, we have placed Wi-Fi devices in an open corridor and in a closed room, then collected RSSIs and ranging results at 1 m intervals in the corridor. The sampling time was 30 s, the sampling frequency was 5 Hz, and the sampling device was a Pixel 3 mobile phone. The solid line denotes the results from a corridor and the dotted line denotes the results from a closed room. It can be seen that the LOS and NLOS ranging results are similar at any distance, but the RSSIs are quite different. This is due to the principle of electromagnetic wave propagation. RSSIs mainly reflect the amplitude of the electromagnetic wave. When electromagnetic waves travel through walls, some particles will not pass through walls, and the amplitude will significantly reduce, such that the RSSI will also be reduced [
38
]. The ranging results mainly reflect the time of propagation. When the electromagnetic waves pass through the wall, their speed will decrease. However, due to the small thickness of the wall and the high electromagnetic velocity, the impact on the time of propagation and ranging result is small. Under such conditions, the ranging results are not obvious when compared with those of an RSSI. The LOS/NLOS identification model was designed based on this phenomenon.
According to Section 2.2 , the attenuation of the RSSIs was greatly affected by the conductivity of obstacles. In the complex indoor environment, it is difficult to model the relationship between the distance and RSSI. Therefore, differing from the literature [ 24 , 25 , 40 ], where two models have been built under LOS and NLOS conditions, respectively, this paper’s identification model was built in the line-of-sight condition, which could output probability with a large difference according to the condition of the signal.
Most existing works [
41
,
42
,
43
] use a Gaussian distribution to model the randomness of RSSI, and consequently, in this paper, a Gaussian model was established to calculate the probability of LOS by Equation (5), as shown in
Figure 4
. The parameters of the model were determined by ranging results, and the inputs of the model were the RSSIs of the FTs. According to the maximum likelihood method, μ is the mean of the RSSI and σ is the variance of the RSSI in Equations (6) and (7), where
R
S
S
I
d
i
is the RSSI collected at the distance d; N is the number of RSSI collected. The determination of
μ
and
σ
is described below in detail. After the parameters were determined, the probability could be determined by inputting the RSSI into the Gaussian model. Then, the probability was compared with the threshold
θ
. If the probability is greater than the threshold, the current signal is a LOS signal, and if it is less than, it is not.
P
L
O
S
(
R
S
)
=
A
2
π
σ
∗
e
x
p
(
−
(
R
S
S
I
−
μ
)
2
2
)
(5)
μ
=
1
N
∑
i
=
1
N
R
S
S
I
d
(
i
)
(6)
σ
2
=
1
N
∑
i
=
1
N
(
R
S
S
I
d
(
i
)
−
R
S
S
I
d
¯
)
2
(7)
3.2.1. The Determination of d
In the paper, it was assumed that the ranging results could reflect the true distance to a certain extent. Therefore, we needed to evaluate the accuracy of the ranging results based on Wi-Fi RTT. As shown in
Figure 5
, a tester collected the ranging results of the FTs at each grid point. Here, the grid side length was 1 m, the sampling time was 30 s, and the sampling frequency was 5 Hz. The MT and FTs were basically at the same height during sampling. The ranging accuracy is shown in
Figure 6
. The red and blue solid lines are the ranging errors of the LOS signals and NLOS signals, respectively. Through calculation, the average ranging error of LOS signals was 0.87 m and the variance was 0.36 m. The average ranging error of the NLOS signals was 1.16 m and the variance was 0.54m. It can be seen that RTT-based ranging results can accurately reflect the true distance between the transceivers. At the same time, the ranging accuracy and stability of the LOS signals were better than those of the NLOS signals.
3.2.2. The Determination of μ
μ
is the mean of RSSIs collected when the distance between an MT and FT is determined. According to the propagation model of electromagnetic waves, in Equation (5), the true distance is exponential with RSSI, so the exponential model was used to fit the ranging results and RSSIs.
A Wi-Fi device was arranged at a fixed point as the FT. The experimenter walked in a straight line with the mobile phone within 23 m from the FT. One thousand, eight hundred groups of ranging results and RSSIs were collected and used as training data. The collected ranging results and RSSIs were used as training data. The fitting of the single exponential model is shown in
Figure 7
a. It can be seen that fitting over 15 m performs poorly. Here, the mean square error (MSE) was used to evaluate the fitting, calculated as per Equation (8), where N is the number of RSSI used for the fitting;
R
S
S
I
(
i
)
is the i-th RSSI for the fitting; and
R
S
S
I
f
i
t
(
i
)
is the i-th fitting result. By calculating the MSE of the fitting from 0 m to a different distance, as shown in
Figure 7
b, it was found that within 0–15 m, as the distance increases, the training data increase, and the MSE decreases. Between 15 and 20 m, the MSE becomes larger, and the fitting effect is not good. Over 20 m, the MSE tends to be stable. It can be concluded that the RSSIs collected at the distance over 15 m have a different tendency from those collected within 15 m. Therefore, the ranging result RSSI model was changed into a double exponential model to calculate μ, as shown in Equation (9). The data in the range of 0–15 m and 15–25 m were fitted, respectively. The result of fitting using the double exponential model is shown in
Figure 7
c. The MSE of the fitting, using the double exponential from 0 m to different distances, is shown in
Figure 7
d. It can be seen that the MSE at different distances is lower than that of the single exponential, except at a distance of 4 m. The average MSE of the single exponential model was 4.85 dBm
2
, and that of the improved double exponential model was 4.15 dBm
2
. Therefore, the double exponential model is more in line with the ranging result–RSSI relationship.
M
S
E
=
1
N
∑
i
=
1
N
(
R
S
S
I
(
i
)
−
R
S
S
I
f
i
t
(
i
)
)
(8)
μ
=
{
a
1
+
b
1
∗
l
g
(
d
)
d
<
15
m
a
2
+
b
2
∗
l
g
(
d
)
d
≥
15
m
(9)
3.2.3. The Determination of σ
σ
is the variance of RSSIs collected at a fixed point. In the literature [
24
,
25
], the variances of RSSIs collected at different distances have traditionally been set as a fixed value. According to the analysis in the second section, we assumed that the variances of RSSIs at different distances were different. For this reason, the variances were calculated, as shown in
Table 2
. It can be seen that the variance decreased by about 1 dBm
2
from 0 to 6 m, while it nearly did not change from 6 to 18 m. According to the trend of change, the exponential function was used to fit the variances and ranging results. To verify if the function was suitable, the sum of squares due to error (SSE) and coefficient of determination (R-square) of the fitting result was compared with that found by other functions, including the Fourier, Gaussian, linear fitting, polynomial, rational, and sum of sine functions, shown in the
Table 3
. SSE and R-square can be calculated by Equation (10) and Equation (11), where
R
S
S
I
¯
is the average of RSSI. The smaller the SSE or the bigger the R-square, the better the fitting results will be. It can be seen that from both the SSE and R-square that the exponential function is more suitable.
S
S
E
=
∑
i
=
1
−
s
q
u
a
r
e
=
∑
i
=
1
N
(
R
S
S
I
¯
−
R
I
f
i
t
(
i
)
)
∑
i
=
1
N
(
R
S
S
I
¯
−
R
I
(
i
)
)
(11)
For the fitting, a large amount of RSSIs with the same ranging results should be obtained. However, due to different ranging results, a credible variance was hard to achieve. The ranging results were divided into several 0.5 m-long ranges. Next, all the training data were put into the corresponding range according to the ranging results. Then, the average of the ranging results and the variances of RSSIs in each range were calculated and used as the input of the fitting. The variances were calculated by the following two methods:
(a)
The variances of RSSIs were directly calculated, according to Equation (7).
(b)
All the RSSIs were counted in a certain interval and the probabilities of each RSSI were calculated. Then, the Gaussian regression was performed on the probability and the corresponding RSSI. σ of the Gaussian model was taken as the σ of the current distance.
After the
σ
values were determined, the ranging results and
σ
values were fitted to generate a ranging result-based σ model.
Figure 8
shows the fitting results of methods A and B. The red dot is the variance calculated by method A, while the blue point is the variance calculated by the other method. The fitting results and raw data are shown in
Figure 8
a, and the residuals of the two methods are shown in
Figure 8
b. It can be seen that variances calculated by method B fluctuate largely, which might be caused by over-fitting. In the range of 0–4 m, the variance of method B is higher than 15.
Table 1
shows that the attenuation of RSSI caused by the reinforced concrete is about 15 dBm, so that when the variance is higher than 15, the output probability of LOS and NLOS is similar, which may make the set of threshold and identification difficult. Furthermore, as shown in
Figure 8
b, the fitting result of method A is better than method B, as the sum of square due to error (SSE) of method A is much smaller than that of method B. Hence, method A was used to calculate the variance used for the later fitting.
3.3. Single Point Positioning
If the number of the ranging results was more than 2 after filtering, the LS algorithm was used for the single point positioning. The observation equation for the ranging results can be expressed as follows:
d
R
T
T
i
=
ρ
i
+
d
D
i
+
d
N
L
O
S
i
(12)
In the equation,
d
R
T
T
i
is the ranging result collected from the i-th FT,
ρ
i
is the Euclidean distance between the i-th FT and the MT,
d
N
L
O
S
i
is the ranging error caused by the NLOS error from the i-th FT; and d is the ranging error caused by the standard time deviation. According to Equation (12), we can derive the error observation as follows:
V
i
=
ρ
i
+
d
D
i
+
d
N
L
O
S
i
−
d
R
T
T
i
(13)
Assuming that the approximate coordinate of MT is X = (X
0
, Y
0
) and that the Euclidean distance from the coordinate of the i-th FT to the approximate coordinate of MT is ρ0, the Taylor series of the above formula is:
V
i
=
ρ
0
i
+
X
0
−
X
F
T
i
ρ
0
i
d
X
+
Y
0
−
Y
F
T
i
ρ
0
i
d
Y
+
d
D
i
+
d
N
L
O
S
i
R
T
T
i
(14)
If we set the following:
L
i
=
d
R
T
T
i
−
ρ
0
−
d
D
i
N
L
O
S
i
(15)
Then the equation could be changed as follows:
V
i
=
X
0
−
X
F
T
i
ρ
0
i
d
Y
0
−
Y
F
T
i
ρ
0
i
d
Y
−
L
i
X
F
T
i
and
F
T
i
are the two coordinate values of the i-th FT. Thus, Equation (14) can be expressed in a matrix form as follows:
V
m
×
1
=
A
m
×
2
×
Δ
2
×
1
×
L
m
×
1
(17)
where m is the number of ranging results after filtering; V is the vector of the correction of ranging results; L is observation error constant matrix;
Δ
is an unknown parameter in Equation (15); and A is the cosine coefficient matrix in Equation (19).
Δ
=
[
d
X
,
d
Y
]
(18)
A
i
=
[
X
0
−
X
F
T
i
ρ
0
,
Y
0
−
Y
F
T
i
ρ
0
]
(19)
The error observation equation can be established using the ranging results from different FTs, and then the parameters of the coordinate can be obtained by solving the equation with the least square method, as shown in Equation (20).
Δ
=
(
A
T
A
)
−
1
×
A
T
×
L
(20)
The pseudocode of single point positioning is shown in
Figure 9
. The observation equation was constructed using the inputs to calculate
Δ
. Through iteration,
Δ
gradually approached 0, where the approximate coordinate of MT was gradually steady. When
Δ
was smaller than a threshold or the iteration number was more than a threshold, the iteration could meet the condition of stopping.
4. Experiment
4.1. Evaluation of the Identification Model
The performance of the identification model was evaluated. A Wi-Fi device was set in the corridor, and the experimenter walked at a constant speed in the corridor and room separately with a mobile phone to collect the RSSIs and ranging results. The data collected in the corridor were seen as LOS data, while those collected in the room were seen as NLOS data. A group of data consisted of an RSSI and a ranging result. A total of 8360 groups of data were collected, among which 1800 groups were used for training and 6560 groups were used for testing. The training data acquisition time was only one day away from that of the testing data, and the training data did not participate in the test.
The identification of NLOS/LOS was a binary problem, so precision and recall were utilized to evaluate the model. They were calculated by Equations (21) and (22), respectively, where the TP (true positive) is the number of LOS signals that were accurately identified, FP (false positive) refers to the number of NLOS signals identified as LOS signals, and FN (false negative) points to the number of LOS signals identified as NLOS signals. All the data were divided into different ranges according to the ranging results in order to evaluate the precision and recall at different distances. Here, 3280 groups of LOS data and 3280 groups of NLOS data were used to test the precision, while 3280 groups of LOS data were used to test the recall. The model output the LOS/NLOS recognition results, then TP, FP, and FN were counted to calculate the precision and recall of each interval. In this experiment, the threshold θ of the model was set as 0.7.
P
Figure 10 shows the precision at different ranges. Through calculation, the average precision was 97.08% and the MSE was 0.07. Figure 11 shows the cumulative distribution of precision. All precisions were higher than 70%, 9.09% of which were lower than 85%, and 15.15% of which were lower than 95%. It can be seen that the precision of the model is poor at some ranges, which might be caused by the poor fitting of the ranging result and RSSI.
The recalls and mean probabilities at different ranges are shown in Figure 12 , where the value of the blue column is roughly the same as that of the red line. It can be seen that the set of θ could distinguish LOS signals and NLOS signals. However, through calculation, the average recall was only 74.97% and the MSE was 0.2. Figure 13 shows the cumulative distribution of recalls. Here, 24.24% of the recalls were lower than 60%, and 51.52% of them were lower than 80%, indicating that the model often misjudges some LOS signals.
4.2. Evaluation of Proposed Positioning Method
The experimental environment is shown in
Figure 14
, which includes two rooms and a corridor adjacent to each other. Both of the rooms were 19.05 m long and 5.83 m wide, while the corridor was 19.51 m long and 1.74 m wide. Totally, 10 FTs were positioned on a tripod with a height of 1.3 m. Among them, 8 were placed in two rooms on average, where 3 were positioned in the corridor, marked with a red five-pointed star. Here, 197 testing points were set, and marked with blue squares, with an interval of 1.2 m. The sampling time of each point was 30 s and the sampling frequency was 1 Hz. Two experiments were conducted to evaluate the proposed positioning method.
In the first experiment, the performance of the method was evaluated when a different number of FTs were set in the NLOS condition. A different number of FTs, from 0 to 7, were set outside the eastern room in turn. The ranging results and RSSIs from all FTs were collected at 67 test points in the eastern room. Then, the data were imported into MATLAB. The location was calculated using single point positioning with identification and discarding (SPP-IAD) NLOS, and that of single point positioning (SPP).
Figure 15 shows the accuracy of the two methods. In the absence of NLOS FTs, the error of SPP-IAD is greater than that of SPP. This is because the identification model discards some ranging results from LOS FTs. However, when adding NLOS FTs, the error of SPP-IAD is smaller than SPP. As the number of NLOS FTs increases, the accuracy of SPP-IAD is basically unchanged, and the error of SPP increases. Hence, the accuracy of SPP-IAD is better than SPP when NLOS FTs are present.
In the second experiment, the ranging results and RSSIs at all the test points were collected and the proposed method was used to carry out the positioning. Here, the maximum error (ME), error mean (EM), and root mean square error (RMSE) were used as indicators of the method.
Figure 16 shows the EM of the SPP-IAD and SPP at each test point. Among them, 18 EMs of SPP-IAD are larger than that of the SPP, and the maximum difference is 0.3 m.
As shown in Table 4 , the SPP-IAD was implemented with a ME of 6.862 m, an EM of 0.932 m, and an RMSE of 0.712 m, while the other has greater error than the proposed method. Compared with SPP, it achieves a ME improvement of 1.041 m (13.17%), an EM improvement of 0.337 m (36.04%), and an RMSE improvement of 0.456 m (64.04%).
The Cumulative Distribution Functions (CDFs) of the positioning errors of SPP-IAD and SPP are shown in Figure 17 . Obviously, the positioning errors of SPP-IAD are smaller than those of SPP with different y-values.
From the two experiments, it can be concluded that the performance of SPP-IAD is better than that of SPP, both in the positioning accuracy and stability, under the condition NLOS FTs.
5. Discussion
In order to reduce the positioning errors caused by NLOS, this paper has proposed a LOS/NLOS identification model which is suitable for complex indoor environments, and the parameters of the model have been adaptively determined. After identifying and discarding NLOS ranging results, the LS-based single point positioning algorithm was used. It has been deduced that the average precision of the model was 97.08% and the average recall was 74.97%. The average error of the positioning results was 0.935 m. The accuracy found here is better than that found without identification and discarded in the case of a different number of NLOS FTs. In conclusion, the proposed method can eliminate some NLOS ranging results and effectively improve the positioning accuracy. However, the recall of the model is not high, which may cause some LOS ranging results to be eliminated during positioning and affect the positioning accuracy. In order to solve this problem, map matching [
44
,
45
] can be added to the proposed method to reduce misjudgment.
Author Contributions
Conceptualization, M.S.; Formal analysis, M.S. and S.X.; Funding acquisition, Y.W.; Methodology, M.S.; Project administration, Y.W.; Data curation, H.C. and M.S.; Writing—original draft preparation, M.S. All authors have read and agreed to the published version of the manuscript.
Funding
This research was funded by the National Key Research and Development Program of China under grant number 2016YFB0502102.
Acknowledgments
In this section you can acknowledge any support given which is not covered by the author contribution or funding sections. This may include administrative and technical support, or donations in kind (e.g., materials used for experiments).
Conflicts of Interest
The authors declare no conflict of interest.
References
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Figure 1. Procedure of Wi-Fi fine timing measurement (FTM).
Figure 1. Procedure of Wi-Fi fine timing measurement (FTM).
Figure 2. Flow chart of the proposed positioning method. RSSIs, received signal strength indicators; NLOS, non-line-of-sight; LOS, line-of-sight; MT, mobile terminal.
Figure 2. Flow chart of the proposed positioning method. RSSIs, received signal strength indicators; NLOS, non-line-of-sight; LOS, line-of-sight; MT, mobile terminal.
Figure 3. Ranging results and the received signal strength indicators (RSSIs) of line-of-sight (LOS/NLOS) signals.
Figure 3. Ranging results and the received signal strength indicators (RSSIs) of line-of-sight (LOS/NLOS) signals.
Figure 4. Flow chart of the LOS/NLOS identification process.
Figure 4. Flow chart of the LOS/NLOS identification process.
Figure 5. Experiment for estimating the accuracy of the ranging results.
Figure 5. Experiment for estimating the accuracy of the ranging results.
Figure 6. Ranging errors of the LOS/NLOS signals.
Figure 6. Ranging errors of the LOS/NLOS signals.
Figure 7. Experimental results of the fitting. ( a ) Comparison of the fitting data using the single exponential model and the raw RSSI data. ( b ) Mean square error (MSE) of the fitting, from 0 m to different distances, using the single exponential model. ( c ) Comparison of the fitting of data using the double exponential model and the raw RSSI data. ( d ) MSE of the fitting, from 0 m to different distances, using the single exponential model.
Figure 7. Experimental results of the fitting. ( a ) Comparison of the fitting data using the single exponential model and the raw RSSI data. ( b ) Mean square error (MSE) of the fitting, from 0 m to different distances, using the single exponential model. ( c ) Comparison of the fitting of data using the double exponential model and the raw RSSI data. ( d ) MSE of the fitting, from 0 m to different distances, using the single exponential model.
Figure 8. Fitting results of the two methods. ( a ) Fitting result and the raw data of methods A and B. ( b ) Residuals of the fitting plans of methods A and B.
Figure 8. Fitting results of the two methods. ( a ) Fitting result and the raw data of methods A and B. ( b ) Residuals of the fitting plans of methods A and B.
Figure 9. Single point positioning algorithm.
Figure 9. Single point positioning algorithm.
Figure 10. Precision at different ranging results.
Figure 10. Precision at different ranging results.
Figure 11. Cumulative distribution function of the precisions.
Figure 11. Cumulative distribution function of the precisions.
Figure 12. Recall of different ranging results.
Figure 12. Recall of different ranging results.
Figure 13. Cumulative distribution function of precisions.
Figure 13. Cumulative distribution function of precisions.
Figure 14. Experimental area.
Figure 14. Experimental area.
Figure 15. Average positioning error with different numbers of NLOS signals.
Figure 15. Average positioning error with different numbers of NLOS signals.
Figure 16. Average positioning error of each testing point.
Figure 16. Average positioning error of each testing point.
Figure 17. Cumulative probability distribution of positioning errors related to single point positioning with identification and discarding (SPP-IAD) and single point positioning (SPP).
Figure 17. Cumulative probability distribution of positioning errors related to single point positioning with identification and discarding (SPP-IAD) and single point positioning (SPP).
Table 1. Signal attenuation through different media.
Table 1. Signal attenuation through different media.
Obstacle Reinforced Concrete Wall Plasterboard Wall Wooden Door Metal Door Glass Window Signal Attenuation Value (dBm) 15–16 3–5 3–5 10–12 6–8
Table 2. Variance of RSSIs at different distances.
Table 2. Variance of RSSIs at different distances.
Distance Range (m) 0–3 3–6 6–9 9–12 12–15 15–18 σ (dBm) 3.48 2.34 1.66 1.69 1.74 1.74
Table 3. Sum of squares due to error (SSE) and coefficient of determination (R-square) values of the different fitting functions.
Table 3. Sum of squares due to error (SSE) and coefficient of determination (R-square) values of the different fitting functions.
Fitting Function SSE (dBm 2 ) R-Square Value Our Model 72.77 0.48 Fourier 85.70 0.40 Linear Fitting 99.85 0.30 Polynomial 115.13 0.19 Rational 92.79 0.35 Sum of Sine 115.14 0.19
Table 4. Statistical results of positioning errors. ME, maximum error; EM, error mean; RMSE, root mean square error.
Table 4. Statistical results of positioning errors. ME, maximum error; EM, error mean; RMSE, root mean square error.
Method ME (m) EM (m) RMSE (m) SPP-IAD 6.862 0.932 0.712 SPP 7.903 1.272 1.268
MDPI and ACS Style
Si M, Wang Y, Xu S, Sun M, Cao H. A Wi-Fi FTM-Based Indoor Positioning Method with LOS/NLOS Identification. Applied Sciences. 2020; 10(3):956.
https://doi.org/10.3390/app10030956
Si, Minghao, Yunjia Wang, Shenglei Xu, Meng Sun, and Hongji Cao. 2020. "A Wi-Fi FTM-Based Indoor Positioning Method with LOS/NLOS Identification" Applied Sciences10, no. 3: 956.
https://doi.org/10.3390/app10030956
| https://www.mdpi.com/2076-3417/10/3/956/html |
Luminalettes: Uses, Price, Dosage, Side Effects, Substitute, Buy Online
Find out about Luminalettes benefits, side effects, price, dose, how to use Luminalettes, interactions and contraindications
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Luminalettes
10 Tablet in 1 Strip
₹ 2
Luminalettes Tablet 10 TABLET 1 Strip ₹ 2
Manufactured by: Bayer Pharmaceuticals Pvt Ltd
Contains / Salt: Phenobarbital (15 mg)
Luminalettes Information
Luminalettes is a prescription drug, available for use as Tablet. Primarily, it is used for the treatment of Epilepsy. Secondary and off-label uses of Luminalettes have also been mentioned below.
Medical history of the patient along with age and gender determines the dosage of Luminalettes. Dosage also depends on the route of administration and your chief complaint for which the drug is prescribed. Refer to the dosage section for a detailed discussion.
The side effects typically associated with Luminalettes include Vertigo. Apart from the aforementioned side effects, Luminalettes can also lead to other problems, which have been listed below. These side effects of Luminalettes are usually temporary and subside with the completion of treatment. If, however, they worsen or do not go away, please speak with your physician.
In addition, Luminalettes's effect is Moderate during pregnancy and Severe for lactating mothers. In addition, Luminalettes's effects on the liver, heart and kidney are discussed below in the Luminalettes related warnings section.
Individuals suffering from medical conditions like Bradycardia (Slow Heart Rate), Respiratory Depression, Liver Disease must refrain from the use of Luminalettes since this can cause severe adverse effects. Other conditions have been mentioned below in the Luminalettes contraindications section.
Besides this, Luminalettes may also have severe interaction with some medicines. A complete list of these interactions is given below.
In addition to these precautions, you may also note that Luminalettes is not safe while driving, and is is not addictive in nature.
Luminalettes Benefits & Uses
Luminalettes Dosage & How to Take
Luminalettes Side Effects
Luminalettes Related Warnings
Severe Interaction of Luminalettes with Other Drugs
Luminalettes Contraindications
Frequently asked Questions about Luminalettes
Luminalettes Interactions with Food and Alcohol
Luminalettes Benefits & Uses
Luminalettes is used to treat the following -
Main Benefits
Epilepsy
Other Benefits
Epilepsy
Insomnia
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Luminalettes Dosage & How to Take
This is the usual dosage recommended in most common treatment cases. Please remember that every patient and their case is different, so the dosage can be different based on the disease, route of administration, patient's age and medical history.
<table><tbody><tr><td> Age Group</td><td> Dosage</td></tr><tr><td>Adult</td><td> Disease:Epilepsy Before or After Meal:Either Single Maximum Dose:1
mg/kg Dosage Form:Tablet Dosage Route:Oral Frequency:2
daily Course Duration:As directed by the doctor Special Instructions:As prescribed by the doctor</td></tr><tr><td>Geriatric</td><td> Disease:Epilepsy Before or After Meal:Either Single Maximum Dose:1
mg/kg Dosage Form:Tablet Dosage Route:Oral Frequency:2
daily Course Duration:As directed by the doctor Special Instructions:As prescribed by the doctor</td></tr><tr><td>13 - 18 years (Adolescent)</td><td> Disease:Epilepsy Before or After Meal:Either Single Maximum Dose:1
mg/kg Dosage Form:Tablet Dosage Route:Oral Frequency:2
daily Course Duration:As directed by the doctor Special Instructions:As prescribed by the doctor</td></tr><tr><td>2 - 12 years (Child)</td><td> Disease:Epilepsy Before or After Meal:Either Single Maximum Dose:3
mg/kg Dosage Form:Tablet Dosage Route:Oral Frequency:2
daily Course Duration:As directed by the doctor Special Instructions:As prescribed by the doctor</td></tr><tr><td>Infant (1 month to 2 years)</td><td> Disease:Epilepsy Before or After Meal:Either Single Maximum Dose:4
mg/kg Dosage Form:Tablet Dosage Route:Oral Frequency:2
daily Course Duration:As directed by the doctor Special Instructions:As prescribed by the doctor</td></tr><tr><td>Neonates (0 to 1 month)</td><td> Disease:Epilepsy Before or After Meal:Either Single Maximum Dose:4
mg/kg Dosage Form:Tablet Dosage Route:Oral Frequency:1
daily Course Duration:As directed by the doctor Special Instructions:As prescribed by the doctor</td></tr></tbody></table>
Luminalettes Side Effects
Based on research, the following side effects have been observed when Luminalettes is used -
Severe
Drowsiness
Moderate
Skin Rash
Depression
Constipation(Read More -Home remedies for constipation)
Bronchospasm
Angioedema
Mild
Diarrhoea
Photosensitivity
Common
Vertigo
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Luminalettes Related Warnings
Is the use of Luminalettes safe for pregnant women?
Luminalettes may cause moderate side effects during pregnancy. If you feel its harmful effects, then stop taking this drug immediately, and do not take Luminalettes again without your doctor's advice.
Moderate
Is the use of Luminalettes safe during breastfeeding?
Women who are breastfeeding may experience severe harmful effects after taking Luminalettes. It should only be taken after medical advice.
Severe
What is the effect of Luminalettes on the Kidneys?
Luminalettes rarely harms the kidneys.
Mild
What is the effect of Luminalettes on the Liver?
Side effects of Luminalettes rarely affect the liver.
Mild
What is the effect of Luminalettes on the Heart?
Very few cases of side effects of Luminalettes on the heart have been reported.
Mild
Severe Interaction of Luminalettes with Other Drugs
Luminalettes should not be taken with following medicines due to severe side effects it may cause to patients -
Severe
Moderate
Mild
Luminalettes Contraindications
If you are suffering from any of the following diseases, you should not take Luminalettes unless your doctor advises you to do so -
Allergy
Depression
Bradycardia (Slow Heart Rate)
Respiratory Depression
Liver Disease
Porphyria
Heart Disease
Frequently asked Questions about Luminalettes
Is this Luminalettes habit forming or addictive?
Yes, you can get addicted to Luminalettes. It is essential that you take [medicine] only after doctor's recommendation.
Yes
Is it safe to drive or operate heavy machinery when consuming?
No, you should do not do anything that requires concentration and attention as the Luminalettes can make you feel drowsy.
Dangerous
Is it safe?
Luminalettes should be used only after doctor's advice.
Safe, but take only on Doctor's advise
Is it able to treat mental disorders?
Yes, in many cases, taking Luminalettes can help with mental disorders.
Yes
Luminalettes Interactions with Food and Alcohol
Interaction between Food and Luminalettes
Taking Luminalettes with food does not cause any problems.
Safe
Interaction between Alcohol and Luminalettes
Taking alcohol with Luminalettes can be dangerous.
Severe
Frequently asked Questions about Luminalettes
How does Luminalettes work?
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Dr. Kishan Barnwal MBBS , General Physician
Luminalettes contains phenobarbitone which is a sedative & hypnotic agent. It is presumed that Luminalettes works by suppressing the abnormal activity of nerve cells in the brain through an increase in the activity of a chemical messenger known as GABA (gamma-aminobutyric acid). It also induces drowsiness or sedation by depressing some parts of the brain such as sensory and motor cortex.
Is Luminalettes safe to use?
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Dr. Piyush Malav MBBS, MS , General Surgery
Yes, Luminalettes is safe to use, if taken in a prescribed amount for a specified time as advised by the doctor. However, some side effects have been observed at regular doses these are drowsiness, nausea, and vomiting. Do not hesitate to inform your doctor if you are facing any of the above.
Can I take Luminalettes and xanax together?
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No, Luminalettes should not be taken along with Xanax (alprazolam). Taking these drugs together is more likely to increase the side effects of both of these medicines such as increased sedation (drowsiness). Hence, you are advised to avoid taking them together.
Is Luminalettes a benzo?
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Dr. Roshni Poonja MBBS , General Physician, Internal Medicine
No, Luminalettes is not a benzo (benzodiazepine). It belongs to the class of drug known as barbiturates and it is mainly used for the prevention of seizures and insomnia.
Can I take clonazepam and Luminalettes together?
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Dr. Braj Bhushan Ojha BAMS , Gastroenterology, Dermatology, Psychiatry, Ayurveda, Sexology, Diabetology
No, Luminalettes should not be taken with clonazepam. Taking these drugs together is more likely to increases the sedative (drowsiness) effect. Hence, you are advised to avoid taking them together.
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Vikas Chauhan
B.Pharma, Pharmacy5 Years of Experience
References
April Hazard Vallerand, Cynthia A. Sanoski. [link]. Sixteenth Edition. Philadelphia, China: F. A. Davis Company; 2019: Page No 85-87
In stock alternatives of Luminalettes (based on Phenobarbital (15 mg))
| https://www.myupchar.com/en/medicine/luminalettes-p37103480?ref=linkstock |
U.S. Call Center Agents Grow as Expats
https://www.destinationcrm.com/Articles/ReadArticle.aspx?ArticleID=44016
U.S. Call Center Agents Grow as Expats
Call center services provider LiveBridge is using its new global facilities not only to provide competitive services to its clients, but also as an engine for unique opportunities within the company. The firm recently launched its 700-seat call center in Cordoba, Argentina, with the oversight and guidance of several stateside employees, many of whom found roles that would not have been open to them as quickly in their home centers.
"One of our key missions is our offshore development strategy," says Chris deLambo, director of marketing for LiveBridge. Although the company has operations already in several states, as well as in Canada and India, LiveBridge needed a Spanish-speaking facility to meet client demand, and selected Argentina for the new site. "There is a readily available, educated workforce there with all of the regular cost-efficiencies you have in an offshore environment," DeLambo says.
But that workforce wasn't ready to be handed the keys to a brand new customer care facility. To bring services online and enforce its quality standards, LiveBridge seeded the new center with several employees up and down the chain of command through internal job postings. In all, LiveBridge moved 10 employees to Cordoba to ramp up the call center, often with a promotion attached to the move that substantially improved their wages. "These are people who were hired in as call center reps--entry level positions--at the end of 2003, but came onboard and showed promise...so when we decided to open Argentina, we tapped [them]," DeLambo says.
One of the transferred employees, Naida Meagher, had just four days to prepare for the move. "It's amazing what you can do when you have to do it," she says. "Honestly, the economy was so bad in Oregon, and I wanted to get back to project management and project implementation, and this seemed like it was a good fit."
Like other employees LiveBridge entrusts with site-launching leadership roles, Meagher went through a month of fast-paced courses at the company's Virginia facilities. Meagher, who served as a phone rep with LiveBridge and a previous employer, was quickly brought up to speed as a professional trainer.
LiveBridge's U.S. agents working offshore can expect a stay of a year or more. "We'll see all of our training staff on site here at least through the fourth quarter, possibly through to 2005," says Ken Carosella, director of operations for the Argentina facility.
The staff has learned Spanish quickly to keep pace with the local teams (neither Carosella nor Meagher, nor many of the other U.S.-based employees, had mastered the language before the engagement), but Meagher says the larger adjustments have been cultural. "It's such a warm, welcome group," she says. But the Argentine pace differs from the American, so work activities tend to be spread out in the day. "It's been a change to my schedule, having meetings at 10 at night."
For his part, Carosella has had to adjust his basic food cravings. "Argentina is known for wine and meat, but I miss Denny's and peanut butter," he says.
Despite the changes in lifestyle neither is in a hurry to leave. "Six months ago if you asked me about Argentina, I wouldn't have been able to tell you anything not in the history books," Meagher says. "I will stay here as long as they want me to, and I will take another [international] assignment."
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| https://www.destinationcrm.com/Articles/CRM-News/CRM-Featured-News/U.S.-Call-Center-Agents-Grow-as-Expats-44016.aspx |
Honoring my Mother / My lockdown overload. - Free Online Library
Free Online Library: Honoring my Mother / My lockdown overload. by " Mindanao Times (Mindanao, Philippines)" ; News, opinion and commentary General interest
Honoring my Mother / My lockdown overload.
MLA style: "Honoring my Mother / My lockdown overload.." The Free Library . 2020 Knowledge Bylanes 11 Jun. 2023 https://www.thefreelibrary.com/Honoring+my+Mother+%2f+My+lockdown+overload.-a0617719757
Chicago style: The Free Library . S.v. Honoring my Mother / My lockdown overload.." Retrieved Jun 11 2023 from https://www.thefreelibrary.com/Honoring+my+Mother+%2f+My+lockdown+overload.-a0617719757
APA style: Honoring my Mother / My lockdown overload.. (n.d.) >The Free Library. (2014). Retrieved Jun 11 2023 from https://www.thefreelibrary.com/Honoring+my+Mother+%2f+My+lockdown+overload.-a0617719757
'Go placidly amid the noise and haste...'
If you will for a minute, try to give a listen to all the voices
online speaking at the same time, during this year of COVID-19. Even as
the urgency of the hour cannot be over-stressed, as sure as I am sure
that there are those who really mean well with their updates and
warnings, the signs are there. One cannot but notice that in a sense, a
veil has been lifted somewhat to reveal that indeed, the world had
become as noisy as a marketplace. A much-sicker analogy would be it
resembling a chicken without its head and running all over the yard.
Dwelling further into this market comparison, consider some
'aisles'of this world supermarket where panic scenes of had
become quite common: Toilet paper sections in Australia, US and UK;
flour and baking sections in Sweden, and last but least, the
antiseptics/rubbing alcohol sections in the Philippines. Unverified
rumors from some Aussie-friends even state that there was a panic buying
incident in SG for condoms, which was weird but who cares? To top them
all, the best aisle yet had been in Amsterdam, the Netherlands. When
people heard that coffee shops might be closed, there was a rush and a
long line of people to them, because that was were they could buy
marijuana (which is legal there).
Each to their own priorities (or poison) I guess.
As in any busy market anywhere moreover, the counterpart of thugs
abounds also. One needs to be wary about those among us who are into the
hating, blaming and the malicious kind of business as their motives are
to the detriment of others. Because of them, the proliferation of fake
news about the outbreak has caused undue panic and misinformation among
the people so much that, some believe that these are some of the causes
of panic buying in places.
In the wake of it all, the rally to isolate one's self through
'social distancing', with the most minimum physical contact
with others to minimize contagion has shaken the human crib even
further. In the city, where a 'community quarantine' had been
implemented, many had opted to stay indoors and worked at home. Truly,
the market place noise may have risen to fever pitch with each passing
day, yet the most unheard voices, drowned off in all the din might as
well be mute.
I had a sad encounter the other day with our neighborhood garbage
man and I had casually asked him what precautions he was doing in the
midst of all these frightening circumstances. His reply had been that of
flat surrender. What can the poor do he said, when they could not even
afford masks, alcohol or other means to ward off exposure? So, in all
the push-and-shove, yup we may have forgotten them. More fortunate for
the hospital workers and front-liners in the corona virus outbreak who
now have received better treatment, despite earlier being ostracized as
'unclean' because of their possible exposure to patients with
the COVID-19. While the mob mentality towards them may have changed
(they are now hailed as heroes), our garbage man and the likes of him
are still left to fend for themselves.
Looking at all that have unfolded so far, I had earlier planned to
post about the Ides of march on the eleventh of this month, as a poke to
some friends, but thought better of it. The world as it is is changed.
It is basically in lockdown, confined to barracks, and celled in
together with its fears as companions. Ironically, this year of 20-20
has indeed become a great reveal, exposing just how low we can go.
The
days ahead may even bring a surprise of sorts when we prove to
ourselves how fast we can organize ourselves to save our skin.
Mar 16, 2020
| https://www.thefreelibrary.com/Honoring+my+Mother+/+My+lockdown+overload.-a0617719757 |
Narcotic analgesia and delayed gastric emptying during labour | Request PDF
Request PDF | Narcotic analgesia and delayed gastric emptying during labour | The rate of gastric emptying in women during labour was estimated indirectly from the kinetics of absorption of orally administered paracetamol... | Find, read and cite all the research you need on ResearchGate
Narcotic analgesia and delayed gastric emptying during labour
July 1975
The Lancet 1(7912):890-3
DOI: 10.1016/S0140-6736(75)91687-6
Authors:
The University of Edinburgh
Abstract
The rate of gastric emptying in women during labour was estimated indirectly from the kinetics of absorption of orally administered paracetamol (acetaminophen). Gastric emptying was normal in patients who had not received a narcotic analgesic but was markedly delayed in women given pethidine, diamorphine, or pentazocine. The inhibitory effect of diamorphine and pethidine on gastric emptying was not reversed by metoclopramide.
... There were 18 studies on acetaminophen PK, using NCA methods, included [12][13][14][22][23][24][25]
[26]
[27][28][29][30][31][32][33][34][35][36]. Table 1 provides the characteristics of the included PK studies. ...
... Of all 18 studies that applied traditional methods, 14 reported absorption-related parameters [12][13][14]22,23,[25]
[26]
[27]29,[32][33][34][35][36]. None of these studies compared, longitudinally, IV with the oral administration of acetaminophen, or reported on the oral bioavailability of acetaminophen in a paired analysis. ...
Modelling Tools to Characterize Acetaminophen Pharmacokinetics in the Pregnant Population
Full-text available
Sofie A. M. Brookhuis
Lidwien M. Hanff
Karel Allegaert
Paola Mian
This review describes acetaminophen pharmacokinetics (PK) throughout pregnancy, as analyzed by three methods (non-compartmental analyses (NCA), population PK, and physiologically based PK (PBPK) modelling). Eighteen studies using NCA were reported in the scientific literature. These studies reported an increase in the volume of distribution (3.5–60.7%) and an increase in the clearance (36.8–84.4%) of acetaminophen in pregnant women compared to non-pregnant women. Only two studies using population PK modelling as a technique were available in the literature. The largest difference in acetaminophen clearance (203%) was observed in women at delivery compared to non-pregnant women. One study using the PBPK technique was found in the literature. This study focused on the formation of metabolites, and the toxic metabolite N-acetyl-p-benzoquinone imine was the highest in the first trimester, followed by the second and third trimester, compared with non-pregnant women. In conclusion, this review gave an overview on acetaminophen PK changes in pregnancy. Also, knowledge gaps, such as fetal and placenta PK parameters, have been identified, which should be explored further before dosing adjustments can be suggested on an evidence-based basis.
... For example, by combining the paracetamol absorption test with the sulfamethizole capsule method, simultaneous measurements of liquid and solid gastric emptying can be achieved [54]. Since the sampling procedure of the marker methods requires no specialized equipment or instruments, such as an MRI scanner, they can be applied under more physiological conditions, or when other methods are not applicable-for example, during pregnancy or labor
[55,
56]. Conveniently, the use of marker substances does not alter the human GI physiology. ...
Application of In Vivo Imaging Techniques and Diagnostic Tools in Oral Drug Delivery Research
Full-text available
Apr 2022
Stefan Senekowitsch
Philipp Schick
Bertil Abrahamsson
Mirko Koziolek
Drug absorption following oral administration is determined by complex and dynamic interactions between gastrointestinal (GI) physiology, the drug, and its formulation. Since many of these interactions are not fully understood, the COST action on “Understanding Gastrointestinal Absorption-related Processes (UNGAP)” was initiated in 2017, with the aim to improve the current comprehension of intestinal drug absorption and foster future developments in this field. In this regard, in vivo techniques used for the characterization of human GI physiology and the intraluminal behavior of orally administered dosage forms in the GI tract are fundamental to gaining deeper mechanistic understanding of the interplay between human GI physiology and drug product performance. In this review, the potential applications, advantages, and limitations of the most important in vivo techniques relevant to oral biopharmaceutics are presented from the perspectives of different research fields.
... Morphine reduces intestinal motility, inhibits gastric emptying, and can induce nausea and vomiting.
3
These side effects are associated with a slower uptake of orally administered P2Y 12 receptor inhibitors, resulting in a delayed onset of effective antiplatelet therapy and potentially early treatment failure (eg, caused by stent thrombosis or incomplete microvascular reperfusion). [4][5][6] Coadministration of the prokinetic drug metoclopramide can attenuate the unintended gastrointestinal effects of morphine and preserve the pharmacokinetics and pharmacodynamics of P2Y 12 receptor inhibitors. ...
Impact of Morphine Treatment With and Without Metoclopramide Coadministration on Myocardial and Microvascular Injury in Acute Myocardial Infarction: Insights From the Randomized MonAMI Trial
Article
Full-text available
Thomas Stiermaier
Philipp Schaefer
Roza Saraei
Ingo Eitel
Background
Intravenous morphine administration can adversely affect platelet inhibition induced by P2Y 12 receptor inhibitors after acute myocardial infarction. In contrast, some evidence suggests that opioid agonists may have cardioprotective effects on the myocardium. The aim of this prospective, randomized MonAMI (Impact of Morphine Treatment With and Without Metoclopramide Coadministration on Platelet Inhibition in Acute Myocardial Infarction) trial was, therefore, to investigate the impact of morphine with or without metoclopramide coadministration on myocardial and microvascular injury.
Methods and Results
Patients with acute myocardial infarction (n=138) were assigned in a 1:1:1 ratio to ticagrelor 180 mg plus: (1) intravenous morphine 5 mg (morphine group); (2) intravenous morphine 5 mg and metoclopramide 10 mg (morphine+metoclopramide group); or (3) intravenous placebo (control group) administered before primary percutaneous coronary intervention. Cardiac magnetic resonance imaging was performed in 104 patients on day 1 to 4 after the index event. Infarct size was significantly smaller in the morphine only group as compared with controls (percentage of left ventricular mass, 15.5 versus 17.9; P =0.047). Furthermore, the number of patients with microvascular obstruction was significantly lower after morphine administration (28% versus 54%; P =0.022) and the extent of microvascular obstruction was smaller (percentage of left ventricular mass, 0 versus 0.74; P =0.037). In multivariable regression analysis, morphine administration was independently associated with a reduced risk for the occurrence of microvascular obstruction (odds ratio, 0.37; 95% CI, 0.14–0.93 [ P =0.035]). There was no significant difference in infarct size ( P =0.491) and extent ( P =0.753) or presence ( P =0.914) of microvascular obstruction when comparing the morphine+metoclopramide group with the control group.
Conclusions
In this randomized study, intravenous administration of morphine before primary percutaneous coronary intervention resulted in a significant reduction of myocardial and microvascular damage following acute myocardial infarction. This effect was not observed in the morphine plus metoclopramide group.
Registration
URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02627950.
... However, pain and anxiety were not considered as having an influence on the occurrence of full stomach after delivery in our study. The oral intake of clear liquids encouraged by the guidelines, 4,13 as well as epidural administration of opioids [27][28]
[29]
may also explain in part why the gastric content did not decrease in a larger part of these laboring women. Interestingly, some parturients exhibited an increase in their antral CSA through labor. ...
Ultrasound assessment of gastric content in the immediate postpartum period: A prospective observational descriptive study
Full-text available
Jun 2017
ACTA ANAESTH SCAND
Florence Vial
N Hime
Jérôme Feugeas
H Bouaziz
Introduction:
Pulmonary aspiration of gastric contents in pregnant women undergoing general anesthesia or sedation/analgesia in the peripartum period is a feared complication in obstetric anesthesia. We assessed the changes in antral cross-sectional area (CSA) with ultrasonography in laboring women and in the immediate postpartum period.
Patients and methods:
In an observational study in a university-affiliated maternity, gastric ultrasonography examinations were performed in non-consecutive laboring women, after epidural analgesia insertion and after childbirth. Assessment of antral CSA, difficulty of performance on a numerical scale, and factors that could influence gastric content were noted. A cut-off value of 381 mm(2) was taken for the diagnosis of empty stomach.
Results:
One hundred women were enrolled in the study. Median antral CSA was 469 mm(2) [25th-75th] [324-591] after epidural insertion and 427 mm(2) [316-574] after delivery. Antral CSA was ≥ 381 mm(2) in 59 of 90 women (65%) after epidural insertion vs. 48 of 100 women (48%) after delivery (P = 0.59). Median variation of antral CSA between two measurements was 36 mm(2) [-42 to 114]. Gastric ultrasonography was significantly more difficult to perform during labor than immediately post-delivery (median difficulty score 5 [2-7] vs. 2 [1-4], P < 0.0001). No risk factors (pain, anxiety, diabetes, smoking) were significantly associated with the occurrence of full stomach post-delivery.
Conclusion:
This study demonstrated that 48% of parturients in the immediate postpartum period presented an antral CSA ≥ 381 mm(2) , cut-off being accepted for diagnosis of empty stomach and emphasizes the need for re-assessing before any general anesthetic procedure.
Gastroparesis in Pregnancy
Sep 2022
AM J OBSTET GYNECOL
Moosavi Sarvee
Min Yang Won
Wong Melissa
Rezaie Ali
Gastroparesis is a functional gastrointestinal disorder that more commonly affects women, with the majority diagnosed during childbearing age. However, there is a paucity of data and guidelines to specifically highlight the epidemiology, disease course, maternal and fetal impact, or the management of existing gastroparesis during pregnancy. Apart from metoclopramide, there is no approved therapy specifically indicated for gastroparesis. More importantly, pregnant and breastfeeding women are excluded from clinical trials evaluating pharmacologic agents in management of gastroparesis. This poses a real challenge to healthcare providers in counselling and management of patients with gastroparesis. In this systematic review, we summarize the current available literature, as well as the knowledge gaps in the impact of pregnancy on gastroparesis and vice versa. We also highlight the efficacy and safety profiles of available pharmacologic and non-pharmacologic therapies in management of patients with gastroparesis, with emphasis on judicious use of dietary approach that are deemed relatively safe during pregnancy.
View
Population Pharmacokinetic Modelling of Acetaminophen and Ibuprofen: the Influence of Body Composition, Formulation and Feeding in Healthy Adult Volunteers
Apr 2022
EUR J DRUG METAB PH
James Morse
Ioana Stanescu
Hartley C Atkinson
Brian J Anderson
Background and objective:
Combined acetaminophen and ibuprofen are common antipyretic and analgesic drugs. Formulation and feeding affect drug absorption. Drug clearance has a nonlinear relationship with total body weight. The covariate effect of fat mass on acetaminophen and ibuprofen pharmacokinetics remains unexplored. This study sought to quantify acetaminophen and ibuprofen pharmacokinetics with intravenous, tablet, sachet and oral suspension formulations in fed and fasted states.
Methods:
Pooled time-concentration data for acetaminophen and ibuprofen were available from fasting and fed healthy adults. Data from intravenous, tablet, sachet and suspension formulations were analysed using nonlinear mixed-effects models. Body composition was considered as a covariate on clearances and volumes of distribution (Vd). Size metrics investigated were total body weight, fat and fat-free mass. Theory-based allometry was used to scale pharmacokinetic parameters to a 70 kg individual. A factor on absorption half-life and lag time quantified delays due to feeding for oral formulations. Pharmacokinetic-pharmacodynamic simulations were used to explore the time courses of pain response for acetaminophen and ibuprofen for each formulation.
Results:
Pooled data included 116 individuals (18-49 years, 49-116 kg) with 6095 acetaminophen and 6046 ibuprofen concentrations available for analysis. A two-compartment pharmacokinetic model with first-order elimination described disposition for both drugs. Normal fat mass was the best covariate to describe acetaminophen clearance (CL), with a factor for fat contribution (FFATCL) of 0.816. Acetaminophen volume of distribution was described using total body weight. Normal fat mass was the best covariate to describe ibuprofen clearance (FFATCL = 0.863) and volume of distribution: (FFATV = 0.718). Clearance and central volume of distribution were 24.0 L/h/70 kg and 43.5 L/h/70 kg for acetaminophen. Ibuprofen clearance and central volume of distribution were 3.79 L/h/70 kg and 10.5 L/h/70 kg. Bioavailability and absorption half-life were 86% and 12 min for acetaminophen and 94% and 27 min for ibuprofen. Absorption lag times were 5.3 min and 6.7 min for acetaminophen and ibuprofen, respectively. Feeding increased both absorption half-life and absorption lag time when compared to the tablet formulation under fasting conditions. Feeding had the most pronounced effect on the lag time associated with tablet formulation for both drugs. Time to a pain score reduction of 2 points (visual analogue score, 0-10) differed by only 5-10 min across all formulations for acetaminophen and ibuprofen.
Conclusion:
Fat mass was an important covariate to describe acetaminophen and ibuprofen pharmacokinetics. The absorption half-lives of acetaminophen and ibuprofen were increased in fed states. The delay in absorption, quantified by a lag time, was protracted for both drugs.
Limiting Oral Intake during Labor: Do We Have It Right?
Feb 2022
Craig M Palmer
Yandong Jiang
Pregnancy and Labor Epidural Effects on Gastric Emptying: A Prospective Comparative Study
Feb 2022
Thomas Schulz
Federica Piana
Lionel Bouvet
D. Chassard
Background:
The lack of reliable data on gastric emptying of solid food during labor has led to some discrepancies between current guidelines regarding fasting for solid food in the parturient. This prospective comparative study aimed to test the hypothesis that the gastric emptying rate of a light meal would be reduced in parturients receiving epidural analgesia and with no labor analgesia compared with nonpregnant and pregnant women.
Methods:
Ten subjects were enrolled and tested in each group: nonpregnant women, term pregnant women, parturients with no labor analgesia, and parturients with epidural labor analgesia. After a first ultrasound examination was performed to ensure an empty stomach, each subject ingested a light meal (125 g yogurt; 120 kcal) within 5 min. Then ultrasound measurements of the antral area were performed at 15, 60, 90, and 120 min. The rate of gastric emptying at 90 min was calculated as [(antral area90 min / antral area15 min) - 1] × 100, and half-time to gastric emptying was also determined. For the Parturient-Epidural group, the test meal was ingested within the first hour after the induction of epidural analgesia.
Results:
The median (interquartile range) rate of gastric emptying at 90 min was 52% (46 to 61), 45% (31 to 56), 7% (5 to 10), and 31% (17 to 39) for nonpregnant women, pregnant women, parturients without labor analgesia, and parturients with labor epidural analgesia, respectively (P < 0.0001). The rate of gastric emptying at 90 min was statistically significant and lower in the Parturient-Epidural group than in the Nonpregnant and Pregnant Control groups. In addition, the rate of gastric emptying at 90 min was statistically significant and lower in the Parturient-No-Epidural group than in the Parturient-Epidural group.
Conclusions:
Gastric emptying in parturients after a light meal was delayed, and labor epidural analgesia seems not to worsen but facilitates gastric emptying. This should be taken into consideration when allowing women in labor to consume a light meal.
Editor’s perspective:
L’échographie antrale peut-elle contribuer à une libéralisation des règles de jeûne préopératoire et durant le travail obstétrical ?
Jun 2021
Francois-Pierrick Desgranges
D. Chassard
Lionel Bouvet
Résumé
L’échographie antrale permet d’apprécier la vidange gastrique mais également d’analyser l’impact de la durée de jeûne sur le risque de présenter un estomac plein avant une anesthésie générale. Les données récentes issues des études portant sur l’échographie de l’antre gastrique pourraient contribuer, à l’avenir, à une libéralisation des règles de jeûne préopératoire concernant, par exemple, la consommation de liquides clairs, de solutions de carbohydrates, d’une tasse de café ou de thé au lait ou de chewing-gum, chez l’enfant et l’adulte en dehors de la grossesse, mais également chez la femme enceinte à terme en dehors du travail. Ces données pourraient également contribuer à autoriser la consommation d’un petit déjeuner léger jusqu’à quatre heures avant l’induction d’une anesthésie générale pour une chirurgie programmée en dehors du contexte obstétrical. Alors que les études issues de l’échographie gastrique peuvent confirmer le caractère sécuritaire de la consommation de liquides clairs ou de solutions de carbohydrates chez la parturiente, elles semblent décourager la consommation d’aliments solides au cours du travail obstétrical. Des études complémentaires utilisant l’échographie antrale seront nécessaires afin d’évaluer l’impact de la libéralisation des règles de jeûne sur le risque de présenter un estomac plein avant une anesthésie générale, avant l’intégration d’une telle libéralisation dans de futures recommandations.
Adverse Effects of Drugs in Later Pregnancy
Jun 1986
Clin Obstet Gynaecol
L Beeley
GASTROESOPHAGEAL REFLUX DISEASE IN PREGNANCY
Article
Dec 1992
GASTROENTEROL CLIN N
Todd H Baron
Joel E. Richter
Heartburn during pregnancy occurs in approximately two thirds of all pregnancies. The origin is multifactorial, but the predominant factor is a decrease in LES pressure resulting from female sex hormones, especially progesterone. Mechanical factors play a small role. Serious reflux complications during pregnancy are rare outside the obstetric setting. Therapy involves lifestyle modifications and nonsystemic medications as the initial choices. H2 blockers are probably safe in severe and refractory cases.
Physiological Alterations of Pregnancy
Jan 1986
Sheila E. Cohen
It is clear that pregnancy is associated with extensive functional and anatomical changes, many of which have important implications for the safe management of pain relief for labour and delivery. Some of these changes, such as increased blood volume, protect against the dangers of childbirth, while others result in diminished cardiorespiratory reserve or are associated with added anaesthetic risk. There is no doubt that pregnant women constitute a unique population which requires skilled personnel with specialized knowledge to provide for their needs.
Emergencies in Paediatric Anaesthesia
Jul 1985
Ian G. James
Paediatric surgical emergencies are common but despite better anaesthetic knowledge and training they are still associated with a high morbidity and mortality. The commonest causes of anaesthetic-related deaths are inadequately treated hypovolaemia and aspiration of gastric contents. Infants are particularly prone to oesophageal reflux and have a high incidence of residual acid gastric contents at induction of anaesthesia. They also readily become dehydrated. Several potential problems may be encountered in the congenital anomalies requiring urgent correction in infancy, and these are outlined. With better awareness and perioperative care it should be possible to prevent many of the problems associated with paediatric emergency anaesthesia.
Aspiration: Risk, Prophylaxis, and Treatment
Chapter
| https://www.researchgate.net/publication/282092210_Narcotic_analgesia_and_delayed_gastric_emptying_during_labour |
World War II Servicemen's Correspondence Collection, 1941-1945 | SDSUnbound
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World War II Servicemen's Correspondence Collection, 1941-1945
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Collection Description
A collection of approximately 5,000 original letters sent by San Diego State students on active duty in the armed forces during World War II, or their families, to Professor Lauren Post who compiled and distributed the Aztec News Letter.
Immediately after Pearl Harbor and as the War progressed, Aztec students were soon scattered all over the globe, disconnected and separated from their college, their friends, their loved ones, and their former lives. In the spring of 1942, Dr. Post, professor of geography from 1937-69 and a veteran of World War I, decided to try a "news service experiment" intended to provide information about the locations of current and former Aztecs dispersed around the world. The Aztec News Letter thus became a crucial lifeline throughout the War for Aztec servicemen and women facing difficulty and danger wherever they were stationed. Lauded as one of the first of its kind in the nation, the Aztec News Letter premiered in May of 1942 and was released monthly until its 48th issue in March of 1946. By then, The Aztec News Letter circulated to more than 3,000 service and home front readers. The project and the letters that made it possible would forever characterize the Aztec spirit during wartime. Not only are the letters historically significant; they also offer a unique perspective about San Diego State during a global crisis.
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Letter from Alfred G. Scott, Jr., 1945
Letter from Alfred L. Leidy, 1945 Letter from Alfred L. Leidy, 1945-03
Letter from Alfred L. Pohl, 1943 Letter from Alfred L. Pohl, 1944 Letter from Alfred Nesvold, 1943
Letter from Alfred Nesvold, 1943-12
Letter from Alfred Rhodes, 1942
Letter from Alfred Rhodes, 1943
Letter from Alfred Rhodes, 1943-09
Letter from Alfred Rhodes, 1944 Letter from Alfred Rhodes, 1944-03
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Browse In Physical Education and Coaching, International Journal of Sports Physiology and Performance | Human Kinetics
Browse In Physical Education and Coaching, International Journal of Sports Physiology and Performance | Human Kinetics
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The Relevance of Muscle Fiber Type to Physical Characteristics and Performance in Team-Sport Athletes
Henry J. Hopwood, Phillip M. Bellinger, Heidi R. Compton, Matthew N. Bourne, and Clare Minahan
Purpose :The aim of this systematic review was to (1) determine the muscle fiber-type composition (or muscle fiber typology [MFT]) of team-sport athletes and (2) examine associations between MFT and the physical characteristics and performance tasks in team-sport athletes. Methods :Searches were conducted across numerous databases—PubMed, SPORTDiscus, MEDLINE, and Google Scholar—using consistent search terms. Studies were included if they examined the MFT of team-sport athletes. Included studies underwent critical appraisal using the McMasters University critical appraisal tool for quantitative research. Results :A total of 10 studies were included in the present review, wherein the MFT of athletes was measured from 5 different team sports (soccer, rugby union, rugby league, handball, and volleyball). There was large variability in the MFT of team-sport athletes both within (up to 27.5%) and between sports (24.0% relative difference). Male football players with a higher proportion of type II fibers had faster 10- and 30-m sprint times, achieved a greater total distance sprinting (distance at >6.67 m·s −1), and a greater peak 1-minute sprint distance. Conclusions :MFT varies considerably between athletes both within and between different team sports. The results from some studies suggest that variation in MFT is associated with high-intensity running performance in a football match, as well as 10- and 30-m sprint times. Further experimental studies should focus on how determination of the MFT of team-sport athletes could be utilized to influence talent identification, team selection, and the individualization of training.
Purpose :The aim of this systematic review was to (1) determine the muscle fiber-type composition (or muscle fiber typology [MFT]) of team-sport athletes and (2) examine associations between MFT and the physical characteristics and performance tasks in team-sport athletes. Methods :Searches we... Show More
In International Journal of Sports Physiology and Performance Volume 18 (2023): Issue 3 (Mar 2023)
Training Quality—An Unexplored Domain in Sport Science
Thomas Haugen, Espen Tønnessen, Silvana Bucher Sandbakk, and Øyvind Sandbakk
In International Journal of Sports Physiology and Performance Volume 18 (2023): Issue 3 (Mar 2023)
Volume 18 (2023): Issue 2 (Feb 2023)
Heating Up to Keep Cool: Benefits and Persistence of a Practical Heat Acclimation Protocol in Elite Female Olympic Team-Sport Athletes
Stephen P. Fenemor, Matthew W. Driller, Nicholas D. Gill, Brad Anderson, Julia R. Casadio, Stacy T. Sims, and C. Martyn Beaven
Purpose :Although recommendations for effective heat acclimation (HA) strategies for many circumstances exist, best-practice HA protocols specific to elite female team-sport athletes are yet to be established. Therefore, the authors aimed to investigate the effectiveness and retention of a passive HA protocol integrated in a female Olympic rugby sevens team training program. Methods :Twelve elite female rugby sevens athletes undertook 10 days of passive HA across 2 training weeks. Tympanic temperature ( T Tymp), sweat loss, heart rate, and repeated 6-second cycling sprint performance were assessed using a sport-specific heat stress test Pre-HA, after 3 days (Mid-HA), after 10 days (Post-HA), and 15 days post-HA (Decay). Results :Compared with Pre-HA, submaximal T Tympwas lower Mid-HA and Post-HA (both by −0.2 [0.7] °C; d≥ 0.71), while resting T Tympwas lower Post-HA (by −0.3 [0.2] °C; d= 0.81). There were no differences in T Tympat Decay compared with Pre-HA, nor were there any differences in heart rate or sweat loss at any time points. Mean peak 6-second power output improved Mid-HA and Post-HA (76 [36] W; 75 [34] W, respectively; d≥ 0.45) compared with Pre-HA. The observed performance improvement persisted at Decay by 65 (45) W ( d= 0.41). Conclusions :Ten days of passive HA can elicit some thermoregulatory and performance benefits when integrated into a training program in elite female team-sport athletes. However, such a protocol does not provide a sufficient thermal impulse for thermoregulatory adaptations to be retained after 15 days with no further heat stimulus.
Purpose :Although recommendations for effective heat acclimation (HA) strategies for many circumstances exist, best-practice HA protocols specific to elite female team-sport athletes are yet to be established. Therefore, the authors aimed to investigate the effectiveness and retention of... Show More
In International Journal of Sports Physiology and Performance Volume 18 (2023): Issue 3 (Mar 2023)
Training Load and Acute Performance Decrements Following Different Training Sessions
Kobe M. Vermeire, Kevin Caen, Jan G. Bourgois, and Jan Boone
Purpose :To examine the differences in training load (TL) metrics when quantifying training sessions differing in intensity and duration. The relationship between the TL metrics and the acute performance decrement measured immediately after the sessions was also assessed. Methods :Eleven male recreational cyclists performed 4 training sessions in a random order, immediately followed by a 3-km time trial (TT). Before this period, participants performed the time TT in order to obtain a baseline performance. The difference in the average power output for the TTs following the training sessions was then expressed relative to the best baseline performance. The training sessions were quantified using 7 different TL metrics, 4 using heart rate as input, 2 using power output, and 1 using the rating of perceived exertion. Results :The load of the sessions was estimated differently depending on the TL metrics used. Also, within the metrics using the same input (heart rate and power), differences were found. TL using the rating of perceived exertion was the only metric showing a response that was consistent with the acute performance decrements found for the different training sessions. The Training Stress Score and the individualized training impulse demonstrated similar patterns but overexpressed the intensity of the training sessions. The total work done resulted in an overrepresentation of the duration of training. Conclusion :TL metrics provide dissimilar results as to which training sessions have higher loads. The load based on TL using the rating of perceived exertion was the only one in line with the acute performance decrements found in this study.
Purpose :To examine the differences in training load (TL) metrics when quantifying training sessions differing in intensity and duration. The relationship between the TL metrics and the acute performance decrement measured immediately after the sessions was also assessed. Methods :Eleven male r... Show More
In International Journal of Sports Physiology and Performance Volume 18 (2023): Issue 3 (Mar 2023)
Travel Across More Time Zones Results in Worse Perceived Fatigue and Sleep in National-Team Footballers
Ewan Clements, Fabian Ehrmann, Andrew Clark, Mark Jones, Alan McCall, and Rob Duffield
Purpose :This study investigated the association between (1) time zone difference and (2) travel direction (east vs west) with posttravel changes in perceptual responses of national-team footballers. Methods :Travel schedules from 355 national-team trips (50 elite soccer players) were verified using an online flight database. All players provided perceptual ratings of fatigue, sleep quality, soreness, and stress to calculate changes in scores up to 2 days after travel. Trips were categorized as <3, 3 to 6, 6 to 9, or 9+ time zone changes, along with travel direction (eastward or westward). The pretravel to posttravel changes in perceptual ratings at days 1 and 2 postarrival were compared between time zone change and travel direction with linear mixed models. Results :For every time zone crossed, poorer ratings of perceptual fatigue ( β= 0.068, P< .001), sleep ( β= 0.095, P< .001), soreness ( β= 0.0049, P< .001), and total wellness ( β= 0.214, P< .001) were observed. However, the models explained only small proportions of the variation in postflight perceptual responses (7%–18%). Regardless, travel across 9+ time zones resulted in significantly worse perceived fatigue, sleep, and total wellness for days 1 and 2 postarrival compared with travel with <6 time zones ( P< .05). Additionally, fatigue, sleep, and total scores were worse on day 2 following trips of 9+ time zones. Eastward travel resulted in poorer sleep ratings ( β= 0.52, P< .001) than westward travel within time zone groupings. Conclusions :Perceptual ratings of fatigue and sleep become progressively worse as travel increases in national-team soccer players, especially after travel across 9+ time zones and eastward travel.
Purpose :This study investigated the association between (1) time zone difference and (2) travel direction (east vs west) with posttravel changes in perceptual responses of national-team footballers. Methods :Travel schedules from 355 national-team trips (50 elite soccer players) were verified usi... Show More
In International Journal of Sports Physiology and Performance Volume 18 (2023): Issue 3 (Mar 2023)
High-Intensity Interval Training, Performance, and Oxygen Uptake Kinetics in Highly Trained Traditional Rowers
Iñigo Mujika, Nicolas Bourdillon, Rafa González De Txabarri, and Gregoire P. Millet
Purpose :Oxygen uptake kinetics (VO 2kinetics) is a measure of an athlete’s capacity to respond to variations in energy demands. Faster VO 2kinetics is associated with better performance in endurance sports, but optimal training methods to improve VO 2kinetics remain unclear. This study compared the effects of 2 high-intensity interval-training (HIIT) programs on traditional rowing performance and VO 2kinetics. Methods :Twelve highly trained rowers performed one of two 6-week HIIT protocols: either 3-minute repetitions at 90% (HIIT90; n = 5) of peak aerobic power (PAP) or 90-second repetitions at 100% (HIIT100; n = 7) of PAP. Before (PRE) and after (POST) the training intervention, they performed an incremental test to exhaustion to determine the individual lactate threshold, onset of blood lactate accumulation and PAP, and two 6-minute rest-to-exercise transitions to determine VO 2kinetics. Results :No significant changes ( P> .05) were observed for rowing ergometer power output at individual lactate threshold (HIIT90 PRE 255 [12], POST 264 [13]; HIIT100 247 [24], 266 [28] W), onset of blood lactate accumulation (279 [12], 291 [16]; 269 [23], 284 [32] W), or PAP (359 [13], 381 [15]; 351 [21], 363 [29] W) or for any parameters of VO 2kinetics. No differences were observed between HIIT interventions. Conclusion :The HIIT interventions did not induce significant performance or VO 2kinetics improvements, although mean power output at individual lactate threshold, onset of blood lactate accumulation, and PAP increased by 5.7%, 5.0%, and 4.5%, respectively. This suggests that the exact intensity and duration of HIIT sessions performed in the same intensity domain may be of lesser importance than other well-established influential factors (eg, training volume progression, training intensity distribution, altitude training) to develop aerobic qualities in endurance athletes.
Purpose :Oxygen uptake kinetics (VO 2kinetics) is a measure of an athlete’s capacity to respond to variations in energy demands. Faster VO 2kinetics is associated with better performance in endurance sports, but optimal training methods to improve VO 2kinetics remain unclear. This study compared the... Show More
In International Journal of Sports Physiology and Performance Volume 18 (2023): Issue 3 (Mar 2023)
Intraindividual Relationships Between Training Loads and Heart-Rate Variability in High-Level Female Futsal Players: A Longitudinal Study
Fábio Y. Nakamura, Júlio A. Costa, Bruno Travassos, Daniel Ortuño, and José Pino-Ortega
Purpose :To investigate the internal training loads of a professional Spanish female futsal team throughout 26 weeks of training including preseason and in-season weeks and verify the impact of training period and/or training load magnitudes on heart-rate variability responses. Furthermore, we aimed to assess, intraindividually, the relationship between training load and the coefficient of variation (CV) of weekly natural log of the root mean square difference of successive normal interbeat (RR) intervals (lnRMSSD CV), obtained from ∼5 measures per week, and recorded in the seated position. Methods :A within-subject design involved 12 high-level outfield female futsal players (mean [SD] age: 23.9 [3.4] y). Results :lnRMSSD was significantly lower and lnRMSSD CVwas significantly higher during the preseason (weeks 1–6) compared to in-season (weeks 7–26) ( P< .001). Individually, players presented moderateto largenegative correlations between lnRMSSD CVand lnRMSSD during the 26 weeks of observation. Correlations ranged between r player4= −.41 (95% CI, −.69 to −.02) and r player12= −.55 (−.78 to −.18). Players also presented moderateto very largepositive correlations between lnRMSSD CVand session rating of perceived exertion. Correlations ranged between r player7= .41 (.04 to .71) and r player1= .71 (.45 to .86). Conclusion :Professional female futsal players in this study presented increased lnRMSSD and reduced lnRMSSD CVduring 20 weeks into the competitive season compared to 6 weeks of preseason. Furthermore, lnRMSSD CVwas negatively associated with lnRMSSD on an intraindividual basis. Finally, higher internal training loads were positively correlated with lnRMSSD CV, indicating that heart-rate variability is responsive to weekly training loads.
Purpose :To investigate the internal training loads of a professional Spanish female futsal team throughout 26 weeks of training including preseason and in-season weeks and verify the impact of training period and/or training load magnitudes on heart-rate variability responses. Furthermore, we... Show More
In International Journal of Sports Physiology and Performance Volume 18 (2023): Issue 3 (Mar 2023)
A 0.1% L-Menthol Mouth Swill in Elite Male Rugby Players Has Different Effects in Forwards and Backs
Marcia L. Jerram, Dane Baker, Tiaki B. Smith, Phil Healey, Lee Taylor, and Katherine Black
Purpose :Menthol mouth swills can improve endurance performance in the heat, which is attributed to attenuations in nonthermally derived thermal sensation (TS) and perception of effort. However, research in elite team-sport athletes is absent. Therefore, this study investigated the performance and TS responses to a 0.1% menthol mouth rinse (MR) or placebo (PLA) among elite male rugby union players. Method :Twenty-seven (15 Forwards and 12 Backs) elite male Super Rugby players completed two 3-minute 15-a-side rugby-specific conditioning blocks, with MR or PLA provided at the start of training (baseline), at the start of each 3-minute block (swill 1 [S1] and swill 2 [S2]), and at the end of training (swill 3 [S3]). TS was assessed using the American Society of Heating, Refrigerating and Air-Conditioning Engineers 9-point Analog Sensation Scale after each swill and at baseline (preconditioning block). Acceptability was measured after baseline swill and S3 using a 5-question Likert scale. Physical performance was measured throughout training using global positioning system metrics. Results :MR attenuated TS from baseline to S1 ( P= .003, SD = 1.01) and S2 ( P= .002, SD = 1.09) in Forwards only, compared with PLA. Acceptability was higher only for Forwards in MR versus PLA at baseline ( P= .003, SD = 1.3) and S3 ( P= .004, SD = 0.75). MR had no effect on physical performance metrics ( P> .05). Conclusion :MR attenuated the rise in TS with higher acceptability at S1 and S3 (in Forwards only) with no effect on selected physical performance metrics. Longer-duration exercise (eg, a match) in hot–humid conditions eliciting markedly increased body temperatures could theoretically allow favorable changes in TS to enhance performance—these postulations warrant experimental investigation.
Purpose :Menthol mouth swills can improve endurance performance in the heat, which is attributed to attenuations in nonthermally derived thermal sensation (TS) and perception of effort. However, research in elite team-sport athletes is absent. Therefore, this study investigated the performance and... Show More
In International Journal of Sports Physiology and Performance Ahead of Print
The Effect of Complex Training on Physical Performance in Rugby League Players
David J. Scott, Massimiliano Ditroilo, Samuel T. Orange, and Phil Marshall
Purpose :To compare the effects of variable-resistance complex training (VRCT) versus traditional complex training (TCT) on strength, power, speed, and leg stiffness (K leg) in rugby league players during a 6-week mesocycle. Methods :Twenty-four rugby league players competing in the British University and Colleges Sport Premier North Division were randomized to VRCT (n = 8), TCT (n = 8), or control (CON; n = 8). Experimental groups completed a 6-week lower-body complex training intervention (2×/wk) that involved alternating high-load resistance exercise with plyometric exercise within the same session. The VRCT group performed resistance exercises at 70% of 1-repetition maximum (1RM) + 0% to 23% of 1RM from band resistance with a 90-second intracontrast rest interval, whereas the TCT group performed resistance exercise at 93% of 1RM with a 4-minute intracontrast rest interval. Back-squat 1RM, countermovement jump peak power, reactive strength index, sprint times, and K legwere assessed pretraining and posttraining. Results :VRCT and TCT significantly improved 1RM back squat, countermovement jump peak power, and 5-m sprint time (all P< .05). VRCT also improved K leg, whereas TCT improved 10- and 20-m sprint times (all P< .05). Between groups, both VRCT and TCT improved 1RM back squat compared with CON (both P< .001). Additionally, VRCT improved K legcompared with CON (right leg: P= .016) and TCT improved 20-m sprint time compared with CON ( P= .042). Conclusions :VRCT and TCT can be implemented during the competitive season to improve strength, power, and 5-m sprint time. VRCT may lead to greater improvements in reactive strength index and K leg, whereas TCT may enhance 10- and 20-m sprint times.
Purpose :To compare the effects of variable-resistance complex training (VRCT) versus traditional complex training (TCT) on strength, power, speed, and leg stiffness (K leg) in rugby league players during a 6-week mesocycle. Methods :Twenty-four rugby league players competing in the British... Show More
In International Journal of Sports Physiology and Performance Volume 18 (2023): Issue 3 (Mar 2023)
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The Role of Social Ties in Factor Allocation
( Published by Oxford University Press on behalf of the World Bank,
2019-10
) Beck, Ulrik ; Bjerge, Benedikte ; Fafchamps, Marcel We investigate whether social structure helps or hinders factor allocation using unusually rich data from the Gambia. Evidence indicates that land available for cultivation is allocated unequally across households; and that factor transfers are more common between neighbors, co-ethnics, and kinship-related households. Does this lead to the conclusion that land inequality is due to flows of land between households being impeded by social divisions? To answer this question, a novel methodology that approaches exhaustive data on dyadic flows from an aggregate point of view is introduced. Land transfers lead to a more equal distribution of land and to more comparable factor ratios across households in general. But equalizing transfers of land are not more likely within ethnic or kinship groups. In conclusion, ethnic and kinship divisions do not hinder land and labor transfers in a way that contributes to aggregate factor inequality. Labor transfers do not equilibrate factor ratios across households. But it cannot be ruled out that they serve a beneficial role, for example, to deal with unanticipated health shocks. Publication
Redistribution and Group Participation: Experimental Evidence from Africa and the UK
( Published by Oxford University Press on behalf of the World Bank,
2019-10
) Fafchamps, Marcel ; Vargas Hill, Ruth We investigate whether the prospect of redistribution hinders the formation of efficiency-enhancing groups. We conduct an experiment in a Kenyan slum, Ugandan villages, and a UK university town. We test, in an anonymous setting with no feedback, whether subjects join a group that increases their endowment but exposes them to one of three redistributive actions: stealing, giving, or burning. We find that exposure to redistributive options among group members operates as a disincentive to join a group. This finding obtains under all three treatments—including when the pressure to redistribute is intrinsic. However the nature of the redistribution affects the magnitude of the impact. Giving has the least impact on the decision to join a group, while forced redistribution through stealing or burning acts as a much larger deterrent to group membership. These findings are common across all three subject pools, but African subjects are particularly reluctant to join a group in the burning treatment, indicating strong reluctance to expose themselves to destruction by others. Publication
Networks and Manufacturing Firms in Africa: Results from a Randomized Field Experiment
( Published by Oxford University Press on behalf of the World Bank,
2018-10
) Fafchamps, Marcel ; Quinn, Simon We run a novel field experiment to link managers of African manufacturing firms. The experiment resembles the many forms of interaction that business and community organizations offer to their members. The design features exogenous link formation, exogenous seeding of information, and exogenous assignment to treatment and placebo.We study the impact of the experiment on firm business practices outside of the lab. We find that the experiment successfully created new variation in social networks. We find significant diffusion of business practices in terms of VAT registration and having a bank current account. This diffusion is a combination of diffusion of innovation and simple imitation. At the time of our experiment, all three studied countries were undergoing large changes in their VAT legislation. Publication
Identifying Gazelles: Expert Panels vs. Surveys as a Means to Identify Firms with Rapid Growth Potential
( Published by Oxford University Press on behalf of the World Bank,
2017-10-01
) Fafchamps, Marcel ;
Woodruff, Christopher We conduct a business plan competition to test whether survey instruments or panel judges are able to identify the fastest growing firms. Participants submitted six- to eight-page business plans and defended them before a three- or four-judge panel. We surveyed applicants shortly after they applied and one and two years after the competition. We use follow-up surveys to construct measures of enterprise growth and baseline surveys and panel scores to construct measures of enterprise growth potential. We find that a measure of ability correlates strongly with future growth, but that the panel scores add to predictive power even after controlling for ability and other survey variables. The survey questions have more power to explain the variance in growth. Participants presenting before the panel were given a chance to win customized management training. Fourteen months after the training, we find no positive effect of the training on growth of the business. Publication
Mobile Phone Coverage and Producer Markets: Evidence from West Africa
( Oxford University Press on behalf of the World Bank, 2015-07
) Aker, Jenny C. ; Fafchamps, Marcel Mobile phone coverage has expanded considerably throughout the developing world, particularly within sub-Saharan Africa. Existing evidence suggests that increased access to information technology has improved agricultural market efficiency for consumer markets and certain commodities, but there is less evidence of its impact on producer markets. Building on the work of Aker (2010), we estimate the impact of mobile phone coverage on producer price dispersion for three commodities in Niger. Our results suggest that mobile phone coverage reduces spatial producer price dispersion by 6 percent for cowpea, a semi-perishable commodity. These effects are strongest for remote markets and during certain periods of the year. The introduction of mobile phone coverage has no effect on producer price dispersion for millet and sorghum, two staple grains that are less perishable and are commonly stored by farmers. There are no impacts of mobile phone coverage on producer price levels, but mobile phone coverage is associated with a reduction in the intra-annual price variation for cowpea. Publication
Network Proximity and Business Practices in African Manufacturing
( Oxford University Press on behalf of the World Bank, 2014-01-23
)
Fafchamps, Marcel ; Söderbom, Måns Patterns of correlation in innovation and contractual practices among manufacturing firms in Ethiopia and Sudan are documented. Network data that indicate whether any two firms in the utilized sample do business with each other, buy inputs from a common supplier, or sell output to a common client are used for the analysis. Only limited support is found for the commonly held idea that firms that are more proximate in a network sense are more likely to adopt similar practices. Indeed, for certain practices, adoption decisions appear to be local strategic substitutes: if one firm in a given location uses a certain practice, nearby firms are less likely to do so. These results suggest that the diffusion of technology and new business practices may play a more limited role in spurring growth in Africa's manufacturing sector than is often assumed in the present policy discussion. Publication
Impact of SMS-Based Agricultural Information on Indian Farmers
( Oxford University Press on behalf of the World Bank, 2012-11
)
Fafchamps, Marcel ; Minten, Bart This study estimates the benefits that Indian farmers derive from market and weather information delivered to their mobile phones by a commercial service called Reuters Market Light (RML). We conduct a controlled randomized experiment in 100 villages of Maharashtra. Treated farmers associate RML information with a number of decisions they have made, and we find some evidence that treatment affected spatial arbitrage and crop grading. But the magnitude of these effects is small. We find no statistically significant average effect of treatment on the price received by farmers, crop value-added, crop losses resulting from rainstorms, or the likelihood of changing crop varieties and cultivation practices. Although disappointing, these results are in line with the market take-up rate of the RML service in the study districts, which shows small numbers of clients in aggregate and a relative stagnation in take-up over the study period. Show statistical information | https://openknowledge.worldbank.org/collections/72f9a9f1-c8d4-491d-a563-8615e94578e5?f.author=Fafchamps%2C%20Marcel%2Cequals&f.dateIssued.max=2019&f.dateIssued.min=2010&f.entityType=Publication%2Cequals&spc.page=1 |
Remote Sensing | Free Full-Text | Formation Mechanism for Upland Low-Relief Surface Landscapes in the Three Gorges Region, China
Extensive areas with low-relief surfaces that are almost flat surfaces high in the mountain ranges constitute the dominant geomorphic feature of the Three Gorges area. However, their origin remains a matter of debate, and has been interpreted previously as the result of fluvial erosion after peneplain uplift. Here, a new formation mechanism for these low-relief surface landscapes has been proposed, based on the analyses of low-relief surface distribution, swath profiles, χ mapping, river capture landform characteristics, and a numerical analytical model. The results showed that the low-relief surfaces in the Three Gorges area could be divided into higher elevation and lower elevation surfaces, distributed mainly in the highlands between the Yangtze River and Qingjiang River. The analyses also showed that the rivers on both sides of the drainage divide have not yet reached equilibrium, with actively migrating drainage divides and river basins in the process of reorganizing. It was concluded that the low-relief surfaces in the Three Gorges area did not share a common uplift history, and neither were they peneplain relicts, but rather that the effect of “area-loss feedback” caused by river capture has promoted the formation of upland low-relief surface landscapes. A future work aims to present the contribution of accurate dating of low-relief surface landscapes.
Formation Mechanism for Upland Low-Relief Surface Landscapes in the Three Gorges Region, China
by
Lingyun Lv 1,2 ,
Lunche Wang 1,2,* ,
Chang’an Li 1,2 ,
Hui Li 1,2 ,
Xinsheng Wang 3 and
Shaoqiang Wang 1,2,4
1
Key Laboratory of Regional Ecology and Environmental Change, School of Geography and Information Engineering, China University of Geosciences, Wuhan 430074, China
3
Hubei Key Laboratory of Regional Development and Environmental Response, Hubei University, Wuhan 430062, China
4
Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing 100101, China
*
Author to whom correspondence should be addressed.
Remote Sens. 2020 , 12 (23), 3899; https://doi.org/10.3390/rs12233899
Received: 9 November 2020 / Revised: 21 November 2020 / Accepted: 26 November 2020 / Published: 27 November 2020
Abstract
Extensive areas with low-relief surfaces that are almost flat surfaces high in the mountain ranges constitute the dominant geomorphic feature of the Three Gorges area. However, their origin remains a matter of debate, and has been interpreted previously as the result of fluvial erosion after peneplain uplift. Here, a new formation mechanism for these low-relief surface landscapes has been proposed, based on the analyses of low-relief surface distribution, swath profiles, χ mapping, river capture landform characteristics, and a numerical analytical model. The results showed that the low-relief surfaces in the Three Gorges area could be divided into higher elevation and lower elevation surfaces, distributed mainly in the highlands between the Yangtze River and Qingjiang River. The analyses also showed that the rivers on both sides of the drainage divide have not yet reached equilibrium, with actively migrating drainage divides and river basins in the process of reorganizing. It was concluded that the low-relief surfaces in the Three Gorges area did not share a common uplift history, and neither were they peneplain relicts, but rather that the effect of “area-loss feedback” caused by river capture has promoted the formation of upland low-relief surface landscapes. A future work aims to present the contribution of accurate dating of low-relief surface landscapes.
Keywords:
three Gorges
;
low-relief surface
;
river profile analysis
;
river capture
;
numerical modeling
Graphical Abstract
1. Introduction
In the 19th century, Davis [
1
] proposed erosion cycle and quasi-plain theories, and in conformity with these, gentle rolling surfaces perched high in rugged mountain ranges, have been considered widely to be the remains of large peneplains. These remains were thought to have been formed by river dissection, after undergoing tectonic peneplain uplift, and have often been referred to as planation surfaces. These planation surfaces were often considered to be the starting points for the evolution of modern drainage and valley systems [
2
,
3
]. As a prominent regional element and an excellent reference level index, planation surfaces are important in the study of long-term geomorphologic evolution.
However, some scholars have questioned the term “quasi-plain” because the modern peneplains are either absent or exceedingly rare [
4
,
5
], with the main argument being whether tectonics could remain stable over a suitably extended period. A balanced uplift will never cause the area where such a landform is located to fall to sea level, where they have been found, and, considering climate change fluctuations, the quasi-plain seems to be an idealized landform, which has never actually been formed. More recently, when the origin and properties of a gentle geomorphologic surface have been unclear, the concept of a “low-relief surface,” which is characterized by slightly undulating mountaintop areas, has been used more often by scholars. This concept emphasizes the gently rolling topography, which is usually described quantitatively as being less than a certain slope angle [
6
].
There have been two main theories regarding the formation mechanism of elevated, low-relief surface landscapes. The conventional explanation has been the “quasi-plain uplift” model, which insists that these surfaces are remnants of a previously continuous landscape [ 7 , 8 ]. This interpretation has usually assumed that the river network has been static in structure and has ignored the impacts of divide migration and reorganization of the river basin as part of the area’s geomorphologic evolution. In contrast, more recent theory refers to a “river piracy” concept, in which it is argued that formation of an in situ, low-relief surface can be promoted by feedback from a lost drainage area [ 9 , 10 ]. These two views may be complementary, but it is important to determine which formation mechanism has been dominant in an active tectonic region [ 11 ].
The widely distributed, low-relief surface landscapes in the Three Gorges area have attracted geographers’ attention over the long-term. Because of the absence of dating materials, the low-relief surfaces here have been controversial, in terms of their period, formation mechanism, and age. Most previous studies interpreted the low-relief surfaces as a planation surface, and divided them into different periods. Sheng [
12
] thought that there were three planation surface levels in the western Hubei Mountains area, while Tian et al. [
13
] proposed further dividing the planation surfaces of the Three Gorges area into three phases—as represented by the E’Xi, Shan Yuan, and Yun Meng planation surfaces—and five levels. Xie et al. [
14
] abandoned the previous naming method, noting that there were only two planation surface levels (high and low), with a single altiplanation surface level in this area, while Li et al. [
15
] believed that the higher planation surface was formed at the end of the Late Tertiary, and that its age was >25 Ma. The formation of the lower planation surface started at the beginning of the Late Tertiary and ended at 3.0–3.4 Ma, with the upper time limit for development of the lowest erosive surface dated to 1.80–2.04 Ma, and the lower limit dated to 3.0–3.4 Ma.
Some scholars have questioned the view that there are planation surfaces in the Three Gorges area. Ding [
16
] considered that there was no multilevel denudation surface in western Hubei, and that the differential lifting that took place during the Himalayan movement divided the previously formed denudation surfaces into different elevations, before eventually destroying them, more or less. Yang and Ren [
17
] believed that the multilevel landform surface of the western Hubei Mountains was not correctly described as a planation surface, and that the Three Gorges area has been in the regional watershed for a long time, making it impossible for a unified peneplain–planation surface to have formed. Wang et al. [
18
] showed that the current, layered landforms in the Three Gorges area may have resulted from crustal uplift that started in the Early Pleistocene. Overall, it seems plausible that the actual landform evolution process may be more complicated than the ideal intermittent uplift needed to form layered landforms, with different regions perhaps having different uplift histories.
Previous research described above has made a positive contribution to understanding the development of the low-relief surface landscapes in the Three Gorges area. However, its origin, and whether it should be labeled as a planation surface remain controversial topics. This shows that analysis of the upland, low-relief surface landscape formation mechanisms is important if the topographic evolution of the Three Gorges area is to be understood. Therefore, the purpose of the study described in this paper was to use 30 m resolution digital elevation model (DEM) to identify the distribution range of low-relief surfaces in the Three Gorges area, from the perspective of geomorphic indicators. To analyze the feedback effect of river basin reorganization on the formation of the upland low-relief surface, we constructed χ maps which provide a valuable metric for the state of disequilibrium. We also selected three low-relief patches, to demonstrate that they were not remnants from previous landforms, and then used a landscape evolution model (LEM) to simulate the low-relief surface formation mechanism visually. By using these tools and morphometric criteria, we emphasized the importance of river capture and drainage adjustment in the landscape evolution. Thus, this work provides both an insight into the geomorphologic origin of the current study area and a method that may apply to other similar research areas.
2. Study Area
The Three Gorges of the Yangtze River is located on the edge of the second transitional belt in China (
Figure 1
a), and its name was derived from the three adjacent gorges (Qutang Gorge, Wu Gorge and Xiling Gorge). Because of the difference in topography caused by the uplift of the Tibetan Plateau, the middle reaches of the Yangtze River reversed in the Three Gorges area, forming a continuous river flowing eastward [
19
]. The Qingjiang River is in western Hubei and a first-level tributary of the Yangtze River. In the study area, the trunk streams of the Yangtze and Qingjiang rivers flow from west to east, parallel to one another, and just tens of kilometers apart (
Figure 1
c).
Figure 1. Overview of the study area. ( a ) Map showing the location of the Three Gorges region, in the Yangtze River basin. ( b ) The mean precipitation over the study region obtained from Tropical Rainfall Measuring Mission. ( c ) Relief map showing study area elevations. The red lines are major faults.
The region’s geology has been controlled by a squeeze extension effect, caused by the northward intracontinental subduction pulsations of the Indian Plate, the Tibetan Plateau uplift, and lateral compression [
20
]. Since the Neogene, neotectonic movements in the Three Gorges area have been represented by vertical motion (formation of multilevel river terraces, multilayer karst, and modern crustal deformation), inherited fault activities and earthquakes. The geology of the study area consists of a crystalline basement structural layer and two sedimentary covering layers [
21
]. The area consists of a series of limestone ridges and gorges, which are predominantly interbedded mudstone, shale, and thin limestone [
22
].
Located in the subtropical monsoon climate zone, the average annual rainfall exceeds 800 mm in the Three Gorges region ( Figure 1 b), which causes severe ground erosion and makes deposit preservation on the low-relief surface landforms problematic. These characteristics make it difficult to obtain material suitable for dating.
3. Data and Methods
3.1. Data
High-accuracy DEM data are essential for many fields such as topographic morphology analysis [ 23 , 24 , 25 ]. The DEM used in this study was derived from SRTM1 Arc-second Global, which has a spatial resolution of 30 m [ 26 ] ( https://earthexplorer.usgs.gov/ ). Because the SRTM1 data have the characteristic of less noise, there are relatively fewer sinks that need to be filled, so the river networks created by SRTM1 in this research were more accurate than those created using other DEM data [ 27 ]. The average annual precipitation was obtained by resampling for the study area with a spatial resolution of approximately 5 × 5 km, based on the 10-year Tropical Rainfall Measuring Mission, 3B43 product (TRMM 3B43), covering the period 2009–2018.
3.2. Low-Relief Surface Mapping
The identification and reconstruction of low-relief surfaces are essential prerequisites for their application to geomorphologic analyses. In the past, identification of low-relief surfaces was usually based on topographic map research combined with field surveys to carry out ground-truthing, mapping and delineation; however, such a method is not only subjective, but also very time consuming [
28
]. With the development of remote sensing technology, DEM has become the most promising data source for extracting low-relief surfaces, as it records absolute elevations, which can be used for landscape visualization [
29
].
There are currently three main methods for mapping low-relief surfaces using DEM data. First involves manually drawing the surface distribution range by visual interpretation [ 22 , 30 ]. Although this method is very accurate, it demands high workload and has low efficiency. The second method involves using fuzzy logic to extract data, through smooth transitions [ 28 , 31 , 32 ], while the third requires the automatic extraction of low-relief surface levels, using certain geomorphic indicators [ 7 , 33 ].
Based on the characteristics of high efficiency and accuracy of the geomorphological factor index method, we adopted the third method for our work. First, using the Three Gorges low-relief surface field investigation results of Xie et al. [
14
], the DEM data were classified into two levels of elevation (
Table 1
). Then, the mean change point analysis method (the point where the degree of relief changes from steep to gentle, or vice-versa, in the curve) was used to determine 18 × 18 points as the optimum statistics window (
Figure 2
). After several trials, different relief parameters for different relief terrain elevation ranges were set (
Table 1
) to extract the distribution of terrain relief from each elevation surface. To eliminate artifacts and terrace effects, low-relief patches <0.1 km
2
were removed. Ultimately, application of this method revealed the Three Gorges region low-relief surface distribution.
Figure 2. Determining the optimal statistical window for topographic relief. ( a ) The coefficient of determination (R 2 ) between the window area and topographic relief, x and y represent window area and topographic relief, respectively; ( b ) mean change point graph. The curve slope changes from steep to shallow at the 18th point, so 18 × 18 pts was selected as the window size.
Table 1. Classification and parameter criteria for study area low-relief surfaces.
Topographic evolution and river channel network changes are linked processes, with river basins being an integral part of a dynamic system, balancing the adjustment between tectonic uplift and erosion [
34
]. Therefore, channel morphology analysis is an effective tool for evaluating the transient state of landforms, where river profiles can reflect signals indicating the dynamic evolution of landforms, and their deformation history, and can inform calibration of erosion models [
35
,
36
,
37
]. In particular, channel steepness, that is, the normalized channel steepness, can predict the response of the channel to the rock uplift rate. Slope-area analysis is an approach widely used in river network erosion pattern interpretation, through the normalized steepness index, or
k s n
[
38
]. There is a proportional relationship between riverbed slope and upstream catchment area in nature, and this can be expressed in the general form as:
S = k s A − θ
(1)
where
S
represents the local channel gradient,
A
indicates the reference drainage area, and
k s
and
θ
stand for the steepness index and reference concavity respectively [
39
].
When the river system is in a steady-state, the erosion rate (
K
) equals the uplift rate (
U
), and the channel steepness
( k s )
is proportional to
U
[
9
], and is expressed as:
K S = ( U K A 0 m ) 1 n
(2)
Obtaining an accurate slope calculation from a low-resolution DEM is challenging. Therefore, this study adopted the χ gradient method [ 35 , 40 ], using elevation instead of slope, and χ instead of catchment to calculate channel steepness. Using the algorithm developed by Schwanghart and Kuhn [ 41 , 42 ], χ plots were generated for the main streams and its tributaries.
The general form of the associated Equation is expressed as:
z = z b + ( U K A 0 m ) 1 n × χ
(3)
where
z b
indicates the position of the river outlet, which is generally assumed to be at the base level.
A 0
represents an arbitrary scaling area, so
χ
has a length unit. The integration method is defined as follows:
χ = ∫ 0 χ ( A 0 A ( x ′ ) ) m / n d x ′
(4)
where
A
(
χ
′) indicates the upstream catchment area,
m
and
n
represent empirical constants, and the ratio
m
/
n
describes the channel concavity (θ)—which is usually between 0.3 and 0.6 [
43
,
44
]. In this study, dynamic anomalies in river networks were detected by calculating the geomorphic index (χ), thereby providing a quantitative method for characterizing the impact of the instantaneous state on both river system evolution and low-relief surface landscape formation. We used the concave index as an empirical value (θ ≈ 0.45),
A 0
was set to 1 km
2
, and the χ values for rivers on both sides of the catchment were calculated from Equations (3) and (4).
Since elevation values along longitudinal river profiles are frequently affected by large scatters (e.g., errors and human factors) in topographic data, we applied the constrained regularization smoothing (crs) algorithm based on the quantile regression method to hydrological correction and to smooth the profiles. The final χ map was drawn using ArcGIS software.
3.3. Swath Profile
Swath profiles are significant when exploring the response of a landscape to tectonic activity and climate change. Compared with the traditional topographic profile, the swath profile is a widely used tool to reduce the randomness of the profile line, and focus on its more important morphological features [ 45 , 46 ]. Generally, low values in swath profiles, where all lines merge, indicate low to moderate incision. Conversely, high local relief and wider swath profiles characterize the dissected landforms that are related to high uplifts or deep river incisions in mountain belts [ 47 ].
Here, swath profiles and low-relief patch distribution were plotted together to explain the changes in the elevation curve better, and show whether the surface patches were spatially continuous. In this study, the Create Fishnet and Zonal Statistic tools in ArcGIS were used to draw swath profiles S1, S2, and S3, perpendicular to the study area. A horizontal swath profile (S4) was also generated, and it was based on the functions available in the Topographic Analysis Kit [
41
]. The maximum, minimum, and mean elevations of the swath profiles were calculated by statistical analysis, and then plotted using Origin. Among these, the relationship between the three curves revealed essential information about the state of the landscape, while the mean elevation curve illustrated the overall topographic trend along the swath profile.
3.4. Numerical Analytical Model
LEMs are 3D numerical simulation forms, and are crucial and valuable tools when studying the coupled tectonic–geomorphic evolution of mountain belts, and the respective effects of geomorphic processes, tectonic forces, and climate [ 48 , 49 , 50 , 51 , 52 , 53 ]. One of the most important ideas derived from numerical simulations is the concept of a steady-state mountain belt: the rapid rise of mountains may lead to an increase in relief, until the topography and exhumation are independent of time [ 54 , 55 ]. The main LEMs include the CASCADE, CHILD, FastScape, and Divide and Capture (DAC) models [ 33 , 50 , 56 , 57 ]. In our work, the DAC numerical analysis model was used to simulate landscape evolution, and included the physical processes associated with drainage divide migration and river capture [ 9 ].
In this study, a 120 × 60 km rectangular domain was defined, which had its four edges at a constant elevation. It was assumed that the slope index (
n
) was 1, the area index (m) was 0.45, the uplift rate (U) was 6 × 10
−4
m·yr
−1
, and the rock erodibility (K) was 4.0 × 1.0
−5
(m·yr)
−0.5
. Steady-state terrain data were generated using the initial random elevation field, assuming that the initial structural uplift rate was uniform in space, without horizontal motion, and that the precipitation levels and rock types were stable, thus forming the point for simulation initialization. After forming a symmetrical mountain range with a maximum elevation of 1500 m, vertical uplift was imposed to represent mountain building. The simulation started at 0 Ma and ended at 32 Ma, with 10,000 year intervals.
4. Results
4.1. Distribution of Upland Low-Relief Surfaces
Identifying the distribution of upland low-relief surfaces was an important foundation for the study of the Three Gorges region long-term geomorphic evolution. Based on previous research [ 14 , 15 ], this study identified two levels of low-relief surface landforms at different mountain heights, which we referred to as the higher and lower elevation surfaces ( Figure 3 ).
Figure 3. The spatial distribution and classification of the Three Gorges region low-relief surfaces.
This work found that the higher elevation surfaces (1700–2000 m), covering an area of 1589 km
2
, were mainly distributed on the high mountain tops in the drainage divide between the Yangtze and Qingjiang rivers, spread along the direction of the major fault lines. While only present in scattered patches on the north bank of the Yangtze River, it was found distributed over a continuous and large area of the south bank, in a distribution related to lithology, particularly the widespread distribution of carbonate rock on the Yangtze River south bank. Different rocks have different anti-erosion capabilities, and so, once a low-relief surface formed on limestone, it could be preserved for a long time, while the sandy shales on the north bank of the Yangtze River have always been more vulnerable to erosion and destruction. The south bank is also the boundary between the Yangtze and Qingjiang rivers drainages, and the mobility of this divide has also played a positive role in promoting low-relief surface formation.
In some instances, lithological effects change the mobility of the drainage divide [ 58 ]. When the widespread existence of carbonate in the south bank of the Yangtze River, which, being a single block, had reduced lithological change on both sides of the divide, was considered, the impact of lithology difference on cross-divide movement in the Three Gorges area did not seem obvious. The landform of the higher elevation surface was found to be a combination of wide shallow depressions and low hills and was found to be in a steep transition with a lower elevation surface.
The lower elevation surface (1200–1500 m), covering 5296 km
2
, was found to be distributed mainly around the low-relief surfaces of the higher elevation areas, with a wider distribution range. It was most developed in the west of the gorge area, with a greater presence on the south bank than on the north bank. The geomorphology at this level was mainly represented by a karst platform in the limestone basin, and the low-relief surfaces near the Yangtze River usually appeared as a platform, in a phenomenon that mainly reflected the extensive karst development in the area.
4.2. Chi (χ) Map Analysis
In this study, χ maps (
Figure 4
) were generated to reflect the horizontal dynamic changes of the river network in the Three Gorges area. The results of the χ mapping showed systematic differences in river geometry, with high χ values focused in two areas: (1) the watershed between the Yangtze River and Qingjiang River, and (2) the rivers in the W of the study area (
Figure 4
a). This feature suggested that these two parts of the overall basin had a relatively low erosion rate, and that the rivers in these areas had not reached geometric equilibrium. This issue deserves attention with respect to the Three Gorges region, as the transient state of landform evolution has often been the local cause of landslides, mudslides, and other regional disasters [
59
].
Figure 4. ( a ) Relationship between χ map and low-relief surfaces distribution in the Three Gorges region. Dashed white ovals show the location of the area shown in panel b. ( b ) Detailed χ map for the Baolong and Mashui River networks. ( c ) Geomorphic parameters showing the direction of the predicted divide migration. Black and white bars represent data from the Baolong River in the north, and the Mashui River in the south, respectively.
The χ values showed a pattern of clear differences on the divide between the tributaries of the Yangtze and Qingjiang rivers, indicating that this divide will move south to an equilibrium state through stream capture. Therefore, the χ-anomalies in this plot may have been reflecting either migration of the present-day divide, or the possibility of future divide movability in this region, due to recent river captures. The χ values were seen to drop off significantly on the E of the Three Gorges region, where drainage divides appeared stationary. There was no distinct contrast in χ values across the drainage divide at any scale that related to a recently captured area, reflecting its near equilibrium state.
4.3. Topographic Analysis
In this study, the swath profiles (see profile locations in Figure 5 a) were considered to describe topographic trends and local relief changes quantitatively. Topographic elevations showed no clear increasing or decreasing trends in the swath profiles, in either the vertical or horizontal direction ( Figure 5 b,c). The topography changed significantly along Sections S1 and S3, and the low-relief surfaces were scattered. S2 showed that the highest altitude and high-relief landforms appeared in the Shennongjia region, which is in the north of the Yangtze River.
Figure 5. Topographic swath (S) profiles in the Three Gorges study area: ( a ) Locations of the S1–4, the length of S1–3 is 150 km and S4 running parallel to the Yangtze River, together with the low-relief surface distribution (planar shown as green); ( b , c ) The upper red curve and the lower blue curve represent maximum and minimum elevations, respectively, with the solid gray line in the middle representing mean elevation. Gray bars indicate low-relief surface patches along the topographic profile.
We could see that a strong link existed between the low-relief surfaces and local relief. The lowest local relief values were found mainly on the highlands of the Yangtze and Qingjiang drainage divide, which roughly matched the distribution range for the upland low-relief surfaces. The relationship between the spatial distribution of low-relief patches and the swath profiles showed that low-relief surfaces were widely distributed at altitudes ranging from 1300–2000 m.
4.4. χ-Transformed Profiles (χ-Plots)
To test whether low-relief surfaces had a common uplift history, we generated χ-plots. In the study area, the knickpoints for most rivers were >1300 m, which was close to the distribution range of low-relief surface landscapes in the study area (
Figure 6
). For individual low-relief surfaces, three low-relief patches (CJ1, QJ1, and QJ2) were selected to analyze the differences in the χ-plots between their internal and external tributaries (
Figure 7
a–c). Internal tributaries are rivers with longer streams and larger drainage areas and are mainly distributed in low-relief surface landscapes. External tributaries are mainly located outside the region of low-relief surfaces and are rivers with short drainage systems and small catchments. It was showed that interior streams (victims) of low-relief surfaces have anomalously high χ-values and low erosion rates, whereas exterior streams (aggressors) have the low χ-values and high erosion rates (
Figure 7
d–f).
Figure 6. χ-transformed profiles of all major streams in the study area catchments. The red and gray lines represent profiles of the main streams and tributaries, respectively.
Figure 7. Relationship between individual low-relief surface patches and streams: ( a – c ) Landscape perspective view captured using Google Earth imagery (locations are those shown in the black boxes in Figure 4 a). The blue lines represent the exterior rivers of the low-relief surface landscape, while red lines represent interior rivers. The white arrows indicate flow direction, the black triangles shows the knickpoint, and the yellow points represents the downstream point common to all the rivers in the figure; ( d – f ) χ-plots for the major rivers in ( a – c ).
4.5. Numerical Analytical Model
To investigate the roles of river capture on the formation of low-relief surfaces, we conducted DAC numerical modeling (
Figure 8
). The model showed that the mountainous region was affected by tectonic uplift, the regional drainage network was disturbed, and the river basin was reorganized, the upstream part of the central stream was gradually captured by the surrounding pirate rivers (
Figure 8
b). This led to a reduced catchment area for the central river, which weakened its ability to erode the bedrock, to the extent that the continuous tectonic uplift was no longer balanced by fluvial erosion. The hillsides around the captured river were continuously eroded by external rivers, reducing local relief, and leading to a net surface uplift, that is erosion [E] < rock uplift [U]. Therefore, the tributaries of the beheaded river near the capture point experienced a period of rise, relative to the base level, eventually forming a low-relief surface located in the rugged peaks (
Figure 8
c).
Figure 8. Topographic evolution in a Divide and Capture (DAC) landscape model, showing river reorganization and low-relief surfaces. ( a – c ) represent the evolutionary sequence of the rivers and associated landforms in a region undergoing tectonic uplift. The rivers are colored based on their χ value, and the larger the χ value, the stronger the river’s ability to capture. The white arrows indicate the direction of drainage divide migration, and the green surface is the low-relief surface formed by river piracy (see also Supplementary movie S1 ).
5. Discussion
5.1. Drainage Evolution and River Basin Reorganization
The χ differences across drainage divides were evidence that the river network geometric structure was in a state of disequilibrium, and of the river capture and the dynamic reorganization processes of the water system [ 34 , 60 , 61 ]. When the rock uplift rate, lithology, and climate conditions does not change significantly on either side of a divide, drainage divide moves away from channels with low χ toward channels with higher χ [ 34 ].
The higher χ value on the southern side of the study area suggested that Qingjiang streams were captured by the Yangtze River, and that, in its search for stable basin geometry, the drainage divide migrated to the Qingjiang Basin. As evidence supporting this, the χ value at the source of the Mashui River, a tributary of the Qingjiang River, was very different to that of the Baolong River, a tributary of the Yangtze River (
Figure 4
b). The Baolong value was lower, and the Mashui value higher, indicating that the Baolong River of the Yangtze system captured the Ancient Mashui River of the Qingjiang system. The position of the ancient divide between the Yangtze and Qingjiang rivers was further north then, and as the Yangtze Basin constantly captured the Qingjiang Basin to the south, this caused the drainage divide to move southward (
Figure 4
c). This phenomenon has also been evident in some nearby river systems, suggesting that the drainage systems in the Three Gorges region have not yet achieved a particularly stable configuration.
The rivers with high χ values in Figure 4 a are close to the low-relief surface distribution range. Our analysis showed that this regular spatial distribution existed in the divide between the Yangtze and Qingjiang rivers, as well as along the south bank of the Qingjiang River. High χ values were found to be located inside the low-relief surface landform, while low χ values were mainly located elsewhere, outside the low-relief surface areas, indicating that low-relief surface landscape formation in the Three Gorges region was related to river capture and the subsequent dynamic reorganization of the river basin.
5.2. Was It Quasi-Plain Uplift or River Piracy Which Generated the Low-Relief Surfaces?
Detailed topographic analysis revealed that the Three Gorges area fulfilled the expectations for in situ generated low-relief upland surfaces formed in response to drainage area-loss, rather than being “relict” landscapes formed by quasi-plain uplift. Whipple et al. [
8
] noted that the diagnostic criteria for low-relief surface landscapes were that the remnants of the surface were all preserved at a similar altitude, they were approximately coplanar, and that they decreased in altitude systematically across the study area [
7
,
28
]. This possibility seems less likely in the Three Gorges area, however, as the distribution elevation of the low-relief surface patches did not show a systematic and obvious downward trend in the horizontal direction, as can be seen in
Figure 5
c.
The study found that the Three Gorges area low-relief surfaces were mostly located in the divide between the Yangtze and Qingjiang rivers, and that the catchments of related tributaries formed the low-relief surface patch boundaries, as shown in Figure 4 and Figure 5 b. The low-relief surfaces were found to be distributed between 1300 and 2000 m; they occurred at various altitudes within this range, their distribution appeared to be random and scattered, rather than continuous, and they did not appear to have been formed as a quasi-plain, which rose uniformly and simultaneously [ 17 ].
Two samples of the ancient fluvial gravel layer located between the Mashui and Baolong rivers were aged, using electron spin resonance dating, and were found to have been formed at 728 ± 72 ka and 789 ± 78 ka, respectively [
62
]. Comparison with the Three Gorges terrace substrates indicated that this gravel layer formed in the same period as the fifth terrace of the Three Gorges, in the early Middle Pleistocene [
15
]. However, it is noted that the elevation difference between the gravel layer and the fifth terrace was >1000 m, which indicated that there had not been a multilevel planation surface in the Three Gorges area. Moreover, the Three Gorges area had been a regional watershed since the Mesozoic, and had not been completely flattened into a “quasi-plain” [
17
]. All of which supported the concept that the upland low-relief surface landscapes in the Three Gorges region were not preserved patches of a landscape formerly at equilibrium.
Abrupt transitions on river profiles and log-transformed slope-area plots are termed slope-break knickpoints [
63
]. If the low-relief surface was a relict formed by river incision into a quasi-plain formed when regional uplift increased and the river network geometry was fixed, the trunk and tributary profiles of all rivers would show slope-break knickpoint changes at similar altitudes [
64
]. However, according to
Figure 6
, the χ-plots of all the major regional catchment streams display different collapse trends—as opposed to a regular change pattern in space. This result indicated that these low-relief surface patches did not experience a common uplift history [
18
], contrary to the relict landscape hypothesis.
The concept of “area-loss feedback” (ALF) refers to a drainage basin that has lost its catchment area, due to the impact of river capture, which leads to a decrease in its erosion rate and an increase in elevation; this increases the vulnerability of the catchment to further reduction, triggering a subsequent cascade of river capture and migration to the inner catchment [
8
]. The river profiles away from dynamic equilibrium and knickpoints are quite clear on the internal stream profile in
Figure 7
d–f. The results here show that even in a single plot, the χ-plots also showed a large scatter, indicating that they had different common uplift histories. Generally, the divide migrates in the direction with the lower erosion rate, which means that rivers outside low-relief surface patches are gaining catchment area by capturing the upper parts of inner rivers. In this work, it is noted three typical ALF mechanism cases in the Three Gorges, which were consistent with the concept of the low-relief surfaces were generated by river piracy. Hence, the study of well-validated cases in the Three Gorges area can improve our understanding of the elevated, low-relief surface landscape associated with drainage captures.
To simulate this mechanism, we established a DAC numerical model, which reflected the vertical uplift effect caused by neotectonic movement in the Three Gorges area (
Figure 8
). The model proved that the low-relief landscape patches formed in situ, in response to drainage area-loss following river capture. Although the dynamics of this landscape evolution could not be fully represented by this simple model, it satisfactorily constructed the concept, demonstrating the key role played by drainage evolution in the formation of low-relief surface landscapes in the Three Gorges region. Moreover, the model also reflected the sensitivity of river reorganization to vertical tectonic and revealed the function mechanism provided by river network geometry in the elucidation of geomorphic evolution.
6. Conclusions
In this study, low-relief surfaces in the Three Gorges area were plotted and quantitatively analyzed based on the geomorphologic index method, by using a 30 m resolution DEM. The analyses showed that the Three Gorges area has many low-relief surfaces distributed throughout, mainly on the highlands of the drainage divide between the Yangtze and Qingjiang rivers. Swath profiles were used to analyze the topographic features, and the spatial distribution of low-relief surfaces was not coplanar, reflecting that these surfaces had different uplift histories in different regions.
By characterizing the χ maps and dividing migrations, the study determined that the landform in the Three Gorges area was in an instantaneous state, and that the rivers were still undergoing dynamic reorganization, with the river basin having not yet reached equilibrium. The χ-transformed profiles were used to analyze the χ value differences between the inner and outer rivers of the landform surfaces, which showed that the low-relief patches in the Three Gorges area conformed to the expectations of an ALF mechanism. A DAC numerical model was then used to simulate landform evolution, and all the evidence taken together allowed us to form the hypothesis that the upland low-relief surface landscapes of the Three Gorges are not relict uplifted surfaces, but rather have formed in situ, based on long-term exchanges between river basins.
Overall, the study described here has allowed us to propose a valuable insight into the evolution of the low-relief surface landscapes of the Three Gorges, from the perspective of feedback effects caused by river piracy. We also recommend that the quasi-plain theory should be used more cautiously when explaining the evolution mechanism of the upland low-relief surface landscape. Because of the absence of dating materials, however, there is no direct evidence to show the formation age of the low-relief surfaces. In the future, accurate dating of low-relief surface landscapes will be required, if a deeper understanding of the long geomorphological history of the study region is to be achieved.
Supplementary Materials
The following are available online at https://www.mdpi.com/2072-4292/12/23/3899/s1 , Movie S1: Numerical simulation showing the evolution of landscape and drainage network.
Author Contributions
L.L. was responsible for the processing, interpretation of data and wrote the manuscript; L.W. and X.W. designed and supervised the work, and revised the manuscript; C.L. led the conception of the research; H.L., X.W., and S.W. were involved in discussion and editing. All authors have read and agreed to the published version of the manuscript.
Funding
This study is funded by the National Natural Science Foundation of China (grant No.41975044, No. 41801021, No.41871019, No.41672355), and the Special Fund for Basic Scientific Research of Central Colleges, China University of Geosciences, Wuhan (CUGCJ1704).
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1. Overview of the study area. ( a ) Map showing the location of the Three Gorges region, in the Yangtze River basin. ( b ) The mean precipitation over the study region obtained from Tropical Rainfall Measuring Mission. ( c ) Relief map showing study area elevations. The red lines are major faults.
Figure 2. Determining the optimal statistical window for topographic relief. ( a ) The coefficient of determination (R 2 ) between the window area and topographic relief, x and y represent window area and topographic relief, respectively; ( b ) mean change point graph. The curve slope changes from steep to shallow at the 18th point, so 18 × 18 pts was selected as the window size.
Figure 3. The spatial distribution and classification of the Three Gorges region low-relief surfaces.
Figure 4. ( a ) Relationship between χ map and low-relief surfaces distribution in the Three Gorges region. Dashed white ovals show the location of the area shown in panel b. ( b ) Detailed χ map for the Baolong and Mashui River networks. ( c ) Geomorphic parameters showing the direction of the predicted divide migration. Black and white bars represent data from the Baolong River in the north, and the Mashui River in the south, respectively.
Figure 5. Topographic swath (S) profiles in the Three Gorges study area: ( a ) Locations of the S1–4, the length of S1–3 is 150 km and S4 running parallel to the Yangtze River, together with the low-relief surface distribution (planar shown as green); ( b , c ) The upper red curve and the lower blue curve represent maximum and minimum elevations, respectively, with the solid gray line in the middle representing mean elevation. Gray bars indicate low-relief surface patches along the topographic profile.
Figure 6. χ-transformed profiles of all major streams in the study area catchments. The red and gray lines represent profiles of the main streams and tributaries, respectively.
Figure 7. Relationship between individual low-relief surface patches and streams: ( a – c ) Landscape perspective view captured using Google Earth imagery (locations are those shown in the black boxes in Figure 4 a). The blue lines represent the exterior rivers of the low-relief surface landscape, while red lines represent interior rivers. The white arrows indicate flow direction, the black triangles shows the knickpoint, and the yellow points represents the downstream point common to all the rivers in the figure; ( d – f ) χ-plots for the major rivers in ( a – c ).
Figure 8. Topographic evolution in a Divide and Capture (DAC) landscape model, showing river reorganization and low-relief surfaces. ( a – c ) represent the evolutionary sequence of the rivers and associated landforms in a region undergoing tectonic uplift. The rivers are colored based on their χ value, and the larger the χ value, the stronger the river’s ability to capture. The white arrows indicate the direction of drainage divide migration, and the green surface is the low-relief surface formed by river piracy (see also Supplementary movie S1 ).
Table 1. Classification and parameter criteria for study area low-relief surfaces.
Low-Relief Surface Elevation (m) Relief (m) Higher elevation surface 1700–2000 350 Lower elevation surface 1200–1500 300
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Lv, L.; Wang, L.; Li, C.; Li, H.; Wang, X.; Wang, S.
Formation Mechanism for Upland Low-Relief Surface Landscapes in the Three Gorges Region, China. Remote Sens. 2020, 12, 3899.
https://doi.org/10.3390/rs12233899
Lv L, Wang L, Li C, Li H, Wang X, Wang S.
Formation Mechanism for Upland Low-Relief Surface Landscapes in the Three Gorges Region, China. Remote Sensing. 2020; 12(23):3899.
https://doi.org/10.3390/rs12233899
Lv, Lingyun, Lunche Wang, Chang’an Li, Hui Li, Xinsheng Wang, and Shaoqiang Wang.
2020. "Formation Mechanism for Upland Low-Relief Surface Landscapes in the Three Gorges Region, China" Remote Sensing12, no. 23: 3899.
https://doi.org/10.3390/rs12233899
| https://www.mdpi.com/2072-4292/12/23/3899 |
ST PAUL’S ANGLICAN CHURCH TRINITY BAY MARRIAGES - 1821 - 1836
Welcome to Newfoundland's Grand Banks Genealogy site. It's a starting point to Newfoundland's unique background and way of life in North American history.
ST PAUL’S ANGLICAN CHURCH
TRINITY BAY
MARRIAGES
1821 - 1836
I must advise all who plan to use these entries for
research purposes, that this particular transcription was as difficult as any
encountered by this transcriber up to this point. In the many cases, the
writing has faded to near invisibility and the person or persons who performed
it, were compelled to write with smaller than usual script in order to fit the
required information onto the form used. The result is that a good many entries are nearly or
completely illegible, and much of this transcription, as indicated by the many
question marks, cannot and should not be interpreted as exact and precise
replications of the original record. Using every tool at my disposal, I have
done as well as I was able, but hope that while viewing these transcriptions,
researchers will bear in mind the difficulties confronting those who produced
them, and, where possible, advise NGB of any corrections or additions they can
offer. (Transcriber's Note) 1821This is to certify that FRANCIS BARNES of ??? Harbour,
Newfoundland, and ANNE BASTON of ???? Harbour,
Newfoundland, were married in this Church with consent of friends on this
third day of January, in the year one thousand eight hundred and twenty-one,
by me, J. Kingley Garland?, Magistrate.This marriage was solemnized between us, (No Information on Page) in the presence of: No Information on page)This is to certify that ROBERT CRANT of this Harbour,
Newfoundland, and ELIZABETH DIDDAMS of this Harbour,
Newfoundland, were married in this Church with consent of friends on this
28th day of January, in the year one thousand eight hundred and twenty-one,
by me, J. Kingley Garland?, Magistrate.This marriage was solemnized between us, (No Information on Page) in the presence of: No Information on page)This is to certify that CHARLES NEWHOOK of New Harbour, Trinity Bay
Newfoundland, and MARTHA PENNY of Carbonear, Conception Bay,
Newfoundland, were married in my house with consent of friends on this
4th day of May, in the year one thousand eight hundred and twenty-one,
by me, J. Kingley Garland?, Magistrate.This marriage was solemnized between us, Charles Newhook and Martha Penny in the presence of: Elizabeth Ash, ???? Grant, and Thomas ????This is to certify that SAMUEL GARLAND? of Trinity,
Newfoundland, (of Shipton George, Dorset, Eng.)* and MARY STILL of Trinity,
Newfoundland, were married in my house? with consent of friends on this
twenty-ninth day of May, in the year one thousand eight hundred and twenty-one,
by me, J. Kingley Garland?, Magistrate.This marriage was solemnized between us, Samuel (X) Garland
and, Mary (X) Still, (X) being their marks), in the presence of: Geo. Skelton,
J. P. James Collis, Frank Peckham, Robert Crawford and John ????*This note was entered in parentheses, as shown. -
Transcriber**There were six witnesses in all, but the ink has faded to
near invisibility, and other names could not be read. - TranscriberThis is to certify that, LAURENT MOLLET( He built old
St. Paul's Church)** and ELIZABETH BURRAGE?, both of Trinity, Newfoundland were
married in ?????, this eighth day of September, one thousand eight hundred and
twenty-one, by me, Geo. Skelton, Magistrate.This marriage was solemnized between us, Lauent Mollet and
G.B.??? in the presence of us, Wm Kelson, Ann. Kelson, S Skelton, John Hall**This note was inserted in parentheses as shown. The
researcher is referred to Doc. 7536 for more information regarding these two
people - TranscriberThis is to certify that, JAMES COLLIS of ??? Parish in the
Island of ??? in Great Britain, but now living at Trinity on the Island of
Newfoundland and MARY JENKINS? of the said Island, were married in ??? James
Collis's house, with consent of friends this twenty-second day of September, in
the year one thousand eight hundred and twenty-one, by me, Geo. Skelton,
Magistrate.This marriage was solemnized between us, James Collis and
Mary (X) Jenkins, (X) being her mark, in the presence of Rich'd Ash, Susanna
Landen, and John Hall,This is to certify that, THOMAS MILLER, of New Bonaventure?,
Island of Newfoundland, ELIZABETH MOORES of Trinity of Newfoundland, were married
on this twenty-third? day of September, in the year one thousand eight hundred
and twenty-one, by me, J.? Kingley Garland, Magistrate.This marriage was solemnized between us, Thomas (X) Miller
and, Elizabeth (X) Moores, (X) being their marks, in the presence of W. C. (X) Noland
and Josiah (X) Moores, (X) being their marks.*This is to certify that WILLIAM MAHER of Bonaventure and
FLORA JEANS of Spaniards Bay, Newfoundland, were married in this Church with
content of Father this twenty-seven day of September in the year one thousand
eight hundred and twenty-one by me, J. Kingsley Garland, Magistrate.This marriage was solemnized between us, William (X) Maher
and Elizabeth (X) Moores, (X) being their marks, in the presence of us, Edward
J. Clinch and Tho's. Dampier,This is to certify that JOHN GUPPY of ???d in
Somersetshire, now of Trinity in Newfoundland, and MARY RICKS? of Ships Cove
in Trinity Bay, were married in this church this thirtieth day of October in
the year one thousand eight hundred and twenty-one, by me, J. Kingsley Garland,
Magistrate,This marriage was solemnized between us John (X) Guppy and
Mary (X) Ricks , (X) being their marks, in the presence of Joseph Ballat, John Peckham ????, and Thomas (X) Cook, (X) being his mark.This is to certify that JOHN HOOKEY in the District of
Trinity and MARY HODDER of Ireland's Eye, in the said District, were married in
this church with consent of friends this thirty-first day of October in the
year one thousand eight hundred and twenty-one, by me, Geo. Skelton,
Magistrate.This marriage was solemnized between us John (X) Hookey and
Mary (X) Hodder , (X) being their marks, in the presence of Edw'd J. Clinch and
Elizabeth Finch,This is to certify that DENNIS MEAGHER of Trinity in the
District of Trinity, and MARY LEONARD? of Trinity, Newfoundland, were married
in my house with consent of friends this eighth day of November in the year one
thousand eight hundred and twenty-one, by me, Geo. Skelton, Magistrate.This marriage was solemnized between us: Dennis Meagher's
Mark, X,Mary Leonard's Mark, XIn the presence of B'w ColemanE.J. Clinch.This is to certify that GEORGE JANES of Trinity parish,
Newfoundland, and ROSE BUGDEN of Trinity parish, Newfoundland, were married in
this church with consent of friends this sixteenth? day November in the year
one thousand eight hundred and twenty-one, by me, Geo. Skelton, Magistrate.This marriage was solemnized between us George (X) Janes and
Rose (X) Bugden , (X) being their marks, in the presence of , Edw'd J. Clinch. 1822This is to certify that ALEXANDER BREMNER? of Trinity and
ANN? WHITE? orLANDER** of Trinity were married in Nada? house in Trinity with
content of friends this eighteenth day of January in the year one thousand
eight hundred and twenty-two, by me, Geo. Skelton, Magistrate.** The bride's name is entered as shown, with what looks
like the word 'or' preceding and actually connected by a writing stroke, to '
Lander', much in the fashion of O'Brien or O'Reilly, although in the case
here, it isn't 'O', it is 'or', in small case. Also, this transcriber can make
no sense out of 'ANN' followed by what appears to be the two surnames; 'WHITE'
and 'orLANDER'. Finally, a word looking like 'Nada', or 'Hada', precedes
'house'. - TranscriberThis marriage was solemnized between us Alex Bremner and Ann
(X) White orLander??? , (X) being her mark, in the presence of Thomas Cowell?,
James Collis, ??? ???, and David ???.This is to certify that JAMES HOBBS?? of New Bonaventure in
the District of Trinity, Island of Newfoundland and PATIENCE? PHILLIPS of said
place?, were married in this Church in Trinity with consent of Friends this
Thirteenth? day of October in the year one thousand eight hundred and
twenty-two, by me, William Bullock, Epis. Miss.*This marriage was solemnized between us James Hobbs and
Patience (X) Phillips, (X) being her mark, in the presence of Mary McGratt ??? and Sam'l
Miller?.This is to certify that JOHN MILLAR of New Bonaventure in
the District of Trinity, Island of Newfoundland and HANNAH WELLS of English
Harbour in the same district and Island, were married in this Church at Trinity
with consent of Brothers and friends, this fifteenth day of October in the year
one thousand eight hundred and twenty-two, by me, William Bullock, Epis. Miss.This marriage was solemnized between us John (X) Millar and
Hannah (X) Wells , (X) being their marks, in the presence of Sam?(X) Millar, of
Bonaventure and William (X) Millar?, (X) being their marks.This is to certify that JOHN WALTERS English Harb'r in the
district of Trinity, Island of Newfoundland, and SARAH WELLS of same place,
were married in this church at Trinity with consent of friends this fifteenth?
day of October in the year one thousand eight hundred and twenty-two, by me,
William Bullock, Epis. Miss.*Could also be 'Wellan', or 'Walsh'This marriage was solemnized between us John (X) Walters and Sarah
(X) Wells , (X) being their marks, in the presence of Joseph? (X) Wells and Sarah (???)
(X) Wells, (X) being their marks. 1823This is to certify that THOMAS STONE of Old Bonaventure of the
District of Trinity, Island of Newfoundland, and ELIZABETH BAYLEY of Trinity in
the same district and island, were married in this church at Trinity with
content of friends this twenty-sixth? day of October in the year one thousand
eight hundred and twenty-three, by me, William Bullock, Miss. E.M.**Episcopal Missionary - TranscriberThis marriage was solemnized between us Thomas (X) Stone and
Elizabeth (X) Bayley , (X) being their marks, in the presence of Maud McGratt, John Megher and his wife (X) being their marks.This is to certify that BENJAMIN MORRIS of Trinity, District
of Trinity, Island of Newfoundland, and MARGARET Gover (?) of the same place, were
married in this church with consent of mother and friends this eleventh day of
November in the year one thousand eight hundred and twenty-three, by me,
William Bullock, E.M.*This marriage was solemnized between us Benjamin Morris and
Margaret Gover (?), in the presence of Thomas Covell (?) and Elizabeth Ash. 1822This is to certify that JOSIAH MOORES of Trinity District in
the Island of Newfoundland and SUSANA WOOLRIDGE of the same place were married
in this church with consent of friends and mother this twelfth day of November
in the year one thousand eight hundred and twenty-two, by me, William Bullock, Epis.Miss.This marriage was solemnized between us Josiah (X) Moores and
Susana (X) Woolridge , (X) being their marks, in the presence of William (X) Moores,
Ann Coleman, and Emma (X) Moores, (X) being their marks. 1823This is to certify that THOMAS COURTNEY of English Harbour
in the District of Trinity in the Island of Newfoundland, and ANN PENNY of the
same place were married with consent of ??? ??? and priest, this ??? day of
November in the year one thousand eight hundred and twenty-three, by me,
William Bullock, Epis. Miss.This marriage was solemnized between us Thomas Courtney and
Ann (X) Penny , (X) being her mark, in the presence of James (X) Penny and Mary
Sheppard (X) being their mark.Here ends the notitia for 1822 (8)*This is to certify that JAMES IVAMY of New Bonaventure of
the District of Trinity in the Island of Newfoundland and SARAH BARNES of
English Harbour in the same district and island were married in this church of
Trinity with consent of father and friends this twenty-eighth day of December
in the year one thousand eight hundred and twenty-two, by me, Wm. Bullock, Epis.
Miss.This marriage was solemnized between us James Ivamy and
Sarah (X) Barnes, (X) being her mark, in the presence of Thomas (X) Miller and
Ann (X) Miller, (X) being their marks.*This note was inserted as and where shown here -
Transcriber 1823This is to certify that JOHN THORN of New Harbour in the
District of Trinity in the Island of Newfoundland and AGNES CLIFFORD of Trinity
Harbour in the same district were married in this church with consent of
friends this twenty-first day of March in the year one thousand eight hundred
and twenty-three, by me, William Bullock Epis. Missionary.This marriage was solemnized between us John (X) Thorn and
Agnes (X) Clifford, (X) being their marks, in the presence of E. J. Clinch and
Hannah Johnson, (X) being her mark.This is to certify that GEORGE BALL? of Mereby? Osborn,
County of Dorset, and ELIZABETH AUSTIN? of Bonavista, Island of Newfoundland,
were married in this church with consent of friends this first day of April in
the year one thousand eight hundred and twenty-three, by me, Wm. Bullock, E.M.This marriage was solemnized between us George Ball and
Elizabeth Austin, in the presence of Geo. Skelton and Thos. Fry.This is to certify that SAMUEL MORRIS aged 74 of the parish of
Edmond's ? Salsbury? in G. Britain and ANN TAYLOR of Bonavista were married in
this church with consent of friends this seventh day of April in the year one
thousand eight hundred and twenty-three, by me, William Bullock Epis. Miss.This marriage was solemnized between us Samuel Morris and
Ann (X) Taylor, (X) being heir mark, in the presence of Robert Clark? and E. J.
Clinch.This is to certify that RICHARD SEVIER of Riders Harbour,
District of Trinity and ELENOR DELANCY of Hearts Ease, of the same district
were married in this (no Entry) with consent of friends this twenty-first day of April
in the year one thousand eight hundred and twenty-three, by me, William
Bullock, Miss. ??This marriage was solemnized between us, Rich'd (X) Sevier
and Elenor (X) Delancy , (X) being their marks, in the presence of Henry (X) Hiscock
and Sarah (X) Stone?, (X) being their marks.This is to certify that JOHN WELCHMAN of Trinity in the
District of Trinity and HANNAH MOORE of the same place, were married in this
church * by me William Bullock, Miss. this District.*No date given -TranscriberThis marriage was solemnized between us John (X) Welchman
and Hannah (X) Moore, (X) being their marks, in the presence of Joseph (X) Janes
and Mary (X) WaldenThis is to certify that JOHN SKELTON of ????, Newfoundland
and ELIZABETH PITTMAN of this Parish were married in this church with consent
of ??? this eleventh day of October in the year one thousand eight hundred and
twenty-three, by me, William Bullock, Epis. Miss.This marriage was solemnized between us John Skelton and
Elizabeth Pittman in the presence of Sam'l Aug't Gent, ??? Skelton and H??? ???bridge**Cannot read witness names. - TranscriberThis is to certify that WILLIAM BULLOCK, bachelor, of Hulliston?,
County of Kent, England, and MARY ELIZABETH CLINCH, spinster, of this parish,
were married in this church, being no impediment, this eighth day of October in
the year one thousand eight hundred and twenty-three, by me, R.J.Burt, Epis.
Miss.This marriage was solemnized between us William Bullock and
Mary Elizabeth Clinch, in the presence of John Clinch, Catherine Bullock?,
Elizabeth Mary AshThis is to certify that SAMUEL HOBBS, bachelor, of Ditchet?
in the County of Somersetshire? and SARAH BARNES, widow, of English Harbor in
this district, were married in this church with consent of friends this
twenty-second day of October in the year one thousand eight hundred and
_________ by me, William Bullock, Miss. of this Church.This marriage was solemnized between us Samuel (X) Hobbs and
Sarah (X) Barnes , (X) being their marks, in the presence of E.J. Clinch and
William Thorne?This is to certify that JOHN HIND bachelor, of Swyre? in the
County of Dorset, and MARY ANN SHEPPARD of English Harbour in this district
were married in this church with consent of friends this Twenty-third day of
October in the year one thousand eight hundred and twenty-three, by me, William
Bullock, Epis.Miss.This marriage was solemnized between us John (X) Hind and
Mary Ann (X) Sheppard , (X) being their marks, in the presence of Charles(X)
Hurdle and George (X) Sheppard , (X) being their marks.This is to certify that PATRICK CHRISTOPHER, bachelor, of
the County of Kilkenny and ANNE RYAN spinster, of this parish of Trinity in
this district, were married in this church with consent of father and friends
this fifth day of November in the year one thousand eight hundred and
twenty-three, by me, William Bullock, Epis.Miss.This marriage was solemnized between us Patrick (X)
Christopher and Anne (X) Ryan , (X) being their marks, in the presence of Mary
(X) ??? and E.J. Clinch, (X) being her mark.This is to certify that CHARLES HODDER, bachelor, of the Parish
of Ireland's Eye in this district, and SARAH VERGE, spinster, of the same
place, were married in this church with consent of friends this eighth day of
November in the year one thousand eight hundred and twenty-three, by me,
William Bullock, Epis. Miss.This marriage was solemnized between us Charles (X) Hodder
and Sarah (X) Verge, (X) being their marks, in the presence of John (X) Hookey
and E.J. Clinch, (X) being his mark.This is to certify that GEORGE FREEMAN of Avon, County of
Hants and ELIZABETH RIX of this parish were married in this church with consent
of friends this eighth day of November in the year one thousand eight hundred
and twenty-three, by me, William Bullock, Epis. Miss.This marriage was solemnized between us George (X) Freeman
and Elizabeth (X) Rix , (X) being their marks, in the presence of Edward (X)
Sprague? and John (X) Freeman,(X) being their marks.This is to certify that ROBERT CURTIS, bachelor, of ??eldorford,
County of Dorset and JANE WATERS, widow, of this parish, were married in this
church, being no impediment, this thirteenth day of Nov. in the year one
thousand eight hundred and twenty-three, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Robert (X) Curtis
and Jane (X) Waters, (X) being their marks, in the presence of George Cooke and
E.J. ClinchThis is to certify that CHARLES WHITE, bachelor, of this
parish, and ELLEN CLARK, of this Parish, were married in this church with
content of friends this fourteenth day of November in the year one thousand
eight hundred and twenty-three, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Charles (X) White
and Ellen (X) Clarke, (X) being their marks, in the presence of Joseph (X) Taverner
and Rich'd? (X) Ash, (X) being their marks.This is to certify that JOHN MORRIS and SARAH RYALS, both of
this parish were married in this church with consent of parents this fifth day
of December in the year one thousand eight hundred and twenty-three by me,
William Bullock, Epis. Miss.This marriage was solemnized between us John (X) Morris and
Sarah (X) Ryals , (X) being their marks, in the presence of Sam Miller (X) and
E.J. Clinch, (X) being her mark.This is to certify that WILLIAM PECKHAM, bachelor, and MARY
FOWLOW, both of this parish were married in this church with consent of parents
this eleventh day of December in the year one thousand eight hundred and
twenty-three by me, William Bullock, Epis. Miss.This marriage was solemnized between us William (X) Peckham
and Mary (X) Fowlow, (X) being their marks, in the presence of John Peckham, and
Wm Gillard..This is to certify that CHARLES PESCHARD, bachelor, and ANN TAVENOR
, spinster, both of this parish, were married in this church with consent of
parents this eighteenth day December in the year one thousand eight hundred and
twenty-three by me, William Bullock, Epis. Miss.This marriage was solemnized between us Charles (X) Peschard
and Ann (X) Tavenor, (X) being their marks, in the presence of Thos. Pitt, ??? Whitford?, Mary? Bullock 1824This is to certify that WILLIAM MILLAR, bachelor, and MARTHA
WELLS, spinster, both of this parish, were married in this church with consent
of friends this second day of January in the year one thousand eight hundred
and twenty-four, by me, William Bullock, Epis. Miss.This marriage was solemnized between us William (X) Millar
and Martha (X) Wells , (X) being their marks, in the presence of William Bestone,
and William Ivamy.This is to certify that THOMAS FRY?, bachelor, of the parish
of Thapereck?, County of Dorset, G. Britain, and CHARLOTTE COLLINGHAM? of
this parish were married in this church, being no impediment ??? ??? friends,
this third day of February in the year one thousand eight hundred and
twenty-four, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Thomas Fry? and
Charlotte Collingham in the presence of Thos Pitt and G. M. Whitford .This is to certify that THOMAS KING, bachelor, of Poole in
the County of Dorset, Great Britain, and SARAH BURKE widow of this parish were
married in this church by being no impediment this eighteenth day of February in the year one
thousand eight hundred and twenty-four, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Thomas King and Sarah
(X) Burke, (X) being her mark, in the presence of John Brine and Anne Brine .This is to certify that GEORGE RIX, bachelor, and ELENOR GOWMAN?
spinster, ofthis parish were married in this church with consent of
friends this eighth day of May in the year one thousand eight hundred and
twenty-four, by me, William Bullock, Epis. Miss.This marriage was solemnized between us George (X) Rix and Elenor
(X) Gowman , (X) being their marks, in the presence of John (X) Leonard and E. J.
Clinch, (X) being his mark.This is to certify that WILLIAM BANISTER?? bachelor of this
parish, and MARY GOLDWORTHY?? both of this parish also, were married in this
church with consent of friends this fifteenth day of October in the year one
thousand eight hundred and twenty-four, by me, William Bullock, Epis. Miss.This marriage was solemnized between us William (X) Banister
and Mary (X) Goldworthy?, (X) being their marks, in the presence of E.J.
Clinch and Charlotte Fry.This is to certify that GEORGE RANDALL, bachelor of this
parish, and MARY COOK, of this parish also, were married with consent of
parents this fifteenth day of October in the year one thousand eight hundred
and twenty-four, by me, William Bullock, Epis. Miss.This marriage was solemnized between us George (X) Randall
and Mary (X) Cook, (X) being their marks, in the presence of E. J. Clinch and
Richard (X) Cook, (X) being her mark.This is to certify that GEORGE IVAMY, bachelor, of this
parish, and SUSANNAH COOK, of this parish also, were married in this church with
content of parents this twenty-fifth day of October in the year one thousand
eight hundred and twenty-four, by me, William Bullock, Epis. Miss.This marriage was solemnized between us George (X) Ivamy and
Susannah (X) Cook , (X) being their marks, in the presence of E.J. Clinch and
Richard (X) Cook, (X) being his mark.This is to certify that ROBERT CLARK, bachelor, and
ELIZABETH BARTLETT, spinster, both of this parish, were married in this church
with consent of friends this twenty-ninth? day of October in the year one
thousand eight hundred and twenty-four, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Robert (X) Clark and
Elizabeth (X) Bartlett , (X) being their marks, in the presence of E.J.
Clinch, Thomas (X) Clark, and ??? (X) Clark, (X) being their marks.This is to certify that WILLIAM FIFIELD, widower, of this
parish and ELENOR FORSTER, spinster,* were married in this church with consent
of parents this eleventh day of November in the year one thousand eight hundred
and twenty-four, by me, William Bullock, Epis. Miss.This marriage was solemnized between us William Fifield and Elenor
Forster in the presence of Ann Fifield, E. J. Clinch, and John Peckham Jun'r.This is to certify that ISAAC DOLE, bachelor, of the County
of K???T, and SARAH? PIERCY, widow, of this parish, were married in this
church, being no impediment, this twelfth? day of November in the year one
thousand eight hundred and twenty-four, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Isaac? (X) Dole and
Sarah (X) Piercy , (X) being their marks, in the presence of E.J. Clinch and
James Pardy .This is to certify that ANDREW? ?ORAMIN?, of the parish of
St. Paul's Church, Halifax, Nova Scotia, and SARAH BRINE, widow, of this
parish, were married in this church, being no impediment, this sixteenth day of
November in the year one thousand eight hundred and twenty-four, by me, William
Bullock, Epis. Miss.This marriage was solemnized between us Andrew ?oramin?,
E??* and Sarah (X) Brine , (X) being her mark, in the presence of John Brine,
Ann Brine, and E.J. Clinch .This is to certify that BEN? THOMPSON, widower, of the
parish of Poole?, County of Dorset?, and MARY PARDY, widow, of
Bonavista in Newfoundland, were married in this Church, being no impediment,
this twenty-fifth day of November in the year one thousand eight hundred and
twenty-four, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Ben Thompson and Mary
(X) Pardy?* , (X) being her mark, in the presence of Geo Buchanan and ??? ????This is to certify that EDWARD WILLIAMS, bachelor, of the
parish of Woolridge in the County of Dorset, and SUSAN JESTICAN, spinster, of
this parish, were married in this church with consent of parents this
fifteenth day of December, in the year one thousand eight hundred and
twenty-four, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Edward (X) Williams
and Susan (X) Jestican? , (X) being their marks, in the presence of E. J. Clinch and Charles AnsworthThis is to certify that, JOHN MOORES, bachelor, of this
parish, and MARY PINHORN?, spinster, of this parish, were married in this
church, with consent of parents this twenty-first day of December in the year
one thousand eight hundred and twenty-four, by me, William Bullock, Epis. Miss.This marriage was solemnized between us John (X) Moores and
Mary (X) Pinhorn? , (X) being their marks, in the presence of Rich'd Ash and
George Moores. 1825This is to certify that GEORGE BUCHANAN, bachelor, of the
parish of ??? in Scotland and ANNE BRINE, of this parish, were married in this
church with consent of parents this twenty-eighth day of April, in the year one
thousand eight hundred and twenty-five, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Geo. Buchanan and
Anne Brine, in the presence of Mary Kelson ?? and Rich'd Ash. Jun'r.This is to certify that JOHN HUFSON?, bachelor, of the
parish of ??? in the county of ???, New ??? in Hants Harbor and MARY PILLY?,
widow, of this parish, were married in this church of ??? ??? this twenty-ninth
day of August, in the year one thousand eight hundred and twenty-five, by me,
William Bullock, Epis. Miss.This marriage was solemnized between us John Hufson and
Mary Pilly? in the presence of Richard? Peckford? and Sarah George.This is to certify that, JOHN CLARK, bachelor, of this
parish, and ELENOR LEONARD, spinster, of this parish also, were married in
????????????????? with consent of friends, this twenty-second? day of Sept. in
the year one thousand eight hundred and, twenty-five by me, William Bullock, Epis.
Miss.This marriage was solemnized between us John (X) Clark and Elenor
( X) Leonard, (X) being their marks, in the presence of William (X) Clark and
Thomas (X) Clark, (X) being their marks.This is to certify that WILLIAM JANES, bachelor, of this parish
and MARY ANN WELDON? spinster, of the Parish of Bonavista, were married in this
church with consent of parent this twenty-sixth day of Sept, in the year one
thousand eight hundred and ____, by me, William Bullock, Epis. Miss.This marriage was solemnized between us William (X) Janes
and Mary Ann (X) Weldon? , (X) being their marks, in the presence of E.J.
Clinch and Josiah Frampton.This is to certify that, JONATHAN IVAMY, bachelor, of this
parish, and AMY MOORES, spinster, of this parish, were married in this church,
with consent of friends, this eleventh day of October in the year one thousand
eight hundred and twenty-five, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Jonathan (X) Ivamy
and Amy (X) Moores , (X) being their marks, in the presence of William Spencer and
Samuel Millar.This is to certify that GEORGE BROWN, bachelor, of the
parish of Bridar? in the county of Hampshire in Great Britain, and MARY
SEXTON? spinster, of this parish, were married in this church, being no
impediment, this seventh? day of November, in the year one thousand eight
hundred and twenty-five, by me William Bullock, Epis. Miss.This marriage was solemnized between us George (X) Brown and
Mary (X) Sexton , (X) being their marks, in the presence of E.J.Clinch and Samuel Edwards.This is to certify that, CHARLES PARKER Batch' of Millon? in
the County of Hants, Great Britain, and JANE SPRAGGE, spinster, of this parish,
were married in this church, with consent of parent, this ninth? day of November
in the year one thousand eight hundred and twenty-five, by me, William Bullock,
Epis. Miss.This marriage was solemnized between us Charles (X) Parker
and Jane (X) Spragge, (X) being their marks, in the presence of Samuel (X) Hobbs
and Grace (X) Ivamy?, (X) being their marks.This is to certify that SAMUEL MILLAR, bachelor, of this
parish, and MARY MOORES, of this parish, were married in this church with
content of friends this eighteenth day of Nov., in the year one thousand eight
hundred and twenty-five, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Samuel (X) Millar
and Mary Moores, (X) being his mark, in the presence of Joseph Millar and
George Moores.This is to certify that JOHN BANNISTER?, bachelor, of this
parish, and MARY STIVEY , spinster, also of this parish, were married in this
church, with consent of friends, this first day of December in the year one
thousand eight hundred and twenty-five, by me, William Bullock, Epis. Miss.This marriage was solemnized between us John (X) Bannister
and Mary (X) Stivey?, (X) being their marks, in the presence of E.J.Clinch and
Edward? Spragge?.This is to certify that JOHN TOBIN?, bachelor, of this
parish, and SARAH GOLDWORTHY?, of this parish, were married in this church with
content of parents this twenty-second day of December in the year one thousand
eight hundred and twenty-five, by me, William Bullock, Epis. Miss.This marriage was solemnized between us John (X) Tobin and
Sarah (X) Goodworthy?, (X) being their marks, in the presence of E.J.Clinch and
Sarah (X) Goodworthy, (X) being his mark.This is to certify that SAMUEL MILLAR, bachelor, of the
parish of Cla???dar, County of Somersetshire?, and MARY TOBIN?, of this parish,
were married in this church, with consent of friends this twenty-ninth? day of
December in the year one thousand eight hundred and twenty-five, by me, William
Bullock, Epis. Miss.This marriage was solemnized between us Samuel (X) Millar
and Mary (X) Tobin , (X) being their marks, in the presence of E.J.Clinch and
William WilshireThis is to certify that JOSEPH ABBOTT, bachelor, of the
parish of Bonaventure in this Island, and AMY IVAMY, spinster, of this parish,
were married in this church with consent of friends this twenty-first day of
April, in the year one thousand eight hundred and twenty-six, by me, William
Bullock, Epis. Miss.This marriage was solemnized between us Joseph Abbott and
Amy (X) Ivamy, (X) being her mark, in the presence of Richard Ivamy, William
Abbott, and E.J.Clinch.This is to certify that ROBERT RICKETTS, of ??????????????,
and RACHEL FOWLOW, spinster, of this parish, were married in this church, with
content of parents, being no impediment, this t??tienth? day of June in the
year one thousand eight hundred and twenty-six, by me, William Bullock, Epis.
Miss.This marriage was solemnized between us Robert (X) Ricketts
and Rachel (X) Fowlow , (X) being their marks, in the presence of Rich'd Ash
and John Peckham.This is to certify that JOHN QUENTEN of Red Cliff Island,
Batch, and GRACE SHORT, spinster, of the parish of Bonavista, were married in Bonavista
church this twenty-fifth day of October in the year one thousand eight hundred
and twenty-five, by me George Cooke.This marriage was solemnized between us John (X) Quenten and Grace
(X) Short , (X) being their marks, in the presence of Joseph Mifflin and John Donely.This is to certify that JOHN CHALK of Bird Island Cove,
bach, and, CATHERINE CARPENTER, of the same, spinster, were married in
Bonavista church, this tenth day of Feb'r in the year one thousand eight
hundred and twenty-five, by me, George Cooke.This marriage was solemnized between us John (X) Chalk and
Catherine (X) Carpenter , (X) being their marks, in the presence of Thomas Chaulk and David Tremlett*Unreadable - TranscriberNote: The comment, "Copied from Bonavista Register by
Act of Parliament" and signed by William Bullock, has been written along
the left hand margin of this document- TranscriberThis is to certify that JOSEPH MARTIN?, of Bird? Island Cove, bach.
and LUCY MILLER?, of the same, spinster, were married in Bonavista? church this
twenty-sixth? day of October, in the year one thousand eight hundred and
twenty-five, by me, George Cooke.This marriage was solemnized between us Joseph (X) Martin? and
Lucy (X) Miller?, (X) being their marks, in the presence of Henry Rowe and
Cornelius Burt?This is to certify that CORNELIUS BURT?, of Bird? Island
Cove, bachelor, and, MARY TUCKER?, of the same? spinster, were married at
Bonavista church, this twenty-ninth? day of October in the year one thousand
eight hundred and twenty five, by me, George Cooke.This marriage was solemnized between us Cornelius Burt? and
Mary (X) Tucker , (X) being her mark, in the presence of Henry Rowe and Henry LornowThis is to certify that JOHN SKIFFINGTON, Bonavista ??? and MARTHA
BEAUMOND, of the same, spinster, were married in this church this fourteehth
day of December, in the year one thousand eight hundred and twenty-five, by me,
George Cooke.This marriage was solemnized between us John Skiffinton and Martha
Beaumond in the presence of Malcolm Campbell? and James SkiffingtonThis is to certify that CHARLES BRIGHT of Bonavista, Bach,
and MARY HEBBARD?, of the same, Spin were married in this church, this
twenty-first day of December in the year one thousand eight hundred and
twenty-five, by me, George Cooke.This marriage was solemnized between us Charles (X) Bright
and Mary (X) Hebbard , (X) being their marks, in the presence of John Donnelly?
and Andrew Evans. 1826This is to certify that, JOHN DOMANEY? of Bonavista, Bach.,
and MARY APGOOD?, of same, were married in this church with consent of parents this
sixth? day of January, in the year one thousand eight hundred and twenty-six,
by me, George Cooke.This marriage was solemnized between us John Dominey? and Mary
(X) Apgood , (X) being her mark, in the presence of Matthew? Rider and John Squires.This is to certify that THOMAS SOPER of Bonavista,
bachelor, and, JANE? EYNES, of the same, widow, were married in this church,
this fifteenth day of January in the year one thousand eight hundred and
twenty-six, by me, George Cooke.This marriage was solemnized between us Thomas (X) Soper and
Jane (X) Eynes , (X) being their marks, in the presence of William Coff? and
William ???ke.This is to certify that THOMAS RUPEL ? of ???? bach.,
and MARY GOSLING? of Bonavista, spinster, were married in this church this
thirtieth day of April, in the year one thousand eight hundred and twenty-six,
by me, George Cooke.This marriage was solemnized between us Thomas (X) Rupel?
and Mary (X) Gosling, (X) being their marks, in the presence of William Cuff and William DykeThis is to certify that THOMAS TAYLOR? of Bonavista, bach.
and HANNAH NEWHOOK, of New Harbor, spinster, were married in this church this
??? day of May, in the year one thousand eight hundred and twenty-six, by me,
George Cooke.This marriage was solemnized between us Thomas Taylor? and
Hannah Newhook in the presence of Samson Mifflin ? and Hannah ? Newhook..This is to certify that ROBERT BELLOWS?, bachelor, of the
parish of Greenspond, and, RYME? SMITH, spinster, were married in this
church, on this thirteenth day of September in the year one thousand eight
hundred and twenty-six, by me, George Cooke. Archdeacon of Newfoundland.This marriage was solemnized between us Robert Bellows and
Ryme Smith , in the presence of Thos? Smith and John Brine?This is to certify that, JOHN McGragh?, bachelor, of this
parish, and MARY STONE, spinster, of this parish, were married in this church,
with consent of parent this twenty-fifth? day of September in the year One
Thousand Eight Hundred and Twenty-six, by me, William Bullock, Epis. Miss.This marriage was solemnized between us John (X) McGragh? and
Mary (X) Stone, (X) being their marks, in the presence of Robert Frampton and
James Grant.This is to certify that WILLIAM BEASTONE, bachelor, of this
parish, and ELIZABETH SPRAGGE, spinster, of this parish, were married in this
church this sixth day of November, in the year one thousand eight hundred and
twenty-sixth, by me, William Bullock, Epis. Miss.This marriage was solemnized between us William (X) Beastone
and Elizabeth (X) Spragge, (X) being their marks, in the presence of James
Penny? and James Sweetland.This is to certify that AMBROSE STONE , bachelor, and, JANE
FRAMPTON?, spinster, both of this parish, were married in this church, with
content of parents, on this thirteenth day of November in the year one thousand
eight hundred and twenty-six, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Ambrose (X) Stone and
Jane (X) Frampton?, (X) being their marks, in the presence of John Verge, Joseph
Short , and May ??? .This is to certify that JAMES STONE, bachelor, of this
parish, and ELIZABETH GOLDWORTHY? , of this parish, were married in this
church with consent of friends on this twenty-first day of November, in the
year one thousand eight hundred and twenty-six, by me, William Bullock, Epis.
Miss.This marriage was solemnized between us James (X) Stone and
Elizabeth (X) Goldworthy? (X) being their marks, in the presence of James Mooney?
and Edward? Spragge.This is to certify that JAMES MOODY, bachelor, and
ELIZABETH STIVEY?, spinster, both of this parish, were married in this
church, with consent of friends this twenty-third day of November in the year
one thousand eight hundred and twenty-six, by me, William Bullock, Epis. Miss.This marriage was solemnized between us James (X) Moody and
Elizabeth (X) Stivey?, (X) being their marks, in the presence of Absalom
Randall and Richard Nurse.This is to certify that WILLIAM HUXTER, bachelor, and MARIA
JANES?, spinster, were married in this church with consent of friends this
twenty-seventh? day of September, in the year one thousand eight hundred and
twenty-six, by me, William Bullock, Epis. Miss.This marriage was solemnized between us William (X) Huxter
and Maria (X) Janes? , (X) being their marks, in the presence of William Earley
and Francis Collings?This is to certify that WILLIAM ANDERSON, bachelor, of
this parish, and ELIZABETH BEASTON?, widow, also of this parish, were married
in this church, being no impediment, this ninth day of December in the year one
thousand eight hundred and twenty-six by me, William Bullock, Epis. Miss.This marriage was solemnized between us William (X) Anderson
and Elizabeth (X) Beaston?, (X) being their marks, in the presence of Richard
Penny and James Penny?. 1827This is to certify that JAMES TIBBS, widower, of this
parish, and MARTHA HISCOCK, spinster, also of this parish, were married in
this church, with consent of mother, this fifth day of May in the year one
thousand eight hundred and twenty-seven by me, William Bullock, Epis. Miss.This marriage was solemnized between us James (X) Tibbs and
Martha (X) Hiscock, (X) being their marks, in the presence of James Brown and E.J.Clinch.This is to certify that SAMUEL SHORT, Bachler, of this parish,
and MARY ANN DEAN?, spinster, of the parish of Bonavista, were married in this
church this tenth day of May, in the year one thousand eight hundred and
twenty-seven by me, William Bullock, Epis. Miss.This marriage was solemnized between us Samuel (X) Short and
Mary Ann (X) Dean, (X) being their marks, in the presence of Margaret Warr?
and Susannah Facey .This is to certify that THOMAS CLARK of this parish, and
HARRIET FLEET, of this parish, were married in this ??? ???, being no
impediment, this twelfth? day of October in the year one thousand eight
hundred and twenty-seven by me, William Bullock, Epis. Miss.This marriage was solemnized between us Thomas (X) Clark and
Harriet (X) Fleet, (X) being their marks, in the presence of William Fleet and
George Fleet.This is to certify that MATTHEW? IVAMY of this parish, and
PATIECE LEDROW, of this parish, were married in the Church? House?, this
first day of October in the year one thousand eight hundred and twenty-seven by
me, John Corbett? ???????????? Missionary. .This marriage was solemnized between us Matthew (X) Ivamy
and Patience (X) Ledrow, (X) being their marks, in the presence of William? Sweet
and Elizabeth Millar .This is to certify that JAMES PENNY, bachelor, of this
parish, and JANE? BARNES?, spinster, of this parish, were married in this
church with consent of parents, this eleventh day of October in the year one
thousand eight hundred and twenty-seven, by me, William Bullock, Epis. Miss.This marriage was solemnized between us James Penny and
Jane? (X) Barnes, (X) being her mark, in the presence of John Bestone and John
Bugden .This is to certify that ROBERT HISCOCK, bachelor, of this
parish, and JANE GOLDWORTHY?, spinster, of this parish, were married in this
church, being no impediment, this eighteenth day of October in the year one
thousand eight hundred and twenty-seven, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Robert (X) Hiscock
and Jane (X) Goldworthy?, (X) being their marks, in the presence of Richard
Cook, William Wolridge and Maria Goldworthy.This is to certify that JAMES EVERLY*?, bachelor, and SUSAN
SHEPPARD, spinster both of this parish, were married in this church, being no
impediment, this twenty-second day of October in the year one thousand eight
hundred and twenty-seven by me, William Bullock, Epis. Miss.This marriage was solemnized between us James (X) Sheppard*
and Susan (X) Sheppard, (X) being their marks, in the presence of Ann Fifield,
Joseph ??? and Elizabeth Fowlow (??).* NOTE: Name of James Everly and James Sheppard are spelled as they were on the original page of the register.This is to certify that EDWARD? RYAN?, bachelor, of this
parish, and MARY LONG?, spinster, of this parish, were married in this church,
with consent of parents, this twenty-first day of October in the year one
thousand eight hundred and twenty-seven by me, William Bullock, Epis. Miss.This marriage was solemnized between us Edward? (X) Ryan and
Mary (X) Long, (X) being their marks, in the presence of William Anderson and Mark?
BastonThis is to certify that JOSEPH? ANDERSON, bachelor, of this
parish, and JUDIAH?? HIGDEN?, widow, of this parish, were married in this
church, being no impediment, this twenty-fourth day of October, in the year one
thousand eight hundred and twenty-seven, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Joseph (X) Anderson
and Judiah? (X) Higden, (X) being their marks, in the presence of Rob't Bale (?) and
Jn'o Bale.This is to certify that WILLIAM BROWN, bachelor, of this
parish, and ANN LAIT? , spinster, both of this parish, were married in this
church, with consent of parents, this twenty-fifth day of October in the year
one thousand eight hundred and twenty-seven by me, William Bullock, Epis. Miss.This marriage was solemnized between us William (X) Brown
and Ann (X) Lait?, (X) being their marks, in the presence of Samuel Garland?
and William Gillard .This is to certify that JOSEPH IVAMEY, bachelor, of this
parish, and MARIE PENNY, spinster, of this parish, were married in this church,
with consent of parents, this first day of November in the year one thousand
eight hundred and twenty-seven by me, William Bullock, Epis. Miss.This marriage was solemnized between us Joseph (X) Ivamey
and Maria (X) Penny, (X) being their marks, in the presence of William Baston
and William Ivamy.This is to certify that FRANCIS? COLLINS, bachelor, of this
parish, and SUSAN HURDLE, spinster of this parish, were married in this church
of S. Pauls? with consent of mother, being no impediment, this third day of
Nov. in the year one thousand eight hundred and twenty-seven by me, William
Bullock, Epis. Miss.This marriage was solemnized between us, Francis (X) Collins
and Susan (X) Hurdle, (X) being their marks, in the presence of John Hurdle and
Phoebe Fleet.This is to certify that JNO COOMBS, bachelor, of Christ
Church, county of Dorset, G. Britain, and ANN McCARTHY, spinster, of the
parish, Carrigan?, in Ireland, were married in S. Mary's Church at Hearts
Content, with consent of ???, this sixth day of November in the year one
thousand eight hundred and twenty-seven by me, William Bullock, Miss. of
Trinity.This marriage was solemnized between us John (X) Coombs and
Ann (X) McCarthy, (X) being their marks, in the presence of Jno Babb, Arthur Scott,
and Mary Way.This is to certify that WILLIAM SPRIGGS, bachelor, of this
parish, and ELIZABETH JESTICAN, spinster, of this parish, were married in St.
Mary's Church, Hearts Content, with consent of friends this twelfth? day of
November in the year one thousand eight hundred and twenty-seven by me, William
Bullock, Epis. Miss. of St. Pauls, Trinity.This marriage was solemnized between us William (X) Spriggs and
Elizabeth (X) Jestican?, (X) being their marks, in the presence of Edward
Williams and Charles Randell.This is to certify that JAMES BROWN, bachelor, of Bonavista
parish and MARY HURDLE, Spinster, of this parish, were married with consent of
friends, this ??? day of ??? in the year one thousand eight hundred and
twenty-seven by me, ??? ???, Miss. ???????????.This marriage was solemnized between us James Brown and Mary
(X) Hurdle, (X) being her mark, in the presence of William Bullock and Maria WeeksThis is to certify that ROBERT MYERS bachelor, of this
parish, Peddlehenton, County of Dorset, and ELENOR HUNT, widow, of this
parish, were married in St. Paul's Church, with consent of friends, this third
day of Dec.in the year one thousand eight hundred and twenty-seven by me,
William Bullock, Minister of St. Paul's, Trinity.This marriage was solemnized between us Robert (X) Myers and
Elenor (X) Hunt, (X) being their marks, in the presence of John Myers and Jacob Chrigtoon (??)This is to certify that PATRICK FOWLER, bachelor, of this
parish, and SARAH PECKHAM, spinster, of this parish, were married in this
church, with consent of ???, this thirteenth day of December in the year one
thousand eight hundred and by me, William Bullock, Epis. Miss.This marriage was solemnized between us Patrick (X) Fowler
and Sarah (X) Peckham, (X) being their marks, in the presence of Elizabeth Fowlow
and Amy? Peckham.This is to certify that JOHN WAY, bachelor, of this parish,
and BRIDGET KINHALEY?, spinster, of this parish, were married in this church with
content of friends, this fourteenth? day of December in the year one thousand
eight hundred and twenty-seven by me, William Bullock, Minister of St.Paul's.This marriage was solemnized between us John (X) Way and
Bridget (X) Kinhaley?, (X) being their marks, in the presence of Francis Collins and
Anne Morris.This is to certify that WILLIAM MOORES, of this parish,
bachelor, and MARY JESTICAN?, spinster, of this parish, were married in this
church, with consent of friends, this twentieth day of December in the year one
thousand eight hundred and twenty-seven, by me, William Bullock, Minister of
St. Paul's.This marriage was solemnized between us William (X) Moores
and Mary (X) Jestican?, (X) being their marks, in the presence of Jpsiah Moores
and Sarah Jestican? . 1828This is to certify that JOSEPH? HEWLET? , bachelor, of the
parish of ???, County of Dorset, and HONOR? WELSHMAN, spinster, of this
parish, were married in the parish'? house, this ??? day of Jun.in the year one
thousand eight hundred and twenty-eight, by me, William Bullock, Minister of
St. Paul's.This marriage was solemnized between us Joseph? (X) Hewlet?
and Honor? (X) Welshman, (X) being their marks, in the presence of James
Lavender? and George Welchman ???.*This is to certify that CHARLES GRANGER, bachelor, of the
parish of M???horn Port in the county of Somerset, and JANE GREEN, spinster,
of this parish, were married with consent of friends, this twenty-sixth day of
March in the year one thousand eight hundred and twenty-eight, by me, William
Bullock, Minister of St. Paul's.This marriage was solemnized between us Charles (X) Granger
and Jane (X) Green, (X) being their marks, in the presence of William Clark, Mary Hiscock, and plus Mary Maria? Green.Immediately following the above entry, the following note
has been inserted: "Here ends the Notitia reported in 18?8".
-TranscriberThis is to certify that ROBERT BAILY and MARY KELSON? were
married in this church this eighteenth day of August in the year one thousand
eight hundred and twenty-eight, by me, William Bullock, Minister of St. Paul's.This marriage was solemnized between us Robert Bailey and
Mary Kelson, in the presence of Wm. Kelson Jun'r and Ann Kelson.This is to certify that DAVID ROGERS and MARY LOWDER? were
married in this church, this ninth? day of September in the year one thousand
eight hundred and twenty-eight, by me, William Bullock, Minister of St.
Paul's.*This marriage was solemnized between us David (X) Rogers and
Mary (X) Lowder?, (X) being their marks, in the presence of Susan Facey?,
Christian Facey?, and Jn'o Facey?This is to certify that RICHARD VIVIAN?, of the parish of
P??? near ??? in ??? ???, and, HANNAH? BAILY both of this parish, were married
in this Cataline, this twenty-second day of September in the year one thousand eight
hundred and twenty-eight, by me, William Bullock, Minister of St. Paul's.This marriage was solemnized between us Richard (X) Vivian?
and Hanna? (X) Baily, (X) being their marks, in the presence of Isaac Short?
and William Stone?This is to certify that STEPHEN? JANES?, bachelor, of this
parish, and ELIZABETH STICKLY?, spinster, of this parish, were married in ???,
this twenty-fifth day of September in the year one thousand eight hundred and
twenty-eight, by me, William Bullock, Minister of St. Paul's.This marriage was solemnized between us Stephen? (X) Janes?
and Elizabeth (X) Stickly?, (X) being their marks, in the presence of Ellen
Manuel and Anne Noone.This is to certify that STEPHEN MARTIN, bachelor, of this
parish, and CECILIA HISCOCK, spinster, of this parish, were married in ???,
this twenty-sixth day of September in the year one thousand eight hundred and
twenty-eight, by me, William Bullock, Minister of St. Paul's.This marriage was solemnized between us Stephen Martin and
Cecilia Hiscock in the presence of Edward Hiscock and Mary Clouter?.This is to certify that JOSEPH SHORT , bachelor, of this
parish, and MARY BAILY, * of this parish, were married in this church, with
content of friends this ninth day of ____in the year one thousand eight hundred
and twenty-eight, by me, William Bullock, Minister of St. Paul's.This marriage was solemnized between us Joseph (X) Short and
Mary (X) Baily (X) being their marks, in the presence of James Pitcher? and
Joseph Millar, both of Bonaventure?This is to certify that SAMUEL HOOKEY, bachelor, of this
parish, and MARIE? McGRAGH?, spinster, of this parish, were married in this
church, this thirteenth day of October in the year one thousand eight hundred
and twenty-eight, by me, William Bullock, Minister of St. Paul's.This marriage was solemnized between us Samuel (X) Hookey
and Maria? (X) McGragh?, (X) being their marks, in the presence of Ambrose?
Stone - Bonaventure and William Newhook - Trinity .This is to certify that MARK BEASTONE, bachelor, of this
parish, and SUSANNAH PENNY, spinster, of this parish, were married in this
church, with consent of parents, this fourteenth day of October in the year one
thousand eight hundred and twenty-eight, by me, William Bullock, Minister of
St. Paul's.This marriage was solemnized between us Mark (X) Beastone and
Susannah (X) Penny in the presence of and {John Penny and William Penny, Jun'r},
both of English Harbour.This is to certify that JOSEPH? WELLS, bachelor, of this
parish, and SARAH PENNY, spinster, of this parish, were married in this
church, this twenty-first day of October in the year one thousand eight hundred
and twenty-eight, by me, William Bullock, Minister of St. Paul's.This marriage was solemnized between us Joseph (X) Wells and
Sarah (X) Penny, (X) being their marks, in the presence of {John Penny and
William Bestone?}, both of English Harbour.This is to certify that HENRY GOLDWORTHY, bachelor, of
Salmon Cove, and MARY BEASTONE?, spinster, of the same, were married in this
church, with consent of friends, this twenty-ninth day of October in the year
one thousand eight hundred and twenty-eight, by me, William Bullock, Minister
of St. Paul's.This marriage was solemnized between us Henry (X) Goldworthy
and Mary (X) Beastone?, (X) being their marks, in the presence of Edward? Spragge
and Mark Grant.This is to certify that JOSEPH MILLAR, bachelor, of
Bonavista parish and DOROTHY HOGARTH?, spinster, of same place, were married in
this church with consent of friends, this thirty-first day of October in the
year one thousand eight hundred and twenty-eight, by me, William Bullock,
Minister of St. Paul's.This marriage was solemnized between us Joseph (X) Millar
and Dorothy (X) Hogarth? (X) being their marks, in the presence of James Hogarth?
and Mary Hogarth?This is to certify that ISAAC BUTLER, bachelor, of the
parish of Christ Church, County of Dorset, and MARY COOK, spinster, of St???ton
parish, were married in this church with consent of friends, this thirtieth day
of October in the year one thousand eight hundred and twenty-eight, by me,
William Bullock, Minister of St. Paul's.This marriage was solemnized between us Isaac Butler and
Mary (X) Cook, (X) being their marks, in the presence of Absalom Randall and
Jno Bannister, both of Ship Cove.This is to certify that JOHN MILLAR?, bachelor, of this
parish, and SUSANNAH BURRAGE, spinster, of the parish of Poole, County of
Dorset, G. Britain, were married in this church with consent of friends, this
second day of November in the year one thousand eight hundred and twenty-eight,
by me, William Bullock, Minister of St. Paul's.This marriage was solemnized between us John Millar? and
Susannah (X) Burridge, (X) being her mark, in the presence of Thomas Dowden and
Laurent M????.This is to certify that JOSEPH? BAILY, bachelor, of this
parish, and MARY PHILLIPS, spinster, of this parish, were married in this
church with consent of friends, this fourth day of November in the year one
thousand eight hundred and twenty-eight, by me, William Bullock, Minister of
St. Paul's.This marriage was solemnized between us Joseph (X) Baily and
Mary (X) Phillips, (X) being their marks, in the presence of and Jn'n Bann??,
Absalom Randall, and Thos. Bailey.This is to certify that JOSIAH? FRAMPTON, bachelor, of this
parish, and ELLEN KIRBY, spinster, of this parish, were married in this
church with consent of friends, this fifth day of November in the year one
thousand eight hundred and twenty-eight, by me, William Bullock, Minister of
St. Paul's.This marriage was solemnized between us Josiah? Frampton?
and Ellen (X) Kirby ?, (X) being their marks, in the presence of Thomas Green and
William ? Frampton.This is to certify that MOSES? SPURRELL ?, bachelor, of this
parish, and HONOR SEXTON ?, spinster, of this parish, were married in this
church with consent of friends, this sixth day of November in the year one
thousand eight hundred and twenty-eight, by me, William Bullock, Minister of
St. Paul's.This marriage was solemnized between us Moses? (X) Spurrell?
and Honor (X) Sexton?, (X) being their marks, in the presence of Philip Moores?This is to certify that WILLIAM? PEARCY?, bachelor of this
parish, and ANNE? GIFFORD , spinster, of this parish, were married in this church
with consent of friends and mother, this 11th day of November in the year one
thousand eight hundred and twenty-eight, by me, William Bullock, Minister of
St. Paul's.This marriage was solemnized between us William (X) Pearcy?
and Anne?(X) Gifford, (X) being their marks, in the presence of George Hutton and James? Pearcy
.This is to certify that JOSEPH BALLART, bachelor,* of this
parish, and MARY RYAN, spinster, of this parish, were married in this church
with consent of ??? and Parish, this eleventh day of November in the year one thousand
eight hundred and twenty-eight, by me, William Bullock, Minister of St. Paul's.*A word looking like 'Ballett' printed heavily in brackets
follows the word, 'Bachelor'. - TranscriberThis marriage was solemnized between us Joseph? (X) Ballart?
and Mary (X) Ryan, (X) being their marks, in the presence of James? Morris and
Mary Rowan .This is to certify that, WILLIAM WOOLRIDGE?, bachelor, of
this parish, and MARY HOUSE?, spinster, of this parish, were married in this
church with consent of parents, this twelfth? day of November in the year one
thousand eight hundred and twenty-eight, by me, William Bullock, Minister of
St. Paul's.This marriage was solemnized between us William (X) Woolridge?
and Mary (X) House?, (X) being their marks, in the presence of Josiah? Moores
and Mary ClouterThis is to certify that WILLIAM SPURRELL, bachelor, of this
parish, and SARAH? CLARKE, spinster, o this parish, were married in this church
with consent of mother, this twenty-eighth day of November in the year one
thousand eight hundred and twenty-eight, by me, William Bullock, Minister of
St. Paul's.This marriage was solemnized between us William (X) Spurrell
and Sarhah (X) Clarke, (X) being their marks, in the presence of Richard?
Clarke and Elizabeth Wheeler, both of ??? Cove?.This is to certify that JOSEPH TAVENOR?, bachelor, and
SUSAN KING, spinster, both of this parish, were married in this church with
content of friends, this twenty-second day of November in the year one
thousand eight hundred and twenty-eight, by me, William Bullock, Minister of
St. Paul's.This marriage was solemnized between us Joseph (X) Tavenor
and Susan (X) King, (X) being their marks, in the presence of William Curtis and
James Taverner? , both of Trinity.This is to certify that JOHN DAY, bachelor, of New Harbor?
and ANN THORN?, spinster, the same? parish, were married in this church with
content of friends, this twenty-fifth day of _____ in the year one thousand
eight hundred and twenty-eight, by me, William Bullock, Minister of St. Paul's.This marriage was solemnized between us John (X) Day and
Anne (X) Thorn, (X) being their marks, in the presence of {Thomas Thorne? and
James Thorne?}, both of New ???.This is to certify that JOHN HURDLE, bachelor, of this
parish, and MARY HISCOCK, spinster, of this parish, were married in my house
with consent of parents, this fifth day of December in the year one thousand
eight hundred and twenty-eight, by me, William Bullock, Minister of St. Paul's.This marriage was solemnized between us John (X) Hurdle and
Mary (X) Hiscock, (X) being their marks, in the presence of Sarah Dole?, Mary
Brown, Mary Newhook , and Charles Granger.This is to certify that WILLIAM WILSHIRE, bachelor, of
Bonavista, Island of Newfoundland, and MARY CROCKER, of ?? parish *, were
married in this church, with consent of parents, this fourteenth day of
December in the year one thousand eight hundred and twenty-eight, by me,
William Bullock, Minister of St. Paul's.This marriage was solemnized between us William Wilshire and
Mary Crocker in the presence of Stephen? Crocket?, John Crocker, and Jn'o?
Crocker Jun'r.*Bride's state, ie. spinster, or, widow, and abode not
entered. It has been well established, however, that the Crockers were from
Hearts Delight, although through marriage, there was some 'emigration' to
nearby surrounding communities - TranscriberThis is to certify that ABSALOM RANDALL, bachelor, of this
parish, and MARY BUTLER, spinster, of this parish, were married in this church
with consent of friends and parents, this fourteenth? day of December in the
year one thousand eight hundred and twenty-eight, by me, William Bullock,
Minister of St. Paul's.This marriage was solemnized between us Absalom (X) Randall
and Mary (X) Butler, (X) being their marks, in the presence of {George Randale
and Thomas? Randale.}*, both of S??? CoveThis is to certify that RICHARD CLARKE, bachelor, of this
parish, and ELIZABETH WHEELER, spinster, of the parish S. John's in this Island,
were married in this church with consent of friends, this twenty-third day of
December in the year one thousand eight hundred and twenty-eight, by me,
William Bullock, Minister of St. Paul's.This marriage was solemnized between us Richard (X) Clarke?
and Elizabeth (X) Wheeler, (X) being their marks, in the presence of {William
Clarke? and John Clarke.}, both of ??? ???*This is to certify that EDWARD ROWE?, bachelor, of this
parish, and SARAH ASH, spinster, of this parish, were married in this church
with consent of friends, this twenty-third day of December in the year one
thousand eight hundred and twenty-eight, by me, William Bullock, Minister of
St. Paul's.This marriage was solemnized between us Edward (X) Rowe? and
Sarah (X) Ash, (X) being their marks, in the presence of {Joseph Pinhorne and
William? Rowe}, both of this Harbor .This is to certify that WILLIAM DAVIS CROSS, bachelor, of
this parish, and SARAH LANDER widow, (of Thos. W. Lander, Vide. Nov 1.
1808)** of this parish, were married in this church with consent of friends,
this Christmas? day of December in the year one thousand eight hundred and
twenty-eight, by me, William Bullock, Epis. Miss.This marriage was solemnized between us William Davis Cross
and Sarah Lander in the presence of Alexander Bremner , S. A. Gent, and Mary Gentt.*A three-letter word immediately follows 'DAVIS', and
appears to be an abbreviation.**This note was scribbled in the space following the word,
'widow'. It appears to refer to the wedding date of Sarah and Thomas Lander. 1828This is to certify that WILLIAM FLEET, bachelor, of this
parish, and MARY RYAL? , spinster, of this parish, were married in this church
with consent of Priest?, this sixth day of January in the year one thousand
eight hundred and twenty-nine, by me, William Bullock, Epis. Miss.This marriage was solemnized between us (X)* and Mary (X) Ryal?,
(X) being her mark, in the presence of Samuel Morris, Anne Morris, and Thomas Reak.This is to certify that HENRY BAKER, bachelor, of this
parish, and HANNAH MARTIN, spinster, of this parish, were married in this
church, this twenty-third day of May in the year one thousand eight hundred and
twenty-nine, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Henry (X) Baker and
Hannah (X) Martin, (X) being their marks, in the presence of John Foster? and
William Fifield.This is to certify that GEORGE WEBBER, bachelor, of the parish
of St. Johns, Newfoundland, and MARY GRANT?, spinster, of this parish, were
married in this church with consent of parents, this fifth day of June in the
year one thousand eight hundred and twenty-nine, by me, William Bullock, Epis.
Miss.This marriage was solemnized between us George Webber and Mary
Grant, in the presence of James Winter, Chas Newhook and .??? ????*The following note is written along the bottom margin of
this page: "Here ends Notitia Reported? 1829 03? - TranscriberThis is to certify that THOMAS NEWTON, bachelor, of this
parish, and ELLEN? WELSH?, spinster, of Portland, county of Waterford, were married in this
church with consent of friends, this fourteenth day of October in the year one
thousand eight hundred and twenty-nine, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Thomas (X) Newton
and Ellen (X) Welsh?, (X) being their marks, in the presence of James Butler and Elizabeth Butler.This is to certify that THOMAS BAILEY?, bachelor, of this
parish, and MARY LAIT?, spinster, of this parish, were married in this church
with consent of friends, this fifteenth? day of October in the year one
thousand eight hundred and twenty-nine by me, William Bullock, Epis. Miss.This marriage was solemnized between us Thomas (X) Bailey
and Mary (X) Lait?, (X) being their marks, in the presence of George Everly and
George Lait Jun'r .This is to certify that RICH'D PENNY, bachelor, of this
parish, and JANE LONG, spinster, of this parish, were married in this church
with consent of friends, this twenty-first? day of Oct. in the year one
thousand eight hundred and twenty-nine, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Rich'd (X) Penny and
Jane (X) Long, (X) being their marks, in the presence of James Penny Jun. and
John Bestone?.This is to certify that JOHN HAITER?, bachelor, and Precilla
HISCOCK, spinster, both of this parish, were married in this church with
content of friends, this twenty-third day of October in the year one thousand
eight hundred and twenty-nine, by me, William Bullock, Epis. Miss.This marriage was solemnized between us John (X) Hayter? and
Prescilla (X) Hiscock, (X) being their marks, in the presence of William Spencer?
and Richard MaidmentThis is to certify that SAMUEL DIDNAM??, bachelor, of this
parish, and JOANNAH CLIFFORD, spinster, of this parish, were married in this
church with consent of friends, this fourteenth day of November in the year one
thousand eight hundred and twenty-nine, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Samuel (X) Didnam?
and Joannah Clifford, (X) being his mark, in the presence of Jasper? Hiscock? and
James Clifford.This is to certify that WILLIAM ROWE, bachelor, of this
parish, and PHOBE? FLEET, spinster, both of this parish, were married in this
church with consent of father and mother, this nineteenth day of November in
the year one thousand eight hundred and twenty-nine, by me, William Bullock, Epis.
Miss.This marriage was solemnized between us William (X) Rowe and
Phobe? (X) Fleet, (X) being their marks, in the presence of Ann Rowe and John Morrisey.This is to certify that JOHN BARNES, bachelor, of this
parish, and HARRIET BUGDEN, spinster, of this parish, were married in this
church with consent of friends, this twenty-sixth day of November in the year
one thousand eight hundred and twenty-nine, by me, William Bullock, Epis. Miss.This marriage was solemnized between us John (X) Barnes and
Harriet Bugden, (X) being his mark, in the presence of Matthew Kemner Bugden and
Joseph Barnes.This is to certify that JOHN BROWN, bachelor, Stratbridge?
County of ??vil, G. Britain, and DINAH MANHEY??, widow, of this parish, were married
in this church, this twentieth day of December in the year one thousand eight
hundred and twenty-nine, by me, William Bullock, Epis. Miss.This marriage was solemnized between us John (X) Brown and
Dinah (X) Manhey??, (X) being their marks, in the presence of Frances? Collings and
Will'm Brown .This is to certify that ROBERT GRANT, widower, of the parish
of Broadmain? County of Dorset, and HONOR CURTIS?, widow, of this parish, were married
in this church, this twenty-first day of December in the year one thousand
eight hundred and twenty-nine, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Rob't Grant and Honor
(X) Curtis, (X) being her mark, in the presence of James Hobbs and Rich'd? Philipes (??) . 1830This is to certify that THOMAS WATERMAN, bachelor, of the
parish of N????, County of Hants?, and SARAH HISCOCK, spinster, of this parish,
were married in Mr. Hiscock's house, with consent of parents, this eighth day
of March in the year one thousand eight hundred and thirty, by me, William Bullock,
Epis. Miss.This marriage was solemnized between us Thos. Waterman and
Sarah (X) Hiscock, (X) being her mark, in the presence of Rich'd Hiscock and
John? Hiscock .This is to certify that JAMES CLIFFORD, bachelor, of this
parish, and CATHERINE MONIE?, spinster, of this parish, were married in this
church, this twenty-first day of April in the year one thousand eight hundred
and thirty, by me, William Bullock, Epis. Miss.This marriage was solemnized between us James (X) Clifford,
Catherine (X) Monie, (X) being their marks, in the presence of Thomas Green
and John Barnes? .This is to certify that EDWARD HISCOCK, bachelor, of this
parish, and ANNE BRYANT?, spinster, of this parish, were married in this
church, this twenty-second day of April in the year one thousand eight hundred
and thirty, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Edward (X) Hiscock and
Anne (X) Bryant?, (X) being their marks, in the presence of Thomas Verge and
Charles Granger .This is to certify that JOHN THORN, bachelor, of this
parish, and CHARITY NEWHOOK, spinster, both of this parish, were married in
this church this twenty-fifth day of May in the year one thousand eight
hundred and thirty, by me, William Bullock, Epis. Miss.This marriage was solemnized between us John (X) Thorn and
Charity (X) Newhook, (X) being their marks, in the presence of {John Hoskins
and Thomas Thorn}, both of New Harbor.This is to certify that RICHARD ASH, bachelor, of this
parish, and MARTHA PINHORN, spinster, also of this parish, were married in this
church with consent of parents, this eleventh day of July in the year one
thousand eight hundred and thirty, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Rich'd Ash and
Martha Pinhorn in the presence of Rich'd Ash Jun. and Sarah? Lander.This is to certify that THOMAS JANES?, bachelor, of this
parish, and ANNE KING, spinster, of the Parish of Harbor? Gros?, were married
in this church with consent of friends, this eleventh day of Sept. in the year
one thousand eight hundred and thirty, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Thomas (X) ?Janes and
Anne (X) King, (X) being their marks, in the presence of Joseph Waldron and William Janes.This is to certify that GEORGE WHITE, bachelor, of Wi???? in
the County of Dorset in G. Britain, and ANNE WALTERS? spinster, of this parish,
were married in this church, this twentieth? day of Sept. in the year one
thousand eight hundred and thirty, by me, William Bullock, Epis. Miss.This marriage was solemnized between us George (X) White and
Anne (X) Walters?, (X) being their marks, in the presence of Charles? Newhook,
John Cotton?, and William Rogers.This is to certify that GEORGE LAIT?, bachelor, of this
parish, and ANNE WHITE, spinster, also of this parish, were married in this
church with consent of parents, this twentieth day of September in the year one
thousand eight hundred and thirty, by me, William Bullock, Epis. Miss.This marriage was solemnized between us George (X) Lait and
Anne (X) White, (X) being their marks, in the presence of Rich'd Ash and
Charles Carter .This is to certify that SAMUEL FACEY?, bachelor, of this
parish, and MARY CLOUTER, spinster, were married in this church with consent of
parents, this thirty-first day of October in the year one thousand eight
hundred and thirty, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Samuel (X) Facey and
Mary (X) Clouter, (X) being their marks, in the presence of Susanna Facey and
Christiana? Facey.This is to certify that RICHARD COOK, bachelor, of this
parish, and MARY BARNES, spinster, of the parish of Conception Bay, were
married in this church with consent of friends, this fourth day of November in
the year one thousand eight hundred and thirty, by me, William Bullock, Epis.
Miss.This marriage was solemnized between us Richard (X) Cook and
Mary (X) Barnes, (X) being their marks, in the presence of Rich'd Ash Jun'r.
and Rich'd Thorn.This is to certify that JAMES AUSTIN, bachelor, of this
parish, and CATHERINE LYTHAGOE??, widow, of the parish of St. Johns, in this
Island, were married in this church, this fifth day of November in the year one
thousand eight hundred and thirty, by me, William Bullock, Epis. Miss.This marriage was solemnized between us James Austin and
Catherine Lytley*, in the presence of Sarah Jestican? and John Hurdle.This is to certify that JAMES PENNY, widower, of this
parish, and GRACE? ??? , widow, of this parish, were married in this church,
this fifteenth? day of Nov. in the year one thousand eight hundred and thirty,
by me, William Bullock, Epis. Miss.This marriage was solemnized between us James (X) Penny and
Grace? (X) ???, (X) being their marks, in the presence of Sam'l Hobbs and John
Penny? .This is to certify that GEORGE HIGDEN, bachelor, of this
parish, and BRIDGET MILLAR?, of this parish also, were married in Mr. Janes?
house in Spaniards Bay, this eighteenth day of November in the year one
thousand eight hundred and thirty, by me, William Bullock, Epis. Miss.This marriage was solemnized between us George Higden and
Bridget Millar? in the presence of John Gardiner, George Young, both of British?
Harbour?, and Sa??? Janes, of Bonavista? Bay.This is to certify that RICHARD ANDERSON, bachelor, of this
parish, and SABRINA HURDLE, widow, of this parish also, were married in this
church, this nineteenth day of Novem'r in the year one thousand eight hundred
and thirty, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Richard (X) Anderson
and Sabrina? (X) Hurdle, (X) being their marks, in the presence of E.J. Clinch
and Mary Hiscock .This is to certify that JAMES COLLIS, bachelor, of the
parish of ???????? in Great Britain, and JOANNA SABBIN? of this parish, were
married in this church, this fifth day of December in the year one thousand
eight hundred and thirty, by me, William Bullock, Epis. Miss.This marriage was solemnized between us James Collis and
Joanna Sabbin? in the presence of M. E. Bullock and James Lockyer.This is to certify that JAMES MORRIS, bachelor, of this
parish, and Elinor Sulivan, spinster, of the parish of St. Johns, Newfoundland were
married in this church, this fifteenth day of December in the year one thousand
eight hundred and thirty, by me, William Bullock, Epis. Miss.This marriage was solemnized between us James (X) Morris and
Elinor (X) Sulivan (X) being their marks, in the presence of Rich'd Dooling and
James Morris .This is to certify that JOSEPH PITTMAN, bachelor, of the
parish ??? in Great Britain,and MARY WARR?, both of this parish, were married
in this church with consent of parents, this twenty-fifth day of December in
the year one thousand eight hundred and thirty, by me, William Bullock, Epis.
Miss.This marriage was solemnized between us Joseph? Pittman and
Mary Warr? in the presence of Will'm Warr and Will'm Kelson Jun'r . 1831This is to certify that BENJAMIN GREGORY bachelor, of the
parish of ?????????, in Great Britain, and, SUSAN FACEY?, spinster, of this
parish, were married in this church with consent of ???, this second day of
Jan. in the year one thousand eight hundred and thirty-one, by me, William
Bullock, Epis. Miss.This marriage was solemnized between us Benjamin (X) Gregory and
Susan (X) Facey?, (X) being their marks, in the presence of James B??? and Charles Newhook.This is to certify that THOMAS GAWLER, bachelor, of Saints, Dorchester, and, PATIENCE BUTLER, spinster, both of this parish, were married in this church
with consent of friends, this ninth day of Feb'r? in the year one thousand eight
hundred and thirty, by me, William Bullock, Epis. Miss.This marriage was solemnized between us Thomas (X) Gawler and
Patience (X) Butler, (X) being their marks, in the presence of Robert King and Jane Spurrell?
.This is to certify that GEORGE S. FIELD?, bachelor, of the
parish of Poole, County of Dorset, and ELIZABETH NEWHOOK, spinster, of this
parish, were married in this church, this twenty-seventh? day of March in the
year one thousand eight hundred and thirty-one, by me, William Bullock, Epis.
Miss.This marriage was solemnized between us Geo. S. Field? and
Elizabeth Newhook in the presence of Chas Newhook and J CarberryThis is to certify that WILLIAM CARBERRY??, bachelor, of this
parish, and HANNAH? BAILEY, spinster, of this parish, were married in this
church this second day of May in the year one thousand eight hundred and
thirty-one, by me William Bullock, Epis. Miss.This marriage was solemnized between us William Carberry and
Hannah Bailey? in the presence of Jn'o Carberry and Mary Hogarth.This is to certify that JAMES STANNER?, bachelor, of the
parish of L?p?????, and SUSAN? EVERLEY?, widow, of this parish, were married in
this ??? with consent of friends? this Seventh? day of May in the year one
thousand eight hundred and thirty-one, by me William Bullock, Epis. Miss.This marriage was solemnized between us, James Stanner and Susan
Everley, in the presence of William Hiscock? and Thomas Ryall.This is to certify that GEORGE? IVAMY?, bachelor, of this
parish, and LEAH BENSON, spinster, also of this parish, were married in this Church
with consent of Friends, this twenty-fourth? day of May in the year one thousand
eight hundred and thirty-one, by me William Bullock, Epis. Miss.This marriage was solemnized between us George Ivamy and
Leah Benson, in the presence of Jeremiah Rose and George Lewis .This is to certify that JOHN HALE?, bachelor, of this parish
and MARY THORN?, spinster, also of this parish, were married in this church with
content of friends this seventh? day of June in the year one thousand eight
hundred and thirty-one, by me William Bullock, Epis. Miss.This marriage was solemnized between us John Hale and Mary
Thorn in the presence of William Moores and Thomas? Jestican?, both of ???This is to certify that JAMES LOCKYER MEWS*, bachelor, of
the parish of Hants Eng., and CHRISTIANA FACEY, spinster, of this parish, were
married in this church with consent of parents this twenty-first? day of August
in the year one thousand eight hundred and thirty-one, by me William Bullock, Epis.
Miss.This marriage was solemnized between us James Lockyer M???ry?
and Christiana Facey in the presence of William Carbery? and Peter James F???
.This is to certify that HENRY BOWERING, bachelor, of the
parish of ???, County of Dorset?, G. Britain and SUSANNA? COOK?, spinster, of
this parish, were married in this church this twenty-sixth? day of September in
the year one thousand eight hundred and thirty-one, by me William Bullock, Epis.
Miss.This marriage was solemnized between us Henry Bowering and
Susanna (X) Cook, (X) being her mark, in the presence of Mary Newhook and Charles NewhookThis is to certify that RICHARD BAILY?, widower, of this
parish, and JANE? SPURREL, widow, of this parish, were married in this church
this tenth of October in the year one thousand eight hundred and thirty-one, by
me William Bullock, Epis. Miss.This marriage was solemnized between us Rich'd (X) B???y and
Jane (X) Spurrell, (X) being their marks, in the presence of Thomas Stone and
William Frampton.This is to certify that CHARLES NEWHOOK, bachelor, of this
parish, and SARAH LANDER, spinster, were married in this church with consent
of parents this sixteenth day of October in the year one thousand eight hundred
and thirty-one, by me William Bullock, Epis. Miss.This marriage was solemnized between us Charles Newhook (Signed) and
Sarah Lander (Signed) in the presence of William Alexoss (???) and William Corderoy.This is to certify that JOHN ??? , bachelor, of this parish,
and THIRZA IVAMY, spinster, of this parish, were married in this church with
content of parents this nineteenth day of October in the year one thousand
eight hundred and thirty-one, by me William Bullock, Epis. Miss.This marriage was solemnized between us John ??? and Thirza
(X) Ivamy, (X) being her mark, in the presence of William Ivamy and William
Nepton? .This is to certify that JAMES PERCY?, bachelor, of this
parish, and JANE RYAL, spinster, of this parish, were married in this church
with consent of parent this twenty-first day of October in the year one
thousand eight hundred and thirty-one, by me William Nisbett, ???.This marriage was solemnized between us James Percy? and
Jane Ryal, in the presence of Thomas Ryal and Joseph Percy .This is to certify that BENJAMIN STIVEY?, widower, of this
parish, and JANE PHILLIPS, spinster, of this parish, were married in this
church this twenty-fourth? day of October in the year one thousand eight
hundred and thirty-one, by me William Nistelt? mission and southern Trinity Bay.This marriage was solemnized between us Benjamin (X) Stivey
and Jane (X) Phillips, (X) being their marks, in the presence of William Dewlines
and George Burns .This is to certify that JAMES WALTERS?, bachelor, of this
parish, and JOHANNAH MATTHEWS, spinster, also of this parish, were married in
this church with consent of friends this thirtieth day of October in the year
one thousand eight hundred and thirty-one, by me William Bullock, Epis. Miss.This marriage was solemnized between us James (X) Walters
and Johannah (X) Matthews, (X) being their mark, in the presence of William Tavener and Thomas ThornThis is to certify that JOHN VERGE, bachelor, of this parish,
and ELIZABETH SHORT, spinster, also of this parish, were married in this
church with consent of friends this thirty-first day of October in the year one
thousand eight hundred and thirty-one, by me William Bullock, Epis. Miss.This marriage was solemnized between us John(X)Verge, and
Elizabeth (X) Short, (X) being their marks, in the presence of James Pitcher
and William Frampton.This is to certify that JAMES BESTONE, bachelorof this
parish, and MARIA? GOLDWORTHY?, spinster, were married in this church this third
day of November in the year one thousand eight hundred and thirty-one, by me
William Bullock, Epis. Miss.This marriage was solemnized between us James (X) Bestone, Maria
(X) Goldworthy? , (X) being their marks, in the presence of Henry? Goldworthy
and William? Bestone?.This is to certify that THOMAS HISCOCK , bachelor, of this
parish, and HANNAH DWYER?, spinster, were married in this church this eighth
day of November in the year one thousand eight hundred and thirty-one, by me
William Bullock, Epis. Miss.This marriage was solemnized between us Thomas (X) Hiscock,
and Hannah (X) Dwyer?, (X) being their marks, in the presence of Hannah Dwyer?*
and Mary Rowe?.This is to certify that HENRY?? MILLAR?, bachelor, of this
parish, and SUSANNA KING, spinster, also of this parish, were married in this
church this fifth? day of November in the year one thousand eight hundred and
thirty-one, by me William Bullock, Epis. Miss.This marriage was solemnized between us Henry (X) Millar and
Susanna (X) King, (X) being their marks, in the presence of Catherine King (?), Amy
Millar, and Jacob Millar.This is to certify that JOHN? GAULTON?, bachelor,
of the parish of Poole, and MARY NEWHOOK, spinster, of this parish, were
married in this church with consent of friends, this twentieth day of November in
the year one thousand eight hundred and thirty-one, by me William Bullock, Epis.
Miss. NOTE: Original entry was Goutren, Someone later wrote in (GAULTON) as original entry not very clear. Entry where he signed his name does appear to be Gaulton.This marriage was solemnized between us John Gaulton and Mary
(X) Newhook, (X) being her mark, in the presence of James Hill and John CrockerThis is to certify that JAMES HILL?, bachelor, of the parish
of ???, St. Mary's Magdeline Church. and ELIZABETH NEWHOOK, spinster, of this
parish, were married in this church with consent of friends this twenty-seventh day of
November? in the year one thousand eight hundred and thirty-one, by me William
Bullock, Epis. Miss.This marriage was solemnized between us James (X) Hill and
Elizabeth (X) Newhook, (X) being their marks, in the presence of Charles Finch and
G. CrockerThis is to certify that GEORGE JEFFREY, bachelor, of the
parish of T???berry?, County of Somerset?, and ANNE TIBBS? , ???, of the parish
of were married in this church with consent of friends this fifth? day of
December in the year one thousand eight hundred and thirty-one, by me William
Bullock, Epis. Miss.This marriage was solemnized between us George (X) Jeffrey and
Anne?(X) Tibbs? , (X) being their marks, in the presence of John FAcey Jun'r and William TibbsThis is to certify that JAMES LOCKER?, bachelor, of the
parish of S. N???, County of ???, Scotland, and AMELIA FRANCES? SKELTON?,
spinster, of the parish S. George?, T??? Square, London? were married in this
church with consent of friends this seventh? day of December in the year one
thousand eight hundred and thirty-one, by me William Bullock, Epis. Miss.This marriage was solemnized between us James Locker? and
Amelia Frances? Skelton?, in the presence of Geo. Skelton and Wm. Kelson? Jr.This is to certify that WILLIAM MARSH, bachelor, of the
parish of ???, County of Somerset, and MARY JANES, widow, of this parish, were
married in this church with consent of friends this fourteenth day of December
in the year one thousand eight hundred and thirty-one, by me William Bullock, Epis.
Miss.This marriage was solemnized between us William (X) Marsh and
Mary (X) Janes , (X) being their marks, in the presence of Charles Hodges and Charles Answorth .This is to certify that JAMES TAVENOR?, bachelor, of this
parish, and ELIZABETH LAIT?, spinster, also of this parish, were married in
this church with consent of friends? this seventeenth day of December in the
year one thousand eight hundred and thirty-one, by me William Bullock, Epis.
Miss.This marriage was solemnized between us James (X) Tavenor ,
Elizabeth (X) Lait, (X) being their marks, in the presence of William Taverner?
and Charles Stone. 1832This is to certify that WILLIAM KELSON, bachelor, of this
parish, and ELIZABETH MARY ASH, of this parish, were married in this church
with consent of parents and friends this twenty-sixth day of January in the year
one thousand eight hundred and thirty-two, by me William Bullock, Epis. Miss.This marriage was solemnized between us William Kelson and
Elizabeth Mary Ash in the presence of Rich'd Ash and Elizabeth Pinhorn.This is to certify that WILLIAM CLIMN, *, and MARGARET WERR,
of this parish, were married in this church with consent of ??? this ???ty-???
day of Jan'y in the year one thousand eight hundred and thirty-two, by me
William Bullock, Epis. Miss.This marriage was solemnized between us William Climn? and Margaret
Warr in the presence of Will'm Corduroy? and Will'm Thornes?*A very faded and blurred inscription follows this name, and
a word vaguely resembling 'Dorset' appears second among them.This is to certify that RICH'D DOOLING, bachelor, of this
parish, and ANNE? MORRISY?, spinster, of this parish, were married in this
church this twenty-fifth day of Feb? in the year one thousand eight hundred and
thirty-two, by me William Bullock, Epis. Miss.This marriage was solemnized between us Rich'd (X) Doolings?
and Anne (X) Morrisey, (X) being their marks, in the presence of Philip Moores,
John Morrisey, and James Morrisey.This is to certify that GEORGE OLD, bachelor, of the parish
of ???, county of Dorset, G. Britain and MARY NEWHOOK, widow, of this parish,
were married in this church this third day of May in the year one thousand
eight hundred and thirty-two, by me William Bullock, Epis. Miss.This marriage was solemnized between us George (X) Old and
Mary (X) Newhook , (X) being their marks, in the presence of Charles Newhook and
Wlliam CollisThis is to certify that WILLIAM DOOLING, bachelor, and MARY
ASH, spinster, both of this parish, were married in this church with consent of
friends this Twelth day of May in the year one thousand eight hundred and thirty-two,
by me William Bullock, Epis. Miss.This marriage was solemnized between us William (X) Dooling
and Mary (X) Ash, (X) being their marks, in the presence of James Sweetland
and John Etheridge.This is to certify that SAMUEL BROOKS, bachelor, of Watte???an,
County of Somersetshire, Wales , and SARAH JANES, of this parish, were married
in this church with consent of friends this twenty-sixth? day of May in the
year one thousand eight hundred and thirty-two, by me William Bullock, Epis.
Miss.This marriage was solemnized between us Samuel (X) Brooks
and Sarah (X) Janes, (X) being their marks, in the presence of Jasper Hiscock, Will'm
Lucas? and Philip G??? .This is to certify that SAMUEL HOOKEY, widower, of this
parish, and ELIZABETH KELSEN spinster, of this parish, were married in this
church with consent of friends this sixteenth day of June in the year one
thousand eight hundred and thirty-two, by me William Bullock, Epis. Miss.This marriage was solemnized between us Samuel (X) Hookey
and Elizabeth (X) Kelsen, (X) being their marks, in the presence of Moses Spurrell
Trinity and John Spurrell, Bonaventure..This is to certify that JOHN COLEMAN widower, and JANE
DELANY, spinster, both of this parish, were married in this church with
content of friends this first day of July in the year one thousand eight
hundred and thirty-two, by me William Bullock, Epis. Miss.This marriage was solemnized between us John Coleman and
Jane (X) Delany in the presence of John Poore and Nicholas BulgerThis is to certify that JAMES SHORT, bachelor, and
ELIZABETH CHURCHILL spinster, both of this parish, were married in this church with
content of friends this first day of October in the year one thousand eight
hundred and thirty-two, by me William Bullock, Epis. Miss.This marriage was solemnized between us James (X) Short and
Elizabeth (X) Churchill, (X) being their marks, in the presence of Samuel? Short
and William Short .This is to certify that GEORGE HOUSE, bachelor, of the
parish of Bonavista, and ELIZABETH SEXTON, spinster, of this parish, were
married in this church with consent of parent? this thirteenth day of October
in the year one thousand eight hundred and thirty-two, by me William Nisbett,
Eminence.This marriage was solemnized between us George House and Elizabeth
Sexton, in the presence of Jacob (X) Sinyard? and George (X) Sheppard, (X)
being their marks.This is to certify that WILLIAM IVAMY, bachelor, and SARAH
HART?, spinster, were married in this church with consent of mother, this
twenty-third? day of October in the year one thousand eight hundred and
thirty-two, by me William Bullock, Epis. Miss.This marriage was solemnized between us William (X) Ivamy
and Sarah (X) Hart?, (X) being their marks, in the presence of Joseph? Wellls?
and Robert? Hart .This is to certify that THOMAS PAWN bachelor, of W?????,
and SUSANNE SPRAGGE spinster, both of this parish, were married in this church
with consent of friends this thirty-first day of October in the year one
thousand eight hundred and thirty-two, by me William Bullock, Epis. Miss.This marriage was solemnized between us Thomas (X) Pawn
and Susanne (X) Spragge, (X) being their marks, in the presence of William ?
Baston ? and Robert Penny.This is to certify that GEORGE? MOORES, bachelor, of this
parish, and MARY ANN FROUD, spinster, of this parish, were married in this
church with consent of friends this thirteenth day of November in the year one
thousand eight hundred and thirty-two, by me William Bullock, P??? ???. Miss.
???.This marriage was solemnized between us George (X) Moores
and Mary Ann (X) Froud?, (X) being their marks, in the presence of James Crocker?
and James? Morrisy?.This is to certify that HENRY GOLDWORTHY, bachelor, of this
parish, and MARY DWYER?, spinster, were married in this church with consent of
friends this twenty-third day of November in the year one thousand eight hundred
and thirty-two, by me William Bullock, Epis. Miss.This marriage was solemnized between us Henry (X) Goldworthy
and Mary (X) Dwyer?, (X) being their marks, in the presence of Thomas Ryal?
and John? Pitt.This is to certify that SAMUEL MILLAR, widower, of this
parish, and ELIZABETH FOWLOW, spinster, also of this parish, were married in
this church with consent of parent this fourteenth day of December in the year
one thousand eight hundred and thirty-two, by me William Bullock, Epis. Miss.This marriage was solemnized between us Samuel Millar and
Elizabeth (X) Fowlow, (X) being her mark, in the presence of Thos Fowlow and
James? Millar .This is to certify that RICH'D HISCOCK, bachelor, of this
parish, and ELIZABETH HEZWOOD?, spinster, of the parish of Bonavista, were married
in this church with consent of friends this twenty-fourth day of December in
the year one thousand eight hundred and thirty-two, by me William Bullock, Epis.
Miss.This marriage was solemnized between us Rich'd (X) Hiscock
and Elizabeth (X) Hezwood?, (X) being their marks, in the presence of William Hiscock
and George Christiana. 1833This is to certify that NICHOLAS BULGER?, bachelor, of the
parish of St. Johns, and CATHERINE DELANEY, spinster, of this parish, were
married in this church with consent of friends this sixteenth day of April in
the year one thousand eight hundred and thirty-three by me William Bullock, Epis.
Miss.This marriage was solemnized between us Nicholas Bulger and
Catherine (X) Delaney, (X) being her mark, in the presence of Robert Pratt of
Bonavista? and M'r Poore of Trinity.This is to certify that THOMAS MEADOWS, bachelor, of the
parish of Camford, County of Dorset? and CHRISTIANA WHITE spinster, of this
parish, were married in this church with consent of parent this twenty-ninth
day of May in the year one thousand eight hundred and thirty-three, by me
William Bullock, Epis. Miss.This marriage was solemnized between us Thomas Meadows and
Christiana (X) White, (X) being her mark, in the presence of John Walters and
M. Walters.This is to certify that ADAM MAITLAND?, bachelor, of the
parish of Lough? in ??shire, and BARBARA PROTHORD?, spinster, of the parish Handa's?
in C????, were married in this church with consent of friends this twenty-???
of August in the year one thousand eight hundred and thirty-three, by me
William Bullock, Epis. Miss.This marriage was solemnized between us Adam Maitland and
Barbara Prothoror, in the presence of Geo. Buchanan and Mrs BullockThis is to certify that JAS COLLIS?, bachelor, of the
parish Millon? Corish? of Honpohia? and SARAH? HODDER, spinster, of this
parish, were married in this church with consent of parents this eighth? day of
September in the year one thousand eight hundred and thirty-three, by me
William Bullock, Epis. Miss.This marriage was solemnized between us James Collis and Sarah Hodder,
in the presence of Geo. Skelton? and Mary Fleet.This is to certify that GEORGE CROCKER, bachelor, and
ELIZABETH? ANDERSON, widow, both of this parish, were married in this church
this twenty-first day of September in the year one thousand eight hundred and
thirty-three, by me William Bullock, Epis. Miss.This marriage was solemnized between us George Crocker and
Elizabeth (X) Anderson, (X) being her mark, in the presence of Charles Granger
and Will'm (X) Verge (X) being his mark.This is to certify that THOMAS HARNHAM?, bachelor, and MARY
POLLETT, spinster, both of this parish, were married in this church with
content of friends and guardian? this twenty-sixth? day of September in the year one
thousand eight hundred and thirty-three, by me William Bullock, Epis. Miss.This marriage was solemnized between us Thomas Hanrham? and
Mary (X) Pollett, (X) being her mark, in the presence of {Charles Hodges and
William Rogers,} born? of Mic Mac?*This is to certify that ROBERT PAUL, bachelor, of the parish
of ??mister, County of Fran??? and ELLEN WISEMAN, spinster, both of this
parish, were married in this church with consent of parish this third day of
October in the year one thousand eight hundred and thirty-three, by me William
Bullock, Epis. Miss.This marriage was solemnized between us Robert (X) Paul and
Ellen (X) Wiseman, (X) being their marks, in the presence of Thomas? Ryal? and Rich'd
Clarke ?.This is to certify that JACOB SINYARD?, bachelor, of this
parish, and ELIZABETH PINHORN, spinster, also of this parish, were married in
this church with consent of parent this twenty-second day of October in the
year one thousand eight hundred and thirty-three, by me William Bullock, Epis.
Miss.This marriage was solemnized between us Jacob (X) Sinyard?
and Elizabeth Pinhorn, (X) being his mark, in the presence of Rich'd.(X) Sinyard
and Geo (X) Sheppard?, (X) being their marks.This is to certify that ROBERT PENNY, bachelor, of this
parish, and RACHAEL HART, spinster, also of this parish, were married in this
church with consent of parents this twenty-third? day of October in the year
one thousand eight hundred and thirty-three, by me William Bullock, Epis. Miss.This marriage was solemnized between us Robert (X) Penny and
Rachael(X) Hart, (X) being their marks, in the presence of Samuel (X) Penny and
Geo. (X) Penny, both of ???, (X) being their marks.This is to certify that BENJAMIN PITTMAN, bachelor, of the
parish of C????horn, Great Britain, and ANNE FINCH, widow, of this parish, were
married in this church with consent of friends this second day of November in
the year one thousand eight hundred and thirty-three, by me William Bullock, Epis.
Miss.This marriage was solemnized between us Benjamin (X) Pittman
and Anne Finch, (X) being his mark, in the presence of Thomas Green and Rich'd Maidment.This is to certify that GEORGE SHEPPARD, bachelor, of this
parish, and MARY SEXTON, spinster, also of this parish, were married in this
church with consent of parents this fifth day of November, in the year one
thousand eight hundred and thirty-three, by me William Bullock, Epis. Miss.This marriage was solemnized between us George (X) Sheppard
and Mary (X) Sexton, (X) being their marks, in the presence of Richard (X) Maidment,
John (X) Sheppard, and Stephen (X) Sexton, (X) being their marks .This is to certify that WILLIAM MAHON?, bachelor, of this
parish, and MARY ANN POWER?, spinster, of the parish of S. Johns?, were
married in this church with consent of friends this fifth day of November in
the year one thousand eight hundred and thirty-three, by me William Bullock, Epis.
Miss.This marriage was solemnized between us Wm. (X) Mahon and
Mary Ann (X) Power, (X) being their marks, in the presence of William Rogers
and Sarah Newhook .This is to certify that BENJAMIN DAY, bachelor, of this
parish, and ELIZABETH PENNY?, spinster, also of this parish, were married in
this church with consent of friends this twelfth day of November in the year
one thousand eight hundred and thirty-three, by me William Bullock, Epis. Miss.This marriage was solemnized between us Benjamin (X) Day and
Elizabeth (X) Penny?, (X) being their marks, in the presence of us, Edward?(X)
SSpragge and Jno? (X) Ash, (X) being their marks.This is to certify that JAMES HANCOCK, bachelor, of this
parish, and ELIZABETH FLEET, spinster, of the parish of S. Johns, were married
in this church with consent of friends this fifteenth? day of Nov. in the year
one thousand eight hundred and thirty-three, by me William Bullock, Epis. Miss.This marriage was solemnized between us James Hancock and
Elizabeth (X) Fleet, (X) being her mark, in the presence of Joseph Brine and
John Gover? .This is to certify that WILLIAM TAVENOR, bachelor, of this
parish, and MARY WALTERS, spinster, also of this parish, were married in this
church with consent of friends this twenty-fourth day of Nov. in the year one
thousand eight hundred and thirty-three, by me William Bullock, Epis. Miss.This marriage was solemnized between us William (X) Tavenor
and Mary (X) Walters, (X) being their marks, in the presence of George White and
Philip Cook .This is to certify that MATTHEW? MILLAR, widower, of this
parish, and SARAH EVERLY, spinster, also of this parish, were married in this
church with consent of Priest this fourteenth day of December in the year one
thousand eight hundred and thirty-three, by me William Bullock, Epis. Miss.This marriage was solemnized between us Matthew (X) Millar
and Sarah (X) Everly, (X) being their marks, in the presence of John Collings (??), and William Slattery?This is to certify that WILLIAM LUCAS, bachelor, of this
parish, and MARY ANN CARBERRY, spinster, also of this parish, were married in
this church with consent of parents this twenty-seventh day of December in the
year one thousand eight hundred and thirty-three, by me William Bullock, Epis.
Miss.This marriage was solemnized between us William (X) Lucas
and Mary Ann (X) Carberry, (X) being their marks, in the presence of Jasper Hiscock and Anne LucasThis is to certify that STEPHEN CROCKER, bachelor, of this
parish, and CATHERINE DOUGHERTY, spinster, of this parish, were married in this
church with consent of friends this thirty-first day of December in the year
one thousand eight hundred and thirty-three, by me William Bullock, Epis. Miss.This marriage was solemnized between us Stephen (X) Crocker
and Catherine (X) Dougherty, (X) being their marks, in the presence of John
Crocker and Daniel??? .This is to certify that WILLIAM CORDEROY?, bachelor, of the
parish of Greenspond, and ANNE FOWLOW, spinster, of this parish, were married
this fifteenth day of April in the year one thousand eight hundred and
thirty-four by me William Bullock, Epis. Miss.This marriage was solemnized between us William Corderoy and
Anne Fowlow, in the presence of Timothy Stark and C. E. Oakley.This is to certify that JOHN MORRIS, bachelor, of this
parish, and MARY WOOLRIDGE, widow, also of this parish, were married in this
??? with consent of parents this eighth day of June in the year one thousand
eight hundred and thirty-three, by me William Bullock, Epis. Miss.This marriage was solemnized between us John (X) Morris and
Mary (X) Woolridge, (X) being their marks, in the presence of Rebecca Toup and Eliz'h Hiscock 1834This is to certify that RICHARD THORN?, bachelor, of this
parish and , ELIZABETH HISCOCK? spinster, also of this parish, were married in this
church with consent of parents this twenty-fourth? day of August in the year
one thousand eight hundred and thirty-four by me William Bullock, Epis. Miss.This marriage was solemnized between us Richard (X) Thorn? and
Elizabeth (X) Hiscock, (X) being their marks, in the presence of Mary Hiscock?
and William Hiscock?.This is to certify that RICHARD STAPLETON, bachelor, of
this parish and MARY ANNE COLE?, widow, of the parish of S. Matge? Bay, were
married in this church this third day of September in the year one thousand
eight hundred and thirty-four by me William Bullock, Epis. Miss.This marriage was solemnized between us Richard (X)
Stapleton? and Mary Ann Cole?, in the presence of James? (X) Sweetland and John?
(X) Long? (X) being their marks.This is to certify that RICH'D KING, bachelor, of this parish,
and SUSANNA FRAMPTON, spinster, both of this parish, were married in this church
with consent of parents this thirty-first? day of August in the year one
thousand eight hundred and thirty-four by me William Bullock, Epis. Miss.This marriage was solemnized between us Richard (X) King and
Susanna (X) Frampton, (X) being their marks, in the presence of Joseph Millar, and
Marie King.This is to certify that WILLIAM PENNY, bachelor, and CATHERINE HIGDEN?, spinster, of ? parish*, were married in this
church with consent of Parish Minister? this second day of October in the year
one thousand eight hundred and thirty-four by me William Bullock, Epis. Miss.This marriage was solemnized between us William (X) Penny
and Catherine (X) Higden?, in the presence of Mark Bestone? and John Ash?This is to certify that WILLIAM RYAN?, bachelor, and ANNE
COOK, spinster, were married in this church this twenty-??? day of October in
the year one thousand eight hundred and thirty-four by me William Bullock,
Miss. Church of EnglandThis marriage was solemnized between us William (X) Ryan and
Anne (X) Cook, (X) being their marks, in the presence of William (X) Randall
and Jane? (X) Ryan.This is to certify that JAMES IVAMY, bachelor, of this
parish and AMY HART, spinster, both of this parish also, were married in this
church with consent of friends this twenty-eighth? day of October in the year
one thousand eight hundred and thirty-four by me William Bullock, Epis. Miss.This marriage was solemnized between us James (X) Ivamy
and Amy (X) Hart, (X) being their marks, in the presence of William (X) Ivamy
and George (X) Penny.This is to certify that WILLIAM BESTONE, bachelor, of this
parish and TABITHA WELLS, spinster, of this parish also, were married in this
church with consent of friends this twety ninth day of October in the year one thousand
eight hundred and thirty-four by me William Bullock, Clergyman of ??? ???.This marriage was solemnized between us William Bestone and
Tabitha (X) Wells, (X) being her mark, in the presence of Mary (X) Bastone and
James (X) Wells, (X) being their marks.This is to certify that WILLIAM GREEN?, bachelor, of this
parish and MARY PINHORN?, spinster, of Silly Cove? parish, were married in
this church this fourth? day of November in the year one thousand eight hundred and
thirty-four by me William Bullock, Clergyman of ??? ???.This marriage was solemnized between us William (X) Green
and Mary (X) Pinhorn, (X) being their marks, in the presence of John Johnson and
Joseph (X) Pearcy, (X) being their marks.This is to certify that JAMES COOK, bachelor, of this
parish and MARTHA PENNY were married in this church with consent of friends
this fifth? day of November in the year one thousand eight hundred and
thirty-four by me William Bullock, Clergyman of ??? ???.This marriage was solemnized between us James (X) Cook and
Martha (X) Penny, (X) being their marks, in the presence of Joseph (X) Wells and
Joseph (X) Cook, (X) being their marks.This is to certify that BENJAMIN BREDDY?, bachelor, of this
parish and MARY SMITH, spinster, of this parish, were married in this church
with consent of friends this fifth day of November in the year one thousand
eight hundred and thirty-four by me William Bullock, Clergyman of ??? ???.This marriage was solemnized between us B. Briddy? and Mary
(X) Smith, (X) being her mark, in the presence of Mary (X) Hiscockand Giles? (X)
Smith, (X) being their marks.This is to certify that THOMAS RANDALL, bachelor, of this
parish and ELIZABETH BUTTER?, spinster, of this parish, were married in this church
with consent of parents this sixth day of November in the year one thousand
eight hundred and thirty-four by me William Bullock, Epis. Miss.This marriage was solemnized between us Thomas (X) Randall
and Elizabeth (X) Butter?, (X) being their marks, in the presence of Will'm
(X) Randall and Charity (X) Randall, (X) being their marks.This is to certify that JOHN RANDALL, bachelor, and
ELIZABETH FOWLOW, spinster, were married in this church with consent of friends
this fourth day of December in the year one thousand eight hundred and
thirty-four by me William Bullock, Epis. Miss.This marriage was solemnized between us John (X) Randall and
Elizabeth (X) Fowlow, (X) being their marks, in the presence of Grace (X)
Randall and William (X) Randall, (X) being their marks.This is to certify that WILLIAM SPENCER?, widower, of this
parish and MARY MOORES?, widow, of this parish, were married in this church
with consent of friends this eighteenth day of March in the year one thousand eight
hundred and thirty-four by me William Bullock, Epis. Miss.This marriage was solemnized between us William (X) Spencer and
Mary (X) Moores?, (X) being their marks, in the presence of William (X) Moores
and Wm (X) Guy, (X) being their marks.This is to certify that WILLIAM ROGERS, bachelor, of this
parish and CATHERINE GRANT, spinster, were married in this church this
twenty-fourth day of December in the year one thousand eight hundred and
thirty-four by me William Bullock, Epis. Miss.This marriage was solemnized between us William Rogers and
Catherine Grant, in the presence of Sarah Jestican and Sarah Grant 1835This is to certify that JOHN GOVER?, bachelor, of this parish
and SARAH ROWE, spinster, of this parish, were married in this church with
content of friends this first day of January in the year one thousand eight
hundred and thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us John Gover? and Sarah
Rowe, in the presence of Toby Stoneman, Wm (X) Rowe, and Thomas Gaseca.This is to certify that WILLIAM TAYLOR?, bachelor, of the
parish of West Come? on the Isle of Wight, and SARAH WATERMAN, widow, of this
parish, were married in this church with consent of friends this fourth day of
February in the year one thousand eight hundred and thirty-five by me William
Bullock, Epis. Miss.This marriage was solemnized between us William (X) Taylor?
and Sarah (X) Waterman, (X) being their marks, in the presence of Jasper (??) X Hiscock (??) and
John (X) Miller (X) being their marks.This is to certify that DAVID RYAN, widower, of this parish
and MARY RANDELL, widow, of this parish also, were married in this church with
content of friends this Twenty-seventhth day of March in the year one thousand eight
hundred and thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us David (X) Ryan and
Mary (X) Randell, (X) being their marks, in the presence of John (X) Butler and
Elizabeth (X) Ploughman, (X) being their marks.This is to certify that WILLIAM ANDERSON, widower, of this
parish and ELIZABETH PENNY, widow, of this parish, were married in this church
this Seventh? day of June in the year one thousand eight hundred and
thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us William (X) Anderson
and Elizabeth (X) Penny, (X) being their marks, in the presence of William Ivamy
and Margaret Wells.This is to certify that JOSEPH? BRENNOCK , bachelor, of this
parish and ANNE MILLER, spinster, of this parish, were married in this church
with consent of parents this sixth day of October in the year one thousand
eight hundred and thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us Joseph? (X) Brennock and
Anne (X) Miller, (X) being their marks, in the presence of Joseph (X) Clarke and
Amy Miller, (X) being his mark.This is to certify that SAMUEL PENNY, bachelor, of this
parish and , ESTHER? BARNES, spinster, of this parish, were married in
this church with consent of friends this eighth day of October in the year one
thousand eight hundred and thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us Samuel Penny and
Esther? (X) Barnes, (X) being their marks, in the presence of Sam'l (X) Hobbs and
Hannah (X) Penny, (X) being their marks.This is to certify that WILLIAM TAVENOR?, widower, of this
parish and SARAH LAIT?, spinster, also of this parish, were married in this
church with consent of friends this eleventh? day of October in the year one
thousand eight hundred and thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us William (X) Tavernor?
and Sarah (X) Lait?, (X) being their marks, in the presence of James Taverner
and Thomas Thorn .This is to certify that RICHARD BARNES?, bachelor, of this
parish and MARY DOOLING, widow, of this parish, were married in this church
with consent of friends this thirteenth day of October in the year one thousand
eight hundred and thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us Richard (X) Barnes
and Mary (X) Dooling, (X) being their marks, in the presence of George (X)
Freeman and John (X) Ash, (X) being their marks.This is to certify that JAMES HOOKEY?, bachelor, of this
parish and MARY HISCOCK, spinster, also of this parish, were married in this
church with consent of friends this fourteenth? day of October in the year one
thousand eight hundred and thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us James (X) Hookey?
and Mary (X) Hiscock, (X) being their marks, in the presence of James Pitcher
and Hennery (sic) StoneThis is to certify that JOHN QUINLAN, bachelor, of this
parish and ELIZABETH IVAMY, spinster, also of this parish, were married in
this church with consent of friends this twenty-fifth day of October in the
year one thousand eight hundred and thirty-five by me William Bullock, Epis.
Miss.This marriage was solemnized between us John (X) Quinlan and
Elizabeth (X) Ivamy, (X) being their marks, in the presence of Sam'l? Miller?
and James IvamyThis is to certify that WILLIAM HISCOCK, bachelor, of this
parish and HONOR IVAMY, spinster, also of this parish also, were married in
this church with consent of friends this second day of November in the year one
thousand eight hundred and thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us William (X) Hiscock
and Honor (X) Ivamy, (X) being their marks, in the presence of John Moores and
John Ryal?This is to certify that RICHARD MAIDMENT, bachelor, of this
parish and JANE BUGDEN, spinster, also of this parish, were married in this
church with consent of parent this third day of November in the year one
thousand eight hundred and thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us Richard Maidment and
Jane (X) Bugden, (X) being her mark, in the presence of William Bugden, Thomas?
Bugden, and Aubrey Crocker?This is to certify that WILLIAM POTTLE, bachelor, of this
parish and HANNAH PENNY, spinster, of this parish, were married in this church
of English Harbour, (S. Side), with consent of parent, this third day of November
in the year one thousand eight hundred and thirty-five by me William Bullock, Epis.
Miss.This marriage was solemnized between usWilliam (X) Pottle and
Hannah (X) Penny, (X) being their marks, in the presence of John Bugden? and
Mark Barton .This is to certify that ROBERT BAKER, bachelor, of this parish
and PRICILLA MILLER?, spinster, of this parish also, were married in this church with
content of friends this fourth day of November in the year one thousand eight
hundred and thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us Robert (X) Baker?
and Pricilla (X) Miller, (X) being their marks, in the presence of Thomas Verge? and
Martha Mills.Note: This document is heavily stained along the left side,
and in the registration section, the groom's full name is totally obscured by
the dark blemish. It is visible in the witness section and looks as written
above -TranscriberThis is to certify that JAMES MORRIS, bachelor, of this
parish and TAMOUR? STONE?, spinster, of this parish, were married in this church
with consent of friends this seventh day of November in the year one thousand
eight hundred and thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us James (X) Morris and
Tamour (X) Stone, (X) being their marks, in the presence of John Warr? and Henry
Stone.This is to certify that GEORGE PENNY, bachelor , of this
parish and MARY WELLS, spinster, of this parish, were married in this church with
content of friends this twelfth? day of November in the year one thousand eight
hundred and thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us George (X) Penny and
Mary (X) Wells, (X) being their marks, in the presence of Rich'd Penny and
William WellsThis is to certify that JOHN POTTLE JAMES, bachelor, of this
parish and MARY FLEET, spinster, of this parish, were married in this church
with consent of friends this fifteenth day of November, in the year one thousand
eight hundred and thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us John Pottle? James and
Mary Fleet, in the presence of Sarah Appgood and John ???This is to certify that THOMAS DAY?, bachelor, and MARY
GROVES?, spinster, were married in this church with consent of friends this
nineteenth day of November in the year one thousand eight hundred and
thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us Thomas (X) Day? and
Mary (X) Groves?, (X) being their marks, in the presence of Johanna Long and Henry Goldworthy.This is to certify that LAURENT? MULLETT?, widower, (1st wife
Burrage)* of this parish (He built old St. Paul's Church)* and MARY HISCOCK,
spinster, of this parish, were married in this church with consent of friends
this sixth day of December in the year one thousand eight hundred and
thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us Laurent? Mullett?
and Mary (X) Hiscock, (X) being her mark, in the presence of Charles? Granger?
and Mary Elizabeth Hiscock.*Both notes are written as found in this entry - TranscriberThis is to certify, bachelor HENRY WILLIAM ANDREWS, of this
parish and SARAH GRANT, spinster, of this parish, were married in this church
with consent of friends this nineteenth day of December in the year one
thousand eight hundred and thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us Henry William (X)
Andrews and Sarah Grant, (X) being their marks, in the presence of ???rles He???yer
and Catherine Rogers.This is to certify that JAMES MURPHY, bachelor, of this
parish and EMMA HOUSE?, of the parish of Bonavista, were married in this
church with consent of friends this twenty?- first day of December? in the year
one thousand eight hundred and thirty-five by me William Bullock, Epis. Miss.This marriage was solemnized between us James (X) Murphy and
Emma (X) House, (X) being their marks, in the presence of John Moores and
Philip Cook. 1836This is to certify that THOMAS FOWLOW, bachelor, of this
parish and CATHERINE WOODMAN, spinster, of this parish also, were married in
this church with consent of friends this fourteenth day of May in the year one
thousand eight hundred and thirty-six by me William Bullock, Epis. Miss.This marriage was solemnized between us James (X) Fowlow and
Catherine (X) W???mar, (X) being their marks, in the presence of Arch Graham and
Samuel Miller.This is to certify that JOHN BRINE, bachelor , of this
parish and REBECCA TOOP, spinster, of this parish, were married in this church
with consent of ??? this eighth day of June in the year one thousand eight
hundred and thirty-six by me William Bullock, Epis. Miss.This marriage was solemnized between us John Brine and
Rebecca (X) Toop, (X) being her mark, in the presence of Joseph Brine and
Charles Newhook.This is to certify that JOHN MILLER, bachelor , of this
parish and SARAH JANES, spinster, of this parish, were married in this church
with consent of friends this twenty-??th day of August in the year one thousand
eight hundred and thirty-six by me William Bullock, Epis. Miss.This marriage was solemnized between us John (X) Miller and
Sarah (X) Janes, (X) being their marks, in the presence of Joseph Miller and
Thomas Miller.This is to certify that JAMES VICK?, bachelor , of the
parish, Christ Church, County of Dorset, and SWEET? SIVIER, widow, of this
parish, were married in this church with consent of friends? this
twenty-seventh day of September in the year one thousand eight hundred and
thirty-six by me William Bullock, Epis. Miss.This marriage was solemnized between us James (X) Vick? and Sweet
(X) Sivier?, (X) being their marks, in the presence of Charles Pitcher and
Robert BekereThis is to certify that JOHN TOOP?, bachelor, of this parish
and MARY KING, spinster, of this parish, were married in this church with
content of parent this sixth day of October in the year one thousand eight
hundred and thirty-six by me William Bullock, Epis. Miss.This marriage was solemnized between us John (X) Toop? and
Mary (X) King, (X) being their marks, in the presence of Jonathan Ivamy and
James Toop.This is to certify that JOHN BAILEY, bachelor, of this
parish and SUSAN EVELEY, ???*, of this parish, were married in this church with
content of friends this eleventh day of October in the year one thousand eight
hundred and thirty-six by me Henry H. Hamilton.This marriage was solemnized between us John (X) Bailey and
Susan (X) Eveley, (X) being their marks, in the presence of Matthew Eveley and
William Hogarth?This is to certify that THOMAS GOLDWORTHY, bachelor, of this
parish and ELIZABETH SEWARD, spinster, of this parish also, were married in
this church with consent of friends this thirtieth day of October in the year
one thousand eight hundred and thirty-six by me William Bullock, Epis. Miss.This marriage was solemnized between us Thomas (X) Goldworthy
and Elizabeth (X) Seward, (X) being their marks, in the presence of Thomas Goldworthy
and James Goldworthy.
| http://ngb.chebucto.org/Parish/ang-mar-1821-1836-tb.shtml |
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| https://lasp.colorado.edu/maven/sdc/public/data/sites/site-20201228T221917/anc/eng/sasm1/sci_anc_sasm119_266_268.drf |
(PDF) Effects of the MEK Inhibitor, SL-327, on Rewarding, Motor- and Cellular-Activating Effects of D-Amphetamine and SKF-82958, and their Augmentation by Food Restriction in Rat
PDF | RationaleFood restriction (FR) enhances learned and unlearned behavioral responses to drugs of abuse and increases D-1 dopamine... | Find, read and cite all the research you need on ResearchGate
Article
Effects of the MEK Inhibitor, SL-327, on Rewarding, Motor- and Cellular-Activating Effects of D-Amphetamine and SKF-82958, and their Augmentation by Food Restriction in Rat
January 2009
Psychopharmacology201(4):495-506
DOI: 10.1007/s00213-008-1313-6
Authors:
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
Kenneth D. Carr
Kenneth D. Carr
<here is a image 1937ee36a50dd27a-fa33d150fae83bfe>
Soledad Cabeza de Vaca
NYU Langone Medical Center
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
Yanjie Sun
Yanjie Sun
<here is a image f2f62089ad6ff61c-d19572ff1996375a>
Lily S. Chau
Lily S. Chau
Abstract and Figures
RationaleFood restriction (FR) enhances learned and unlearned behavioral responses to drugs of abuse and increases D-1 dopamine (DA)
receptor-mediated activation of extracellular signal-regulated kinases (ERK) 1/2 MAP kinase in nucleus accumbens (NAc). While
a role has been established for ERK signaling in drug-mediated associative learning, it is not clear whether ERK regulates
unconditioned behavioral effects of abused drugs.
ObjectivesThe purpose of this study was to determine whether blockade of ERK signaling, using the brain-penetrant MEK inhibitor, SL-327,
decreases behavioral or NAc cellular responses to acute drug treatment and their augmentation by FR.
Materials and methodsSeparate experiments assessed the effects of SL-327 (50mg/kg, intraperitoneally) on (1) the reward-potentiating effect of
d-amphetamine in an intracranial self-stimulation protocol, (2) the locomotor-activating effect of the D-1 agonist, SKF-82958,
and (3) Fos-immunostaining induced in the NAc by SKF-82958.
ResultsFR rats displayed enhanced responses to drug treatment on all measures. SL-327 had no effect on sensitivity to rewarding brain
stimulation or the reward-potentiating effect of d-amphetamine. The MEK inhibitor, U0126, microinjected into the NAc was also without effect. The locomotor-activating effect
of SKF-82958 was unaffected by SL-327. In contrast, SL-327 decreased NAc Fos-immunostaining and abolished the difference between
feeding groups.
ConclusionsThese results support the conclusion that ERK signaling does not mediate unlearned behavioral responses to drug treatment.
However, the upregulation of ERK and downstream transcriptional responses to acute drug treatment may underlie the reported
enhancement of reward-related learning in FR subjects.
<here is a image 766357319959a94e-68ea35b05be1780f>
Mean (±SEM) percentage changes in the M-50 ( top ) and theta- 0 ( middle ) measures of reward threshold and maximum reinforcement rate ( bottom ), derived from self-stimulation rate – frequency curves, 10 min following i.p. injection of D -amphetamine (0.5 mg/kg) or …
<here is a image 332c25a46cc40e2a-8e9906ebd5bfaae8>
Mean (±SEM) percentage changes in the M-50 ( top ) and theta-0 ( bottom ) measures of reward threshold derived from self-stimulation rate – frequency curves, 10 min following i.p. injection of D -amphetamine …
<here is a image 9f4f89eb96e7a874-d4bfde4908d82a79>
Schematic diagrams adapted from Paxinos and Watson (1998), indicating sites of U0126 microinjection in nucleus accumbens …
<here is a image 9dd308eeb362e628-8bfeb3be82f67f5a>
Top mean (±SEM) horizontal activity counts in the 30-min period following i.p. injection of DMSO vehicle or SL-327 (50 mg/kg) — indicated by bars to the left of each arrow — and following a subsequent i.c.v. injection of SKF-82958 (20 μ g) — indicated by bars to the right of each arrow — in ad libitum fed ( black fill ) and food-restricted ( gray fill ) rats. ** p <0.001 compared to AL subjects; * p <0.001 compared to vehicle treatment. Bottom horizontal activity counts per 5-min time bin following i.p. injection of vehicle ( left side of left graph ), SL-327 ( left side of right graph ), and following subsequent i.c.v. injection of SKF- 82958 ( right side of both graphs ) in ad libitum fed ( open symbols ) and food-restricted ( filled symbols ) rats …
<here is a image 26c54cc52dc738ab-02cd150839ff08f9>
Bottom mean (±SEM) bilateral count of Fos-immunoreactive cells in NAc shell (left) and NAc core (right) of ad libitum fed and food-restricted rats following i.c.v. injection of SKF-82958 (20 μg) preceded, 30 min earlier, by i.p. injection of DMSO vehicle (white bar) or SL-327 (50 mg/kg; hatched bar). Top representative photomicrographs depicting Fos-immunostaining in the NAc of foodrestricted rats injected i.c.v. with SKF-82958 preceded by i.p. injection of vehicle (left) versus SL-327 (right) …
ORIGINAL INVESTIGATION
Effects of the MEK inhibitor, SL-327, on rewarding,
motor- and cellular-activating effects of D -amphetamine
and SKF-82958, and their augmentation by food restriction in rat
KennethD.Carr & SoledadCabezadeVaca &
YanjieSun & LilyS.Chau & YanPan & Julie Dela Cruz
Received:7 January2008 /Accepted:20August 2008 / Publishedonline: 3September2008
# Springer-Verlag 2008
Abstract
Rationale Food restriction (FR) enhances learned and
unlearned behavioral responses to drugs of abuse and
increases D-1 dopamine (DA) receptor-mediated activation
of extracellular signal-regulated kinases (ERK) 1/2 MAP
kinase in nucleus accumbens (NAc). While a role has been
established for ERK signaling in drug-mediated associative
learning, it is not clear whether ERK regulates uncondi-
tioned behavioral effects of abused drugs.
Objectives The purpose of this study was to determine
whether blockade of ERK signaling, using the brain-
penetrant MEK inhibitor, SL-327, decreases behavioral or
NAc cellular responses to acute drug treatment and their
augmentation by FR.
Materials and methods Separate experiments assessed the
effects of SL-327 (50 mg/kg, intraperitoneally) on (1) the
reward-potentiating effect of D -amphetamine in an intracranial
self-stimulation protocol, (2) the locomotor-activating effect
of the D-1 agonist, SKF-82958, and (3) Fos-immunostaining
induced in the NAc by SKF-82958.
Results FR rats displayed enhanced responses to drug
treatment on all measures. SL-327 had no effect on
sensitivity to rewarding brain stimulation or the reward-
potentiating effect of D -amphetamine. The MEK inhibitor,
U0126, microinjected into the NAc was also without effect.
The locomotor-activating effect of SKF-82958 was unaf-
fected by SL-327. In contrast, SL-327 decreased NAc Fos-
immunostaining and abolished the difference between
feeding groups.
Conclusions These results support the conclusion that ERK
signaling does not mediate unlearned behavioral responses
to drug treatment. However, the upregulation of ERK and
downstream transcriptional responses to acute drug treat-
ment may underlie the reported enhancement of reward-
related learning in FR subjects.
Keywords Food restriction . Reward . Self-stimulation .
SKF-82958 . D -amphetamine . c- fos . ERK 1/2 . SL-327 .
U0126
Introduction
It is well-established that chronic food restriction (FR)
enhances the acquisition and maintenance of drug self-
administration behavior in animal subjects (Carroll and
Meisch 1984 ). Using learning-free measures, it has also
been found that the reward-potentiating and locomotor-
activating effects of D -amphetamine (as well as a variety of
other abused drugs) and the D-1 dopamine (DA) receptor
agonist, SKF-82958, are greater in FR than ad libitum fed
(AL) rats (Cabeza de Vaca and Carr 1998 ; Carr et al. 2000,
2003 ). Drug treatments that produced stronger behavioral
responses also produced greater activation of extracellular
signal-regulated kinases (ERK) 1/2 MAP kinase, cAMP
response element-binding protein (CREB), c- fos ,and
preprodynorphingene expression in the nucleus accumbens
(NAc) of FR relative to AL subjects (Carr and Kutchukhidze
Psychopharmacology (2009) 201:495 –506
DOI 10.1007/s00213-008-1313-6
K. D. Carr( * ) : S.C.deVaca : Y.Sun : L.S.Chau : Y. Pan :
J. Dela Cruz
Department of Psychiatry, School of Medicine,
New York University,
550 First Avenue,
New York, NY 10016, USA
e-mail: kc16@nyu.edu
K. D. Carr
Department of Pharmacology, School of Medicine,
New York University,
550 First Avenue,
New York, NY 10016, USA
2000 ; Carr et al.2003 ; Haberny et al.2004 ; Haberny and
Carr 2005a , b ). The possibility that increased ERK 1/2
MAPK signaling is necessary for the enhanced behavioral
and transcriptional responses to psychostimulant and D-1
DA agonist challenge is consonant with a number of
findings. All drugs of abuse examined to date activate ERK
throughout the striatum in a D-1 DA receptor-dependent
manner (Valjent et al. 2004 ). Moreover, the ERK cascade
activates RSK2, an S6 kinase that activates transcription
factors, including CREB, which bind to the promoter
region of the c- fos gene (Thomas and Huganir 2004).
MEK inhibitors — drugs that block the kinase upstream of
ERK — abolish the conditioned place preference (CPP)
otherwise reinforced by cocaine, amphetamine, tetrahydro-
cannabinol, and 3,4-methylenedioxy- N -methylamphet-
amine (Valjent et al. 2000 , 2001 ; Salzmann et al. 2003;
Gerdjikov et al. 2004).
In the CPP studies, MEK inhibitors were administered in
conjunction with a drug of abuse prior to each conditioning
session. Consequently, it is not clear whether the blockade
of ERK signaling attenuated the unconditioned rewarding
effect of drugs or exclusively interfered with the consoli-
dation of the learned association between drug and context
(Gerdjikov et al. 2004 ; Miller and Marshall 2005 ; Valjent
et al. 2006 ). There have been no behavioral studies
designed to assess whether the inhibition of ERK signaling
attenuates the unconditioned rewarding effect of any abused
drug in AL, let alone in FR subjects. This is not an
unreasonable questionto pose in as much as not all
functional consequences of ERK phosphorylation would
be expected to require transcription, translation, and a long
latency to behavioral effects. Upon activation, ERK is not
only translocated to the nucleus but is also present in
cytoplasm and dendrites, suggesting that ERK controls the
phosphorylation state of local targets within or close to
synapses, providing a rapid mechanism for modulating
synaptic plasticity (Girault et al. 2006 ; Wang et al. 2007). A
specific example is the rapid inactivation of voltage-gated
K
+
channels (Yuan et al. 2002 ). Behaviorally, ERK
signaling in the NAc core and central amygdala, induced
by exposure to cocaine-paired environmental cues, mediates
the expression of a CPP (Miller and Marshall 2005 ) and
reinstatement of cocaine-seeking during extinction (Lu
et al. 2005 ). Most germane to the present study, there have
been two reports that pretreatment with a MEK inhibitor
attenuates the unconditioned motor-activating effects of
psychostimulants (Valjent et al. 2000 ; Shi and McGinty
2006 ). Consequently, the first aim of this study was to
determine whether the reward-potentiating effect of D -
amphetamine, passively administered to FR and AL rats
responding in a curve – shift protocol of intracranial self-
stimulation testing, is diminished by pretreatment with the
brain-penetrant MEK inhibitor, SL-327.
While SL-327 previously decreased the activation of
striatal ERK 1/2 induced by intracerebroventricular (i.c.v.)
injection of SKF-82958 and eliminated the enhanced
activation otherwise observed in FR subjects (Haberny
and Carr 2005a ), the acute behavioral and c- fos responses
to SKF-82958 treatment were not measured. Consequently,
a second aim of this study was to administer SKF-82958 as
in prior studies and determine whether SL-327 decreases
the resultant hyperlocomotion, NAc c- fos expression, and/
or the augmentation of these responses by FR.
Materials and methods
Subjects and surgical procedures
Subjects were mature male Sprague – Dawley rats (Taconic
Farms, Germantown, NY, USA) initially weighing 375 –
425 g. Food (pelleted Purina rat chow) and water were
available ad libitum except when FR conditions applied.
Animals were individually housed in clear plastic cages
with bedding under a 12-h light/dark photoperiod with
lights on at 0700 hours. Subjects to be tested for reward-
potentiating effects of D -amphetamine were deeply anes-
thetized with ketamine (100 mg/kg; intraperitoneally [i.p.])
and xylazine (10 mg/kg; i.p.) and stereotaxically implanted
with a 0.25-mm diameter monopolar stimulating electrode
(Plastics One) in the lateral hypothalamic medial forebrain
bundle (coordinates: 3.0 mm posterior to bregma, 1.6 mm
lateral to the sagittal suture, and 8.5 mm ventral to skull
surface). An anterior ipsilateral stainless steel skull screw
served as ground. Subjects to be tested for locomotor-
activating effects of SKF-82958 were implanted with a
26-gauge guide cannula (inner diameter=0.24 mm; Plastics
One, Roanoke, VA, USA) in the right lateral ventricle using
the following coordinates with bregma and lambda suture
landmarks in the same horizontal plane: 1.0 mm posterior
to bregma, 1.5 mm lateral to the midsagittal suture, and
3.5 mm ventral to skull surface. Subjects to be tested for the
effects of MEK inhibitor microinjection in the NAc were
implanted with 26-gauge guide cannulae bilaterally, 2 mm
dorsal to the intended injection site at the core/shell border
using the coordinates: 1.6 mm posterior to bregma, 2.5 mm
lateral to the midsagittal suture (tips angled 8° toward the
midline), and 5.7 mm ventral to skull surface. The electrode
and/or cannula(e) were permanently affixed to the skull by
flowing dental acrylic around them and four surrounding
mounting screws. Patency of guide cannulae was main-
tained with an occlusion stylet. Five to 7 days after surgery,
the accuracy of lateral ventricular cannula placements was
verified by a short latency, sustained drinking response to
microinjection of angiotensin II (50 ng in 5 μ L). Experi-
mental procedures were approved by the Institutional
496Psychopharmacology (2009) 201:495 –506
Animal Care and Use Committee at the New York
University School of Medicine and were consistent with
the Principles of Laboratory Animal Care (NIH Publication
no. 85-23).
Food restriction and habituation training
Beginning 2 days after angiotensin testing of subjects in the
locomotor study, half the rats were switched from ad
libitum feeding to a restricted feeding regimen in which a
single 10-g meal was delivered at approximately 1700
hours each day. FR rats continued to have ad libitum access
to water. Once body weight decreased by 20% (approxi-
mately 14 days), daily food allotments were titrated to
maintain this target body weight for the remainder of the
study. Experimental testing was initiatedwhen body
weights in this group had been stabilized for 1 week.
During the ∼ 3 week period preceding experimental testing,
all rats were habituated, on at least six occasions, to
transport (along an interior corridor from animal facility to
laboratory), handling, microinjection (mock) procedures,
and the activity chamber (30 min) to be employed
throughout the study. Additional sets of eight AL and eight
FR rats with lateral ventricular cannulae were habituated to
all but the activity chamber and would ultimately be used to
assess Fos-immunostaining. Half the subjects in the self-
stimulation experiments were food-restricted, though the
regimen was only initiated after subjects had achieved
certain milestones in self-stimulation training (see below).
Self-stimulation (LHSS) apparatus
Brain stimulation training and testing were conducted in
eight standard test chambers (26×26×21 cm) placed within
sound-attenuating cubicles. Each chamber had a retractable
lever mounted on one wall and a house light mounted on
the opposite wall. Four constant current stimulators (PHM-
152B/2; Med-Associates, Georgia, VT, USA) with dual
outputs were used to deliver trains of 0.1 mscathodal
pulses, which were conducted to implanted electrodesby
way of commutators and flexible cables. Electrical stimu-
lation, contingencies, and data recording were controlled
through Dell XPS R400 computers and interface (Med-
Associates). All stimulation parameters were monitoredon
Tektronix (TAS 455) oscilloscopes.
Self-stimulation (LHSS) procedures
After 1 week of postsurgical recovery, rats were trained to
lever press for 0.5 s trains of electrical stimulation at a
frequency of 100 pulses per second (pps). The initial
stimulation intensity of 120 μ A wassystematicallyvariedto
locate, for each rat, the lowest intensity that maintained
vigorous lever pressing. On subsequent days, rats were
trained in a discrete-trials procedure. Each training session
consisted of 24 60-s trials. Extension of the lever and a 2-s
train of “ priming ” stimulation initiated each trial. Each trial
was terminated by retraction of the lever and followed by a
10-s intertrial interval. Each lever press produceda 1-s train
of stimulation, except for those presses emitted during the
stimulation train, which did not increase reinforcement
density. The number of reinforcements was recorded for
each trial.
Discrete-trials training was followed by rate – frequency
training, which continued for approximately 2 weeks. Rate –
frequency curves were generated by presenting 12 trials in
which the frequency of brain stimulation decreased over
successive trials (approximately 0.05 log units each trial)
from an initial frequency of 100 pps to a terminal frequency
of 28 pps. At least two such series were presented in each
training session. During the second week of training,
subjects were divided into two groups matched for body
weight and M-50 (the brain stimulation frequency that
supported 50% of the maximum reinforcement rate) and
one of the groups was placed on the food restriction
regimen described above. Training and mock test sessions
(see below) continued, at least twice per week, for all rats,
during the ensuing ∼3-week period during which the FR
group achieved and then stabilized at the target body
weight ( ∼ 80% of prerestriction value).
Self-stimulation testing
Each test session began with a preinjection test consisting
of three rate – frequency series (42 min). The first series in a
session was considered a “ warm-up ” and data were
excluded. Injection of SL-327 (50 mg/kg, i.p.; a generous
gift from Dr. James Trzaskos and the Bristol Myers Squibb
Company) or vehicle (dimethyl sulfoxide [DMSO]) was
followed, 30 min later, by injection of D -amphetamine
(0.5 mg/kg, i.p.) or 0.9% saline vehicle, which was then
followed, in 10 min, by a postinjection behavioral test
consisting of two rate – frequency series (28 min). For each
rate – frequency series, the number of reinforcements delivered
as a function of stimulation frequency was recorded. For each
rat, the two series from each test were averaged to yield a
single rate – frequency function per test.
Groups of seven AL and seven FR rats were tested on
four occasions separated by a minimum of 3 days. Each
subject received the following treatment combinations:
vehicle/vehicle; vehicle/ D -amphetamine; SL-327/vehicle;
SL-327/ D -amphetamine in a semirandom order matched
between feeding groups.
In a follow-up experiment, two new groups of six AL
and six FR rats were tested on four occasions. In all
sessions, all subjects were injected with D -amphetamine
Psychopharmacology (2009) 201:495 – 506 497
(0.5 mg/kg, i.p.) which was then followed, in 10 min, by a
postinjection test. In the second and third sessions, D -
amphetamine injection was preceded, 5 min earlier, by
intra-NAc microinjection of U0126 (Sigma-Aldrich) at
doses of 0.1 and 1.0 μ g/0.5 μ L bilaterally with half the
subjects in each feeding group receiving the lower dose first
and half receiving the higher. In the first and fourth test
sessions, D -amphetamine was preceded by intra-NAc
microinjection of vehicle (50% DMSO) and results of the
two tests were averaged.
Microinjection procedure
For microinjections, solutions were loaded into two 30-cm
lengths of PE-50 tubing attached at one end to 25- μL
Hamilton syringes filled with distilled water and at the
other end to 31-gauge injector cannulae, which extended
2.0 mm beyond the implanted guides. The syringes were
mounted on the twin holders of a Harvard 2272 microliter
syringe pump which delivered the 0.5- μ L injection vol-
umes over a period of 100 s. One minute following the
completion of injections, injector cannulae were removed
from guides, stylets were replaced, and animals were
returned to home cages for 5 min prior to systemic injection
of D -amphetamine.
Self-stimulation data analysis
For each test, the rate – frequency function was used to
derive three parameters. The maximum reinforcement rate,
described by a line that parallels the x -axis, was defined as
the mean of all consecutive values within 10% of the
highest rate for the curve. All remaining values comprised
the descending portion of the curve with the lowest point
being at the highest frequency to produce fewer than 2.5
reinforcements per minute. Regression analysis of the
descending portion of the curve was used to calculate the
M-50 and theta-0 reward thresholds which are defined as
the log pulse frequency sustaining half the maximum
reinforcement rate and x -axis intercept of the regression
line, respectively. The M-50 is a conventional threshold
measure in this protocol, though the theta-0 indicates the
lowest frequency at which stimulation becomes rewarding.
Changes in the reinforcing efficacy of stimulation produced
by drugs of abuse are typically reflected as parallel leftward
shifts in the rate – frequency curve with similar effects on the
M-50 and theta-0 measures (Wise 1996).
For each parameter, antilog transformations were then
applied and natural frequencies used to calculate the
percentage change occurring in postinjection tests relative
to a preinjection test. Changes in reward threshold are
considered to be reflective of changes in drug reward
magnitude, while changes in the maximum rate are
reflective of changes in performance capacity (Edmonds
and Gallistel 1974 ; Miliaressis et al. 1986). In the SL-327
experiment, results for each parameter were analyzed by
three-way analysis of variance (ANOVA) with repeated
measures on two factors. In the U0126 experiment, results
for each parameter were analyzed by two-way ANOVA
with repeated measures on one factor.
Motor activity apparatus and data recording
Horizontal activitywas measured using the VersaMax
System (Accuscan, Columbus, OH, USA) which monitored
animal activity via a grid of 16×16 infrared light beams
that traverse the animal cage (42×42×30 cm) front to back
and left to right. Information about beam status, scanned at
a rate of 100 times per second, was stored to disk. Activity
was expressed as the total number of beam interruptions in
a 30-min session.
Experimental testing
Treatment groups were similar to the self-stimulation
experiment except that i.c.v. injection of SKF-82958 was
substituted for systemic D -amphetamine. Four test sessions
were conducted 3 – 4 days apart in which rats were first
injected with SL-327 or vehicle and then placed in the motor
activity test chamber for a 30-min period of pre-i.c.v.
injection data acquisition. This was followed by i.c.v.
injection of vehicle (saline) or SKF-82958 (20 μ g/2.5 μL),
10 min after which, animals were returned to the activity
chamber for 30-min data acquisition.
Microinjection procedure
As above, except for the use of a single 31-gauge injector
cannula extending 1.0 mm beyond the implanted guide
through which the 2.5- μ L injection volume was delivered
over a period of 1 min.
Locomotor data analysis
Results from the 30-min period that preceded i.c.v. injections
were analyzed separately from the post-i.c.v. injection period
with results obtained in the post-i.c.v. injection session being
expressed as difference scores and analyzed by two-way
ANOVAwith repeated measures on one factor.
c- fosimmunohistochemistry
Subjects were eight AL and eight FR rats. Treatments
consisted of a combination of i.p. injection and i.c.v.
498Psychopharmacology (2009) 201:495 –506
injection prior to transcardial perfusion. Half the subjects in
each feeding condition received vehicle/SKF-82958 (20 μg/
2.5 μ L) and half received SL-327-SKF/82958. Based on
the previous observation that Fos-immunostaining in the
NAc of rats injected i.c.v. with saline vehicle is weak and
does not differ between feeding groups (Carr et al. 2003),
the present test excluded the i.c.v. vehicle treatment
condition.
Perfusion
All injections were made between 1000 and 1500 hours
and members of the two feeding groups were matched
with respect to timing of injections. Thirtyminutes
following the injection of SL-327 or vehicle, animals
were injected i.c.v. with SKF-82958. Ninety minutes
following the second injection, they were transcardially
perfused with isotonic phosphate buffered saline (PBS)
followed by 4% paraformaldehyde in PBS using a Cole-
Parmer Masterflex console drive (model 7518-10). Brains
were then removed and maintained in 20% sucrose at
4°C for 48 h.
Immunostaining
Forty micrometer coronal sections of each brain were cut
on a Reichert-Jung 2800 Frigocut cryostat and collected in
a cryoprotective solution. At least six consecutive sections
were sampled from a coronal level corresponding to +1.2
to +1.6 mm in the atlas of Paxinos and Watson ( 1998).
Sampling was guided by light microscopic examination to
ensure anatomical matching of sections across rats. Immu-
nohistochemical staining was carried out using the avidin –
biotin method. Sections were washed in 1% sodium
borohydride followed by PBS and incubated for 2 h in
4% normal goat serum plus 1% bovine serum albumin in
PBS containing 0.2% Triton X-100 (Sigma) to block
nonspecific binding. This was followed by incubation
overnight with rabbit polyclonal c- fos antiserum (Oncogene
Science; 1:5,000 dilution). Following several PBS washes,
sections were incubated with a secondary antiserum
(Vector) for 60 min and subsequently reacted with avidin –
biotin complex (ABC) (Vector). The peroxidase reaction was
visualized with a chromogen solution containing100 mM
nickel sulfate, 125 mM sodium acetate, 10 mM imidaz-
ole, 0.03% diaminobenzidine, and 0.01% hydrogen
peroxide at pH 6.5. Sections were then mounted on
chrome – alum-coated slides, dehydrated, and coverslip-
ped. To control for variation in the immunohistochem-
ical reaction for Fos, tissue from the different treatment
groups was reacted together to minimize potential
histochemical variability.
Quantification of c- fos immunopositive cells and data
analysis
Counting of c- fos -positive cells in the NAc core and shell
was accomplished by obtaining images using a Nikon
Eclipse 50i microscope equipped with a Nikon S5500
digital camera and counting grains using the NIH Image J
software. Medial shell and core were demarcated basedon
the schematics of the Paxinos and Watson atlas ( 1998 ). For
nuclei counting, the Image J (NIH) program was set to
accept black areas between 10 and 100 pixels at a
magnification of ×100 using a common background.
Bilateral grain counts from three to five sections were
averaged to arrive at a value for a particular rat with the
large areas counted expected to reduce selection bias and
variability. Manual grain counts were taken in several cases
to verify accuracy of automatic counts. NAc core andshell
were analyzed separately using two-way ANOVA.
Results
Self-stimulation
When subjects received i.p. injection of 0.9% saline 10 min
prior to the postinjection tests of self-stimulation, the M-50
measure of reward threshold did not change, regardless of
whether the saline injection was preceded, 30 min earlier,
by the injection of DMSO or SL-327 (Fig. 1 , top panel,
left). When subjects were injected with D -amphetamine
10 min prior to postinjection tests, the M-50measure of
reward threshold decreased (main effect of D -amphetamine,
F
1,11
=78.4, p <0.001) with FR subjects displaying a
significantly greater effect than AL subjects (main effect
of feeding condition, F
1,11
=23.7, p <0.001; Fig. 1 , top
panel, right). SL-327 pretreatment had no effect on the
threshold-lowering effect of D -amphetamine in either
feeding group (Fig. 1 , top panel, right). The identical
pattern of results was obtained for the theta-0 measure of
reward threshold (Fig. 1 , middle panel; main effect of D -
amphetamine, F
1,11
=35.1, p <0.001; main effect of feeding
condition, F
1,11
=7.8, p <0.02). A different pattern of results
was obtained for the maximum reinforcement rate measure
with the one significant effect being a decrease produced by
SL-327 treatment (Fig. 1 , bottom panel; maineffect of
SL-327, F
1,11
=7.8, p <0.02).
In the follow-up experiment, D -amphetamine produced a
greater lowering of the M-50 reward threshold in FR
relative to AL subjects (Fig. 2 , top panel; main effect of
feeding condition, F
1,10
=7.58, p <0.025) with no effect of
intra-NAc U0126 microinjection. The sameresult was
obtained for the theta-0 measure of reward threshold
Psychopharmacology (2009) 201:495 – 506 499
(Fig. 2 , bottom panel; main effect of feedingcondition,
F
1,10
=10.99, p <0.01). Neither feeding condition nor
U0126 treatment affected the maximum reinforcement rate
(data not shown). Microinje ction sites were generally
located in the medial shell bordering the core, or in medial
core (Fig. 3).
Locomotor activity
During the initial 30-min period of activity monitoringthat
followed i.p. injections, no differences were observed
Fig. 2 Mean (±SEM) percentage changes in the M-50 ( top ) and theta-0
( bottom ) measures of reward threshold derived from self-stimulation
rate – frequency curves, 10 min following i.p. injection of D -amphetamine
(0.5 mg/kg) or vehicle in ad libitum fed ( black fill ) and food-restricted
( gray fill ) rats. These injections were preceded, 5 min earlier, by intra-
NAc microinjection of U0126 (0.1 and 1.0 μ g/0.5 μ L, bilaterally) or
vehicle (50% DMSO). * p <0.025 compared to AL subjects; ** p <0.01
compared to AL subjects
Fig. 1 Mean (±SEM) percentage changes in the M-50 ( top ) and theta-
0( middle ) measures of reward threshold and maximum reinforcement
rate ( bottom ), derived from self-stimulation rate – frequency curves,
10 min following i.p. injection of D -amphetamine (0.5 mg/kg) or
vehicle in ad libitum fed ( black fill ) and food-restricted ( gray fill) rats.
These injections were preceded, 30 min earlier, by i.p. injection of SL-
327 (50 mg/kg) or DMSO vehicle. ** p <0.001 compared to AL
subjects; * p <0.02 comparedto AL subjects; # p <0.02 compared to
vehicle pretreatment
500Psychopharmacology (2009) 201:495 –506
between AL and FR subjects. However, SL-327 decreased
locomotor activity across feeding conditions (main effect of
SL-327, F
1,13
=70.6, p <0.001; Fig. 4 ). Activity scores for
the subsequent 30-min period of monitoring, which
followed i.c.v. microinjections, were analyzed as difference
scores (i.e., post-i.c.v. activity −pre-i.c.v. activity; data not
shown). Accordingly, FR subjects displayed significantly
greater locomotor activation than AL subjects (main effect
of feeding condition, F
1,13
=19.6, p =0.001) with no effect
of SL-327 treatment.SL-327 produced uniformly low
levels of spontaneous forward locomotion across 5-min
time bins of the 30-min monitoring period inboth feeding
groups (Fig. 4 , bottom). Nevertheless, the activating effect
of SKF-82958 and the difference between FR and AL
groups was evident whether preceded by vehicle or SL-327.
The effects described for horizontal activity were also
observed as trends in the vertical activity measure, although
the difference between feeding groups in response to SKF-
82958 was not significant (data not shown).
Fos-immunostaining
In both the NAc shell and core, SKF-82958 produced
greater Fos-immunostaining in FR than AL subjects ( F
(shell)
1,12
=5.9, p <0.05; F(core)
1,12
=5.6, p <0.05). SL-327
pretreatment suppressed Fos-immunostaining in both
regions across feeding conditions ( F (shell)
1,12
=12.4,
p <0.01; F (core)
1,12
=7.3, p <0.02; Fig. 5 ). At the coronal
levels examined, it was also observed that SL-327
eliminated the relatively weak immunostaining otherwise
seen in caudate – putamen and weakened the otherwise
strong immunostaining seen in the piriform cortex of both
feeding groups (not shown).
Fig. 4 Top mean (±SEM) horizontal activity counts in the 30-min period
following i.p. injection of DMSO vehicle or SL-327 (50 mg/kg) —
indicated by bars to the left of each arrow — and following a subsequent
i.c.v. injection of SKF-82958 (20 μ g) — indicated by bars to the right of
each arrow — in ad libitum fed ( black fill ) and food-restricted ( gray fill)
rats. ** p <0.001 compared to AL subjects; * p <0.001 compared to
vehicle treatment. Bottom horizontal activity counts per 5-min time bin
following i.p. injection of vehicle ( left side of left graph ), SL-327 ( left
side of right graph ), and following subsequent i.c.v. injection of SKF-
82958 ( right side of both graphs ) in ad libitum fed ( open symbols )and
food-restricted ( filled symbols )rats
Fig. 3 Schematic diagrams adapted from Paxinos and Watson ( 1998),
indicating sites of U0126 microinjection in nucleus accumbens
Psychopharmacology (2009) 201:495 – 506 501
Discussion
Striatal ERK phosphorylation in response toD-1 DA
agonist and psychostimulant drug treatment is rapid and
transient, peaking at about 15 – 20 min postinjection (Valjent
et al. 2000 ; Gerfen et al. 2002 ). Consequently, the self-
stimulation and locomotor testing conducted in this study,
which commenced 10 min after drug injection and
continued for ∼ 30 min should have coincided with the
period of ERK phosphorylation. Yet, administration of a
dose of SL-327 similar to those previously used to block
D-1 DA agonist and psychostimulant-induced ERK phos-
phorylation (e.g., Valjent et al. 2000 ; Gerfen et al. 2002;
Haberny and Carr 2005a ; Shi and McGinty 2006) had no
effect on sensitivity to rewarding electrical brain stimula-
tion or the reward-potentiating effect of D -amphetamine,
which was markedly greater in FR than AL rats. However,
this result does not conclusively indicate that ERK
phosphorylation in the NAc does not affect the reward-
potentiating effect of D -amphetamine; it is possible that an
unexpected interaction between MEK inhibition andFR
occurred outside of the NAc and precluded the detection of
an effect in the self-stimulation task. To address this
possibility, a follow-up experiment was conducted in which
the MEK inhibitor U0126 was microinjected directly into
NAc, using a 1.0- μ g dose which previously blocked the
expression of a cocaine-conditioned place preference
(Miller and Marshall 2005 ) and a 0.1- μ g dose which has
blocked cue-induced cocaine-seeking when injected into the
central amygdala (Lu et al. 2005 ). However, neither dose
decreased the reward-potentiating effect of D -amphetamine
in AL or FR rats. One caveat is that cannulae were
generally placed at the medial shell/core border. Should
behaviorally significant ERK phosphorylation occur in a
region bordering the olfactory tubercle or in lateral core,the
present test may not have been adequate to ascertain it.
Nevertheless, the result obtained adds support to the
conclusion that ERK signaling in the NAc does not mediate
or modulate the reward efficacy of acute electrical brain
stimulation or D -amphetamine. This contrasts with the
processes through which associations are formed between
environmental contexts and subjective rewarding effects of
drugs and the sensitization that develops with chronic drug
treatment — both of which are blocked when each psychos-
timulant treatment is preceded by the administration of SL-
327 or other MEK inhibitor (for reviews, see Girault et al.
2006 ; Lu et al.2006 ). The one modest but significant effect
of SL-327 in the self-stimulation experiment was a decrease
in maximum reinforcement rate. This is indicative of a
decrease in performance capacity and is consonant with the
decrease in basal locomotor activity produced by this
treatment (see below).
The apparent lack of ERK involvement in the uncondi-
tioned behavioral response to DA-enhancing drugs of abuse
is further supported by results of the locomotor activity
experiment. The dose and route of administration chosen
for SKF-82958 were based on the previous observation that
this treatment not only resulted in greater locomotor
activation in FR than AL subjects, but also greater NAc
ERK phosphorylation, CREB phosphorylation, and c- fos
and preprodynorphin gene expression (Carr et al. 2003;
Haberny et al. 2004 ; Haberny and Carr 2005a , b ). Most
importantly, when preceded by i.p. injection of SL-327, the
ERK phosphorylation was markedly decreased and the
difference between feeding groups was eliminated (Haberny
and Carr 2005a ). Yet, in the present study, SL-327
pretreatment did not diminish the locomotor-activating
effect of SKF-82958 nor alter the difference between
feeding groups. However, in the 30-min period following
SL-327 injection prior to SKF-82958 injection, there was
a clear decrease in spontaneous locomotor activity across
feeding conditions. This observation is consistent with
the inferred decrease in performance capacity produced
by SL-327 in the self-stimulation experiment. It is
unlikely that the depressant effect of SL-327 on basal
locomotor activity is reflective of malaise or an aversive
Fig. 5 Bottom mean (±SEM) bilateral count of Fos-immunoreactive
cells in NAc shell ( left ) and NAc core ( right ) of ad libitum fed and
food-restricted rats following i.c.v. injection of SKF-82958 (20 μg)
preceded, 30 min earlier, by i.p. injection of DMSO vehicle ( white
bar ) or SL-327 (50 mg/kg; hatched bar ). Top representative photo-
micrographs depicting Fos-immunostaining in the NAcof food-
restricted rats injected i.c.v. with SKF-82958 preceded by i.p. injection
of vehicle ( left ) versus SL-327 ( right)
502Psychopharmacology (2009) 201:495 –506
state because intracranial self-stimulation thresholds were
unaffected by this treatment and aversive/dysphoric states
generally increase reward thresholds (for recent review,
see Carlezon and Chartoff 2007 ). Furthermore, systemic
injections of SL-327 similar to those used in the present
study failed to reinforce a conditioned place aversion
(Valjent et al. 2000).
Several studies have examined the effects of SL-327 on
the unconditioned locomotor-activating effect of psychosti-
mulants in AL mice and rats. While Valjent et al. ( 2000)
originally reported that SL-327 decreased cocaine-induced
motor activation, their subsequent work indicated that doses
of SL-327 that were sufficient to block cocaine-induced
ERK phosphorylation in striatum did not affect the
unconditioned locomotor response to cocaine (Valjent
et al. 2006 ). The same observation was made by Ferguson
et al. ( 2006 ). Similarly, NAc microinjections of the MEK
inhibitor, PD98059, blocked the acquisition of a D -
amphetamine-reinforced CPP but had no effecton D -
amphetamine-induced locomotion (Gerdjikov et al. 2004).
In contrast, Shi and McGinty ( 2006 ) reported that both
systemic injection of SL-327 and microinjection of U0126
in the caudate – putamen decreasedthe motor-activating
effect of D -amphetamine without affecting basal locomotor
activity. The absence of effect of SL-327 on basal activity
differs from the present observation and may reflect
procedural differences between the two studies. In the
present study, rats were habituated to the activity chambers
on at least six occasions prior to the test session while
subjects in the Shi and McGinty study were habituated on
| https://www.researchgate.net/publication/226942235_Effects_of_the_MEK_Inhibitor_SL-327_on_Rewarding_Motor-_and_Cellular-Activating_Effects_of_D-Amphetamine_and_SKF-82958_and_their_Augmentation_by_Food_Restriction_in_Rat |
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Impact of the Drought on Prices and Production : Hearing Before the Subcommittee on Economic Stabilization of the Committee on Banking, Finance, and Urban Affairs, House of Representatives, One-Hundredth Congress, Second Session, July 6, 1988
The Impact of the Federal Reserve's Money Policies on the Economy : Hearings Before the Subcommittee on Domestic Monetary Policy of the Committee on Banking, Currency and Housing, House of Representatives, Ninety-Fourth Congress, Second Session, June 8, 9, 10, and 24, 1976
The Impact of the Federal Reserve System's Monetary Policies on the Nation's Economy : Staff Report of the Subcommittee on Domestic Monetary Policy of the Committee on Banking, Currency and Housing, House of Representatives, Ninety-Fourth Congress, Second Session
The Impact of the Payment of Interest on Demand Deposits : A Study of the Staff of the Board of Governors of the Federal Reserve System
Impact of the War on Employment in 181 Centers of War Activity : Bulletin of the United States Bureau of Labor Statistics, No. 826
Impact on Money and Credit Policy of Federal Debt Management : Hearing Before the Subcommittee on Domestic Monetary Policy of the Committee on Banking, Finance, and Urban Affairs, House of Representatives, Ninety-Eighth Congress, First Session, April 25, 1983
Impact on Workers and Community of a Plant Shutdown in a Depressed Area : Bulletin of the United States Bureau of Labor Statistics, No. 1264
Impaired Workers in Industry: The Comparative Performance of Impaired Workers and Their Able-Bodied Fellow Workers : Bulletin of the United States Bureau of Labor Statistics, No. 857
Implications of Automation and Other Technological Developments: A Selected Annotated Bibliography (1963) : Bulletin of the United States Bureau of Labor Statistics, No. 1319-1
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Improving Federal Consumer Protection in Financial Services : Hearing Before the Committee on Financial Services, U.S. House of Representatives, One Hundred Tenth Congress, First Session, June 13, 2007
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Increase in Permanent Debt Limitation : Hearing Before the Committee on Finance, United States Senate, Eighty-Fifth Congress, Second Session, on H.R. 13580, August 15, 1958
Increase the Public Debt Limit : Hearing Before the Committee on Ways and Means, House of Representatives, Eighty-Fifth Congress, Second Session, on H.R. 13580 and H.R. 13581, July 30, 1958
Indebtedness in the United States, 1929-41
The Independent Treasury of the United States and Its Relations to the Banks of the Country
Indexes of Output Per Man-Hour: Corrugated and Solid Fiber Boxes Industry, 1958-66 : Bulletin of the United States Bureau of Labor Statistics, No. 1641
Indexes of Output Per Man-Hour: Gray Iron Foundries Industry, 1954-66 : Bulletin of the United States Bureau of Labor Statistics, No. 1636
Indexes of Output Per Man-Hour: Motor Vehicles and Equipment Industry, 1957-66 : Bulletin of the United States Bureau of Labor Statistics, No. 1613
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Indexing With the Consumer Price Index : Problems and Alternatives
Index Numbers of Wholesale Prices in the United States and Foreign Countries : Bulletin of the United States Bureau of Labor Statistics, No. 173
Index Numbers of Wholesale Prices in the United States and Foreign Countries : Bulletin of the United States Bureau of Labor Statistics, No. 284
Index of Volumes 72-83: Monthly Labor Review, January 1951 to December 1960 : Bulletin of the United States Bureau of Labor Statistics, No. 1335
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Index to Proceedings of International Association of Industrial Accident Boards and Commissions, 1914-1924 : Bulletin of the United States Bureau of Labor Statistics, No. 395
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Inflation and Growth : The Economic Policy Dilemma
Inflation Control : Hearing Before the Committee on Banking and Currency, House of Representatives, Eightieth Congress, Second Session, on S.J. Res. 157, July 29, 30, August 2, 3, and 4, 1948
Information Respecting United States Bonds, Paper Currency and Coin, Production of Precious Metals, Etc. : Revised July 1, 1915
Injuries and Accident Causes in Carpentry Operations : Bulletin of the United States Bureau of Labor Statistics, No. 1118
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Injuries and Accident Causes in Textile Dyeing and Finishing : Bulletin of the United States Bureau of Labor Statistics, No. 962
Injuries and Accident Causes in the Boilershop-Products Industry : Bulletin of the United States Bureau of Labor Statistics, No. 1237
Injuries and Accident Causes in the Brewing Industry, 1944 : Bulletin of the United States Bureau of Labor Statistics, No. 884
Injuries and Accident Causes in the Foundry Industry, 1942 : Bulletin of the United States Bureau of Labor Statistics, No. 805
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Injuries and Accident Causes in the Manufacture of Clay Construction Products : Bulletin of the United States Bureau of Labor Statistics, No. 1023
Injuries and Accident Causes in the Manufacture of Paperboard Containers: A Detailed Analysis of Hazards and of Injury Rates for 1950 by Region, Plant Size, and Operating Departments : Bulletin of the United States Bureau of Labor Statistics, No. 1139
Injuries and Accident Causes in the Manufacture of Pulp and Paper: A Detailed Analysis of Hazards and of Injury Rates for 1948 by Region, Plant Size, and Operating Departments : Bulletin of the United States Bureau of Labor Statistics, No. 1036
Injuries and Accident Causes in the Pulpwood-Logging Industry, 1943 and 1944 : Bulletin of the United States Bureau of Labor Statistics, No. 924
Injuries and Accident Causes in the Slaughtering and Meat-Packing Industry, 1943 : Bulletin of the United States Bureau of Labor Statistics, No. 855
Injuries and Accident Causes in Warehousing Operations: A Detailed Analysis of Injuries, Injury Rates, and Hazards for 1950, by Type of Warehouse, Region and Occupation : Bulletin of the United States Bureau of Labor Statistics, No. 1174
Injuries in Oil and Gas Drilling and Services : Bulletin of the United States Bureau of Labor Statistics, No. 2179
Injuries in the Logging Industry : Bulletin of the United States Bureau of Labor Statistics, No. 2203
Injuries Related to Servicing Equipment : Bulletin of the United States Bureau of Labor Statistics, No. 2115
Injuries Resulting From Falls From Elevations : Bulletin of the United States Bureau of Labor Statistics, No. 2195
Injuries Resulting From Falls on Stairs : Bulletin of the United States Bureau of Labor Statistics, No. 2214
Injuries to Construction Laborers : Bulletin of the United States Bureau of Labor Statistics, No. 2252
Injuries to Warehouse Workers : Bulletin of the United States Bureau of Labor Statistics, No. 2257
Injuries to Women in Personal Service Occupation in Ohio : Women's Bureau Bulletin, No. 151
Injury Rates by Industry
Inquiry Into Consumer Instalment Lending : A Progress Report on the Mobile Consumer Loan Survey
Inquiry Into Continental Illinois Corp. and Continental Illinois National Bank : Hearings Before the Subcommittee on Financial Institutions Supervision, Regulation, and Insurance of the Committee on Banking, Finance, and Urban Affairs, House of Representatives, Ninety-Eighth Congress, Second Session, September 18, 19 and October 4, 1984
An Inquiry Into the Nature and Effects of the Paper Credit of Great Britain
Inquiry on Membership in Federal Reserve System : Joint Hearings Before the Committees on Banking and Currency, Congress of the United States, Sixty-Eighth Congress, Pursuant to Public Act No. 503, October 2, 3, 4, 5, 9, 10, 11, and 12, 1923
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Installment Buying by City Consumers in 1941 : Bulletin of the United States Bureau of Labor Statistics, No. 773
Institutional Investors and the U.S. Government Securities Market : Staff Study
Instructions to Examiners and Assistant Examiners of the Federal Deposit Insurance Corporation
Insurance of Bank Obligation in Six States During the Period 1829-1866
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Interim Adjustment of Consumers' Price Index: Correction of New Unit Bias in Rent Component of Consumers' Price Index and Relative Importance of Items : Bulletin of the United States Bureau of Labor Statistics, No. 1039
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International Comparisons of Unemployment : Bulletin of the United States Bureau of Labor Statistics, No. 1979
International Documents on the Status of Women : Women's Bureau Bulletin, No. 217
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Philosophies | Free Full-Text | Is Organization of Living Systems Explained by Probability?
Traditionally, life has been thought improbable without assuming a special principle, such as vital power. Here, I try to understand organization of living systems in terms of a more rational and materialistic notion. I have introduced the notion of inhomogeneity, which is a novel interpretation of “negentropy”, and equivalent to “bound information”, according to the probabilistic interpretation of entropy. Free energy of metabolites is a labile inhomogeneity, whereas genetic information is a more stable inhomogeneity. Dynamic emergence can result from the conflict between two inhomogeneities, one labile and another stable, just like dialectic synthesis results from the conflict between thesis and antithesis. Life is a special type of dynamic emergence, which is coupled with reproduction mediated by genetic information. Biological membrane formation is taken as an example to formulate self-organization of biological systems through dynamic emergence. This system is ultimately driven by the Sun/Earth temperature difference, and is consistent with an increase in probability in the world. If we consider all entropy production related to life, such as degradation of materials and death of organisms, and ultimately the cooling of the Sun, probability always increases with the progress of living systems.
Is Organization of Living Systems Explained by Probability?
by Naoki Sato
Department of Life Sciences, University of Tokyo, Tokyo 153-8902, Japan
Philosophies 2021 , 6 (1), 3; https://doi.org/10.3390/philosophies6010003
Received: 29 November 2020 / Revised: 24 December 2020 / Accepted: 8 January 2021 / Published: 12 January 2021
(This article belongs to the Special Issue Probability in Living Systems )
Abstract
:
Traditionally, life has been thought improbable without assuming a special principle, such as vital power. Here, I try to understand organization of living systems in terms of a more rational and materialistic notion. I have introduced the notion of inhomogeneity, which is a novel interpretation of “negentropy”, and equivalent to “bound information”, according to the probabilistic interpretation of entropy. Free energy of metabolites is a labile inhomogeneity, whereas genetic information is a more stable inhomogeneity. Dynamic emergence can result from the conflict between two inhomogeneities, one labile and another stable, just like dialectic synthesis results from the conflict between thesis and antithesis. Life is a special type of dynamic emergence, which is coupled with reproduction mediated by genetic information. Biological membrane formation is taken as an example to formulate self-organization of biological systems through dynamic emergence. This system is ultimately driven by the Sun/Earth temperature difference, and is consistent with an increase in probability in the world. If we consider all entropy production related to life, such as degradation of materials and death of organisms, and ultimately the cooling of the Sun, probability always increases with the progress of living systems.
Keywords:
biological membrane
;
inhomogeneity
;
life
;
lipid
;
photosynthesis
;
probability
;
self-organization
Graphical Abstract
1. Introduction
Life has long been a subject of continuing quests of philosophers and scientists. From the age of ancient Greek philosophy, distinction between living beings and non-living things has been an essential enigma that philosophers tried to answer. A simple and clear solution was to assume a special principle in living beings, as was introduced by Aristotle under the notion of “psyche” or “anima” [ 1 ]. Various different kinds of anima were supposed to characterize different kinds of living beings, such as plants, animals, and humans. Although Aristotle’s notion of “anima” seemed non-scientific or pre-scientific, we might be able to consider “anima” as a principle of life rather than a special force of life. In the nineteenth century, supporters of vitalism supposed a special force that drives life in cellular activity, morphogenesis, and reproduction. It was called either “vital force,” “Lebenskräfte,” or “Entelechie,” among others [ 2 ]. “Élan vital” of Henri Bergson [ 3 ] was sometimes confused with vital force, but could have meant something different [ 4 ]. Garrett [ 2 ] called recurrence of a conflict between vitalism and emergent materialism “intellectual amnesia.”
Various properties are used to characterize life: controlled metabolism, sensibility, self organization of cell and body structure, reproduction, autonomy, and consciousness. These are only representatives of many qualifications of life. Mechanistic understanding could be possible for some of these, such as metabolism, sensibility, reproduction, and autonomy. Obviously, we cannot find a plausible explanation of consciousness in the current status of understanding, although efforts to naturalize consciousness continue [
5
]. In addition, self-organization is a curious property of life that we cannot easily provide a mechanistic or materialist answer, because it is different from crystallization of minerals or self-assembly of bacteriophages and ribosomes, which are stabilizing reactions that occur spontaneously. Self-organization of living beings is a dynamic process that requires free energy and information, which was discussed from the viewpoint of “molecular vitalism” [
6
]. Apparently, it proceeds spontaneously, but it is an important aspect of life and a part of a vital process that needs explanation. In the present article, I will discuss self-organization of living beings in the light of dynamic emergence, which involves conflict of two inhomogeneities and production of emergent inhomogeneity. The notion of inhomogeneity [
4
] is used to understand life in terms of inhomogeneity and dynamic emergence.
2. Inhomogeneity and Emergence
Self-organization of living systems, such as cells, organisms, and ecosystems, is explained by ingestion of “negative entropy” by Schrödinger [
8
] in the middle of the 20th century. Since then, various different versions of formulation were proposed, but the essential point remained identical, namely, that free energy flow into the living systems is coupled with dissipation of entropy to the outer world. Free energy is equivalent to negative entropy, and entropy increase is equivalent to realization of a more probable state. In other words, self-organization of living systems is part of a transition to a more probable world. In the following arguments, I intend to rationalize this apparently paradoxical statement by presenting realistic explanation using examples based on current biological knowledge.
I have introduced “inhomogeneity”
I
, which is defined as the “entropy deficit” or difference between the maximum entropy
S
max
and the actual entropy
S
[
4
]:
I = S max − S .
(1)
Historically, inhomogeneity is equivalent to “bound information” of Brillouin [ 9 ], who also used “negentropy” for what I call inhomogeneity. I prefer inhomogeneity, because this term adequately describes the situation in which something is not distributed evenly. This is equivalent to the situation in which entropy is lower than the maximum possible entropy. The relationship between inhomogeneity and probability is simply illustrated in an example of binomial distribution ( Figure 1 ).
Let us consider a box with two parts, A and B. There is a virtual wall between the two parts, but there is no real obstacle that prevents movement of particles between the two parts. If ten particles are present in the box, and the particles can displace freely, under this circumstance, we can imagine 11 different states in which part A contains different numbers of particles. The multiplicity factor
W
(
n
) of each state, or the number of different combinations of identical but distinguishable particles, can be obtained by a simple calculation:
W ( n ) = 10!/ n ! (10 − n )!,
(2)
where
n
is the number of particles in A. Since the total number of
W
(
n
) (0 ≤
n
≤ 10) is 1024, the probability
p n
of each state is given by:
p n = W ( n )/1024.
(3)
We find that
p n
is the largest when
n
= 5, namely, if an equal number of particles are partitioned in A and B. This probability is valid if the particles are freely displaced in the box, and the displacement is rapid enough for the time scale of measurement. We can also calculate entropy
S n
of arrangement
n
:
S n = k B ln W ( n ),
(4)
where
k
B
is the Boltzmann constant, and “ln” represents natural logarithm. This entropy calculation is similar to that used in the Boltzmann distribution of electron configuration (see e.g., Figure 4.2 in [
10
]). In this very simple example,
S n
is also the largest (
S
max
= 5.5
k
B
) when
n
= 5, with an even distribution. Inhomogeneity of each state is given by Equation (1), and we find that inhomogeneity is maximal when the distribution is the most uneven, namely, all particles are localized in either part. Although this is a simple example, we can extend a similar estimation of probability and entropy in more complicated systems in which the number of parts is larger or the number of particles is larger. In another extension, we may suppose uneven probability
q n i
of microstates
i
realizing a single macrostate
n
shown in
Figure 1
. In this case, the entropy
S n
of this macrostate is given by:
S n = − k B ∑ q n i ln( q n i ),
(5)
where summation is calculated for all
i
. Equation (5) is the common formula of entropy calculation [
9
], which is reduced to Equation (4) if all
q n i
are identical for all
i
. By this simple example, we can understand that entropy is maximal when the probability is maximal. If various macrostates are freely and rapidly interchangeable, the state of even distribution is the most probable, and the entropy of the system is maximized. In this example, the value of
W
(
n
) has a broad peak around the even distribution, but with larger number of total particles
N
, the binomial distribution will be approximated by a normal distribution, having a half width proportional to
N
1/2
, and therefore, the distribution will have a relatively sharper peak at the even distribution (relative width
N
−1/2
). This is just a case of the
Principle of Maximum Entropy
(PME) [
10
].
Various forms of inhomogeneity are found in nature. Pressure of a gas or osmosis is a result of uneven distribution of molecules. Potential energy in gravitational, electric, or magnetic field may be a form of inhomogeneity due to concentration of energy, although we cannot say exactly where the energy is localized (tentative assumed to be in the target material). Internal energy of a chemical is also a form of inhomogeneity due to energy concentration within the molecule. All these forms of inhomogeneity are quantitatively expressed in terms of free energy, which produces entropy upon its release (see Equation (6) in
Section 3.1
).
In terms of inhomogeneity, we may formulate that inhomogeneity tends to decrease spontaneously. But we have to remember the essential premise of the problem, namely, that all states in Figure 1 can be exchanged freely and rapidly within the time scale of observation, as in the Boltzmann distribution of electronic states [ 10 ]. The same is true for various other cases described in the previous paragraph. Therefore, some inhomogeneity decays rapidly, whereas some other inhomogeneity such as nucleotide sequence of DNA remains fairly stable [ 11 ].
Inhomogeneity is defined with a fixed reference to a certain state of “maximum” entropy (Equation (1) and
Figure 1
). This is important, because any system can be made infinitely homogeneous, if we decompose materials, molecules, atoms, etc., and mix them thoroughly. Nevertheless, we have to consider a plausible final state after any change. The final state of “maximum” entropy cannot be determined without judgment of an observer. This depends on the physical and time scales of the phenomenon that we are analyzing. For example, when we are analyzing a biological system, we do not consider nuclear reaction that could happen under extensive radiation in a reactor. In contrast, we are not satisfied with our daily activity of sleeping, walking, and talking, to analyze the origin of biological organization. We have to determine the level of analysis to find an appropriate value of “maximum” entropy. In the analysis of biological organization that we are interested in, we should focus on biochemical activity of cells, and in cases, interaction of cells and organs depending on target of analysis. In such analysis, it is best to consider free energy of biochemical reaction as a principal source of inhomogeneity. Additionally, genetic information will have to be taken into consideration.
3. Inhomogeneity in Biological Systems
3.1. Free Energy in Biochemical Reactions
Decay of inhomogeneity often occurs spontaneously and serves as a driving force for various living and non-living processes. Biochemical free energy is a form of inhomogeneity. Note that energy itself is conserved upon any change, either a physical or chemical one. It is free energy but not energy that can drive changes. We can say that the entropy term of free energy represents the extent to which atoms, particles, or energy can be potentially dissipated. If many atoms are restricted to be bound within a molecule, configuration entropy (entropy of distribution in the sense shown in
Figure 1
) is decreased. A “high-energy” molecule such as ATP (adenosine triphosphate) harbors inherent instability (repulsion of negative charges in proximity), and thus keeps excess energy within its structure. Both of these are potential sources of driving force for chemical reactions by releasing free energy or dissipating entropy, if an appropriate reaction route is provided by a catalyst or an enzyme. In this way, biochemical reactions proceed spontaneously in the direction of decreasing free energy. Each enzyme contributes to the reduction of activation energy of the reaction in which it is involved, but the direction of reaction is governed by free energy change, namely, the difference in free energy of the reactants and products. Free energy change ∆
G
(under a constant pressure) consists of two terms, enthalpy change ∆
H
and entropy change ∆
S
of the reaction system. According to the formulation of Atkins [
12
]:
−∆ G / T = −∆ H / T + ∆ S .
(6)
The first term of the right side of Equation (6) describes dissipation of reaction heat, or the entropy increase in the world (outside the system), and the second term is the entropy production in the system. The latter represents a decrease in the extent of concentration of particles and energy within the molecules involved in the reaction. Therefore, the left side of Equation (6) is the total increase in entropy, or ∆
S
total
. In other words, free energy change (divided by temperature) is a measure of entropy increase in the entire world (system plus outside world). A biochemical reaction proceeds by consuming free energy and producing ∆
S
total
(≡ −∆
G
/
T
).
The relationship between free energy and inhomogeneity is more clearly formulated by using the notion “affinity”
A
as used in the Belgian school of thermodynamics (see Chapter 4 in [
13
]). Affinity is defined as the difference between the total chemical potentials of products and reactants. Note that chemical potential is partial molar free energy. Therefore, affinity is a measure of the state of chemical system, in which affinity becomes zero at the equilibrium. Entropy production rate is expressed by using affinity as follows [
13
]:
d S /d t = ( A / T ) d ξ /d t ,
(7)
where d
ξ
/d
t
is the reaction rate. In this formulation, (
A
/
T
) is the driving force of the reaction, which corresponds exactly to the notion of inhomogeneity. However, because affinity is ultimately a derived notion of free energy, we consider free energy (or free energy change) as inhomogeneity in the following text for simplicity.
3.2. Dialectics in Dynamic Emergence
Several models may be presented for self-organization without vital force. A simple model is a stick pile in a river stream (
Figure 2
A). Depending on the flow rate and the shape of the pile, turbulence with complex eddies is created. The driving force is the flow of water blocked by the pile. This is a conflict between two inhomogeneities: water flow is a directional movement of water, whose momentum is a directional inhomogeneity; a pile stuck in a river is a stable structure, which is an organization inhomogeneity. The former is a labile inhomogeneity, whereas the latter is a stable inhomogeneity. The conflict between the two inhomogeneities yields turbulence, which is another kind of inhomogeneity. Turbulence may be regarded as a kind of inhomogeneity involving complex, organized water flow. The formation of turbulence is characterized as an organization driven by the conflict between two inhomogeneities. The formation of this new kind of inhomogeneity is called “emergence” here. This definition of emergence removes any mysterious appearance associated with the term. The process is dynamic, because continuous flow of water is necessary for the formation of turbulence. This is a very simple example of dynamic emergence (
Figure 3
).
Convection is another example of dynamic emergence (
Figure 2
B). If the water is warmed at the bottom of the casserole, convection occurs spontaneously. Typically, the convective flow is organized in a form of honeycombs. Prigogine called this “dissipative structure,” because structured flow is formed at the expense of entropy dissipation [
13
,
14
]. This can also be described in our framework of dynamic emergence. Heat is a form of labile inhomogeneity that serves as a driving force, while gravity is another form of inhomogeneity, which is not labile. Convective structure is dynamic, because it stays as long as heat is provided. We call it emergence, because convection is an inhomogeneity different from heat and gravity.
Dynamic emergence may be viewed as a dialectic process. In Hegelian dialectics, the conflict between the thesis and the antithesis will be resolved into synthesis by the action of “Aufheben.” This dialectic was introduced to explain changes in ideas during the long history of human culture. Hegel did not exactly explain the action of Aufheben. Nevertheless, we can apply a similar framework of explanation to our dynamic emergence ( Figure 3 ): The conflict between the two different inhomogeneities will be resolved by the emergence of a new kind of inhomogeneity. Dynamic emergence is certainly different from the Hegelian dialectic, because, in our framework, inhomogeneity is associated with material support. It is not an abstract idea or mental activity. Dynamic emergence has a physical or material basis underlying it. The emergence is not a miracle or something supernatural. We can give a perfect physical explanation of dynamic emergence. I use the term emergence to focus on the novelty of inhomogeneity that is produced from the conflict between the two original inhomogeneities. Many authors tried to understand natural phenomena and life in terms of “emergence” [ 15 , 16 , 17 , 18 , 19 ]. A common usage of the term is to denote something happening from complex interactions. But complexity is not an explanatory notion. In addition, precise and quantitative measure of emergence has not been provided in the analysis of emergence created by complexity. The dynamic nature of emergence should be emphasized here. We apply the notion of dynamic emergence to biological systems in the following sections.
Before proceeding, however, I have to explain possible roles of chaos in dynamic emergence. Complex systems sometimes show chaotic behavior, in which apparently random states of disorder is governed by essentially deterministic laws (see, for example, Section 2.3 in [ 20 ]). This could be the origin of variable outcome in dynamic emergence. In the actual biological systems, variability is kept to minimum, but the possibility of chaotic behavior could be a source of novelty or evolution. This is an interesting point, which we will have to develop in the future.
3.3. Role of Genetic Information
Understanding the nature of genetic information is essential to formulating the dynamic emergence of biological systems. An organism is reproduced by the action mediated by genetic information, whose expression leads to synthesis of biological molecules and cell structure. In this respect, genetic information appears to be specific to biological systems. However, we can imagine a non-living system that has a little but significant information. Using convection as an example again, just imagine a situation in which we repeat convection experiments. Eventually, the bottom of the casserole will rust. Then, the rust could act as an initial trigger that induces fluctuation within the water to promote convection, which is otherwise caused by very small fluctuations within the water. The rust could be part of the information that initiates convection at the same location each time. This primitive information could be a model of genetic information in living systems, in which biological activity promotes the replication of genetic material, which will direct the biological activity in the next round. We certainly recognize a clear difference between the rust on the bottom of casserole and the genetic information encoded by genomic DNA. The former gives just a single bit of information, but genetic information is more complicated with four bases. Rust does not have a specific recognition system that characterizes the genetic information. Nevertheless, the rust model provides the fundamental basis for genetic information in biological systems.
Now, we inspect the nature of genetic information (
Figure 4
). The information of DNA is encoded by four nucleotides, A, T, G, and C. Genetic information is often understood in terms of nucleotide sequence of a gene or a coding sequence. Here, we consider a gene as a set of a regulatory sequence and a coding sequence (or a set of exons). However, a gene can start anywhere within the genome if steric or structural restrictions, such as telomere or centromere, are not imposed. Therefore, information content should be considered for each gene, rather than calculated as a deviation from a random sequence. To calculate information content of a gene, we first focus on a single nucleotide within a conserved gene. Information content depends on whether the site is highly conserved or more variable. For a single site of DNA, average information content
H
is given by the following formula:
H = −∑ p i log 2 ( p i ),
(8)
where
p i
is the probability of nucleotide
i
(
i
= A, T, G, or C). This gives the extent of variation of nucleotides, and corresponds to entropy as defined in
Section 2
. Note that
H
is not itself the actual content of genetic information. Average information content is also known as “information entropy” [
21
].
H
and
S
are different in unit and calculation method, but both are supported by probability behind them. As shown in
Figure 1
in
Section 2
, both values are the largest when the probability is the highest. This is shown by the probabilistic interpretation of entropy [
7
] and is consistent with the PME [
10
]. If each nucleotide is expected to occur at an identical probability (
Figure 4
A,B), the average information content is 2 bits. In other words, the information gain of knowing the nucleotide is 2 bits. This is the logically possible, maximal value of information content at a single site. However, the actual probability is not evident. In a typical estimation in bioinformatics [
11
], average nucleotide composition of a gene or a genome is used as probability of nucleotide at each position. In this case, the value of average information content is identical over all sites of the entire gene or entire genome, and this is the maximum value of information entropy
H
max
.
If we take a single nucleotide sequence, such as a human gene sequence, we are not able to evaluate the information content of the sequence. Using phylogenetic data, a large number of homologous sequences are used to construct a multiple alignment. Occurrence of each nucleotide is calculated for each site and used as the probability of the nucleotide for this site. For a highly conserved site, only a single nucleotide might be found in all sequences. For a neutral site, the four nucleotides might occur at an average frequency.
Figure 4
C depicts an intermediate situation. The average information content determined with this set of probabilities
H
is a measure of extent of permitted variability. It is used to estimate the actual information content harbored by the site which is again called inhomogeneity
I
.
I = H max − H .
(9)
By summing up all values of
I
over a single gene, we can estimate the inhomogeneity or the information content of the gene. A similar value of information can be calculated for an amino acid sequence. Genetic information is, therefore, relative to the available sequence data. This is the limit of current status of bioinformatics. Theoretically, information content could be calculated by functional constraint of enzyme, but it is not feasible at present.
Genetic information can be considered as a stable inhomogeneity, as long as the genomic sequence is maintained by highly conservative, high fidelity replication and repair systems. Genetic information conferred to each enzyme is also stable during the catalytic reaction. Genetic information of DNA and enzymes is not absolutely unchangeable, but can be changed during the process of mutation and genetic drift. Nevertheless, we can imagine that the inhomogeneity of a gene or an enzyme does not vary a lot unless its function is fundamentally altered.
3.4. Dynamic Emergence in Biological Systems
3.4.1. Inhomogeneities in Biology
The two classical examples of non-living systems in Section 3.2 give us a hint of dynamic emergence in living systems. We have to consider two major types of inhomogenetity in life: free energy of metabolites and genetic information of DNA (and RNA and proteins). However, the ultimate source of metabolic free energy is the sunlight, or more precisely, the temperature difference between the Sun and the Earth, or inhomogeneity of temperature. This is the essential point to understand in explaining life and biosphere. Schrödinger did not understand the importance of photosynthesis when he formulated the notion of negentropy in explaining biological activity in 1944 [ 8 ], because the mechanism of photosynthesis was uncovered later in the 1950s and 1960s. The first experiment of photophosphorylation was performed by Arnon et al. [ 22 ], and the basic mechanism of oxidation-reduction reactions induced by the photosynthetic reaction centers was proposed by Hill and Bendall [ 23 ]. Schrödinger [ 8 ] was able to explain the life of heterotrophs, but the life of plants and the food chain remained unexplained. Genetic information of DNA, bioenergetics of mitochondria and chloroplasts, and morphogenesis, all these essential notions of biology were unraveled in the 1960s or later. Unfortunately, fundamental understanding of these in terms of entropy or inhomogeneity remained obscure until recently, or even now.
3.4.2. Hierarchy of Emergent Processes in Biology
I have formulated various biological processes in terms of inhomogeneity in a previous paper [ 4 ]. In many bioenergetic processes, the free energy of incoming metabolites is an inhomogeneity to be degraded, and the metabolic pathway consisting of various enzymes functions as a stable inhomogeneity that determines the fate of metabolites. The conflict between these two kinds of inhomogeneities results in a new kind of inhomogeneity, which is characterized as an emergence. In photosynthesis, temperature difference of Sun/Earth is the incoming inhomogeneity, which is then converted to an inhomogeneity of reductant/oxidant pair, or an inhomogeneity of excess/deficit of electrons, via a conflict with the photosynthetic electron transfer pathway located in the thylakoid membranes of chloroplasts and cyanobacteria ( Figure 5 A). The reducing power of the initial reductant NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) is then transferred to sugars, whereas the oxidant remains oxygen, which has filled an important part (currently 21%) of the atmosphere since more than 2 billion years. Atmospheric oxygen is entirely the product of past photosynthesis of plants, algae, and cyanobacteria. In the metabolism of heterotrophs, the reductant is supplied as food, whereas the oxidant is supplied from the air. The same is true for nonphotosynthetic tissues of plants. Figure 5 A is presented for the understanding of the entire biosphere. If some readers tend to find the situation in heterotrophs, it is shown in Figure 5 B. But it is my intention to understand the whole biological world in a single scheme like Figure 5 A, including all processes of life in an integral network. This network may be completed within a single photosynthetic organism, but it is also realized in the whole biosphere, if we do not consider individual cells and organisms separately.
In the metabolic processes in heterotrophs (and nonphotosynthetic tissues of plants), the incoming inhomogeneity is the reductant/oxidant pair (sugar/oxygen), and the emergent inhomogeneity is the chemical power of ATP and other high-energy metabolites. The metabolic pathways serve as a stable inhomogeneity. In each of photosynthesis and bioenergetic processes, we might be able to imagine simply a chain of biochemical reactions, rather than an emergent process. But the reaction chains are highly ordered with elaborate enzymes under fine regulations. All these require a large amount of information, which is ultimately encoded by the genomic DNA. The information is a kind of inhomogeneity, which selects substrates to process, and directs biochemical reactions to occur. Biochemical reactions are often compartmentalized within a cell according to the information conveyed by the protein sequence. We should bear in mind the equivalence of information and inhomogeneity [
4
]. In this sense, genetic information is an inhomogeneity that directs the flow of free energy of metabolites, through the realization of metabolic pathways with highly selective, and highly efficient, and well-localized enzymes. Each metabolic substrate, in general, bears a high free energy, which tends to decay if a reaction pathway is present. Nevertheless, every metabolic substrate is stable enough in its own. It is subject to a biochemical reaction if an appropriate enzyme is provided. Each enzyme holds information necessary for selecting a substrate, and directing a precisely determined reaction. In this sense, any enzyme is an inhomogeneity that act as a constraint. These reflections lead us to view metabolic processes as emergent processes resulting from the conflict between two different inhomogeneities, namely, free energy of metabolites and genetic information. We should not forget, however, that both kinds of inhomogeneities have probabilities behind their entropic appearance. When a metabolic reaction proceeds, free energy decreases to achieve the final state with higher probability, if we take all resulting products and heat in consideration. Several reactions might be possible, but only one of them is selected by an enzyme. This is also a probabilistic process, in which genetic information conferred to the enzyme is used. The conflict between labile and stable inhomogeneities is an origin of emergence, the formation of a new kind of inhomogeneity.
Theoretically, the distinction between labile and stable inhomogeneities in dynamic emergence might not be inherent in the substances involved in the process. A single substance can be a driving force and constraint in different processes. An enzyme is itself a polypeptide, which can give metabolic free energy when degraded. But an enzyme acts as a constraint in determining the metabolic pathways. Nucleotides may also act as metabolic energy and constraint. The two types of inhomogeneities should be identified for individual processes. Note that I use “type” and “kind” in qualifying inhomogeneity. Type refers to the distinction between labile/stable or driving force/constraint. Kind refers to the different entities that represent inhomogeneity, such as temperature, free energy, electron, information, etc. As explained above, each kind of inhomogeneity could be two types of inhomogeneity acting differently in dynamic emergence.
In biochemical reactions, however, the emergent inhomogeneity is still a form of free energy of metabolites. In this case, we may consider a complex network of metabolic pathways as a single emergent process that engenders a new kind of inhomogeneity, such as cellular structure. This is a morphogenic process that characterizes a part of biological self-organization.
4. Self-Organization in Living Systems
Self-organization of living systems is essentially understood as a dynamic emergence originating from the conflict between metabolic free energy dissipation (driving force) and genetic information (constraint). Membrane formation will be explained according to this scheme.
4.1. Lipid Bilayer Structure of Biological Membrane
Biological membrane consists of lipids and proteins, but it is amphiphilic lipids that form bilayer structure of biological membranes (
Figure 6
). A molecule is called amphiphilic if it has both hydrophilic and hydrophobic parts, and this is the essential point in organization of biological membranes. If amphiphilic lipid molecules, such as phosphatidylcholine and phosphatidylethanolamine, are placed in an aqueous environment, they will form spontaneously lamellar structure or micelles, depending on the size and nature of component hydrophilic and hydrophobic groups. Both lamellae and micelles are formed as a result of repulsion of hydrophobic groups and water. If the cross-sectional areas of the hydrophilic head group and the hydrophobic acyl groups are equal, then a planer structure called “bilayer” consisting of two layers of lipids will be formed, in which the hydrophobic groups of both layers faces to each other and the hydrophilic groups contact surrounding water molecules. The lipid bilayer is the standard basic structure of biological membranes, with protein molecules embedded within it. If the cross-sectional area of the hydrophilic head group is larger than that of the hydrophobic groups, such as the case in lysophosphatidylcholine (lacking an acyl group) and free fatty acid anion (common soap), spherical aggregates of lipids called micelles are formed, in which hydrophobic parts are centered, leaving the hydrophilic head groups facing the aqueous phase.
Note that the formation of bilayer or micelle structure as explained above is a stabilizing process analogous to crystallization. This is a static organization but not a dynamic one, because we have already lipids and water in hand and mix them in a laboratory experiment. The situation is different in living organisms because lipids are synthesized within the membrane and inserted into the membrane in expanding membranes within a growing cell. Introductory biochemistry textbooks such as [ 24 ] will be helpful for the readers who are not familiar with biological membrane and lipids.
4.2. Biosynthesis of Fatty Acids and Lipids
In general, biological membranes are not synthesized from scratch. Each existing membrane within the cell is enlarged by incorporating additional lipid molecules within its bilayer. Cell division is a process of partitioning the enlarged membranes to daughter cells. Biological membranes contain amphiphilic lipids, but many metabolites are hydrophilic. When an amphiphilic lipid molecule is synthesized from its components, an excess free energy is necessary to accommodate it in an aqueous environment.
Figure 7
shows a schematic pathway of fatty acid and membrane lipid biosynthesis. Fatty acids that form membrane lipids are called long-chain fatty acids, because they contain 14 or 16 methylene groups (-CH
2
-) as well as a methyl group (-CH
3
). Such fatty acid molecules are very hydrophobic. Nevertheless, fatty acids are synthesized by a soluble enzyme called fatty acid synthase using hydrophilic substrates. The growing chain of fatty acid is embedded within a hydrophobic pocket of a small protein called acyl carrier protein (or its equivalent within the large fatty acid synthase molecule, depending on organisms) to keep the hydrophobic molecule apart from the aqueous environment. Each step of fatty acid synthesis involves an extension of the acyl chain by two-carbon (C2) units, which is provided by malonyl Coenzyme A (CoA). The reaction is accompanied by a release of a carbon dioxide molecule, which is an entropy dissipating process. Malonyl CoA is synthesized from acetyl CoA by adding carbon dioxide, accompanied by the hydrolysis of an ATP molecule. After addition of the C2 unit, the carbonyl group is reduced to the methylene group by two molecules of NADPH, a powerful biological reductant. The reducing power of NADPH is conserved within the molecule of fatty acid, which is eventually used as a biological energy source when it is oxidized. In this sense, biological membranes are both structure and energy reserve (reserve of reductant). Therefore, the synthesis of a hydrophobic molecule, such as fatty acid, requires enormous consumption of free energy, or entropy dissipation, in other words, decay of inhomogeneity.
The protein part is removed when the acyl group is transferred to glycerol phosphate to make phosphatidic acid, which is then hydrolyzed to diacylglycerol. These are already incorporated into the membrane. A hydrophilic head group is provided as a precursor, in which a nucleotide carrier (cytidine diphosphate, CDP, or uridine diphosphate, UDP) binds the head group. Transfer of the head group to phosphatidic acid or diacylglycerol (depending on the kinds of lipids) produces an amphiphilic lipid molecule, an authentic member of the membrane. Hydrolysis of nucleotides (equivalent to ATP) is again required to build an amphiphilic lipid molecule. All these processes of lipid synthesis are catalyzed by respective enzymes, many of which are embedded in the membrane. Therefore, the site of lipid synthesis is already within the membrane.
In this way, the process of lipid biosynthesis consumes a large amount of free energy to produce an amphiphilic molecule and to embed it within an existing membrane. We can characterize this process as a dynamic emergence. The labile inhomogeneity that acts as a driving force is the free energy of ATP or equivalent nucleotides (needed to produce glycerol phosphate, the precursors of the hydrophilic part, and malonyl CoA) and the reducing power of NADPH (needed to synthesize fatty acids), and the inhomogeneity acting as a constraint is both biosynthetic enzymes and existing membranes within an aqueous environment. Enzymes determine which molecules are to be synthesized, whereas existing membranes provide sites of incorporation of synthesized lipid molecules. Both actions can be classified as inhomogeneities acting as constraints, because they select a single fate of the molecule among various probable ones.
4.3. Dynamism of Membrane Biogenesis
The fact that an existing membrane is enlarged by the action of lipid biogenesis is interpreted as a positive feedback driven by consumption of free energy. The feedback exerts in two ways: First, existing membranes are themselves basis of constructing and incorporating new lipid molecules; Second, the membrane structure allows cells to function as sites for metabolic processes, which provides necessary substrates for building lipid molecules. These two types of positive feedback support the dynamic emergence of biological membrane formation that looks like self-organization. In contrast to the formation of lipid bilayer in laboratory experiments, which is characterized as a static and stabilizing organization, biological membrane formation is a dynamic process characterized as an emergence. Membrane formation may be used as a typical example of self-organizing activities of cells or organisms. As a summary of this section, I repeat that self-organization of biological membranes and, therefore, the cell structure is a dynamic emergence resulting from the conflict between metabolic free energy (ATP and NADPH are different forms of inhomogeneities) and inhomogeneity constraint consisting of enzymes and the hydrophobic/hydrophilic environmental structure. This is also included in the scheme of the entire biosphere in
Figure 5
.
5. Problems Related to Inhomogeneity and Probability in Biological Systems
5.1. Evolution
In this short article, I do not try to describe details of organization of organism structure, and ecological structure, although I believe some kinds of dialectical processes or dynamic emergence are involved in these self-organization processes. Evolution is another aspect of dynamic emergence in biosphere (see [
25
] for an introductory textbook). Biological evolution is mainly a result of mutation and natural selection as far as selectable characters or nonsynonymous mutations are concerned. Changes and accumulation of silent or synonymous mutations are subject to a probabilistic process called genetic drift. Macroscopic or morphological changes could be explained by mutations in developmental switches according to the typical model of evolutionary developmental biology. In addition, speciation is sometimes characterized by the existence of genomic islands harboring mutational hot spots. The role of epigenetics and phenotypic flexibility is also argued.
Evolution may be viewed as a dynamic emergence resulting from the conflict between mutational diversification and competition of reproductive rates imposed by resource restrictions (see [
26
] for a comprehensive narrative). We can describe the traces of past evolution by either fossil comparison or phylogenetic reconstruction. But we cannot foresee future evolution, because we do not know exactly which mutations to occur and how selective pressures act on them. Even orthogenesis may not be predicted based on the past evidence of directed evolution. Preadaptation or exaptation is an explanation of the result of evolution, but not a predictive notion. Evolution looks adaptive because we are focusing on the organisms that have survived the past environmental changes. A thought experiment in which organisms never die suggests that evolution would not occur in such an immortal world. Evolution occurs because almost all organisms die without offspring. Only a small number of species succeeded in maintaining their lineages, which we characterize as having higher fitness. Therefore, evolutionary innovation is a result of vast extinction.
An objection to this statement could be that an organism with high plasticity might show an evolution by changing its property. This could be achieved by epigenetics or a huge genome equipped with various alleles that can be switched depending on the environment. This curious creature could survive environmental changes, and change its form each time. In this case, trait changes do not result from extinction. As a biological entity, however, this type of organism does not exist in nature, and is not a topic of evolutionary explanation. In addition, such a plastic organism does not change its genome after its adaptive changes in traits. Nevertheless, an idea or a cultural entity could survive infinitely in a flexible way, because such entity remains as a record even though it becomes unpopular. After some time, it will revive, like fashion trends.
Evolution may be viewed as a self-organization that contradicts the second law of thermodynamics claiming monotonous entropy increase. In fact, evolutionary innovation is compensated by the waste entropy of extinct organisms. Evolution is a process of entropy production, in which inhomogeneity of metabolic free energy (ultimately the Sun/Earth temperature difference) is degraded in conflict of spatial and environmental constraints that limit survival of organisms. If we focus on the survivors, then evolution appears as a creative process, but if we think of all dead creatures of the past, then evolution is a large-scale, destructive process, in which entropy increases, inhomogeneity decreases, and probability increases. The creative, organizing nature of evolution that we recognize in biology is an emergence resulting from such conflict between inhomogeneities. It is an entropy producing process in entirety, and the whole process of biosphere is directed to a world with a higher probability.
5.2. Probability of Life
Probability is, therefore, compatible with the existence of actual life forms, but we still do not know whether other forms of life are equally likely to exist. Jacques Monod wrote in 1970 that the probability of emergence of life was minute, and the existence of life on Earth, and even the existence of human beings, was a result of very rare chance [
27
]. Current astrobiology does not support this view, and supposes rather that we are only one of the probable forms of life, many of which are certainly present somewhere in the cosmos [
28
]. We agree with the astrobiologists, because decay of inhomogeneity might occur in various ways, and our living world might not be a unique one.
If life is defined as a principle of dynamic emergence coupled with reproducing ability with genetic information as described above, the type of life forms that we find on Earth may not be the only one. There could be various possible forms of life in the universe. Astrobiologists tend to search life forms that are similar, in some way, to the actual life forms on Earth. We are not sure if human-like creature exists somewhere in the universe. Nevertheless, the actual life forms are a consequence of the past dynamic emergence occurring on Earth. It is not possible to predict future life forms on Earth or possible life forms elsewhere in the universe.
6. Conclusions
Our initial question was whether organization of living systems is explained by probability. Various opinions in the past were rather negative to this question, namely, life has been thought improbable without assuming a special principle, such as vital power. In the present article, I introduced the notion of inhomogeneity, which is a novel interpretation of “negentropy” and equivalent to “bound information”. Relying on the probabilistic interpretation of entropy, we use inhomogeneity as a unified notion in physical chemistry and information science. There are two types of inhomogeneity, namely, labile and stable ones. Free energy of metabolites is a labile inhomogeneity, whereas genetic information is a more stable inhomogeneity. Then, I formulated three theses: First, labile inhomogeneity is the driving force of various phenomena in nature, and any decrease in inhomogeneity corresponds to an increase in probability. Second, the conflict between labile and stable inhomogeneities could result in dynamic emergence, producing a new kind of inhomogeneity through complex dynamics involving positive feedback. Third, life is a special kind of dynamic emergence coupled with reproduction mediated by genetic information. According to these considerations, self-organization of living systems, such as cells, multicellular organisms, and ecosystems, is a consequence of consumption of inhomogeneity, which results ultimately from the Sun/Earth temperature difference, and represents an increase in probability in the world. This seems to contradict with the common idea that the evolution of living systems is a rare, special phenomenon that contradicts the second law of thermodynamics asserting increase in entropy. However, if we consider all entropy production related to life, such as degradation of materials and death of organisms, and ultimately the cooling of the Sun, probability always increases with the progress of living systems.
Institutional Review Board Statement
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Informed Consent Statement
Conflicts of Interest
There is no conflict of interest to declare.
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Figure 1. Uneven distribution is evaluated by inhomogeneity and probability.
Figure 1. Uneven distribution is evaluated by inhomogeneity and probability.
Figure 2. Turbulence and convection as examples of emergence. ( A ) Turbulence in water flow blocked by a stick pile. ( B ) Convection of water in a casserole heated evenly. These images are just schemes for explanation, but not based on observation.
Figure 2. Turbulence and convection as examples of emergence. ( A ) Turbulence in water flow blocked by a stick pile. ( B ) Convection of water in a casserole heated evenly. These images are just schemes for explanation, but not based on observation.
Figure 3. Schematic model of dynamic emergence. In dynamic emergence, a conflict between two inhomogeneities, one labile and another stable, produces another kind of inhomogeneity. At the same time, the process produces a large amount of entropy, which corresponds to the decrease in labile inhomogeneity. In most cases, the process includes positive feedback, which is the direct origin of the emergent inhomogeneity. The amount of emergent inhomogeneity is much smaller than the amount of consumed inhomogeneity.
Figure 3. Schematic model of dynamic emergence. In dynamic emergence, a conflict between two inhomogeneities, one labile and another stable, produces another kind of inhomogeneity. At the same time, the process produces a large amount of entropy, which corresponds to the decrease in labile inhomogeneity. In most cases, the process includes positive feedback, which is the direct origin of the emergent inhomogeneity. The amount of emergent inhomogeneity is much smaller than the amount of consumed inhomogeneity.
Figure 4. Graphical explanation of average information content of DNA. ( A ) Plot of equal probability. ( B ) Logarithmic plot of equal probability. ( C ) Logarithmic plot of unequal probabilities at a partially conserved site. In this case, the inhomogeneity or information content of the site is 1/4.
Figure 4. Graphical explanation of average information content of DNA. ( A ) Plot of equal probability. ( B ) Logarithmic plot of equal probability. ( C ) Logarithmic plot of unequal probabilities at a partially conserved site. In this case, the inhomogeneity or information content of the site is 1/4.
Figure 5.
Hierarchy of the network of emergent processes in biological organization. (
A
) Network of the entire biosphere, valid also for photosynthetic organisms. (
B
) Network of heterotrophic organisms. Each circle represents an emergent process, in which one or more incoming inhomogeneities are shown by black arrows, whereas an emergent inhomogeneity is shown by a grey arrow. Inhomogeneities acting as constraints are shown by dashed arrows. Note that the constraints are not inhibitors. Rather, they also contribute to the emergence. In the entire biosphere, the ultimate driving force is provided by the sunlight, and various positive feedback loops enable self-organization of cell structure. The network is not closed within a single organism, but extends over the entire biosphere including various organisms. However, the constraints work only within a single cell or an organism. Heredity and evolution are not explicitly included in this scheme, which may be extended to include them as shown in [
4
]. The network in (
A
) is applied for the entire biosphere, but it is also valid for photosynthetic organisms, although excess reductants and oxygen are released for consumption by heterotrophs. In the partial network of heterotrophic organisms, incoming inhomogenetities are food and oxygen, which represent reductant and oxidant, respectively.
Figure 5. Hierarchy of the network of emergent processes in biological organization. ( A ) Network of the entire biosphere, valid also for photosynthetic organisms. ( B ) Network of heterotrophic organisms. Each circle represents an emergent process, in which one or more incoming inhomogeneities are shown by black arrows, whereas an emergent inhomogeneity is shown by a grey arrow. Inhomogeneities acting as constraints are shown by dashed arrows. Note that the constraints are not inhibitors. Rather, they also contribute to the emergence. In the entire biosphere, the ultimate driving force is provided by the sunlight, and various positive feedback loops enable self-organization of cell structure. The network is not closed within a single organism, but extends over the entire biosphere including various organisms. However, the constraints work only within a single cell or an organism. Heredity and evolution are not explicitly included in this scheme, which may be extended to include them as shown in [ 4 ]. The network in ( A ) is applied for the entire biosphere, but it is also valid for photosynthetic organisms, although excess reductants and oxygen are released for consumption by heterotrophs. In the partial network of heterotrophic organisms, incoming inhomogenetities are food and oxygen, which represent reductant and oxidant, respectively.
Figure 6. Amphiphilic lipid molecule and organization of bilayer and micelle. Phosphatidylcholine is shown as an example of amphiphilic lipid. Any biological membrane is far more complicated, having various different kinds of lipids with different acyl groups. Lipid bilayer is a planer structure formed by two layers of lipids, in which the acyl groups of the two layers contact each other, whereas the hydrophilic head groups face the aqueous phase. A micelle is formed by lyso lipids lacking an acyl group or soap (fatty acid salt), in which the hydrophobic groups form the central core and the hydrophilic groups are exposed to the spherical surface and contact water.
Figure 7.
Fatty acid synthesis and biosynthesis of biomembrane. Fatty acids in membrane lipids are composed of 16 or 18 carbon atoms (14 or 16 methylene groups plus methyl and carboxyl groups), and synthesized by condensing C2 units. The hydrophobic chain of growing fatty acid is encapsulated in the hydrophobic pocket of acyl carrier protein. The condensation reaction is performed with dissipating entropy in the form of carbon dioxide, originally attached to the C2 unit via hydrolysis of ATP. Reduction of acyl chain by NADPH is not explicitly shown in the figure. The synthesized fatty acid is transferred to glycerol phosphate in the membrane to form phosphatidic acid, which is then dephosphorylated to diacylglycerol. Hydrophilic head group is transferred to either phosphatidic acid or diacylglycerol (depending on lipid to synthesize) to form an amphiphilic lipid molecule. See text for details.
Figure 7. Fatty acid synthesis and biosynthesis of biomembrane. Fatty acids in membrane lipids are composed of 16 or 18 carbon atoms (14 or 16 methylene groups plus methyl and carboxyl groups), and synthesized by condensing C2 units. The hydrophobic chain of growing fatty acid is encapsulated in the hydrophobic pocket of acyl carrier protein. The condensation reaction is performed with dissipating entropy in the form of carbon dioxide, originally attached to the C2 unit via hydrolysis of ATP. Reduction of acyl chain by NADPH is not explicitly shown in the figure. The synthesized fatty acid is transferred to glycerol phosphate in the membrane to form phosphatidic acid, which is then dephosphorylated to diacylglycerol. Hydrophilic head group is transferred to either phosphatidic acid or diacylglycerol (depending on lipid to synthesize) to form an amphiphilic lipid molecule. See text for details.
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Miyazaki Sangyo-Keiei University | Japan |
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Miyazaki Sangyo-Keiei University
Japan
Recent publications
LEARNERS' CONFESSION FOR BIDIRECTIONAL TRANSCRIPTION EFFECTIVENESS FOR BEGINNERS IN THE PROGRAMMING COURSE
Article
Full-text available
International Journal of Modern Education
Tatsuhiro Tamaki
Harumi Hashimoto
Atsushi Onishi
Yasuo Uchida
The Adoption of programming education has become a global trend. In Japan, the Japan Revitalization Strategy 2016, announced by the Headquarters for Japan's Economic Revitalization in 2016, set forth the aim of making programming education compulsory in primary and secondary education. The purpose of this is to cultivate basic logical thinking skills through programming education, as part of efforts to develop and secure human resources for sparking economic growth. On the other hand, it will likely be necessary to review previously existing programming education in ICT human resources development courses at various types of schools. In the programming education for beginners that we are implementing at a college of technology, there is a considerable percentage of students who feel they are not up to programming. Thus, this study proposes "bidirectional transcription learning" for beginner programmers as an educational method to help strengthen programming education. It focuses on the process of converting a natural language to a programming language in the final stage of unplugged to code writing. Based on experience, transcription learning is regarded as effective for mastering programming, but we have conducted a trial to further improve efficiency and deepen understanding, and here we provide an overview and report on our results.
Recent Advances in Hybrid Priority-based Genetic Algorithms for Logistics and SCM Network Design
Article
September 2018
Computers & Industrial Engineering
Mitsuo Gen
Lin Lin
Youngsu Yun
Hisaki Inoue
Design and optimization of logistics and supply chain management (SCM) network is very important issue, which plans, implements and controls the efficient, effective forward and reverse flow and storage of goods, services and related information between the point of origin and the point of consumption to meet customers’ requirements. A multistage based logistics or SCM network can be modeled by means of a sequence of stages, each consisting of a set of functions, i.e. the existing or potential facilities located in several countries or regions of the world where goods are transformed or manufactured or stocked and delivered: suppliers, plants, distribution centers (DCs) and customers. The structure of each stage of the supply chain is completed by a set of arcs connected to the nodes and representing the flow of goods: each arc has a weight proportional to the cost incurred in between the two nodes it connects together.
In this paper, we survey a recent advance on hybrid priority-based genetic algorithms for solving a multistage logistics or SCM network problems. In particular, the following multistage based logistics or SCM network models will be introduced: (1) the sugarcane SCM network model, (2) multiobjective supply chain network model, (3) flexible multistage logistics network model, and (4) multiobjective reverse logistics network model. In each model, we summarize the background, mathematical model, hybrid priority-based genetic algorithm and numerical experiment. We also enhance a hybrid genetic algorithm (HGA) by combining a local search (LS) technique and tuning GA parameters by a fuzzy logic control (FLC) to fast the search ability of GA. Finally, numerical experiment of each case study is carried out to show the effectiveness of the proposed approach by the hybrid priority-based genetic algorithms.
Multi-stage Logistics Inventory for Automobile Manufacturing by Random Key-Based GA
Conference Paper
Hisaki Inoue
Jung Bok Jo
Mitsuo Gen
When evaluating a logistics system, automobile companies commonly search for the minimum transportation cost, which is significantly influenced by inventory problems. These inventory problems are extensive and varied. In many actual logistics systems, there are the three-stage network models take inventory values into consideration. Safety inventories are kept in distribution centers (DCs). In this study, we adapted a model to set-up a number of plants and DCs. We then performed numerical experiments by using demand data that we created on the basis of data disclosed by an automobile company. In this study, we propose a random key-based genetic algorithm (rk-GA) with the distributed environment scheme, we compared it with random key and spanning tree-based GAs, and report the advantages of the proposed method, random key-based genetic algorithm with distributed environment scheme (des-rkGA).
A DP MOVEMENT APPROACH TO RELATIVIZATION FROM VP IDIOMS: TOWARD A UNIFIED APPROACH
Article
ENGLISH LINGUISTICS
YOHEI TAKAHASHI
This paper examines two problems concerning relativization that have remained unaccounted for in syntactic research: i) the lack of reconstruction effects of the relative head in wh-relatives; and ii) the source of the choice of a complementizer C/that or wh-relative pronoun. The primary aim of this study is to provide a detailed explanation for these problems, using the general approach to relativization, Tonoike's (2008) DP movement approach, with necessary elaboration added. The description of the elaboration is twofold: concerning problem (i), we adopt the Late Merge Strategy of Takahashi (2016); and concerning problem (ii), it is proposed that the partitive Case feature assignment is a deciding factor executed in parallel with the case of the relativization of the existential there subject.
Turning Research on Implicit Memory to Something New【WS30周年記念企画】潜在記憶からの展開:New Trend, New Ideas―この30年を振り返りながら―
Article
September 2015
The Proceedings of the Annual Convention of the Japanese Psychological Association
Nobuo Ohta
Hidetsugu Tajika
Kyoko Yamada
[...]
Yuji Itoh
The effectiveness of active learning based on future sessionsフューチャーセッションを用いたアクティブ・ラーニングの効果
Article
September 2015
The Proceedings of the Annual Convention of the Japanese Psychological Association
Kyoko Yamada
Minoru Ideyama
Motoko Tanaka
An Analysis of Attitudes toward Non-Japanese Residents from the Viewpoint of the Transformation of Collective Consumption in an Area Densely Populated by Brazilians in Yokkaichi, Mie Prefecture集合的消費の変質に着目した外国人受入れ意識の分析——三重県四日市市の日系ブラジル人集住地区を事例に——
Article
Full-text available
July 2015
Geographical review of Japan series A
Taku Fukumoto
FUJIMOTO Hisashi
ENARI Miyuki
NAGAO Naohiro
While numerous efforts have been made to analyze the attitudes of local Japanese residents toward immigrant minorities in densely populated areas, few studies have focused on the resulting effects of the diversity that is prevalent in those areas. This study investigated the views of native residents toward Japanese-Brazilians in the Sasagawa district of the city of Yokkaichi, Mie prefecture, focusing on differences in the types of housing. Data were obtained from a questionnaire survey targeting Japanese residents, and the findings are summarized below.
First, the results of logistic regression analysis showed that the type of housing (e.g., owner-occupied, rented by the Urban Renaissance Agency, or rented by the prefecture) does not have an obvious effect on whether an accommodating view is extended toward non-Japanese; however, social relations with Brazilians are strongly associated with such a view. Although no statistically significant variation was found among the types of housing, situations considered problematic with non-Japanese residents differed between those who were owner-occupiers and those in rented housing.
Second, the variations in attitudes can be partly attributed to the concentration of Brazilians in rented housing and their occupational characteristics. For example, the high proportion of night-shift employees among Brazilians causes conflicts with their Japanese neighbors in the context of everyday living. Meanwhile, owner-occupiers tend to focus on the decline in the educational competitiveness of their school district when they refer to problems involving Brazilians.
Third, such variations should be understood from the viewpoint of the transformation of collective consumption (in regard to changes in rented housing space) as well as the fact that the district is located in a suburban area. The above-cited problems in rented housing are not Brazilian specific; rather, they are derived from the concentration of socioeconomically disadvantaged tenants, which usually occurs in public housing. Conversely, owner-occupiers who have resided in the district since its initial development as a desirable suburban neighborhood enjoyed an educational environment that enabled the reproduction of high socioeconomic status before the influx of the non-Japanese population. Therefore, they tend to attribute this change to the presence of Brazilians, although the declining situation is actually a consequence of the general transformation of collective consumption. The emigration of Japanese residents' children also fuels their negative view of the influx of Brazilians due to comparisons of the present with the past.
The above findings indicate that merely managing the cultural differences that cause problems in residents' daily lives, as discussed in previous studies, is inadequate. Rather, the processes of differentiation between the host society and immigrant minorities must be analyzed, with close attention paid to areal characteristics, including collective consumption.
16th National Conference of the Japanese Association for Asian Englishes
Article
Asian Englishes
Shinji Tokuchi
Apocalypse in Contemporary Japanese Science Fiction
Book
January 2014
Motoko Tanaka
Starting with the history of apocalyptic tradition in the West and focusing on modern Japanese apocalyptic science fiction in manga, anime, and novels, Motoko Tanaka shows how science fiction reflected and coped with the devastation in Japanese national identity after 1945.
The Persistence of the Residential Concentration of Koreans in Osaka from 1950 to 1980: Its Relation to Land Transfers and Home-work Relationships
Article
Full-text available
Jimburn Chiri/Human Geography, Kyoto
Taku Fukumoto
Although numerous efforts have been made to investigate the various causes for spatial segregation, existing studies have tended to overlook home-work relationships, which may influence the (un) changed features of segregation. This study considers the persistence of Korean residential concentration in Osaka, Japan, with data obtained from land registration and directories of Korean businesses, and clarifies the effects stemming from non-movers and the home-work relationships of Koreans. It confirms that Koreans began to purchase the land on which they lived after the 1960s, and that this process seems to have resulted in a decrease in their residential mobility. At the same time, non-resident Koreans, who tended to live within ethnic concentrations, also obtained land therein. Moreover, information about mortgages indicates that a significant number of Korean landowners, whether residents or non-residents, were entrepreneurs and that the lands they held operated as a source of funds. However, the same information reveals that Koreans also frequently resorted to using Japanese financial institutions. Thus, it is worth noting that the persistence of ethnic concentration is not always linked with the apparent existence of ethnic-related resources.
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The interval between encoding and retrieval influences the environmental context dependency for false recognition
The Proceedings of the Annual Convention of the Japanese Psychological Association
Kyoko YAMADA
Study on Multistage Logistics System Design Problem with Inventory Considering Demand Change by Hybrid Genetic Algorithm
IEEJ Transactions on Electronics Information and Systems
Hisaki Inoue
Mitsuo Gen
The logistics model used in this study is 3-stage model employed by an automobile company, which aims to solve traffic problems at a total minimum cost. Recently, research on the metaheuristics method has advanced as an approximate means for solving optimization problems like this model. These problems can be solved using various methods such as the genetic algorithm (GA), simulated annealing, and tabu search. GA is superior in robustness and adjustability toward a change in the structure of these problems. However, GA has a disadvantage in that it has a slightly inefficient search performance because it carries out a multi-point search. A hybrid GA that combines another method is attracting considerable attention since it can compensate for a fault to a partial solution that early convergence gives a bad influence on a result. In this study, we propose a novel hybrid random key-based GA(h-rkGA) that combines local search and parameter tuning of crossover rate and mutation rate; h-rkGA is an improved version of the random key-based GA (rk-GA). We attempted comparative experiments with spanning tree-based GA, priority based GA and random key-based GA. Further, we attempted comparative experiments with ``h-GA by only local search'' and ``h-GA by only parameter tuning''. We reported the effectiveness of the proposed method on the basis of the results of these experiments.
Study on Multi-Stage Logistic System using Random Key-Based Multi-Objective Genetic Algorithm
Hisaki Inoue
Mitsuo Gen
Virtual universities revealed: More than just a pretty interface?
Distance Education
Roger Boshier
Steve Brand
Azra Dabiri
Chiao Yen Joy Tsai
Search for ‘virtual university’ or ‘virtual campus’ on a popular search engine like Google and, in March 2001, we were rewarded with 71 600 and 58 700 hits. This in contrast to the situation just a few years ago. Apart from the increasing sophistication of search engines, this enormous number of hits arises from the mad rush to get courses online. Everywhere, policy analysts and university administrators fear being ‘left behind’ and virtual universities are being created and virtual components laced onto traditional operations in the name of distributed learning. Virtual universities don't respect boundaries and there is fierce competition and, when trolling for students, some things are emphasised and others hidden. Each virtual university has an opening (or ‘gate') page which is a text that reveals and conceals. The authors examined the gate‐page associated with 231 virtual universities (or virtual campuses). The authors were particularly interested in the extent to which virtual university iconography replicated the face‐to‐face campus or opted for the motifs of distributed learning. They then used discriminant function analysis to examine the extent to which Political Economy (Public/Private), Corporate Presence (Absent/Present), Institutional Configuration (Stand‐Alone/Consortia/Orange Peel) was associated with a difference in gate‐page iconography (i.e. aesthetic properties, use of traditional icons, use of distributed learning icons and discursive elements). The greatest differences were between gates of virtual operations where a corporate presence was absent or present. Although globalisation has smoothed out culturally constructed aesthetic preferences, gate‐page iconography is not just a matter of ‘Web design’.
[Affiliative achievement motivation and non-affiliative achievement motivation of female students]
Shinrigaku kenkyu: The Japanese journal of psychology
Kiyoharu Doi
The purpose of this study was to investigate the two dimensional theory of achievement motivation (Doi, 1982) in female students. Doi's motivation scale were administered to 81 female university students, 58 female students of school of nursing and 77 female students of school of English Language, and the Yatabe-Guilford personality inventory was also administered to the first and the second groups. Affiliative achievement motivation and non-affiliative achievement motivation were extracted by principal component analyses and canonical correlation analyses. Non-affiliative achievement motivation was found to be related to personality type: emotional instability and introversion. These findings differ from achievement motivation concepts (Murray, 1938; McClelland, Atkinson, Clark, & Lowell, 1953), that include emotional stability and extraversion.
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| https://www.researchgate.net/institution/Miyazaki_Sangyo-Keiei_University |
Rehanging Reynolds at the British Institution | Article index | Articles | British Art Studies
Catherine Roach explores the possibility of rediscovering not only the appearance of historic displays, but also some of their multiple, shifting, and contingent meanings, by looking at the British Institution's 1823 exhibit of works by Joshua Reynolds.
Rehanging Reynolds at the British Institution: Methods for Reconstructing Ephemeral Displays
John Scarlett David, The Interior of the British Institution Gallery (detail), 1829, oil on canvas, 113 × 142.2 cm
Abstract
Reconstructions of historic exhibitions made with current technologies can present beguiling illusions, but they also put us in danger of recreating the past in our own image. This article and the accompanying reconstruction explore methods for representing lost displays, with an emphasis on visualizing uncertainty, illuminating process, and understanding the mediated nature of period images. These issues are highlighted in a partial recreation of a loan show held at the British Institution, London, in 1823, which featured the works of Sir Joshua Reynolds alongside continental old masters. This recreation demonstrates how speculative reconstructions can nonetheless shed light on ephemeral displays, revealing powerful visual and conceptual dialogues that took place on the crowded walls of nineteenth-century exhibitions.
The study of exhibitions is of necessity the study of lost spaces. Even the best-preserved ensembles undergo change over time, and many more have left only scant material traces. Today, digital technologies offer a new avenue to a long-held desire, the reconstruction of ephemeral displays. Such reconstructions bring together images of works that are now scattered, but were once viewed and understood in concert. They thus raise the possibility of rediscovering not only the appearance of historic displays, but also some of their multiple, shifting, and contingent meanings. Beguiling as this prospect may be, it also presents methodological challenges. Today’s digital reconstructions contain great potential, but they also contain great potential for distortion. We are now creating our own objects of study. Like a scientist designing an experiment, we must be careful that in building our research tools we do not simply confirm our own preconceptions.
The temptation to recreate the past in our own image was not born with digital technologies. Translating existing sources into a reconstruction of a lost display has always required conjecture, which is inevitably coloured by the translator’s worldview.
1
2
As a result, it is essential that authors of reconstructions identify the choices they have made in the process of creation. Particularly pressing is the issue of how best to represent uncertainty—moments when a gap in the historical record has been supplemented by informed conjecture or a sheer leap of faith.
3
Without acknowledgment of such decisions, “a single, highly polished reconstruction of a building or site can, in fact, be too convincing. While such a reconstruction records one plausible interpretation of incomplete and usually contested data, it risks being received as wholly authoritative and above dispute.”
4
Visualizing uncertainty is thus a vital concern.
Equally important is the relationship between these new projects and traditional sources of knowledge about images and their production, including the catalogue raisonné. The printed catalogue raisonné is in many ways a utopian project. It imagines the possibility of certainty and completion, presupposing that an entire life’s artistic production can be located, correctly attributed, and codified. In the process, it privileges the idea of the unique creator in ways that the discipline of art history still struggles to shrug off. Just as we have come to be sceptical of some aspects of the catalogue raisonné project, we should also have a healthy scepticism of utopian attitudes towards digital projects. All historical inquiries are shaped by the concerns of the present moment. But if in forging our new reconstructions we ignore the work of previous generations, including the carefully collated information of catalogues raisonnés, we risk distorting our understanding of past displays more than is necessary. So much is absent in current reconstructions: the shifting presence of viewers; the smells of fabric, bodies, perfumes, and dirt; and, most of all, the conversations and perceptions of those visitors who left no written trace. But art-historical knowledge need not be absent. Indeed, if we are to create compelling and useful reconstructions, it must not be.
This essay offers some thoughts on best practices for exhibition reconstructions by considering recent attempts, undertaken by myself and others, to visualize a series of ground-breaking exhibitions of the works of Sir Joshua Reynolds, first President of the Royal Academy, staged by the British Institution, London, in the early nineteenth century. First, I will offer a critique of
What Jane Saw
In 1813 the British Institution for Promoting the Fine Arts in the United Kingdom, a collector-run philanthropic arts society, staged what has been called “the first true monographic exhibition” surveying the career of Sir Joshua Reynolds.
5
6
What Jane Saw? Rehanging Reynolds at the British Institution in 1813
Period images of the installation of the Reynolds exhibition in 1813 have yet to be discovered. But almost two centuries after the event, a leading figure in collection studies, Francis Haskell, noted that with the help of the catalogue, “it would be just possible to reconstruct the hanging in our minds with reasonable accuracy.”
7
In 2013, Haskell’s suggestion was taken up; the result was not a mental image, but an impressive website providing a navigable scale recreation of the exhibition. Titled
What Jane Saw
by its creator, English literature scholar Janine Barchas, this important project takes its inspiration from the fact that Jane Austen attended this event. It invites users to “time travel” to the exhibition that Austen visited.
8
As a pioneering example in the field, this project illustrates both the potentials and the pitfalls of digital exhibition reconstructions.
9
10
Interviews in these outlets, as well as the text of the website and accompanying scholarly articles, make bold claims for the project.
11
Barchas told the
New York Times
: “I feel pretty sure this is the way the exhibit was actually hung.”
12
But does the site measure up to this claim?
Figure 1.John Scarlett Davis, Interior of the British Institution, 1829, oil on canvas, 113 x 142.2 cm. Collection of the Yale Center for British Art, Paul Mellon Collection (B1981.25.212)
Digital image courtesy of Yale Center for British Art
One area of concern regarding
What Jane Saw
is the way period images were used as sources of information. Barchas notes the risk of an “anachronistic wall aesthetic”, which she sought to combat by consulting “surviving contemporary images”.
13
While no images survive of the Reynolds exhibition, other displays at the British Institution galleries were depicted in oil, watercolour, and engraving (
fig. 1
). Period images can provide a wealth of visual information, but should be consulted advisedly. As Christopher Whitehead has noted, the authors of these images “worked within pictorial conventions and agendas which may have conflicted with current ideas of accurate recording”.
14
Like their close cousin, the exhibition catalogue, these images provide an idealized, synthesized version of a display, what Victor Stoichita has called “the dream of any collection”.
15
Even diagrams that were intended to guide a viewer may have simplified or distorted the contents in order to facilitate use, conform to contemporary taste, or convey a more favourable impression of the installation depicted.
16
And, as I have argued elsewhere, the conventions of the genre of gallery painting encourage artistic licence, as artists rearranged the contents of the actual display in order to create programmatic statements.
17
As sources for exhibition reconstructions, historic images are best used in concert with one another and with textual sources: features that appear in multiple images are less likely to be the fancy of an individual artist. For instance, the pink wall colour used in
What Jane Saw
was based on a hand-coloured aquatint published in
The Microcosm of London
in 1808. Yet most images of the Institution show red walls, a fact confirmed by textual sources, including a critic who complained in 1806 that the gallery was furnished with “a paper of the brightest and most vivid scarlet, which fatigues and distresses the eye”.
18
By neglecting such evidence and instead relying on a single image,
What Jane Saw
19
20
But these guesses do not always take advantage of the lessons of existing scholarship on period hanging practices, leading to a recreation that reflects present-day aesthetic preferences, rather than those of the early nineteenth century.
21
22
As Waterfield observes, this style was familiar to the patrons of the Institution, many of whom employed it in their personal collections.
23
As I will discuss in more detail below, these patrons played a central role in arranging the Institution’s exhibitions. The decorative style was also employed by the Hanging Committee of the Royal Academy, whose displays reflected a “commitment to lateral symmetry, or at least to a fairly close approximation thereof”.
24
This mode of display was widely used over a long period of time. Its currency can be judged by its appearance in two images of exhibitions, created over a century apart: a watercolour of the Royal Academy summer exhibition of 1784 (
fig. 2
) and a photograph of the Victoria Gallery in Dundee in 1889 (
fig. 3
). As such images suggest, the desire for symmetry led to the creation of temporary pendants out of works of similar scale and orientation.
Figure 2.
Edward Francis Burney, West Wall, The Great Room, Royal Academy,, 784, pen, grey ink, grey wash, and watercolour, 33.5 × 42.9 cm. Collection of the British Museum, London (1904,0101.1)
Digital image courtesy of Trustees of the British Museum.
Figure 3.
Unknown photographer, Victoria Gallery, Dundee, 1889, photograph, dimensions unknown
Digital image courtesy of Libraries, Leisure and Culture Dundee
The application of these principles would have led to very different arrangements than those seen on
What Jane Saw
. Consider, for example, the north wall of the North Room. At the Institution, this room was generally acknowledged to be the main gallery; its north wall, where the catalogue numbers started, was frequently the site of a major visual statement.
25
In 1813 this wall contained two full-length portraits depicting the monarch, George III, and the great tragic actress Sarah Siddons, as well as three “fancy” pictures, small-scale and expressive images of children.
26
The designers of
What Jane Saw
have chosen to place the portrait of George III in the centre, on the assumption that it should face a portrait of George’s wife, Queen Charlotte, which hung at the opposite end of the space.
27
28
To my mind, the prevalence of this practice suggests that the portraits of king and actress were most likely displayed side by side. The fancy pictures might then have been hung in a row above or, more likely, below, so that they could be examined closely.
29
30
The wide divergence between my proposed arrangement and that presented on
What Jane Saw
illuminates the degree of speculation involved in such endeavours. Authors of reconstructions should strive to highlight such uncertainties.
Some images of individual works presented on the site also pose problems. Locating images is a major challenge for any reconstruction project. In the case of the Reynolds exhibition of 1813, many of the canvases shown have changed hands, changed titles, exist in multiple variants, or are known only through prints. In sourcing images for
What Jane Saw
, overall visual appearance was prioritized over obtaining images of the objects displayed in 1813. As a statement in the “About” section explains:
31
In the meantime, however, these images are misleadingly presented. Individual instances where an image of an alternate object has been used are not clearly marked.
32
fig. 4
). Instead, it represents a replica painted by Matthew Shepperson in 1824, now in the collection of the National Maritime Museum, Greenwich (
fig. 5
).
33
This substitution of a copy by another artist is nowhere indicated. The vast majority of visitors to the site will mistakenly believe they are looking at an image of a work that was painted by Reynolds and present in 1813, neither of which is true; indeed, the Shepperson replica was created eleven years after the exhibition took place.
DOI
34
This would have been a good choice: the Petworth painting is an autograph Reynolds dated around 1761; a colour photograph of it has recently been published; and Mannings speculates that it may even have been the object shown in 1813 (
fig. 6
).
35
But instead, the image provided is of a copy by an unknown artist now in the collection of the National Portrait Gallery (NPG), although it is not labelled as such (
fig. 7
).
These unmarked substitutions may initially seem to be of interest only to experts in the field. Indeed, one of the most laudable aspects of
What Jane Saw
36
37
But in the
What Jane Saw
reconstruction, the digital image has been expanded to fill the space occupied by the object shown in 1813, which was roughly three times that size.
38
As a consequence, the figure looms larger in the frame than those in the surrounding compositions, although this would not have been the case in the actual installation.
DOI
The precise visual and material qualities of individual canvases matter: as the site notes, the two portraits of Admiral Rodney discussed here were part of a fascinating moment in the installation. Hung near each other on adjoining walls, the juxtaposition of two works “painted 30 years apart . . . allows the viewer to see Rodney age before their eyes”.
39
What Jane Saw
site, as the images provided do not depict works by Reynolds.
The designers of
What Jane Saw
have exhibited an admirable commitment to bringing their project to a wider audience. But such projects do that audience a disservice if the information presented is inaccurate or misleading. Too often
What Jane Saw
becomes not even what Jane might have seen, but rather what Jane did
not
What Jane Saw
reconstruction they have been estimated using “averaging of typical dimensions” of works (the precise calculations used to determine the scale of individual canvases are not provided).
40
Uncertainty is a necessary element of any digital reconstruction. But one cannot employ as many elisions, speculations, and unmarked substitutions as
What Jane Saw
does, and at the same time assert “we believe that we have ‘frozen’ the gallery precisely as it looked in 1796.”
41
To do so abuses the trust of the audience and discredits the practice of exhibition reconstructions.
Accuracy of the type claimed by its creators for
What Jane Saw
42
Rehanging Reynolds at the British Institution in 1823
The exhibition of 1813 was the first in a series of Institution-sponsored Reynolds exhibitions, held once every ten years for forty years. By returning repeatedly to the subject of Reynolds, the administrators of the Institution kept his works before the eyes of the public and continued to fuel debates about the status of Reynolds and of the national school of art. Here, I will focus on the second of these events, held in 1823. The first exhibition presented Reynolds in splendid isolation; the second put him in conversation with the continental old masters, making an even bolder claim for his art-historical significance.
In order to understand how this installation might have appeared, we must first understand who organized it, and why.
43
The British Institution was a collectively funded philanthropic organization established in 1805.
44
Its founders sought to increase the quality of British art, so that it might compete internationally. Controversially, they advocated study and emulation of continental art; the idea was to beat the old masters at their own game, as it were. By the 1820s, the mission had expanded; the administrators also sought “to extend to a wider circle the love and admiration, and patronage of the arts”.
45
Vertù
, is best acquired by conversation, and a constant examination of the best works of the best masters; and is formed by comparison of one of them with another, each predominant example having been stored in the memory.”
46
The arrangement of Institution exhibitions encouraged this kind of viewing. Period aesthetics valued juxtaposition over strict categorization, and the arrangement of the works into symmetrical patterns invited visual comparisons, for example among works of like size but unlike subject or style.
47
Reviewers took up this suggestion, routinely assessing artists and works in relation to each other. “Comparison is the great test of excellence”, wrote Robert Hunt in the
Examiner
.
48
The displays that elicited such responses were developed and installed by a group of administrators. The patrons of the Institution are often described as “aristocratic” or “patrician”.
49
But, in fact, its membership was diverse, including representatives of most political persuasions and religious tendencies.
50
51
52
Although Seguier is sometimes described as a curator in all but name, he was not the sole author of these displays: the Directors also participated in hanging days.
53
In 1821, Joseph Farington visited the Institution in company with Charles Long. He found that “the arranging pictures the works of the Old Masters was going on”, attended by Directors Samuel Rogers, Lord Carlisle, Lord Mulgrave, and Beaumont.
54
DOI
55
To reconstruct these visual narratives, we must first reconstruct the contents of the exhibition. The development of the video presented here was a collective endeavour, made possible by the support of
British Art Studies
56
In addition, as the text in video strives to make clear, many elements of the depiction are conjecture rather than fact. Text panels interspersed throughout the video provide additional historical information; they also puncture the illusion of exactitude by explaining, within the reconstruction itself, the many decisions and guesses that went into its creation (
fig. 8
).
Figure 8.Duck Duck Zeus, Digital Reconstruction, Pictures by Sir Joshua Reynolds, with a Selection from the Italian, Spanish, Flemish, and Dutch Schools, exhibition held at the British Institution, London, 1823
DOI
DOI
Information about the architecture and dimensions of the room was taken from Thomas Smith’s
Recollections of the British Institution
, published in 1860.
57
Microcosm of London
and the
Magazine of Fine Arts
(
fig. 9
).
58
These images provide only a starting point for analysis of the space’s possible appearance: as I have shown elsewhere, John Scarlett Davis, in particular, often invented more than he transcribed when representing a display space.
59
Even in images, such as the Stephanoff watercolour, where the hang depicted closely tracks the number order in the catalogue, its appearance might have been tidied up to enhance the aesthetic appeal of the overall image (
fig. 10
).
60
These images were therefore consulted in concert; an individual architectural or decorative feature was considered likely to have actually been in the space only if it appeared in multiple images, preferably confirmed by a textual source.
DOI Figure 10.James Stephanoff and Francis Philip Stephanoff, The Interior of the British Institution, 1817, watercolour on paper, 20 × 29.4 cm. Collection of the Victoria & Albert Museum, LondonDigital image courtesy of Victoria & Albert Museum, London
DOI
Interior of the British Institution
, which instead shows a geometric pattern (see
fig. 1
). Examination of other works by this artist, including his representations of the Louvre, the Uffizi, and the National Gallery of Naval Art in Greenwich Hospital, reveal that Davis habitually represented floors with this pattern, perhaps to reinforce a sense of perspectival recession.
61
62
63
The result of all these choices, however, is still potentially deceptive in its precision, an effect we sought to combat with the inclusion of the source images and of explanatory text in the reconstruction itself.
The centrepiece of the reconstruction is the depiction of the north wall of the North Room, which visualizes several different kinds of uncertainty. According to the catalogue (which might not reflect last-minute alterations or later additions), ten paintings hung on this wall (
fig. 11
).
64
Arranging these works presented fresh methodological challenges: translating a catalogue numbering order into a historically appropriate hang is not a straightforward task, even when the dimensions of both works and wall are known (figs.
12
–21
65
These large works then formed anchors around which symmetrical patterns could be formed. This approach has obvious benefits, as it avoids the headache of finding space for a massive canvas on an already crowded wall.
Figure 12.
Sir Joshua Reynolds, George IV, 1784, oil on canvas, 238.7 × 266.7 cm. Private Collection, UK. Mannings no. 719. This image represents the exact object shown at the British Institution loan exhibition of 1823 as cat. no. 1, His Majesty when Prince of Wales
Digital image courtesy of Private Collection
Figure 13.
Sir Joshua Reynolds, Lady Barbara Bagot, 1762, oil on canvas, 76 × 63.5 cm. Private Collection. Mannings no. 92. This image represents the exact object shown at the British Institution loan exhibition of 1823 as cat. no. 2, Lady Bagot
Digital image courtesy of Private Collection
Figure 14.
Sir Joshua Reynolds, Richard Robinson, 1763, oil on canvas, 124 × 99 cm. Collection of Christ Church, Oxford (LP 190). Mannings no. 1535. This image represents the exact object shown at the British Institution loan exhibition of 1823 as cat. no. 3, The Primate Robinson
Digital image courtesy of Governors of Christ Church, Oxford
Figure 15.
Sir Joshua Reynolds, A Beggar Boy and His Sister, 1775, oil on canvas, 76.2 × 63.5 cm. The Faringdon Collection Trust, Buscot Park. Mannings no. 2016. This image represents the exact object shown at the British Institution loan exhibition of 1823 as cat. no. 4, Boy with Cabbage Nets
Digital image courtesy of The Faringdon Collection Trust, Buscot Park
Figure 16.
Sir Joshua Reynolds, The Banished Lord, circa 1777, oil on canvas, 76.2 × 63.5 cm. Collection of Tate, London (N00107). Mannings no. 2013. This image represents the exact object shown at the British Institution loan exhibition of 1823 as cat. no. 5, The Captive
Digital image courtesy of Tate Images
Figure 17.
Sir Joshua Reynolds, View from Sir Joshua Reynolds’s House, Richmond Hill, 1788, oil on canvas, 69.8 × 90.8 cm. Tate, London (N05635). Mannings no. 2189. This image represents the exact object shown at the British Institution loan exhibition of 1823 as cat. no 6, Landscape: View from Richmond Hill
Digital image courtesy of Tate Images
Figure 18.
Sir Joshua Reynolds, Shepherd Boy, circa 1773, oil on canvas, 94 × 63.5 cm. Antony House, National Trust. Mannings no. 2156. This image represents the exact object shown at the British Institution loan exhibition of 1823 as no. 7, The Piping Boy
Digital image courtesy of National Trust Images / Photo: John Hammond
DOI
Figure 19.
Thomas Chambers, after Sir Joshua Reynolds, Mrs Quarrington as St Agnes, 1787, engraving and etching, 39.8 × 27.4 cm. Collection of the British Museum, London (1833,0715.62). The exact object shown in the British Institution loan exhibition of 1823 as no. 8, Saint Agnes, was Sir Joshua Reynolds, Mrs. Quarrington, 1772. Oil on canvas, 76 × 63 in. Private Collection. Mannings no. 1504. An image of this work could not be located; it is here represented by an engraving after it
Digital image courtesy of Trustees of the British Museum.
Figure 20.
Sir Joshua Reynolds, Mary Horneck, circa 1775, oil on canvas, 127 × 100 cm. Cliveden Estate. Mannings no. 936. This image represents the exact object shown at the British Institution loan exhibition of 1823 as cat. no. 9, Mrs. Gwyn in a Turkish dress
Digital image courtesy of National Trust Images
Figure 21.
John Jones, after Sir Joshua Reynolds, Miss Kemble, 1784, mezzotint, 37.7 × 27.5 cm. Collection of the British Museum, London (Q,3.164). The precise object shown in the British Institution loan exhibition of 1823, cat. no. 10, as Mrs. Twiss, has yet to be identified. Mannings noted that it could be as yet unlocated, or it could be identical with the version in Louvre or with the version in the National Museum, Havana, Cuba (Mannings nos. 1027, 1028, 1028c). Here the object is represented by an image of an engraving by John Jones after the canvas now in Havana
Digital image courtesy of Trustees of the British Museum.
Once the central anchor is in place, the question becomes how to arrange the nine smaller pictures around it. After paintings were hung at the Institution they were labelled with small numbered pieces of tin that were reused every year.
66
The catalogue helpfully specifies that the numbers began “on the left hand”; in other words, pictures were numbered from left to right on the wall.
67
fig. 22
). The works are arranged so that the numbers proceed clockwise, starting with
George IV
at the centre, then moving to the work numbered two in the catalogue
, Lady Barbara Bagot
, at lower left, and so on. Option B instead places
Lady
Bagot
at the upper left and proceeds counter-clockwise, an arrangement that lofts
George IV
above a row of smaller works, including one of Reynolds’s rare landscapes, that are thus made available for close perusal (
fig. 23
). Option C presents a broad, vertical hang, inspired by the arrangement of pictures shown in Stephanoff’s watercolour (
fig. 24
). These are certainly not the only options that might be considered, and none of these rehangs can be declared to be definitive.
DOI Figure 22.Catherine Roach, Option A, a possible hanging arrangement of works by Joshua Reynolds displayed on the North Wall of the British Institution’s exhibition Pictures by Sir Joshua Reynolds, with a Selection from the Italian, Spanish, Flemish, and Dutch Schools, 1823
DOI Figure 23.Catherine Roach, Option B, a possible hanging arrangement of works by Joshua Reynolds displayed on the North Wall of the British Institution’s exhibition Pictures by Sir Joshua Reynolds, with a Selection from the Italian, Spanish, Flemish, and Dutch Schools, 1823
DOI Figure 24.Catherine Roach, Option C, a possible hanging arrangement of works by Joshua Reynolds displayed on the North Wall of the British Institution’s exhibition Pictures by Sir Joshua Reynolds, with a Selection from the Italian, Spanish, Flemish, and Dutch Schools, 1823
68
These objects are currently used to display works by Reynolds at the Yale Center for British Art, and all date from the eighteenth century; however, it is also possible that some lenders had reframed their pictures in more up-to-date, early nineteenth-century styles.
69
To highlight the high level of uncertainty about the frames, they rotate with each hanging option.
DOI
Sourcing images for the reconstruction also raised significant methodological issues and provided further opportunities to visualize uncertainty. Simply obtaining images requires a considerable commitment of resources. This project was made possible by the willingness of the editors of
British Art Studies
70
Many of these paintings were also engraved. In the case where the actual object exhibited cannot be located, which is the preferable stand-in, an engraving of the precise object, or an oil variant or copy? All are imperfect substitutes that alter even as they reiterate. Artists of this period were well aware of the specific visual qualities of these various media.
71
As engravers argued in defence of their own profession, the creation of an engraving is an act of translation, one that not only transfers a colour image to black and white (and may reverse the composition), but also reflects the judgment of the highly skilled artist who produced the engraving.
72
Images of oil variants created by Reynolds might seem preferable, since they provide colour and were produced by the artist himself. Yet, as the exhibition
Experiments in Paint
recently demonstrated, Reynolds used variants as an opportunity for exploration, creating subtly but potently different versions of the same composition.
73
Making the existence of these various options clear to viewers helps convey the complex nature of replication in this period.
The first stop for tracing the works shown on the north wall is David Mannings and Martin Postle’s
Sir Joshua Reynolds: A Complete Catalogue of his Paintings
74
fig. 25
), or a colour photograph of an oil variant now held by the Wernher Foundation (
fig. 26
).
75
76
Here it is represented by a 1784 mezzotint by John Jones.
The result of all of these choices is an amalgam of different types of images, each with its limitations and advantages. With the varied tones of mezzotints, line engravings, black-and-white and colour photographs, this assemblage lacks visual unity. But it does allow us to begin to analyse visual relationships among the works. By shifting between various hanging options, viewers can assess the proposed arrangements for themselves. Hopefully, they will also begin to notice visual affinities among the works that remain constant across the various hanging options. Although deliberately, transparently speculative, this reconstruction is also revealing, as the next section seeks to demonstrate.
Analysing the Reconstruction of the North Wall
DOI
77
Multiple genres are represented in these works, which include one of Reynolds’s very rare landscapes, two fancy pieces featuring young children, and six portraits of different sizes and subjects. The remaining work,
The Banished Lord
This sense of social heterogeneity is enhanced by the formal patterns of the hang. In all of the options proposed here, each of the portraits forms a temporary pendant with a companion of like size. These pairings exhibit vivid visual and social contrasts (see
fig. 22
). For instance,
The Banished Lord
forms a temporary pendant with a fancy piece of a similar size,
Shepherd Boy
78
Equally intriguing is the pairing of the portrait of Mary Horneck with that of Richard Robinson. Both sitters were personal friends of Reynolds. He was the Archbishop of Armagh in the Church of Ireland, famed for his generous hospitality.
79
She was the daughter of an army officer, well known for her beauty and charm in London’s artistic circles. (Reynolds is alleged to have been so moved by her attractions that he proposed to her during a sitting.
80
) She later married the courtier Colonel Francis Gwyn and served as Woman of the Bedchamber to Queen Charlotte.
81
A formal rhyme links these elite sitters: the billowing white skirt of Horneck’s fancy dress outfit echoes the snowy fabric of Robinson’s voluminous sleeve. But these temporary pendants are also held in tension by a series of contrasts: male and female, age and youth, sideward glance and frontal gaze, “Turkish” dress and Anglican vestments.
Similar resonances can be found among the groups of three pictures that fall to the left and the right of the central canvas in each hanging option. On the left is an unlikely triumvirate, providing maximum social contrast: the earl’s daughter, the bishop, and
A Beggar Boy and His Sister
22
–
24
). His gaze falls instead on the clergyman, while his horse’s rear end is pointed towards the ladies. These arrangements forestall rude insinuations about the royal image ogling portraits of women, which had been made by critics reviewing eighteenth-century exhibitions.
82
Yet these likenesses still share a wall. This assemblage of images generates many potential narratives, ranging from a patriotic celebration of Reynolds’s versatility to a humorous commentary on the monarch’s predilections.
“Dangerous Juxtaposition”: Reynolds Among the Old Masters
Of course, this reconstruction considers only ten works in an installation that contained 175 paintings, roughly two-thirds of which were continental old masters. The visual resonances among the works on the north wall would have been amplified and complicated by the presence of works on the surrounding walls and adjacent galleries. For instance,
George IV
was not the only monumental equestrian portrait on view. On the east side of the adjoining middle room hung a work attributed to Rubens, then titled
Philip the Fourth of Spain on Horseback
(now identified as a portrait of Philip II from Rubens’s studio;
fig. 27
).
83
Mark Hallett has argued that when Reynolds’s martial equestrian portrait of George was first exhibited at the Royal Academy in 1784, viewers would have compared it with their memories of previously exhibited entries in the genre by Reynolds and his rivals.
84
In 1823, a different, more direct visual comparison was offered, one that asserted that Reynolds could compete with the continental old masters.
85
This conspicuous royal support of the Institution earned George some much-needed good press in the aftermath of his highly unpopular efforts to rid himself of his despised wife, Caroline. One reviewer noted, “His MAJESTY is, as usual, a liberal and valuable contributor.”
86
87
One critic declared victory: “This exhibition furnished to an Englishman abundant matter for pride and exultation. The power and the grasp of the mind of Reynolds are here seen and felt; seen too in the most dangerous juxtaposition with works that have stood the test of centuries.”
88
As this comment suggests, Institution exhibitions were engines for comparative viewing, encouraging their audience to assess works in concert.
89
90
The repeated act of assembling Reynolds’s works together affirmed the abilities of the work of art to carry the memory of an artist, and his subjects, beyond a human lifetime.
Exhibition reconstructions are not, in fact, time travel. Reconstructions should be crafted with an awareness of their limitations and presented in a way that makes those limitations transparent to the viewer. But while we cannot revisit the galleries of the past, we can rediscover information about them. In particular, we can revive the ephemeral, powerful, and shifting meanings generated through the temporary combination of individual artworks. The works presented in 1823 emphasized Reynolds’s range as a painter and his worthiness to hang alongside the continental old masters. The organizers of the Reynolds exhibitions aspired to a different type of time travel: they sought to send Reynolds forward through time, to claim a place for him in posterity. The fact that we are still talking about him today, and arguing about the best way to reconstruct exhibitions of his work, suggests that they were successful.
Acknowledgements
An early version of this project was presented at the Association of Art Historian's conference in 2015, on the panel organized by Mark Hallett, Sarah Victoria Turner, and Martina Droth, “British Art Through its Exhibition Histories, 1760 to Now.” I would like to thank the editors of
British Art Studies
About the author
Catherine Roach is an Associate Professor of Art History at Virginia Commonwealth University. She is the author of Pictures-Within-Pictures in Nineteenth-Century Britain, which received the Historians of British Art Book Award for Exemplary Scholarship on the Period after 1800. She was awarded a National Endowment for the Humanities Fellowship at the Huntington Library to support work on her second book, a history of the ground-breaking nineteenth-century exhibition society, the British Institution.
Footnotes
See, for example, Norman Bryson’s critique of Karl Lehmann-Harleben’s mid-twentieth-century diagrams based on an ancient ekphrastic text. “Philostratus and the Imaginary Museum”, in Vision andTextuality, ed. Stephen Melville and Bill Readings (London: Macmillan, 1995), 174–94.
1
Johanna Drucker, “Is There a ‘Digital’ Art History?”, Visual Resources29, no. 1–2 (2013): 12.
2
Karen M. Kensek, “A Survey of Methods for Showing Missing Data, Multiple Alternatives, and Uncertainty in Reconstructions”, CSA Newsletter19, no. 3 (Winter 2007),http://www.csanet.org/newsletter/winter07/nlw0702.html. Representing uncertainty was also the subject of a recent session at the College Art Association.http://caa2014.thatcamp.org/2014/02/11/representing-uncertainty/.
3
Sheila Bonde, Clarke Maines, Elli Mylonas, and Julia Flanders, “The Virtual Monastery: Re-Presenting Time, Human Movement, and Uncertainty at Saint-Jean-des-Vignes, Soissons”, Visual Resources25, no. 4 (2009): 363.
4
Nicholas Penny, The Sixteenth-Century Italian Paintings, Vol. II: Venice, 1540–1600(London: National Gallery, 2008), xviii; for an alternate candidate, see Konstantinos Stefanis, “Nathaniel Hone’s 1775 Exhibition: The First Single-Artist Retrospective”, Visual Culture in Britain14, no. 2 (2013): 131–53.
5
Martin Postle, “In Search of the ‘True Briton’: Reynolds, Hogarth, and the British School”, in Towards a Modern Art World, ed. Brian Allen, Studies in British Art 1 (New Haven and London: Yale Univ. Press, 1995), 121–43.
6
Francis Haskell, The Ephemeral Museum: Old Master Paintings and the Rise of the Art Exhibition(New Haven and London: Yale Univ. Press, 2000), 54.
7
http://www.whatjanesaw.org/index.php.
8
On the site’s lack of engagement with “visualizing uncertainty”, see also Jodi Cranston, “What Jane Saw”, 18 June 2015, doi:10.3202/caa.reviews.2015.74.
9
Jennifer Schuessler, “Seeing Art Through Austen’s Eyes”, New York Times, 24 May 2013, C1; John Mullen, “New Website Displays Celebrities of Jane Austen’s Youth”, Guardian, 24 May 2013,https://www.theguardian.com/books/2013/may/24/website-celebrities-jane-austen-youth; Richard De Ritter, “What Jane Saw”, British Society for Eighteenth-Century Studies, 20 June 2013,https://www.bsecs.org.uk/criticks-reviews/what-jane-saw; Susan Spencer, “What Jane Saw”, Eighteenth-Century Life38, no. 1 (Winter 2014), doi:10.1215/00982601-2390034; Cranston, “What Jane Saw”.
10
Janine Barchas, “Digitally Reconstructing the Reynolds Retrospective Attended by Jane Austen in 1813: A Report on E-Work-in-Progress”, ABO: Interactive Journal for Women in the Arts, 1640– 18302, no. 1, doi:10.5038/2157-7129.2.1.12.
11
Schuessler, “Seeing Art Through Austen’s Eyes”, C1.
12
Barchas, “Digitally Reconstructing the Reynolds Retrospective”.
13
Christopher Whitehead, “Architectures of Display at the National Gallery: The Barry Rooms as Art Historiography and the Problems of Reconstructing Historical Gallery Space”, Journal of the History of Collections17, no. 2 (2005): 204; see also C. S. Matheson, “‘A Shilling Well Laid Out’: The Royal Academy’s Early Public”, in Art on the Line: The Royal Academy Exhibitions at Somerset House, 1780– 1836, ed. David Solkin (New Haven and London: Yale Univ. Press, 2001), 39–53.
14
Victor I. Stoichita, The Self-Aware Image: An Insight into Early Modern Meta-Painting, trans. Anne-Marie Glasheen (Cambridge: Cambridge Univ. Press, 1997), 105.
15
Catherine Roach, “Domestic Display and Imperial Identity: A Visual Record of the Art Collections of Edward Hawke Locker”, Huntington Library Quarterly75, no. 3 (Autumn 2012): 411–28.
16
Catherine Roach, “Images as Evidence? Morse and the Genre of Gallery Painting”, in Samuel F. B. Morse’s Gallery of the Louvre and the Art of Invention, ed. Peter John Brownlee (New Haven and London: Yale Univ. Press, 2014), 46–59.
17
“Monthly Retrospect of the Fine Arts”, Monthly Magazine, March 1806, 157; on the “much-hated red wallpaper” see also Peter Fullerton, “Patronage and Pedagogy: The British Institution in the Early Nineteenth Century”, Art History5 (March 1982): 63.
18
Women (and professional artists of both genders) were excluded from the Institution’s seat of power, the Committee of Directors; the Governors, who met once a year to hear a report from the Directors and vote on major issues, included a few women, who were invited to vote by proxy rather than attending in person. However, unlike the Royal Academy, the Institution did allow women to enroll in its school. See An Account of the British Institution for Promoting the Fine Arts in the United Kingdom(London: John Hatchard, 1805), 6.
19
Barchas, “Digitally Reconstructing the Reynolds Retrospective”.
20
Barchas cites, without fully taking on board, both Haskell’s Ephemeral Museumand Solkin’s Art on Line. Prominent studies of period hanging conventions that do not appear in Barchas’s bibliography include: Francis Russell, “The Hanging and Display of Pictures, 1700 –1850”, in The Fashioning and Functioning of the British Country House, ed. Gervase Jackson-Stops, Studies in the History of Art 25 (Hanover, NH: Univ. Press of New England, 1989), 133–53; Giles Waterfield, “Picture Hanging and Gallery Decoration”, in Palaces of Art: Art Galleries in Britain, 1790–1990, ed. Giles Waterfield (London: Dulwich Picture Gallery, 1991), 49 –65; and Whitehead, “Architectures of Display at the National Gallery”. Barchas, “Digitally Reconstructing the Reynolds Retrospective”.
21
Waterfield, “Picture Hanging”, 51.
22
Waterfield, “Picture Hanging”, 51.
23
David Solkin, “Staging the Spectacle”, in Art on the Line, 24.
24
On the North Room as the principal gallery, see “Fine Arts Exhibition”, Belle Assemblée, March 1828, 133.
25
As listed in the Catalogue of Pictures by the Late Sir Joshua Reynolds, Exhibited by Permission of the Proprietors, in Honour of the Memory of that Distinguished Artist, and for the Improvement of BritishArt (London: W. Bulmer, 1813): no. 1, Portrait of His Majesty(Mannings no. 717, George III, 1779, Royal Academy, London); no. 2, Portrait of Mrs. Siddons as the Tragic Muse(Mannings no. 1619, Sarah Siddons as the Tragic Muse, 1784, Huntington Library, San Marino, CA); no. 3, Piping Boy(Mannings no. 2156, Shepherd Boy, about 1773, Antony House, National Trust, Swindon, UK); no. 4, Sleeping Girl(Mannings no. 2077, Girl Sleeping, untraced, 1788); no. 5 Boy with Cabbage Nets(Mannings no. 2016, A Beggar Boy and His Sister, 1775, The Faringdon Collection Trust, Buscot Park, Oxfordshire, UK). David Mannings, ed., with Martin Postle, Sir Joshua Reynolds: A Complete Catalogue of his Paintings(New Haven and London: Yale Univ. Press, 2000).
26
Barchas, “Digitally Reconstructing the Reynolds Retrospective”.
27
Russell, “Hanging and Display of Pictures, 1700 –1850”, 144.
28
Waterfield, “Picture Hanging”, 50.
29
For the interrelationship of royal celebrity and theatrical celebrity in this period, see Joseph Roach, It(Ann Arbor: Univ. of Michigan Press, 2007).
30
http://www.whatjanesaw.org/1813/about.php.
31
The potential for confusion here is high: one reviewer noted the use of images of prints as stand-ins for some objects, but also praised the site’s creators for their “considerable success” in locating “images of all but three of the works originally displayed”. De Ritter, “What Jane Saw”. Engravings or photographs of variants by Reynolds or of later copies are not, in fact, images of the works originally displayed.
32
http://collections.rmg.co.uk/collections/objects/14444.html.
33
http://www.whatjanesaw.org/1813/rooms.php?location=SRES#wjs[painting]/14/.
34
Mannings, ed., Sir Joshua Reynolds: A Complete Catalogue of his Paintings, 397. The Petworth canvas was included in Martin Postle, ed., Joshua Reynolds: The Creation of Celebrity(London: Tate Publishing, 2005), 98–99.
35
John Ingamells, National Portrait Gallery: Mid-Georgian Portraits, 1760– 1790(London: National Portrait Gallery, 2004), 406.
36
Ingamells, National Portrait Gallery, 406.
37
http://www.whatjanesaw.org/1813/rooms.php?location=SRES.
38
http://www.whatjanesaw.org/1813/rooms.php?location=SRES#wjs[painting]/14/.
39
http://www.whatjanesaw.org/1796/about.php.
40
Janine Barchas, “Reporting on What Jane Saw 2.0: Female Celebrity and Sensationalism in Boydell’s Shakespeare Gallery”, ABO: Interactive Journal for Women in the Arts, 1640–18305, no. 1, doi:10.5038/2157-7129.5.1.2. This claim is repeated in Janine Barchas and Kristina Straub, “Curating Will & Jane”, Eighteenth-Century Life40, no. 2 (April 2016), doi:10.1215/00982601-348864.
41
Christopher Johanson, “Visualizing History: Modeling in the Eternal City”, Visual Resources25, no. 4 (2009): 407; see also Pamela Fletcher, “Reflections on Digital Art History”, doi:10.3202/caa.reviews.2015.73, 18 June 2015.
42
This section draws on research for my current book project, “The British Institution: A History”.
43
On the Institution, see Fullerton, “Patronage and Pedagogy”, 59–72; Ann Pullan, “Public Goods or Private Interests? The British Institution in the Early Nineteenth Century”, in Art in Bourgeois Society, 1790– 1850, ed. Andrew Hemingway and William Vaughan (Cambridge: Cambridge Univ. Press, 1998), 27–44; Nicholas Tromans, “Museum or Market? The British Institution”, in Governing Cultures: Art Institutions in Victorian London, ed. Paul Barlow and Colin Trodd (Aldershot: Ashgate, 2000), 44–55; and Catherine Roach, Pictures-within-Pictures in Nineteenth-Century Britain(London: Routledge, 2016), 24–63.
44
An Historical Catalogue of Portraits, Representing Distinguished Persons of the History and Literature of the United Kingdom(London: W. Bulmer, 1820), 14. The author of the preface was Charles Long. British Institution Minutes, National Art Library, Victoria & Albert Museum (hereafter Minutes), 21 March 1820; Joseph Farington, Diary of Joseph Farington, 17 vols., ed. Kenneth Garlick, Angus Macintyre, and Kathryn Cave (New Haven and London: Yale Univ. Press, 1978–98), 16: 5515.
45
Rev. J. Dalloway, An Account of all the Pictures, Exhibited in the Rooms of the British Institution, From 1813 to 1823, Belonging to the Nobility and Gentry of England: with Remarks Critical and Explanatory(London: Priestley and Weale, 1824), ix.
46
Mark Hallett, “Reading the Walls: Pictorial Dialogue at the British Royal Academy”, Eighteenth-Century Studies37, no. 4 (Summer 2004): 586.
47
Robert Hunt, “Fine Arts”, The Examiner, 17 June 1821, 380.
48
Waterfield, “Picture Hanging”, 51; Linda Colley, Britons: Forging the Nation, 1707–1837(London: Pimlico, 2003), 176.
49
Peter Funnell, “The London Art World and its Institutions”, in London: World City, 1800–1840, ed. Celina Fox (New Haven and London: Yale Univ. Press, 1992), 158.
50
In 1822 the minimum subscription was raised from one guinea to three. Minutes, 11 June 1822.
51
The Directors drafted the initial checklists for their first two loan exhibitions, but starting in 1815 this task was delegated to Seguier. Minutes, 15 February 1813; 16 June 1814; and 9 June 1815.
52
On Seguier as curator, see Tromans, “Museum or Market?”, 50.
53
Farington, Diary, 16: 5664.
54
A Catalogue of Pictures by Sir Joshua Reynolds, with a Selection from the Italian, Spanish, Flemish, and Dutch Schools, with which the Proprietors Have Favoured the Institution(London: W. Nicol, 1823), 12.
55
The actual number of visitors was even larger, as the admission receipts do not include visits by members and their guests, who did not pay at the door. Minutes, 1 June 1824.
56
Thomas Smith, Recollections of the British Institution(London: Simpkin and Marshall, 1860), 19. On this publication, see Pullan, “Public Goods or Private Interests?”, 27–44.
57
John Scarlett Davis, Interior of the British Institution(1829, Yale Center for British Art); Alfred Joseph Woolmer, Interior of the British Institution (Old Master Exhibition, Summer 1832)(1833, Yale Center for British Art); James Stephanoff and Francis Philip Stephanoff, The Interior of the British Institution(1817, Victoria & Albert Museum); Thomas Rowlandson and Augustus Pugin, The British Institution,from The Microcosm of London(London: R. Ackerman, 1808–10); R. Grave after A. Pugin, Gallery of the British Institution, from Magazine of Fine Arts(London: John Warren and G. and W. B. Whittaker, 1821).
58
Roach, Pictures-Within-Pictures, 24–63; Roach, “Images as Evidence?”, 46–59.
59
On this work as a “prescriptive rather than descriptive image”, see Philippa Simpson, “Titian in post-Orléans London”, in The Reception of Titian in Britain: From Reynolds to Rubens, ed. Peter Humfrey (Turnhout: Brepolis, 2013), 106.
60
For these works, see Tony Hobbs, John Scarlett Davis: A Biography(Almeley, Herefordshire: Logaston Press, 2004); Roach, “Images as Evidence?”; and Catherine Roach, “‘My Hero’: Women and the Domestic Display of Marine Paintings”, in Spreading Canvas: Eighteenth-Century British Marine Painting, ed. Eleanor Hughes (New Haven and London: Yale Univ. Press, 2016), 112–33.
61
Minutes, 19 July 1819; 17 March 17 1820; 8 June 1820.
62
For discussion of this feature, seehttp://www.whatjanesaw.org/1813/about.php.
63
They were, as listed in the Catalogue of Pictures by Sir Joshua Reynolds(1823): no. 1, His Majesty when Prince of Wales(Mannings no. 719, George IV, 1784, Lord Lloyd-Webber); no. 2, Lady Bagot(Mannings no. 92, Lady Barbara Bagot, 1762, private collection); no. 3, The Primate Robinson(Mannings no. 1535, Richard Robinson, 1763, Christ Church, Oxford); no. 4, Boy with Cabbage Nets(Mannings no. 2016, A Beggar Boy and His Sister, 1775, The Faringdon Collection Trust, Buscot Park); no. 5, The Captive(Mannings no. 2013, The Banished Lord, about 1777, Tate Britain); no. 6, Landscape: View from Richmond Hill(Mannings no .2189 , View from Sir Joshua Reynolds’s House, Richmond Hill, 1784, Tate Britain); no. 7, The Piping Boy(Mannings no. 2156, Shepherd Boy, about 1773, Antony House, National Trust); no. 8, Saint Agnes(Mannings no. 1504, Mrs. Quarrington, 1772, private collection); no. 9, Mrs. Gwyn in a Turkish dress(Mannings no. 936, Mary Horneck, about 1775, Cliveden Estate, National Trust); no. 10, Mrs. Twiss(Mannings no. 1028c, Frances Kemble, unlocated. Mannings notes this object could be identical with nos. 1027 or 1028 in his catalogue) .Mannings, Sir Joshua Reynolds: A Complete Catalogue.
64
George Dunlop Leslie, The Inner Life of the Royal Academy, with An Account of its Schools and Exhibitions Principally in the Reign of Queen Victoria(London: J. Murray, 1914), 77.
65
Minutes, 8 June 1821.
66
Catalogue of Pictures by Sir Joshua Reynolds(1823), 13.
67
Nicholas Penny, “Frame Studies: I. Reynolds and Picture Frames”, Burlington Magazine128, no. 1004 (Nov. 1986): 810–25; Jacob Simon, Art of the Picture Frame: Artist, Patrons, and the Framing of Portraits in Britain(London: National Portrait Gallery, 1996), 64–66, 94–95. Thank you to Jacob Simon for sharing his thoughts on the matter; any errors in frame selection are, of course, my own.
68
Penny notes that there was an enthusiasm for reframing works in the rococo style after 1815. Penny, “Frame Studies”, 824.
69
Jeffrey Muller, “Measures of Authenticity: The Detection of Copies in the Early Literature on Connoisseurship”, in Retaining the Original: Multiple Originals, Copies, and Reproductions, ed. Kathleen Preciado, Studies in the History of Art 20 (Washington: National Gallery of Art, 1989), 147.
70
Anne Higonnet, “Manet and the Multiple”, Grey Room48 (Summer 2012): 102–16.
71
Celina Fox, “The Engravers’ Battle for Professional Recognition in Early Nineteenth-Century London”, London Journal2 (1976): 3–31.
72
Lucy Davis and Mark Hallett, eds., Joshua Reynolds: Experiments in Paint(London: The Wallace Collection, 2015).
73
Mannings, Sir Joshua Reynolds: A Complete Catalogue, no. 92.
74
Mannings, Sir Joshua Reynolds: A Complete Catalogue, no. 1504, no. 1505.
75
Mannings, Sir Joshua Reynolds: A Complete Catalogue, no. 1028c.
76
Catalogue of Pictures by Sir Joshua Reynolds(1823), 12.
77
Roach, It, 38.
78
G. Le G. Norgate, “Robinson, Richard, first Baron Rokeby ( bap.1708, d.1794)”, rev. Eoin Magennis, in Oxford Dictionary of National Biography, ed. H. C. G. Matthew and Brian Harrison (Oxford: Oxford Univ. Press, 2004); online ed., ed. David Cannadine, Sept. 2010,http://www.oxforddnb.com/view/article/23867.
79
Richard Wendorf, Sir Joshua Reynolds: The Painter in Society(Cambridge, MA: Harvard Univ. Press, 1996), 65.
80
Ian McIntyre, Joshua Reynolds: The Life and Times of the First President of the Royal Academy(London: Penguin Books, 2004), 168–69; Maurice Brockwell, A Catalogue of Paintings in the Collection of Mr. and Mrs. Charles P. Taft(New York: Privately printed, 1920), 97–99.
81
Hallett, “Reading the Walls”, 581.
82
Christopher White, The Later Flemish Pictures in the Collection of Her Majesty the Queen(London: Royal Collection Publications, 2007), 256.
83
Hallett, “Reading the Walls”, 597–601.
84
Catalogue of Pictures by Sir Joshua Reynolds(1823), 12.
85
“Fine Arts: The British Institution”, Morning Post, 19 May 1823, 3.
86
Catalogue of Pictures by Sir Joshua Reynolds(1823), 12.
87
“British Institution”, La Belle Assemblée, June 1823, 277.
88
“British Institution”, La Belle Assemblée, June 1823, 277.
89
“British Gallery”, Times, 19 May 1823, 3.
90
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– – –. “Reporting on What Jane Saw 2.0: Female Celebrity and Sensationalism in Boydell’s Shakespeare Gallery.” ABO: Interactive Journal for Women in the Arts, 1640–18305, no. 1: doi:10.5038/2157-7129.5.1.2.
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– – –. The Sixteenth-Century Italian Paintings, Vol. II: Venice, 1540–1600.London: National Gallery, 2008.
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– – –. “Images as Evidence? Morse and the Genre of Gallery Painting.” In Samuel F. B. Morse’s Gallery of the Louvre and the Art of Invention. Ed. Peter John Brownlee. New Haven and London: Yale Univ. Press, 2014, 46–59.
– – –. “‘My Hero’: Women and the Domestic Display of Marine Paintings.” In Spreading Canvas: Eighteenth-Century British Marine Painting. Ed. Eleanor Hughes. New Haven and London: Yale Univ. Press, 2016, 112–33.
– – –. Pictures-within-Pictures in Nineteenth-Century Britain.London: Routledge, 2016.
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Smith, Thomas. Recollections of the British Institution.London: Simpkin and Marshall, 1860.
Solkin, David, ed. Art on the Line: The Royal Academy Exhibitions at Somerset House, 1780– 1836. New Haven and London: Yale Univ. Press, 2001.
Spencer, Susan. “What Jane Saw.” Eighteenth-Century Life38, no. 1 (Winter 2014). doi:10.1215/00982601-2390034.
Stefanis, Konstantinos. “Nathaniel Hone’s 1775 Exhibition: The First Single-Artist Retrospective.” Visual Culture in Britain14, no. 2 (2013): 131–53.
Stoichita, Victor I. The Self-Aware Image: An Insight into Early Modern Meta-Painting. Trans. Anne-Marie Glasheen. Cambridge: Cambridge Univ. Press, 1997.
Tromans, Nicholas. “Museum or Market? The British Institution.” In Governing Cultures: Art Institutions in Victorian London. Ed. Paul Barlow and Colin Trodd. Aldershot: Ashgate, 2000, 44–55.
Waterfield, Giles. “Picture Hanging and Gallery Decoration.” In Palaces of Art: Art Galleries in Britain, 1790–1990. Ed. Giles Waterfield. London: Dulwich Picture Gallery, 1991, 49 –65.
Wendorf, Richard. Sir Joshua Reynolds: The Painter in Society.Cambridge, MA: Harvard Univ. Press, 1996.
White, Christopher. The Later Flemish Pictures in the Collection of Her Majesty the Queen.London: Royal Collection Publications, 2007.
Whitehead, Christopher. “Architectures of Display at the National Gallery: The Barry Rooms as Art Historiography and the Problems of Reconstructing Historical Gallery Space.” Journal of the History of Collections17, no. 2 (2005): 189–211.
Imprint
Author
Catherine Roach
Date
28 November 2016
Category
Article
Review status
Peer Reviewed (Double Blind)
Licence
CC BY-NC International 4.0
Downloads
PDF format
Article DOI
https://doi.org/10.17658/issn.2058-5462/issue-04/croach
Cite as
Catherine Roach, "Rehanging Reynolds at the British Institution: Methods for Reconstructing Ephemeral Displays", British Art Studies, Issue 4, https://doi.org/10.17658/issn.2058-5462/issue-04/croach
NextInsurgent Citizenship: Dr John Nicholas Tresidder's Photographs of War and Peace in British India
| https://www.britishartstudies.ac.uk/index/article-index/rehanging-reynolds/issue-5/scott-skidmore/page/11 |
DANIEL PATRICK LEE CAA, NPI 1952919482 - Anesthesiologist Assistant in Indianapolis, IN
Daniel Lee a provider in 705 Riley Hospital Dr Indianapolis, In 46202. Taxonomy code 367H00000X with license number 75000062A (IN) and 4 years of experience.
DANIEL PATRICK LEE CAA NPI 1952919482
Anesthesiologist Assistant in Indianapolis, IN
Table of Contents
NPI Profile Information
Primary Taxonomy
PECOS Enrollment and Medicare Participation Status
Hospital Affiliations
NPI Validation
Other Providers Same Location
About DANIEL PATRICK LEE CAA
Daniel Leeis a provider established inIndianapolis, Indianaand his medical specialization isAnesthesiologist Assistantwith more than 4 years of experience. The NPI number of this provider is1952919482and was assigned on July 2020. The practitioner's primary taxonomy code is367H00000Xwith license number 75000062A (IN). The provider is registered as an individual and his NPI record was last updated 3 years ago.
NPI 1952919482
Provider Name DANIEL PATRICK LEE CAA
Location Address 705 RILEY HOSPITAL DR INDIANAPOLIS, IN 46202
Location Phone (317) 944-9981
Mailing Address 250 N SHADELAND AVE STE 200 INDIANAPOLIS, IN 46219
Gender Male
NPI Entity Type Individual
Medical School Name OTHER
Graduation Year 2020
Is Sole Proprietor? No
Enumeration Date 07-21-2020
Last Update Date 08-24-2020
Daniel Lee isregistered with Medicareandaccepts claims assignment, this means the provider accepts Medicare's approved amount for the cost of rendered services as full payment. Participating providers may not charge Medicare beneficiaries more than Medicare's approved amount for their services. Medicare beneficiaries still have to pay a coinsurance or copayment amount for a visit or service.
Primary Taxonomy
The primary taxonomy code defines the provider type, classification, and specialization. There could be only one primary taxonomy code per NPI record. For individual NPIs the license data is associated to the taxonomy code.
Taxonomy Code 367H00000X
Classification Anesthesiologist Assistant
Type Physician Assistants & Advanced Practice Nursing Providers
License No. 75000062A
License State IN
Taxonomy Description
An individual certified by the state to perform anesthesia services under the direct supervision of an anesthesiologist. Anesthesiologist Assistants are required to have a bachelor's degree with a premed curriculum prior to entering a two-year anesthesiology assistant program, which is focused upon the delivery and maintenance of anesthesia care as well as advanced patient monitoring techniques. An Anesthesiologist Assistant must work as a member of the anesthesia care team under the direction of a qualified Anesthesiologist.
Business Address
705 RILEY HOSPITAL DR
INDIANAPOLIS, IN
ZIP 46202
Phone: (317) 944-9981
Mailing Address
250 N SHADELAND AVE STE 200
INDIANAPOLIS, IN
ZIP 46219
Location Map
PECOS Enrollment and Medicare Participation Status
What is PECOS?
PECOS is the Medicare Provider, Enrollment, Chain and Ownership System. PECOS is Medicare's enrollment and revalidation system and it is the primary source of information about verified Medicare professionals. A NPI number is necessary to register in PECOS. Providers must enroll in PECOS to avoid denied claims.
<table><tbody><tr><td> PECOS PAC ID</td><td> 5395160360</td></tr><tr><td> PECOS Enrollment ID</td><td> I20220914002204</td></tr><tr><td> Accepts Medicare Assignment?</td><td> Yes "What does it mean "accepts medicare assignment"? When a provider accepts Medicare assignment, the provider agrees to be paid directly by Medicare and to accept the payment amount approved by Medicare. Additionally, the provider agrees to not bill patients for more than the Medicare deductible and coinsurance amounts. A provider who doesn't accept assignment may charge you up to 15% over the Medicare-approved amount. This is known as the limiting charge. You may have to pay this amount, or it may be covered by another insurer. </td></tr></tbody></table>
Hospital Affiliations
Medicare hospital affiliation is identified through self-reporting data, inpatient, outpatient, physician and ancillary service claims linked by the Medicare claims NPI number and place of service code. Additionally, to further determine provider hospital affiliation the clinician must have provided services to at least three patients on three different dates in the last 12 months. Daniel Lee is affiliated with the following medical facilities:
<table><tr><th> Hospital Name</th><th> Address</th><th> Phone</th><th> Hospital Type</th><th> CMS Certification Number (CCN)</th><th> Overall Rating</th></tr><tbody><tr><td> CHRISTUS ST VINCENT REGIONAL MEDICAL CENTER</td><td> 455 ST MICHAEL'S DRIVE
SANTA FE, NM 87505</td><td> (505) 913-3361</td><td> Acute Care Hospitals</td><td> 320002</td><td></td></tr></tbody></table>
NPI Validation Check Digit Calculation
The following table explains the step by step NPI number validation process using the ISO standard Luhn algorithm.
Start with the original NPI number, the last digit is the check digit and is not used in the calculation.
1 9 5 2 9 1 9 4 8 2
Step 1: Double the value of the alternate digits, beginning with the rightmost digit.
2 9 10 2 18 1 18 4 16
Step 2: Add all the doubled and unaffected individual digits from step 1 plus the constant number 24.
2 + 9 + 1 + 0 + 2 + 1 + 8 + 1 + 1 + 8 + 4 + 1 + 6 + 24= 68
Step 3: Subtract the total obtained in step 2 from the next higher number ending in zero, the result is the check digit.
70 - 68 = 2 2
The NPI number 1952919482 is valid because the calculatedcheck digit 2using the Luhn validation algorithm matches the last digit of the original NPI number.
1710097142
ROBERT J FALLON MD, PHD
Individual
Pediatrics (Pediatric Hematology-Oncology)
705 RILEY HOSPITAL DR ROC 4340
INDIANAPOLIS, IN 46202
(317) 944-5611
1134223647 MARTIN B KLEIMAN MD
Individual Pediatrics (Pediatric Infectious Diseases) 705 RILEY HOSPITAL DR ROC 4380
INDIANAPOLIS, IN 46202
(317) 944-7260
Frequently Asked Questions
What is Daniel Lee CAA NPI number?
The NPI number assigned to this healthcare provider is 1952919482, registered as an "individual" on July 21, 2020
Where is Daniel Lee CAA located?
The provider is located at 705 Riley Hospital Dr Indianapolis, In 46202 and the phone number is (317) 944-9981
Which is Daniel Lee CAA specialty?
The provider's speciality is Anesthesiologist Assistant
How many years of experience does Daniel Lee CAA have?
The provider has more than 4 years of experience.
Is Daniel Lee CAA affiliated to any hospitals?
The practitioner is affiliated to the following hospitals:CHRISTUS ST VINCENT REGIONAL MEDICAL CENTER. Hospital affiliations are identified through self-reporting data and service claims based on the place of service.
How do I update my NPI information?
The NPI record of Daniel Lee CAA was last updated on July 21, 2020. To officially update your NPI information contact the National Plan and Provider Enumeration System (NPPES) at 1-800-465-3203 (NPI Toll-Free) or by email atcustomerservice@npienumerator.com.
NPI Profile data is regularly updated with the latest NPI registry information, if you would like to update or remove your NPI Profile in this website pleasecontact us.
| https://npiprofile.com/npi/1952919482 |
ISO 8573.1 – Contaminants and Purity Classes | Compressed Air Best Practices
Industry standards serve a very important purpose for the end users of compressed air equipment. If the standards are well written, they can help to promote the equipment that they govern, as long as the equipment manufacturers properly apply and promote the standards. One of the most widely used standards in use today in the compressed air industry is ISO8573. It is a multipart standard that seeks to establish a method of classifying the purity of compressed air in part 1, then gives us the tools for measuring and quantifying that purity in parts 2 through 9. ISO8573 is arranged as follows: Part 1: Contaminants and Purity Classes Part 2: Test methods for oil aerosol content Part 3: Test methods for measurement of humidity Part 4: Test methods for solid particle content Part 5: Determination of oil vapor and organic solvents content Part 6: Determination of content of gaseous contaminants Part 7: Test methods for viable microbiological contaminant content Part 8: Test methods for solid particle content by mass concentration Part 9: Test methods for determining liquid water content In this article I will focus on Part 1 of ISO 8573, and describe why the standard was developed, how it should be used, and what the future holds for this standard in the compressed air industry. But before we look at Part 1 of ISO8573, we need to take a look at what causes compressed air to be “impure”. How successfully compressed air stream cleanliness requirements are met, can have a dramatic impact on overall plant operating costs. Excessive contamination shortens the life of components and systems, adversely affects product quality, can result in excessive maintenance costs, and can even create health and safety problems. Contaminants in the form of solid particulates, oil aerosols and vapor, water aerosols and vapor, and even unwanted gaseous vapors can be introduced from the plant environment, ingested by the compressors, or created by the air compressor and distribution system. While many compressed air applications require a high degree of purity, all compressed air applications work better if the air is clean and dry. However, when the air leaves a compressor, it is anything but clean and dry. Chart taken from ISO8573.1 : 2001 Sources of Contamination Contaminants in compressed air systems have three possible points of origin. They can come from the air drawn into the compressor, from internal compressor mechanisms, and from the compressed air distribution system. Compressors draw in virtually all particles, vapors, and gases in the air within a six-foot radius of the inlet. Smaller particles, less than 10 microns in size, can be drawn in from a larger radius. The compressor inlet filter is designed to stop larger particles that could cause rapid wear of compressor parts. This design prevents excessively frequent replacements of the air intake filter element, but it does little to protect sensitive applications downstream of the compressor. Most of the airborne particles smaller than 10 microns can enter the compressor. Also, any gases and vapors around the intake will enter the compressor, and become part of the compressed air supply. These include combustion by-products such as carbon dioxide, carbon monoxide, nitrous oxides, or sulfur dioxides.
ISO 8573.1 – Contaminants and Purity Classes
Industry standards serve a very important purpose for the end users of compressed air equipment. If the standards are well written, they can help to promote the equipment that they govern, as long as the equipment manufacturers properly apply and promote the standards. One of the most widely used standards in use today in the compressed air industry is ISO8573. It is a multipart standard that seeks to establish a method of classifying the purity of compressed air in part 1, then gives us the tools for measuring and quantifying that purity in parts 2 through 9.
ISO8573 is arranged as follows:
Part 1: Contaminants and Purity Classes
Part 2: Test methods for oil aerosol content
Part 3: Test methods for measurement of humidity
Part 4: Test methods for solid particle content
Part 5: Determination of oil vapor and organic solvents content
Part 6: Determination of content of gaseous contaminants
Part 7: Test methods for viable microbiological contaminant content
Part 8: Test methods for solid particle content by mass concentration
Part 9: Test methods for determining liquid water content
In this article I will focus on Part 1 of ISO 8573, and describe why the standard was developed, how it should be used, and what the future holds for this standard in the compressed air industry. But before we look at Part 1 of ISO8573, we need to take a look at what causes compressed air to be “impure”.
How successfully compressed air stream cleanliness requirements are met, can have a dramatic impact on overall plant operating costs. Excessive contamination shortens the life of components and systems, adversely affects product quality, can result in excessive maintenance costs, and can even create health and safety problems.
Contaminants in the form of solid particulates, oil aerosols and vapor, water aerosols and vapor, and even unwanted gaseous vapors can be introduced from the plant environment, ingested by the compressors, or created by the air compressor and distribution system.
While many compressed air applications require a high degree of purity, all compressed air applications work better if the air is clean and dry. However, when the air leaves a compressor, it is anything but clean and dry.
<here is a image d3cdfc4e6c77bbb5-f6e25c2165e84b64>
Chart taken from ISO8573.1 : 2001
Sources of Contamination
Contaminants in compressed air systems have three possible points of origin. They can come from the air drawn into the compressor, from internal compressor mechanisms, and from the compressed air distribution system. Compressors draw in virtually all particles, vapors, and gases in the air within a six-foot radius of the inlet. Smaller particles, less than 10 microns in size, can be drawn in from a larger radius. The compressor inlet filter is designed to stop larger particles that could cause rapid wear of compressor parts. This design prevents excessively frequent replacements of the air intake filter element, but it does little to protect sensitive applications downstream of the compressor. Most of the airborne particles smaller than 10 microns can enter the compressor. Also, any gases and vapors around the intake will enter the compressor, and become part of the compressed air supply. These include combustion by-products such as carbon dioxide, carbon monoxide, nitrous oxides, or sulfur dioxides.
Another factor affecting air contamination is that during compression to 100 PSI, the air volume is reduced by a factor of seven, meaning seven cubic feet of ambient air becomes one cubic foot of compressed air. The result is an increase in the concentration of airborne particles in the compressed air stream. After compression, some of the most common airborne contaminants include dirt & pollen particles, iron oxide (rust) particles, microorganisms, unburned hydrocarbons, liquid water, water aerosols and water vapor, and oil aerosols and vapor.
Now that we know what the contaminants are made up of, we can take a look at how the ISO standard is used to classify the type and amount of contamination in compressed air.
The Purity Classes
The current version of ISO8573 Part 1 was published in 2001, although it is currently in the process of being revised. Every 5 years ISO standards are reviewed to determine whether they are still timely, accurate, and useful to the industries that they serve. If the Working Group, which is made up of volunteer industry experts, decides that the standard requires no revision, then nothing is done to change the standard, and it retains its current publication date. If the standard is revised, then a new publication date is assigned to it once the revision has completed the required balloting procedure. When referring to an ISO standard, it’s common practice to include the publication date, so you may see Part 1 of this standard referred to as ISO8573.1 : 2001.
There are three categories of contaminants that have been assigned classes in ISO8573.1 : 2001. The first category is solid particulates. The second category is made up of a combination of liquid water and water vapor. The third category is called oil, and it too consists of the sum of the liquid oil (in aerosol or liquid droplet form) and oil vapor. The chart below summarizes the three categories of contaminants, and shows the limits of contamination that are required to differentiate one purity class from another.
The purity classes range from the cleanest, class 0, to the most impure, class 9. Note that not all of the categories have the full range of classes; only the water category does. Also, notice that class 0 does not have any numbers associated with it in any of the categories. In the text of ISO8473.1 : 2001 class 0 is defined by stating “As specified by the equipment user or supplier and more stringent than class 1”. It is very important to understand that class 0 does not imply that there are no contaminants present; it simply means that there are fewer contaminants than in class one.
Solid Particulates
There are eight possible classes for solid particulates, from class 0 to class 7. Class 0 is the most pure, but it is numerically undefined, other than to say that it must be more pure (fewer particles in each size range) than class 1. Classes 0 through 5 are defined by the number of particles in a particular size range, in one cubic meter of compressed air. Measurement methods are described in Part 4 of ISO8573 for classes 0 through 5.
Classes 6 and 7 are used to describe compressed air that is typically too “dirty” to be measured with a particle counter. Instead, mass measurements are used to determine the amount of particulate contamination in the compressed air, according to Part 8 of ISO8573.
Water
There are ten possible classes for water contamination, from class 0 to class 9. Class 0 is the driest, but it is numerically undefined, other than to say that it must be drier (a lower pressure dew point) than class 1. Classes 0 through 6 are defined by the pressure dew point of the compressed air. Pressure dew point is defined as the temperature at which moisture begins to condense in the pipes and storage tanks of a compressed air system while it is operating, and hence, under pressure. Pressure dew point is a useful method of describing the humidity in compressed air because it tells us that we must keep the ambient temperature that surrounds the compressed air distribution system above the pressure dew point in order to prevent liquid water from condensing inside the piping. Pressure dew point measurements are described in Part 3 of ISO8573.
Classes 7 through 9 are used to describe compressed air that contains liquid water. As mentioned, liquid water appears in the distribution piping and storage when the pressure dew point of the compressed air is higher than the temperature of the ambient air, and it means that the compressed air contains as much water vapor as is possible for it to contain. This condition is usually called “saturated” air. When liquid water is present in the compressed air line, we use the methods described in ISO8573 Part 9 to measure the amount.
Oil
There are only five classes for oil in the standard, but they describe a wide range of concentrations. Again, class 0 is the most pure, and according to the standard, it describes compressed air that must be more pure than class 1. Classes 1 through 4 cover the range from less than 0.01 mg of oil content per cubic meter of compressed air to less than 5 mg per cubic meter.
It is very important to understand that the oil classes can only be determined by adding the contribution from a.) any liquid oil in the compressed air, b.) the oil aerosols in the compressed air (typically generated by the reciprocal or rotary motion in lubricated compressors), and c.) oil vapors that can come from the oil in the compressor crankcase or sump, or from ingestion at the inlet of the compressor. Liquid oil and oil aerosols are measured using the techniques in ISO8573 Part 2, and the oil vapors are measured using the methods in Part 5.
Reporting the Purity Classes
According to the standard, the purity classes of compressed air shall be expressed by stating the standard reference number and part, the date of issue, and the three class designations in a specific order: Particulate Water Oil. For example, if the compressed air purity of an audited air system was expressed as ISO8573.1 : 2001 1 2 1, the Particulate Class would be 1, the Water Class would be 2, and the Oil Class would be 1. If the class for a particular category is omitted, then a hyphen is used in its place.
Many manufacturers of equipment powered by compressed air are now using this standard to express the purity level of the compressed air supply required in order to keep their tool or process running smoothly and in control. Air tool manufacturers and paint and powder coating suppliers are just two examples of entities that are using ISO8573 to improve their customer’s satisfaction with their products.
| https://www.airbestpractices.com/standards/iso-and-cagi/iso-85731-contaminants-and-purity-classes?_exception_statuscode=404&page=18&page=17 |
A survey on knowledge-aware news recommender systems - IOS Press
News consumption has shifted over time from traditional media to online platforms, which use recommendation algorithms to help users navigate through the large incoming streams of daily news by suggesting relevant articles based on their preferences
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A survey on knowledge-aware news recommender systems
Article type:
Research Article
Authors: Iana, Andreea a ; *
| Alam, Mehwish b ; c
| Paulheim, Heiko a
Affiliations: [
a ]
Data and Web Science Group, University of Mannheim, Germany | [
b ]
Karlsruhe Institute of Technology, Institute AIFB, Germany | [
c ]
FIZ Karlsruhe – Leibniz Institute for Information Infrastructure, Germany
Correspondence: [*]
Corresponding author. E-mail:
andreea@informatik.uni-mannheim.de .
Keywords:
News recommender system, knowledge graphs, ontologies, semantic similarity, knowledge graph embeddings, evaluation methodology, survey
DOI:
10.3233/SW-222991
Journal: Semantic Web
, vol. Pre-press, no. Pre-press, pp. 1-62, 2022
Published:
6 September 2022
Get PDF
Abstract
News consumption has shifted over time from traditional media to online platforms, which use recommendation algorithms to help users navigate through the large incoming streams of daily news by suggesting relevant articles based on their preferences and reading behavior. In comparison to domains such as movies or e-commerce, where recommender systems have proved highly successful, the characteristics of the news domain (e.g., high frequency of articles appearing and becoming outdated, greater dynamics of user interest, less explicit relations between articles, and lack of explicit user feedback) pose additional challenges for the recommendation models. While some of these can be overcome by conventional recommendation techniques, injecting external knowledge into news recommender systems has been proposed in order to enhance recommendations by capturing information and patterns not contained in the text and metadata of articles, and hence, tackle shortcomings of traditional models. This survey provides a comprehensive review of knowledge-aware news recommender systems. We propose a taxonomy that divides the models into three categories: neural methods, non-neural entity-centric methods, and non-neural path-based methods. Moreover, the underlying recommendation algorithms, as well as their evaluations are analyzed. Lastly, open issues in the domain of knowledge-aware news recommendations are identified and potential research directions are proposed.
1. Introduction
In the past two decades, there has been a shift in individuals’ news consumption, from traditional media, such as printed newspapers or radio and TV news broadcasts, to online media platforms, in the form of news websites and aggregation services, or social media. News platforms use a form of a recommender system to help users navigate through the overwhelming amount of news published daily by suggesting relevant articles based on their interests and reading behavior. Recommender systems have proven successful over time in numerous domains [ 124
], ranging from music [ 31
, 106
], movies [ 7
, 110
], or books recommendation [ 36
, 62
, 77
], to e-commerce [ 141
, 142
, 149
], travel and tourism [ 15
], or research paper recommendation [ 5
].
In comparison to these domains, news recommendation poses additional challenges which hinder a direct transfer of traditional recommendation techniques [ 132
]. Firstly, the relevance of news changes quickly within short periods of time and is highly dependent on the time sensitiveness and popularity of articles [ 84
, 120
]. Secondly, articles may be semantically related and users’ interests evolve dynamically over time, meaning that it is not trivial to accurately capture the preferences of individual users [ 120
]. Thirdly, common limitations of recommender systems (i.e. the cold-start problem, data sparsity, scalability), are further intensified by the greater item churn of news [ 39
], the fact that usually user profiles are constrained to a single session [ 44
], and that their feedback is typically collected implicitly, from their reading behavior rather than explicitly provided during a session [ 101
]. Additionally, news articles contain a large number of knowledge entities and common sense knowledge, which are not incorporated in conventional news recommendation methods [ 170
].
Enhancing classic information retrieval and recommendation methods with external information from knowledge bases has been proposed as a potential solution for some of the aforementioned shortcomings of recommender systems in the news domain. Knowledge graphs are directed, labeled heterogeneous graphs which describe real-world entities and their interrelations [ 126
]. Knowledge-aware recommender systems inject information contained in knowledge graphs or domain-specific ontologies to capture information and reveal patterns that are not contained directly in an item’s features [ 66
]. In the case of news recommendation, such knowledge-enhanced models have been developed to capture the semantic meaning and relatedness of news, remove ambiguity, handle named entities, extend text-level information with common sense knowledge, discover knowledge-level connections between news, and overcome cold-start and data sparsity issues.
Previous works provide overviews of this field from two directions. On the one hand, surveys such as [ 66
] or [ 59
], focus on knowledge-aware recommender systems applied to a variety of domains, such as movies, books, music, or products. Although a few of the discussed models come from the news domain, none of these works extensively review how external knowledge can be used to enhance news recommendation. On the other hand, a vast number of surveys analyze the news recommendation problem from various angles, including challenges and algorithmic approaches [ 11
, 14
, 47
, 84
, 94
, 95
, 120
, 132
], performance comparison in online news recommendation challenges [ 43
, 44
], user profiling [ 67
], news features-based methods [ 129
], or impact on content diversity [ 114
]. However, the focus of these studies is not on the use of external knowledge resources. In contrast to existing studies, this survey focuses on categorizing and examining knowledge-aware news recommender systems, developed either specifically for or evaluated also on the news domain, as a solution for enhancing recommendations and overcoming limitations of traditional recommendation models. The analysis of such systems covers both a review of the algorithmic approaches used for computing recommendations, as well as a comparison of evaluation methodologies and a discussion of limitations and research gaps.
The contributions of the paper are threefold:
1.
We propose a new taxonomy
of knowledge-aware news recommender systems. The recommendation approaches are classified into non-neural and neural-based methods, where the former category further distinguishes between entity-centric and path-based methods.
2.
This survey aims to provide a
comprehensive review
of recommender systems for the news domain which use knowledge bases as external sources of information. For each category of models, we provide a detailed analysis of the representative models, including relevant comparisons and descriptions of the algorithms, as well as of the evaluation methodologies used.
3.
We examine the limitations of existing models and open issues in the field of knowledge-aware news recommender systems, and we identify eight potential
future research directions
in terms of comparability of evaluations, scalability of systems, explainability and fairness of results, multilingual and multi-modal news recommenders, multi-task learning for recommendation, sequential and timely recommendations, and changing user preferences.
The rest of the article is structured as follows. Section 2
introduces recommender systems and outlines challenges specific to the news domain, while Section 3
outlines the methodology used in this survey, including the search strategy, the sources, the inclusion and exclusion criteria, as well as the study execution process. Section 4
covers related work in news and knowledge-aware recommender systems. Section 5
introduces and defines commonly used notations and concepts, and analyses different aspects of knowledge-aware news recommenders. Section 6
classifies and discusses knowledge-aware news recommender systems, whereas Section 7
investigates various evaluation approaches adopted by the different models. Section 8
discusses open issues identified in the field. We close with a short summary in Section 9
.
2. Challenges in news recommendation
Recommender systems consist of techniques that filter information and generate recommendations of items deemed potentially interesting for users, based on their preferences and past behavior, in order to help individuals overcome information overload [ 136
]. User’s preferences are learned using either explicit (e.g. ratings) or implicit (e.g. browsing history) feedback [ 79
]. Recommender systems are generally categorized into collaborative filtering, content-based, and hybrid methods, based on the underlying algorithm. Collaborative filtering systems recommend items liked in the past by users with similar preferences to the current user [ 1
]. In content-based algorithms, the recommendations depend only on the user’s past ratings of items, meaning that the suggested items will have similar characteristics to the ones preferred in the past by the current user [ 1
]. Hybrid models combine one or more types of recommendation approaches to alleviate the weaknesses of a single technique, such as the cold-start problem (which refers to the difficulty in the computation of the recommendations for new items, without ratings, or new users, without a profile) or the over-specialization issue (i.e. the lack of diversity and serendipity in results) [ 18
].
The unique characteristics of news not only distinguish them from items in domains such as online retail, movies, music, or tourism, where recommender systems have already proven successful, but also impede the straightforward application of conventional recommendation algorithms to the task of news recommendation. A large quantity of news is published every day, with articles being continuously updated. Such a
large volume of data
, spread over short periods of time, combined with the
unstructured format
of news articles, requires more complex analyses and heavier computations [ 94
]. In addition, the news is characterized by short shelf lives
and
high item churn
, as their relevance highly depends on the recency
of articles, since users prefer reading about the latest events that took place [ 39
, 94
]. A topic’s
popularity
also significantly influences the importance of an article, as stories can become quickly outdated and lose relevance when they are superseded by “breaking news” [ 84
]. For example, while readers might be concerned with news about the elections in a country for multiple days or even weeks, they will be less likely to be interested in the results of a tennis match a week after a tournament has finished.
Furthermore, the user’s interests evolve over time as individuals display both
short-term and long-term preferences
. On the one hand, individuals display long-term interests in certain topics, motivated by their socio-economic and personal background, such as a user being interested in climate change for several years [ 3
, 67
]. On the other hand, highly popular news might affect a user’s short-term interest, which changes more rapidly, within a short time span [ 3
]. For example, a user might read several news articles related to GameStops’s short squeeze after browsing the “latest news” section of a website that announced that Robinhood has limited the buying and trading of GameStop stocks.
In addition to the previously described challenges, in the news domain, users are usually not required to sign in and create profiles in order to read articles.
Another related challenge is that the users rarely provide explicit feedback in terms of likes and ratings, and, unlike for, e.g., online retail, there is no difference between looking at an item
and buying an item
. In turn, this consumption behavior
means that their profiles are either limited to a single session or tracked through browser cookies, and that
feedback is gathered implicitly
by analyzing the clicks stored in logs [ 43
, 44
]. Overall, these characteristics of users in the news domain pose an additional challenge for creating an accurate user profile for the recommendation algorithms. Additionally, the lack of feedback on news articles and the small amount of data available for user profiling further amplifies the cold-start and data sparsity problems of recommender systems [ 84
, 120
].
Furthermore, users often read multiple news stories in a sequence [ 132
]. Although
sequential consumption
is also characteristic of music items, the major difference lies in the fact that in the news domain readers do not want items to be repeated multiple times in a row, as may be the case with songs. Instead, they prefer being recommended either updates on ongoing stories, or completely different articles [ 132
].
News articles often describe events that occur in the world, which can be represented in terms of named entities
that indicate what, when, where the event happened, as well as who was involved [ 94
].
Additionally, news recommendations can also be subjected to over-specialization
issues as users are being suggested articles semantically similar to the ones already read, but published in different sources and written using terms that are related through semantic relations, such as synonymy or antonymy [ 95
, 120
]. In turn, over-specialized news suggestions can reduce the diversity
and novelty
of the content being shown to the readers, by decreasing both their exposure to diversified information from various sources, as well as their likelihood of discovering new content that is not highly similar or related to the previously consumed articles [ 95
]. Over time, the over-personalization of news recommenders might trap users into
filter bubbles
, namely states in which the recommended articles are concentrated only on a certain standpoint, thus narrowing the readers’ perspective and reducing their freedom of choice regarding the news content they consume [ 123
].
Another significant challenge for the news domain is the existence of fake news
, namely fabricated articles that mimic true news media content, but whose information lacks credibility and accuracy, and aims to propagate misinformation [ 89
]. In the context of news recommendation, this can be represented as a second dimension, namely trustworthiness, which is orthogonal to the actual recommendation fit [ 68
], and which does not exist in other fields, such as movie or music recommendation. By working with large volumes of data whose credibility has not been checked, news recommendation algorithms can contribute to the spread of fake content from unreliable sources [ 113
].
3. Methodology
As aforementioned, this survey aims to provide a comprehensive review of knowledge-aware news recommender systems. The following subsections will describe the methodology used for conducting the study. More specifically, we firstly present our search strategy, including the platforms and queries used to retrieve relevant publications. Afterwards, we discuss the criteria for including and excluding papers from our study, followed by the description of the selection process.
3.1. Search strategy
The search strategy of our survey consists in defining a set of queries for retrieving relevant publications from a list of sources. The results are then de-duplicated, as explained in the following paragraphs.
3.1.1. Search queries
We defined two queries, targeting the task of (Q1) news recommendation
and the usage of (Q2) external knowledge
, in order to collect relevant literature. Table 1
illustrates the search strings used for each of the two queries. Keywords meant to capture (Q2) external knowledge
include multiple terms referring to widely used sources of knowledge, such as knowledge graphs or ontologies. As such, the results of query (Q2)
are given by the union of the results of the corresponding search strings. Since we are interested only in news recommender systems that use a form of external knowledge, the final query used in the publications’ search process represents the intersection of queries (Q1)
and (Q2)
.
Table 1
Search strings used in the search process
Query Search strings
(Q1) news recommendation news recommend*
(Q2) external knowledge knowledge base*, knowledge graph*, ontolog*, linked data*, semantic*
3.1.2. Sources
The following bibliographic databases and archives constitute the sources used for the literature search: (i) DBLP 1 1
(ii) ACM Digital Library 2 2
(iii) IEEE Xplore 3 3
(iv) Science Direct 4 4
(v) Springer Link 5 5
(vi) Web of Science 6 6
3.1.3. De-duplication
The results collected from the previously specified sources are then merged and de-duplicated in a threefold process. Firstly, for all the publications retrieved during the keyword-based search, we gather the associated bibtex files produced by each of the digital libraries and store them using the Zotero 7 7
bibliographic tool, which also performs automatic detection of duplicates based on the papers’ metadata. Secondly, we serialize as a spreadsheet the retrieved publications and their metadata, including title, DOI, abstract, authors, publication venue, and date. Lastly, we use the spreadsheet to perform manual de-duplication of the papers which could not be detected by the bibliographic tool due to large differences in their metadata, such as the publication venue which can be reported by some digital libraries as the conference venue and referred to by others as Lecture Notes in Computer Science (LNCS). The manually de-duplicated results of the keyword-based search constitute the final list of papers used for selecting the relevant literature in the next step.
Table 2
Selection inclusion and exclusion criteria
Criteria Inclusion Criteria (IC) Exclusion Criteria (EC)
C1 Publication date The paper is published between 2008 and 2020. The paper is published before 2008 or after 2020.
C2 Language The paper is written in English. The paper is written in a language different than English.
C3 Publication type The paper has been peer reviewed (e.g. conference or workshop proceedings, journal paper, book chapter). The paper has not been peer reviewed (e.g. theses, books, technical reports, (extended) abstracts, talks, presentations, tutorials).
The paper is a primary study. The paper is a secondary study (e.g. systematic literature review, survey).
C4 Accessibility The paper’s content can be accessed from a technical university (e.g. University of Mannheim) without additional payment. The paper’s content cannot be accessed from a technical university (e.g. University of Mannheim) without additional payment.
C5 Duplicate If the same system and results are presented in multiple publications of the same study (e.g. conference and journal paper), the most recent version of the study will be included. Studies for which a newer or more complete version exists.
C6 Recommender system scope The paper presents a recommendation system applied only in the news domain, or in multiple domains, including the news one. The paper presents a recommendation system which is not applied in the news domain.
The paper presents a system or algorithm mainly aimed at item recommendation. The paper presents a system or algorithm which is not mainly aimed at item recommendation (e.g. an algorithm for improving the diversity of recommendations generated by another system).
C7 Use of external knowledge The paper presents a system that uses external knowledge from a knowledge base. The paper presents a system that does not use external knowledge from a knowledge base.
C8 Interaction of Recommendation Model and External Knowledge Source The external knowledge source is used to enhance the performance and accuracy of the news recommender system. The external knowledge source and recommender system do not jointly target news recommendation (e.g. knowledge graph construction, where the new graph is evaluated on the downstream task of recommendation using an existing recommender system).
C9 Recommender system evaluation The paper presents a recommender system whose performance is evaluated on the task of news recommendation. The paper only describes the theoretical idea of a recommender system or its implementation, but lacks an evaluation of the proposed system on the task of news recommendation.
3.2. Selection strategy
The publications retrieved during the keyword-based search need to be further filtered in order to eliminate false positives, which are irrelevant for the current survey. Consequently, a pre-defined set of inclusion criteria (Section 3.2.1
) are applied to the retrieved papers in two stages, as described in Section 3.2.2
.
3.2.1. Selection criteria
The list of inclusion criteria displayed in Table 2
was developed based on the goals of the survey in order to filter out irrelevant publications. Each criterion is composed of both an
inclusion criterion (IC)
and an exclusion criterion (EC)
. A paper needs to fulfill all inclusion criteria to be selected for the study.
3.2.2. Selection process
The study selection process is composed of two phases. 8 8
Firstly, relevant papers are pre-filtered based on their metadata. More specifically, the validity of criteria C1-C4 is assessed by examining the publications’ language, publishing year, venue, type, keywords, title and abstract. The validity of the remaining criteria is also checked if the information contained in the metadata allows it. Papers not fulfilling all of these criteria are excluded from the rest of the study. Papers whose relevance cannot be determined solely from the metadata will be kept until the next stage of the selection process. In the second phase, the fulfillment of criteria C5-C9 is checked using the complete content of the pre-filtered publications. The papers meeting all the requirements of this phase will be included in the final set of publications for the survey. Table 3
shows the number of papers remaining after different stages of the selection process.
Table 3
Number of papers in different phases of the selection process
Phase Number of remaining papers
Keyword-based search 717
De-duplication 681
Pre-filtering on metadata 64
Filtering on content 40
4. Related work
This section gives an overview of surveys published in the areas of news recommendation and knowledge-aware recommender systems.
4.1. News recommender systems
Several surveys on news recommender systems and corresponding issues have been conducted. A comparison and evaluation of content-based news recommenders are performed in [ 11
]. Borges and Lorena [ 14
] first provide a high-level overview of recommender systems in general, including similarity measures and evaluation metrics, followed by an in-depth analysis of six models applied in the news domain. A more general overview and comparison of the mechanisms and algorithms used by news recommendation approaches, as well as corresponding strengths and weaknesses, is provided by Dwivedi and Arya [ 47
].
Özgöbek et al. [ 120
] identify the challenges specific to the news domain and discuss twelve recommendation models according to the targeted problems, without considering evaluation approaches. In contrast to these studies, Karimi et al. [ 84
] provide a comprehensive review of news recommender systems, not only by taking into account a large number of challenges and algorithmic approaches proposed as a solution, but also by discussing approaches and datasets used in evaluating such systems, as well as proposing future research directions from the perspectives of algorithms and data, and the aspect of evaluation methodologies.
Li et al. [ 94
] review issues characterizing the field of personalized news recommendation and investigate existing approaches from the perspectives of data scalability, user profiling, as well as news selection and ranking. Additionally, the authors conduct an empirical study on a collection of news articles gathered from two news websites in order to examine the influence of different methods of news clustering, user profiling, and feature representation on personalized news recommendation. More recently, Li and Wang [ 95
] analyzed state-of-the-art technologies proposed for personalized news recommendation, by classifying them according to seven addressed news characteristics, namely data sparsity, cold-start, rich contextual information, social information, popularity effect, massive data processing, and privacy problems. Furthermore, they discuss the advantages and disadvantages of different kinds of data used in personalized news recommendation, as well as open issues in the field [ 95
].
In comparison to the previous general studies, Harandi and Gulla [ 67
] investigate and categorize approaches used for user profiling in news recommendation according to the problems addressed and the types of features used. Additionally, Qin and Lu [ 129
] survey feature-based news recommendation techniques, which they categorize into location-based, time-based (i.e. further classified into real-time and session-based), and event-based methods.
Lastly, Feng et al. [ 52
] conduct a systematic literature review of research published in the area of news recommendation in the past two decades. They firstly classify and discuss challenges from this domain according to the three main types of recommendation techniques. Various recommendation frameworks are then categorized according to application domain, such as social media-based, semantics-based, and mobile-based systems. Even though Feng et al. [ 52
] briefly review a small number of semantic-based recommenders, their analysis is limited to older models, and does not include any of the newer approaches of the past five years. Furthermore, the authors briefly examine evaluation approaches and datasets used, before discussing which of the numerous challenges of news recommendation have been addressed by the surveyed recommenders [ 52
].
Although these surveys provide comprehensive overviews of news recommendation methods, domain-specific challenges, and evaluation methodologies, they do not discuss knowledge-aware models or the latest state-of-the-art recommendation methods. In contrast, our survey focuses solely on news recommender systems that incorporate external knowledge to enhance the recommendations and to overcome the limitations of conventional recommendation techniques.
4.2. Knowledge-aware recommender systems
Knowledge graphs, a type of directed heterogeneous networks, describe real-world entities (represented as nodes) and multiple kinds of relations between them (represented as edges), either spanning multiple domains (e.g. Freebase [ 12
], DBpedia [ 92
], YAGO [ 151
], Wikidata [ 167
], Microsoft Satori [ 10
]) or focusing on a particular field (e.g. Bio2RDF [ 6
]) [ 49
, 126
]. In addition, such graphs can capture higher-order relations connecting entities with several related attributes [ 66
].
This strong representation ability of knowledge graphs has attracted the attention of the research community working on developing and improving recommender systems for several reasons. Firstly, using knowledge graphs as side information in recommendation models can help diminish common limitations, such as data sparsity and the cold-start problem [ 66
]. Secondly, the precision of recommendations can be improved by extracting latent semantic connections between items, while the diversity of results can be increased by extending the user’s preferences taking into account the variety of relations between items encoded in a knowledge graph [ 59
, 183
]. Another advantage of using knowledge graphs as background information is improving the explainability of recommendations, to ensure trustworthy recommendation systems, by considering the connections between a user’s previously liked items and the generated suggestions, represented as paths in the knowledge graph [ 183
].
Guo et al. [ 66
] provide a detailed review and analysis of knowledge graph-based recommender systems, which are classified into three categories, according to the strategy employed for utilizing the knowledge graph, namely embedding-based, path-based and unified methods. In addition to comparing the algorithms used by the three types of methods, the authors also analyze how knowledge graphs are used to create explainable recommendations. Lastly, the survey clusters relevant works according to their application and introduces the datasets commonly used for evaluation in each category [ 66
].
Recent advancements in deep learning techniques for graph data, in the form of Graph Neural Networks (GNN) [ 183
, 196
], have given rise to new knowledge-aware, deep recommender systems. Gao et al. [ 59
] are the first to provide a comprehensive overview of Graph Neural Network-based Knowledge-Aware Deep Recommender (GNN-KADR) systems, in which they analyze recommendation techniques, discuss how challenges such as scalability or personalization are addressed, and briefly summarize the domain-specific datasets and metrics used for evaluation, before suggesting a number of directions for future research.
Gao et al. [ 59
] categorize GNN-KADRs depending on the type of graph neural network components used for recommendation. More specifically, graph neural networks are comprised of an aggregator, that combines the feature information of a node’s neighborhood to obtain the context representation, and an updater, which uses this contextual information together with the input information for a given graph node in order to compute its new embedding. According to Gao et al. [ 59
], aggregators are divided into relation-unaware (i.e. the relation information between nodes is not encoded in the context representation) and relation-aware aggregators (i.e. the information contained in different relations is considered in the context representation). The latter category is further split into relation-aware subgraph aggregator and relation-aware attentive aggregator, depending on how the relations in the knowledge graph are modeled in the framework [ 59
]. The first subcategory creates multiple subgraphs for each relation type found in a node’s neighborhood graph, while the second encodes the semantic information contained in the edges of the knowledge graph using weights which measure how related different knowledge triples are to the target node [ 59
]. Similarly, updaters are also categorized into three clusters, namely context-only updaters (i.e. only the node’s context representation is used to produce its new embedding), single-interaction updaters (i.e. both the target node’s current embedding, as well as its context representation are used to obtain its updated representation), and multi-interaction updaters (i.e. different binary operators combine multiple single-interaction updaters), where the first two groups of updaters are more often encountered [ 59
].
GNN-based recommender systems are investigated also by Wu et al. [ 183
], who classify the recommendation models based on whether the models consider the item’s ordering (i.e. general vs. sequential methods) and on the type of information used (i.e. without side information, social network-enhanced, and knowledge graph-enhanced). According to the proposed taxonomy of Wu et al. [ 183
], knowledge-aware models can be found only in the group of general recommender systems. In this category, four representative recommendation frameworks are examined from the aspects of graph simplification, multi-relation propagation, and user integration.
The research commentary of Sun et al. [ 155
] consists of an extensive, systematic survey of recent advancements in recommender systems that use side information. The models, mostly hybrid techniques, are analyzed from two perspectives. On the one hand, Sun et al. [ 155
] categorize the models according to the evolution of fundamental methodological approaches into memory-based and model-based frameworks, where the latter category is further split into latent factor models, representation learning models and deep learning models. On the other hand, the recommender systems are classified based on the evolution of side information used for recommendation, into models using structural data and models using non-structural data. The first group includes information in the form of flat features, network features, feature hierarchies, and knowledge graphs, whereas the second consists of text, image, and video features [ 155
].
In the surveys discussed above, knowledge-aware news recommender systems are rarely analyzed. In comparison to these works, the current survey focuses on the investigation of approaches for injecting external knowledge only into the news recommendation model. To this end, it provides a categorization and an extensive overview of the knowledge-aware recommender systems developed either for or evaluated also in the news domain.
5. Definitions and categorization
This section firstly introduces and defines commonly used concepts and notations. Afterwards, it provides an overview of knowledge-aware news recommender systems according to multiple criteria.
5.1. Definitions
Firstly, a minimal set of concepts and notations referred to in the rest of the article are defined. Bold uppercase characters denote matrices, while bold lowercase characters generally indicate vectors. The notations used throughout this article are illustrated in Table 4
, unless specified otherwise.
Table 4
Commonly used notations
Notations Descriptions
| · |
| ⋅ |
Set size
⊙ Element-wise product
⊕ Vector concatenation
∗ Convolution operation
tanh
tanh
Hyperbolic tangent function
σ ( · )
σ ( ⋅ )
Nonlinear transformation function
X T
X T
Transpose of matrix X
G
G
A knowledge graph
c i
c i
Concept i in the ontology O
O
or knowledge graph G
G
e i
e i
Entity i in G
G
(either head or tail)
N ( e i )
N ( e i )
Neighbours of entity e i
e i
k Dimension of knowledge graph embedding
e i ∈ R k × 1
e i ∈ R k × 1
Embedding of entity e i
e i
in G
G
r ∈ R k × 1
r ∈ R k × 1
Embedding of relation r in G
G
u i
u i
Profile of user i
v j
v j
Profile of item j
U = { u 1 , u 2 , … , u M }
U = { u 1 , u 2 , … , u M }
Set of users
V = { v 1 , v 2 , … , v N }
V = { v 1 , v 2 , … , v N }
Set of items
M The number of users in U
U
N The number of items in V
V
ˆ y u , v
y ˆ u , v
User u ’s probability of interacting with item v
d Dimension of a feature vector
u i ∈ R d × 1
u i ∈ R d × 1
Feature vector of user u i
u i
v j ∈ R d × 1
v j ∈ R d × 1
Feature vector of item v j
v j
V i
V i
, W i
W i
, w i
w i
Trainable weight matrices and vectors
b i
b i
Trainable bias vectors
Definition 1.
An ontology
is defined as a set of k ontology concepts
[ 78
]:
C O = { c 1 , c 2 , … , c k }
C O = { c 1 , c 2 , … , c k } (1)
In many cases, concepts are distinguished into classes C
C
and relations R
R
, so that
O = C ∪ R
O = C ∪ R
, and C ∩ R = ∅
C ∩ R = ∅
.
In the recent years, knowledge graphs comprising a large number of instances have been developed and utilized also in news recommender systems.
Definition 2.
A knowledge graph
(KG) G = ( V , E )
G = ( V , E )
is a labeled directed graph, where the nodes represent entities
. Edges are of the form
⟨ e h , r , e t ⟩ ∈ E
⟨ e h , r , e t ⟩ ∈ E
, and indicate a relationship
r ∈ R
r ∈ R
from head entity e h
e h
to tail entity
e t
e t
, where e h , e t ∈ V
e h , e t ∈ V
. Edges can be interpreted as subject-property-object triple facts [ 20
]. Often, entities are assigned one or more types, defined by type statements of the form ⟨ e , t ⟩
⟨ e , t ⟩
, where e ∈ E
e ∈ E
and t ∈ C
t ∈ C
.
In the scope of this paper, we consider concepts in knowledge graphs C G
C G
as
C G = C ∪ R ∪ I
C G = C ∪ R ∪ I
, where I
I
is a set of instances.
Definition 3.
The semantic neighborhood
of a concept
c i ∈ G
c i ∈ G
is defined as the set of concepts that are directly related to concept c i
c i
, including itself [ 78
]:
N ( c i ) = { c i
1 , c i
2 , … , c i
k }
N ( c i ) = { c i 1 , c i 2 , … , c i k } (2)
5.2. Categorization of knowledge-aware news recommender systems
Knowledge-aware news recommendation models can be investigated according to multiple criteria, ranging from the used knowledge resource to target function types or addressed challenges.
5.2.1. Types of recommendation techniques
News recommendation systems generally adopt one of the three main techniques for predicting whether a user will interact with a certain article, namely content-based, collaborative filtering, and hybrid. However, content-based approaches are the most widely used in the field of news recommendation [ 84
].
5.2.2. Knowledge base
The knowledge resources used by knowledge-aware recommender systems can be grouped into domain ontologies and knowledge graphs. In the remainder of the paper, these will be referred to as
knowledge bases
(KB), if the type of resource is not explicitly specified. The former category can be further split into self-constructed ontologies – built either from combining smaller domain ontologies or subsets of large knowledge bases (e.g. DBpedia [ 92
], Hudong encyclopedia [ 177
]) or directly from news articles (i.e. financial domain ontology using information from Yahoo! Finance [ 78
]) – and controlled vocabularies used in the news domain, such as the IPTC News Codes 9 9
[ 160
].
In the latter category, one can distinguish between open source and commercial knowledge graphs. In the first subgroup, cross-domain knowledge graphs such as Wikidata, DBpedia, and Freebase are widely used in news recommender systems. Freebase [ 12
] was initially launched by Metaweb in 2007, and later acquired by Google in 2010, before being shut down in 2015 [ 126
]. The latest version of Freebase, available at Google’s Data Dumps 10 10
has been estimated to contain 1.9 billion triples [ 63
]. Wikidata [ 167
], a collaboratively edited knowledge graph, containing several language editions of Wikipedia, as well as data previously contained in Freebase [ 126
], consists of 92 million items 11 11
and over 1174 million statements. 12 12
DBpedia [ 92
] is a knowledge graph built by extracting structured data from various language versions of Wikipedia, and contains in its most recent and largest version, DBpedia Largest Diamond, 220 million entities and 1.45 billion triples. 13 13
WordNet [ 111
], a large English lexicon containing nouns, verbs, adjectives, and adverbs grouped into synsets (i.e. sets of synonyms), which are further interconnected via semantic relations of antonymy, hyponymy, meronymy, troponomy, or entailment, is often used in knowledge-aware news recommender systems for word sense disambiguation. More specifically, each word in WordNet is associated with a set of senses, which denote the set of possible meanings that the word might have. For example, the noun “Jupiter” can refer to either the planet in the solar system or the supreme god of the Romans. WordNet 3.0 14 14
contains 117,659 synsets and 206,941 word-sense pairs.
In the subgroup of commercial knowledge bases, Satori [ 10
], the knowledge graph proposed by Microsoft, is the most often used one, especially by recent deep learning-based news recommender systems. Although very little information about the data contained in Satori is publicly available, it was estimated to contain in 2012 approximately 300 million entities and 800 million relations [ 126
].
5.2.3. Structure of knowledge base
News recommendation models use knowledge bases by exploiting their different structures in order to extract either semantic, structural, or both types of information. A few knowledge-aware news recommender systems exploit only the semantic information contained in a knowledge graph or ontology, by extracting concepts or entities that appear in a news article, which will be denoted as concepts/entities only
models for the rest of this article. A larger share of models however enriches the basic set of knowledge entities by expanding it with the neighborhoods of extracted entities in the knowledge graph and by considering the paths and relationships between entities (denoted as entities
+ paths
). Another method for enhancing the set of concepts or entities extracted from a knowledge base is by taking into account its structure, namely the different types of relations between nodes in an ontology, such as synonymy or hyponymy relationships in semantic lexicons, or the distances between concepts, entities or classes (denoted as concepts
+ KB structure
or entities
+ KB structure
). Differently from these categories of models, the newer deep-learning-based recommendation techniques exploit simultaneously both the semantic and the structural information encoded in knowledge graphs, by means of knowledge graph embeddings (denoted as
entities
+ KG structure
).
5.2.4. Target function
Two main target functions can be distinguished in news recommendation models, namely click-through rate (CTR) prediction and item ranking. Models classified in the first group aim to predict the probability that the user will click on the target article, whereas methods in the second group recommend the top N
most similar articles to the articles previously read by the user.
5.2.5. Addressed challenge
In addition to enhancing the accuracy of recommendations, knowledge-aware news recommender systems aim to address different challenges of the news domain or limitations posed by conventional recommendation techniques. Several news articles, written in different manners, using semantically related terms, can describe the same piece of news, and numerous words have different meanings depending on the context in which they are used. While humans can easily distinguish ambiguous words, or words connected via certain semantic relations, such as synonyms, this constitutes a challenge for recommendation models using text representations. Knowledge-aware recommender systems propose to remove such ambiguity from text by representing an article using only disambiguated knowledge entities or concepts from a controlled vocabulary, instead of all the terms. In turn, this leads to faster computations, since the model is required to consider a limited number of concepts or entities, which is significantly smaller than the total number of words contained in an article. Moreover, the semantic meaning of news, as well as the semantic relatedness of concepts (i.e. news describing similar or related concepts might indicate different interests of a user) can be captured by further considering the relations between the different concepts found in an article.
News articles contain a large number of named entities, used to denote information regarding the events described, such as the location, actors involved, time, or what the event refers to. However, named entities are not taken into account in traditional text-based recommendation models. In contrast, knowledge-aware techniques handle named entities by extracting them from the text and enriching them with external information encoded in knowledge graphs. Furthermore, using external information for recommendation can help overcome the data sparsity and cold-start problems, as articles can be connected using relations in the knowledge graph between the entities extracted from text, such that new items without user feedback can also be included in the recommendations.
Moreover, injecting external knowledge into the recommendation model has three additional benefits. Firstly, it extends text-level information with common sense knowledge which is encoded in knowledge graphs but cannot be extracted only from an article’s text. For example, a user reading the titles of the news articles in Fig. 1
will probably know that Elon Musk
and Robinhood
were participants in the
GameStop short squeeze
event that affected GameStop
, or that the New York Stock Exchange
is located on Wall Street
. However, a text-based recommendation model does not possess such common knowledge information. Additionally, using external information also helps the model discover latent knowledge-level connections between the news, such as the fact that the two snippets in the example from Fig. 1
are connected, although they do not appear related when considering only the words in their titles. Lastly, exploiting the knowledge-level and semantic connections between news can improve the diversity of recommendations, as the model learns to avoid recommending articles that are too semantically similar, even if they are published in different sources and have different writing styles.
Fig. 1.
Illustration of a knowledge graph-enhanced news recommender system (reproduced from [ 170
]).
6. Knowledge-aware news recommendation models
Table 5
Overview of knowledge-aware news recommendation approaches. We present the model’s category, abbreviated name, publishing year, type of recommendation technique, external knowledge resource and its used structures, target function, and challenges addressed by injecting external knowledge in the recommendation model. “Accuracy” is not explicitly mentioned as a challenge, as all discussed models aim to improve recommendations on this measure. The following abbreviations are used: NNECM = Non-Neural, Entity-Centric Methods, NNPM = Non-Neural, Path-Based Methods, NM = Neural Methods, RS = Recommender System, CB = Content-Based, CF = Collaborative Filtering, H = Hybrid, DO = Domain Ontology
Category Model Year RS type KB KB structure Target function Addressed challenge
NNECM Semantic context-aware recommendation [ 21 , 23 ]
2008 H DO (IPTC + Wikipedia) entities + paths Item ranking Capture semantic relatedness of concepts
Social tags enriched recommendations [ 24 ]
2008 CB Wordnet, Wikipedia DO (IPTC + Wikipedia) entities + paths Item ranking Data sparsity, cold-start problem
Semantic relatedness [ 60 ]
2009 CB DO entities + paths Item ranking Capture semantic relatedness of concepts
RSR [ 78 ] 2010 CB DO entities + paths Item ranking Capture semantic meaning, faster computations, eliminate ambiguity
CF-IDF [ 64 ] 2011 CB DO concepts/entities only Item ranking –
Hybrid context-aware recommendation [ 23 ]
2011 H DO (IPTC + Wikipedia) entities + paths Item ranking Data sparsity, cold-start problem
RSR 2 [ 55 ] 2012 CB DO entities + paths Item ranking Capture semantic meaning, faster computations, eliminate ambiguity
SF-IDF [ 26 ] 2012 CB WordNet concepts/entities only Item ranking Capture semantic meaning
SF-IDF+ [ 112 ] 2013 CB WordNet entities + paths Item ranking Capture semantic relationships between synsets
Bing-SF-IDF [ 71 ] 2013 CB WordNet entities + paths Item ranking Handle knowledge entities
Bing-SF-IDF+ [ 28 ] 2015 CB WordNet entities + paths Item ranking Capture semantic meaning
Agarwal and Singhal [ 2 ]
2014 CB DO (IPTC) concepyts/entities only Item ranking –
OF-IDF [ 133 ] 2015 CB DO entities + paths Item ranking Eliminate ambiguity
CF-IDF+ [ 40 ] 2018 CB DO entities + paths Item ranking Handle relationship types between concepts
Bing-CF-IDF+ [ 17 ] 2019 CB DO entities + paths Item ranking Handle knowledge entities
Bing-CSF-IDF+ [ 161 ]
2020 CB DO, WordNet entities + paths Item ranking Capture semantic meaning, handle knowledge entities
Table 5
(Continued)
Category Model Year RS type KB KB structure Target function Addressed challenge
NNPM ePaper [ 105 ]
2008 CB IPTC News Codes concepts + KB structure Item ranking –
Magellan [ 45 ]
2011 CB DO concepts + KB structure Item ranking –
SS [ 26 ] 2012 CB WordNet concepts + KB structure Item ranking Capture semantic meaning
BingSS [ 27 ]
2013 CB WordNet concepts + KB structure Item ranking Handle knowledge entities
OBSM [ 130 ]
2013 CB Ontologies based on DBpedia and Hudong concepts + KB structure Item ranking Eliminate ambiguity
Kumar and Kulkarni [ 88 ]
2013 CB Wikipedia concepts + KB structure Item ranking –
Werner and Cruz [ 179 ]
2013 CB DO concepts + KB structure Item ranking –
BKSport [ 117 ]
2016 H DO concepts + KB structure Item ranking Capture semantic meaning
SED [ 83 ] 2019 CB Freebase entities + KB structure Item ranking Cold-start problem
Table 5
(Continued)
Category Model Year RS type KB KB structure Target function Addressed challenge
NM CETR [ 193 ]
2017 CF Wikidata entities + KG structure CTR Extend text-level information
Colombo-Mendoza et al. [ 35 ]
2018 H DO entities + KG structure Item ranking –
DKN [ 170 ] 2018 CB Microsoft Satori entities + KG structure CTR Extract knowledge-level news connections, extend text-level information with common sense
Gao et al. [ 58 ]
2018 CB KG entities + KG structure CTR Extract knowledge-level news connections
RippleNet [ 168 ]
2018 CB Microsoft Satori entities + KG structure CTR Data sparsity, cold-start problem
RippleNet-agg [ 169 ]
2019 CB Microsoft Satori entities + KG structure CTR Data sparsity, cold-start problem
MKR [ 172 ] 2019 CB Microsoft Satori entities + KG structure CTR Item ranking Data sparsity, cold-start problem
IGNN [ 128 ] 2019 CB Wikipedia entities + KG structure CTR Mine high-order connectivity of users and news
Saskr [ 33 ] 2019 CB News-specific KG entities + KG structure CTR Extract knowledge-level news connections, diversity, cold-start problem, handle knowledge entities
KRED [ 100 ] 2020 CB Microsoft Satori entities + KG structure CTR Handle knowledge entities
TEKGR [ 91 ] 2020 CB Microsoft Satori entities + KG structure CTR Handle knowledge entities, capture topical relatedness between news
KCNR [ 176 ] 2020 CB Douban entities + KG structure CTR Handle knowledge and content factors
KG-RWSNM [ 188 ]
2020 H Wikidata entities + KG structure CTR Extract deep semantic features from news
MUKG [ 152 ]
2020 CB Microsoft Satori entities + KG structure CTR Data sparsity, cold-start problem Mine high-order interactions between item and entities
CAGE [ 145 ] 2020 CB Wikidata entities + KG structure CTR Include semantic-level structural information between articles in session-based recommendation
Knowledge-aware news recommendation systems can be classified into different categories based on how external knowledge is injected in the recommendation model, on the used structures of the knowledge base, as well on how latent representations of users and articles are computed. Our proposed taxonomy, illustrated in Fig. 2
, distinguishes between the methods based on how the latent representations are generated from entities and/or concepts in a knowledge base, i.e., Non-Neural Methods and methods based on neural networks (Section 6.3
). We further split Non-Neural Methods into Entity-Centric (Section 6.1
) and Path-Based (Section 6.2
), depending on whether the recommendation approach defines the similarity between users and news articles based on distances between the concepts or entities from the knowledge base. To support readers reviewing the literature, the surveyed models are listed in Table 5
according to the aforementioned criteria.
Fig. 2.
The categorization of knowledge-aware news recommender systems. We divide existing frameworks into three categories, based firstly on how latent representations of user and news article profiles are generated, and secondly, on the type of similarity measure used.
Factorization models constitute some of the state-of-the-art recommendation techniques in various fields [ 9
, 87
, 147
], and have already been adopted in the area of news recommendation [ 131
, 185
]. Moreover, latent factor models have also been adapted to support knowledge graphs in hybrid knowledge-aware recommendation engines [ 30
, 146
, 154
, 191
]. Nonetheless, as it can be observed from Table 5
, factorization models are rarely used by knowledge-aware news recommender systems. More specifically, only one model from the 39 surveyed ones uses matrix factorization (see Section 6.3
). Hence, we have not added a dedicated subcategory for such methods to our taxonomy.
Recommenders based on factorization models are collaborative filtering-based approaches. However, this recommendation technique is the least adopted one in the domain of news recommendation [ 132
]. Raza et al. [ 132
] have shown that content-based methods are the most widely used recommendation techniques in this field, followed by hybrid approaches. This phenomenon can be explained by the challenges faced by recommender systems in the news domain, explained in Section 2
, such as the lack of explicit feedback (i.e. ratings), or limited amount of data available for user profiling. In turn, this affects collaborative-filtering approaches such as factorization models, which rely on a large amount of information regarding the user-item interactions in order to generate accurate recommendations.
Comparison with existing taxonomies
Several taxonomies have already been proposed for general knowledge-aware recommender systems. Gao et al. [ 59
] categorize GNN-based knowledge-aware deep recommender systems based on the different types of the two basic components of the graph embedding module, namely the aggregator and the updater. In comparison to the work of Gao et al. [ 59
], in the current survey, we neither limit our analysis to knowledge-aware deep news recommenders, nor to those based necessarily on GNNs. Hence, there is no overlap between the two taxonomies.
Another categorization of knowledge graph-based recommender systems divides models into different categories based on how they utilize the knowledge graph information, namely into embedding-based methods, path-based methods, and unified methods [ 66
]. Embedding-based methods encode the knowledge graph information by means of knowledge graph embeddings and directly use it to enhance the representations of users or items. This category is further split into models that construct knowledge graphs of items and their relations, extracted from a dataset or external knowledge base, and those that build user-item graphs, in which the users, items, and their attributes form the graph’s nodes, while user-related and attribute-related relations constitute the edges [ 66
]. In our survey, this category overlaps with the neural-based models, which use a form of knowledge graph embedding, as it will be explained in Section 6.3
. However, we do not further differentiate between neural-based recommenders depending on how the underlying knowledge graph is created.
Guo et al.’s [ 66
] second category of path-based methods includes those recommenders that leverage connectivity patterns of entities in the user-item graph. In this context, this category has similarities with our proposed non-neural, path-based methods. However, in our case, the connectivity patterns are exploited from any source of structured knowledge base and are not restricted to user-item graphs.
The third category proposed by Guo et al. [ 66
], namely unified methods, incorporates models that combine the first two types of techniques by leveraging both the connectivity information, as well as the semantic representation of entities and relations. This class, containing the RippleNet [ 168
] and RippleNet-agg [ 169
] models, overlaps again with our neural-based methods due to the neural nature of latent representations used to profile items and users.
Lastly, Sun et al. [ 155
] classify recommender systems on two dimensions. The first dimension is concerned with the recommendation technique and differentiates between memory-based methods, latent factor models, representation learning models, and deep learning models. The second dimension focuses on the type of side information used, namely structural data (i.e. flat, network, hierarchical features, and knowledge graphs) and non-structural data, in the form of text, image, and video features. According to this categorization scheme, models classified by Sun et al. [ 155
] under deep learning methods that use knowledge graphs as side information would correspond to neural-based methods in our taxonomy.
The following subsections analyze the knowledge-aware recommender systems presented in Table 5
according to the taxonomy introduced above. For each category of models, the overall framework, as well as representative models are investigated.
6.1. Entity-centric methods (non-neural)
Recommender systems classified in this category represent the profiles of users and news articles using latent representations generated from concepts and/or entities in a knowledge base using non-neural methods. Generally, such representations are computed using a Vector Space Model [ 140
], most often variants of the Term Frequency-Inverse Document Frequency (TF-IDF) model [ 139
], modified to take into consideration side information from a knowledge base. The similarity between articles and the preference of a user for a candidate article are determined using different semantic or non-semantic similarity metrics.
6.1.1. Overall framework
Non-neural, entity-centric methods first create a vector representation of both the target article and the user profile, where the latter consists of the user’s reading history. Afterwards, the models compute the similarity between the two representations and recommend a list of the top N
articles whose similarity scores exceed a predefined threshold. As such, the majority of techniques listed here adopt a content-based recommendation approach. We analyze these systems in terms of three differentiating factors:
– Profile representation.
The representation of the items and users determines which kind of semantic information is incorporated in the model.
– Weighting scheme.
Several weighting approaches are used to measure the importance of the components used to represent the news articles.
– Similarity metric.
The recommendation is based on the similarity of target articles to the articles from the user’s profile, which is calculated using a variety of methods.
6.1.2. Representative models
In this subsection, we discuss 12 representative non-neural, entity-centric recommendation techniques.
Cantandor et al. [ 21
, 23
] developed a
semantic context-aware recommendation
model which aims to contextualize the users’ interests, such that the model learns to ignore preferences that are out of focus in a particular session, and to place a higher importance on those that are in the semantic scope of the ongoing user activity. The profiles of both user and news articles are described using semantic concepts from a domain ontology, as
u = ( w u
1 , w u
2 , … , w u
q )
u = ( w u 1 , w u 2 , … , w u q )
, and
v = ( w n
1 , w n
2 , … , w n
p )
v = ( w n 1 , w n 2 , … , w n p )
, respectively. The concepts in the user’s vector representation are weighted with weights
w u
i ∈ [ − 1 , 1 ]
w u i ∈ [ − 1 , 1 ]
, which indicate the intensity of the user’s interest for concept
c i ∈ O
c i ∈ O
. A negative weight is equivalent to a dislike for the concept, while a positive value shows that the user is interested in the given concept. Similarly, concepts weights w n
i ∈ [ 0 , 1 ]
w n i ∈ [ 0 , 1 ]
place the article’s representation in the same vector space as the user’s preferences [ 23
].
A personalized content retrieval approach assigns a relevance measure
pref ( v , u ) = cos ( v , u )
pref ( v , u ) = cos ( v , u )
of an item v
to user u
using the cosine similarity between their vector representations. However, a good recommendation model should be able to differentiate between a user’s short and long-term preferences, which could be accomplished by enhancing it with contextualized semantic preferences. More specifically, Cantandor et al. [ 23
] define a semantic runtime context as the background topics C t
u
C t u
under which user u
performs a set of activities in the unit of time t
. The runtime context, illustrated in Eq. ( 3
), comprises a set of weighted concepts from a domain ontology, collected from the articles accessed by the user during a session.
C t
u [ c i ] = ξ · C t − 1
u [ c i ] + ( 1 − ξ ) · Req t
u [ c i ]
C t u [ c i ] = ξ ⋅ C t − 1 u [ c i ] + ( 1 − ξ ) ⋅ Req t u [ c i ] (3)
where Req t
u ∈ [ 0 , 1 ] | O |
R e q t u ∈ [ 0 , 1 ] | O |
is a vector whose elements indicate the extent to which the concepts c i
c i
are relevant to the user’s request at time t
, which can be defined in several ways, including a query concept-vector, or an average concept-vector [ 23
]. The decay factor ξ
determines the speed with which the importance of a concept c i
c i
fades over time, specifically how many actions should be performed before a concept is no longer considered to be in the current semantic context.
Following the construction of the runtime context, Cantandor et al. [ 23
] introduce a semantic preference spreading strategy which expands the user’s initial preferences through semantic paths towards other concepts in the ontology. This contextual activation of user preferences constitutes an approximation of conditional probabilities. According to this formulation, the probability that concept c i ∈ O
c i ∈ O
is of interest for a user is determined by the probability that the concept c i
c i
itself, as well as all other concepts c j ∈ O
c j ∈ O
directly connected to it in the ontology, belong to the same topic, and the probability that the related concept c j
c j
is also relevant for the user.
Consequently, the semantic spreading mechanism requires weighting every semantic relation r
in the ontology with a value w ( r , c i , c j )
w ( r , c i , c j )
which denotes the probability that concepts c i
c i
and c j
c j
belong to the same topic given the fact that they are connected by relation r
. The initial set of user preferences expressed in terms of concepts,
P u = { c u
i ∈ O | w u
k ≠ 0 }
P u = { c u i ∈ O | w u k ≠ 0 }
, is expanded as follows:
EP u [ c j ] = { P u [ c j ] , if P u [ c j ] > 0
R ( { EP u [ c i ] · power ( c i ) } c i ∈ O , r ( c i , c j ) ) , otherwise
E P u [ c j ] = { P u [ c j ] , R ( { E P u [ c i ] ⋅ power ( c i ) } c i ∈ O , r ( c i , c j ) ) , if P u [ c j ] > 0 otherwise (4)
where power ( c i ) ∈ [ 0 , 1 ]
power ( c i ) ∈ [ 0 , 1 ]
represents a propagation power assigned to each concept and
R ( X ) = ∑ S ⊂ N n { ( − 1 ) | S | + 1 × ∏ i ∈ S x i }
R ( X ) = ∑ S ⊂ N n { ( − 1 ) | S | + 1 × ∏ i ∈ S x i }
, with X = { x i } n
i = 0
X = { x i } n i = 0
, x i ∈ [ 0 , 1 ]
x i ∈ [ 0 , 1 ]
.
The context-aware personalized recommendation model computes the relevance measure of an item v
for user u
using the expanded profiles of the user and the article, in the following way:
pref c ( v , u ) = λ · pref ( v , EP u ) + ( 1 − λ ) · pref ( v , EC u )
pref c ( v , u ) = λ ⋅ pref ( v , E P u ) + ( 1 − λ ) ⋅ pref ( v , E C u )
. In this case, the parameter λ ∈ [ 0 , 1 ]
λ ∈ [ 0 , 1 ]
weights the strength of the personalization component with regards to the current context.
The weights spreading strategy addresses both the cold-start and the data sparsity problems, whereas incorporating contextual information captures the changing utility of a news article to a user based on temporary circumstances. While this model applies to single users, Cantandor et al. [ 23
] also employ a hybrid context-aware recommendation
technique which exploits the connections between users and concepts to discover relations among users in a collaborative fashion. The goal, in this case, is to leverage partial similarities between users with similar preferences in a focused domain, but who are globally dissimilar. On a high level, the strategy is accomplished by clustering users according to layers of preferences shared among them. Hence, the user similarities depend on sub-profiles, which increase the likelihood of extracting conjunctions of rare preferences.
Semantic Communities of Interest are derived from the users’ relations at different semantic levels [ 23
]. More specifically, each ontology concept c u
i
c u i
occurring in a user’s reading history is represented as a vector of weights measuring its importance for the user, namely
c u
i = ( w 1 , i , w 2 , i , … , w M , i ) ∈ [ − 1 , 1 ] M
c u i = ( w 1 , i , w 2 , i , … , w M , i ) ∈ [ − 1 , 1 ] M
. A hierarchical clustering method is used to determine groups of preferences in the concept-user vector space, and each user is assigned to a concept cluster based on the similarity of his profile to cluster C q
C q
, computed as
sim ( u , C q ) =
∑ c u
i ∈ C q w u
1
| C q |
sim ( u , C q ) = ∑ c u i ∈ C q w u 1 | C q |
, where c i
c i
is the concept associated with the w u
i
w u i
element in the user’s preference vector.
Cantandor et al. [ 23
] propose two recommendation models that use the extracted latent communities of interests among users. On the one hand, model UP
computes a unique ranked list of news articles based on the similarities between news and all semantic clusters, meaning that it compares a user’s interests to those of the other users and utilizes these user-user similarities to weight preferences for candidate articles. As such, the preference score of article v
to user u
is computed using Eq. ( 5
):
pref ( u , v ) = ∑ q nsim ( v , C q ) ∑ y ≠ u nsim q ( u , y ) · sim q ( y , v )
pref ( u , v ) = ∑ q nsim ( v , C q ) ∑ y ≠ u nsim q ( u , y ) ⋅ sim q ( y , v ) (5)
Here
sim ( v , C q ) =
∑ c i ∈ C q w n
i
v √ | C q |
sim ( v , C q ) = ∑ c i ∈ C q w n i v | C q | √
represents the similarity between item v
and cluster
C q
C q
, and nsim ( v , C q )
nsim ( v , C q )
denotes the normalized similarity over the set of all clusters. Moreover sim q ( u , y )
sim q ( u , y )
and
nsim q ( u , y )
nsim q ( u , y )
are the single and normalized similarities at layer q
between users u
and y
, defined as the cosine similarity of the projections of their corresponding concept vectors onto cluster C q
C q
. Therefore, model UP
takes into account both the characteristics of news articles, as well as the relations between user, at different semantic layers.
On the other hand, model UP-q
generates recommendations separately for each layer by computing a ranked list for each semantic cluster. The preference between user and target article is calculated as follows:
pref ( u , v ) = ∑ y ≠ u nsim q ( u , y ) · sim q ( y , v )
pref ( u , v ) = ∑ y ≠ u nsim q ( u , y ) ⋅ sim q ( y , v ) (6)
The recommendations corresponding to the cluster to which the user has the highest similarity will be suggested ( q
maximizes sim ( v , C q )
sim ( v , C q )
in Eq. ( 6
)).
The same context-aware and multi-facet, group-oriented hybrid recommendations are also adopted by Cantandor et al. [ 24
] to generate
social tags enriched recommendations
. The authors expand the original user profiles with personal tag clouds collected from two websites (Flickr and del.icio.us). The extracted tags are incorporated into the ontological user profiles by mapping them to ontology concepts.
Concept Frequency – Inverse Document Frequency ( CF-IDF
) [ 64
] constitutes a variant of the TF-IDF weighting scheme that uses concepts instead of terms in order to represent news articles. In the framework proposed by Goossen et al. [ 64
], the profile of a user u
consists of a set of q
concepts from an ontology, namely
u = { c u
1 , c u
2 , … , c u
q }
u = { c u 1 , c u 2 , … , c u q }
, c u
i ∈ O
c u i ∈ O
. In turn, each concept c u
c u
from the user profile is represented as a set of k
news articles v j
v j
in which it occurs, namely
c u = { v 1 , v 2 , … , v k }
c u = { v 1 , v 2 , … , v k }
. An article is thus composed of a set of p
concepts occurring in it, denoted as v = { c n
1 , c n
2 , … , c n
p }
v = { c n 1 , c n 2 , … , c n p }
,
c n ∈ O
c n ∈ O
.
In the CF-IDF recommender, each user’s interests are represented as a vector of CF-IDF weights w u
w u
corresponding to the concepts appearing in the user’s previously read articles, as shown in Eq. ( 7
). Analogously, the article’s profile is computed according to Eq. ( 8
).
u = [ ⟨ c u
1 , w u
1 ⟩ , … , ⟨ c u
q , w u
q ⟩ ]
v = [ ⟨ c n
1 , w n
1 ⟩ , … , ⟨ c n
p , w n
p ⟩ ]
u v = = [ ⟨ c u 1 , w u 1 ⟩ , … , ⟨ c u q , w u q ⟩ ] [ ⟨ c n 1 , w n 1 ⟩ , … , ⟨ c n p , w n p ⟩ ] (7) (8)
The CF-IDF weights are computed similarly to TF-IDF weights. Firstly, the
Concept Frequency cf i , j
cf i , j
calculates the frequency of a concept c i
c i
in an article v j
v j
as the ratio between the number of occurrences in the given article, n i , j
n i , j
, and number of occurrences of all concepts appearing in the article, n k , j
n k , j
. Since highly frequent concepts are less informative than rarer ones, the Inverse Document Frequency
idf i
idf i
penalizes such concepts by increasing the weight of concepts rarely occurring across all | D |
| D |
articles in the corpus. For a concept c i
c i
, this is achieved by computing the logarithmically scaled inverse fraction of documents containing the concept. The final weight is given by multiplying the two components according to Eq. ( 9
).
cf-idf i , j = cf i , j × idf i =
n i , j
∑ k n k , j
× log
| D |
| d : c i ∈ d |
cf-idf i , j = cf i , j × idf i = n i , j ∑ k n k , j × log | D | | d : c i ∈ d | (9)
A major difference between the TF-IDF and CF-IDF lies in the fact that the latter considers only the ontology concepts contained in the text, instead of all the terms. Therefore, it assigns a larger value to the concepts deemed more important, and results in faster computations, as it considers a smaller amount of elements during similarity computations. In turn, this also implies that CF-IDF can assign a single representation to multi-word expressions (e.g. “Elon Musk” is one concept), compared to TF-IDF which would compute an embedding for each word individually (e.g. for “Elon” and for “Musk”). Consequently, if the concepts are disambiguated, CF-IDF can handle ambiguous terms, in contrast to TF-IDF.
The Synset Frequency – Inverse Document Frequency ( SF-IDF
) approach of Capelle et al. [ 26
] modifies the TF-IDF weighting scheme to take into account the semantic meaning of terms in a text. In comparison to CF-IDF, Capelle et al. [ 26
] represent the user’s and article’s profile as sets of WordNet synsets of the terms appearing in the news article. Mathematically, the news item’s profile is represented as:
v = { s n
1 , s n
2 , … , s n
p }
v = { s n 1 , s n 2 , … , s n p } (10)
where s n
i
s n i
denotes a WordNet synset of a term from the article, and p
the total number of synsets contained in it. The user profile is obtained by aggregating the vector representations v q
v q
of all the Q
news articles in his reading history, denoted as:
u = ⋃ q ∈ Q v q = ⋃ q ∈ Q { s u
1 , s u
2 , … , s u
q }
u = ⋃ q ∈ Q v q = ⋃ q ∈ Q { s u 1 , s u 2 , … , s u q } (11)
The synsets in both profiles are weighted using SF-IDF weights, obtained from TF-IDF by replacing terms with synsets s
, i.e.
sf-idf s , d = sf s , d × idf s , d
sf-idf s , d = sf s , d × idf s , d
. The main advantage of SF-IDF is that the same synset is used to represent words with identical meaning, thus reducing the ambiguity of terms and taking into account their semantic relatedness.
However, SF-IDF yields a limited understanding of the semantics of news. Therefore, SF-IDF
+ [ 112
] additionally considers the semantic relationships between synsets in order to overcome this drawback. This is achieved by extending a set of synsets S ( s )
S ( s )
with the concepts connected through semantic relationships with the included synsets, as shown in Eq. ( 12
), where s
denotes a synset, R ( s )
R ( s )
represents the set of relationships of this synset extracted from a semantic lexicon, such as WordNet, and r ( s )
r ( s )
indicates the corresponding synset according to relationship r
.
S ( s ) = s + ⋃ r ∈ R ( s ) r ( s )
S ( s ) = s + ⋃ r ∈ R ( s ) r ( s ) (12)
Hence, the item’s and user’s profiles, v
and
u
, are extended according to Eqs ( 13
) and ( 14
), respectively.
v = { S ( s n
1 ) , S ( s n
2 ) , … , S ( s n
p ) }
u = { S ( s u
1 ) , S ( s u
2 ) , … , S ( s q
u ) }
v u = = { S ( s n 1 ) , S ( s n 2 ) , … , S ( s n p ) } { S ( s u 1 ) , S ( s u 2 ) , … , S ( s q u ) } (13) (14)
Furthermore, SF-IDF+ not only uses extended synsets instead of synsets, as is the case for the SF-IDF model, but also assigns different weights w r
w r
to the relationship r
connecting a synset with its semantically related synset, as per Eq. ( 15
).
sf-idf+ s , d , r = sf s , d × idf s , d × w r
sf-idf+ s , d , r = sf s , d × idf s , d × w r (15)
A similar strategy to the one proposed in SF-IDF+ is also adopted by CF-IDF
+ [ 40
], an extension of the original CF-IDF model in which the initial set of identified concepts is expanded with related neighbors. Nonetheless, a shortcoming of the SF-IDF+ recommendation model is not being able to take into consideration named entities, which are prevalent in news articles. Thus, Capelle et al. [ 28
] proposed Bing-SF-IDF
+, a method which extends the SF-IDF+ technique with named entity similarities computed using Bing page counts. The main assumption made by the authors is that the likelihood of two entities being similar is directly proportional to the amount of times they co-occur on websites [ 28
]. The Bing-SF-IDF+ similarity score combines two elements, namely the Bing component which measures the similarity between pairs of named entities, 15 15
and the SF-IDF+ component which computes the similarity between synsets.
The SF-IDF+ profiles and weights are built and calculated according to Eqs ( 12
)-( 15
). For the Bing component, new user and item profiles are built using sets of named entities extracted from the text with a named entity recognizer, denoted as follows:
v = { e n
1 , e n
2 , … , e n
k }
u = { e u
1 , e u
2 , … , e u
l }
v u = = { e n 1 , e n 2 , … , e n k } { e u 1 , e u 2 , … , e u l } (16) (17)
where e n
e n
and e u
e u
denote a named entity in the profile of a news article, and of a user, respectively. The total number of named entities in the article’s and user’s profile is indicated by k
, and respectively, l
. All possible pairs of named entities from the two profiles are combined into a vector
V
, as per Eq. ( 18
).
V = ( ⟨ e n
1 , e u
1 ⟩ , … , ⟨ e n
k , e u
l ⟩ ) , ∀ e n ∈ v , e u ∈ u .
V = ( ⟨ e n 1 , e u 1 ⟩ , … , ⟨ e n k , e u l ⟩ ) , ∀ e n ∈ v , e u ∈ u . (18)
Subsequently, the Bing search engine is used to compute the page count
c ( e n , e u )
c ( e n , e u )
for each pair ( e n , e u )
( e n , e u )
of named entities in V
, namely how many pages found by querying Bing contain either one or both of the entities in a pair. A page rank-based Point-Wise Mutual Information (PMI) [ 16
] co-occurrence similarity measure is afterwards used to calculate the difference between the actual and the expected joint probability of the occurrence of a pair of named entities in a query on a web search engine [ 28
]. PMI assumes independence between the two named entities and is based on their marginal probabilities, as illustrated in Eq. ( 19
).
sim PMI ( e n , e u ) = log
c ( e n , e u )
N
c ( e n )
N ×
c ( e u )
N
sim PMI ( e n , e u ) = log c ( e n , e u ) N c ( e n ) N × c ( e u ) N (19)
where c ( e n )
c ( e n )
and c ( e u )
c ( e u )
denote the page counts of the named entities e n
e n
and e u
e u
from the unread news article’s and user’s profiles, respectively, whereas N
represents the total number of web pages indexed by Bing. The average of these PMI scores over all pairs of named entities in V
constitutes the Bing similarity score:
sim Bing ( V ) =
∑ ( e n , e u ) ∈ V sim PMI ( e n , e u )
| V |
sim Bing ( V ) = ∑ ( e n , e u ) ∈ V sim PMI ( e n , e u ) | V | (20)
The SF-IDF+ similarity sim sf-idf+ ( u , v )
sim sf-idf+ ( u , v )
, and the Bing similarity sim Bing ( u , v )
sim Bing ( u , v )
scores, namely the cosine similarity of the user and target news article profiles, are then normalized using a min-max normalization between 0 and 1 in order to ensure compatibility of scores. Lastly, the Bing-SF-IDF+ score is defined as the weighted average of the two components’ normalized similarity scores, according to Eq. ( 21
).
sim Bing − s f − i d f + ( u , v ) = alpha ×
‾
sim Bing ( u , v ) + ( 1 − α ) ×
‾
sim s f − i d f + ( u , v )
sim Bing − s f − i d f + ( u , v ) = a l p h a × sim ¯ ¯ ¯ ¯ ¯ ¯ ¯ ¯ Bing ( u , v ) + ( 1 − α ) × sim ¯ ¯ ¯ ¯ ¯ ¯ ¯ ¯ s f − i d f + ( u , v ) (21)
where ‾
sim Bing ( u , v )
sim ¯ ¯ ¯ ¯ ¯ ¯ ¯ ¯ Bing ( u , v )
and
‾
sim s f − i d f + ( u , v )
sim ¯ ¯ ¯ ¯ ¯ ¯ ¯ ¯ s f − i d f + ( u , v )
represent the normalized Bing and SF-IDF+ similarity scores, and α
is a weight optimized on the training set.
This approach of enhancing semantics-driven recommender systems with named entity similarities using the Bing page counts are prototypical also for other models, such as Bing-SF-IDF
[ 71
], Bing-CF-IDF
+ [ 17
], or Bing-CSF-IDF
+ [ 161
].
An approach combining CF-IDF and SF-IDF, which aims to address the ambiguity problem by representing news articles using key concepts, synonyms, and synsets from a domain ontology, is represented by the OF-IDF
method proposed by Ren et al. [ 133
]. In this case, a news article is described in terms of key concepts contained in a financial domain ontology. Additionally, the lexical representation of a concept is disambiguated by enriching it with its corresponding synset retrieved from WordNet. Similar to CF-IDF, the concepts in the article’s profiles are weighted using an Ontology Frequency-Inverse Domain Frequency scheme. Thus, the article can be represented as a vector of OF-IDF weights w n
w n
associated with the concepts it contains, namely
v = ( w n
1 , w n
2 , … , w n
p )
v = ( w n 1 , w n 2 , … , w n p )
, where the weights are computed as follows:
w i , j = OF i , j × IDF i =
n i , j
max i n i , j
× log
N
n i
w i , j = OF i , j × IDF i = n i , j max i n i , j × log N n i (22)
In Eq. ( 22
), n i , j
n i , j
is the number of occurrences of concept c i
c i
in article j
, and 1 ⩽ i ⩽ p
1 ⩽ i ⩽ p
, where p
denotes the total number of concepts in j
. The user’s interests in the read news can be described by means of a user-concept matrix whose rows denote the read articles, columns indicate the concepts appearing in these articles, and the entries correspond to OF-IDF weights. According to Ren et al. [ 133
], such a user-concept matrix can be modified using relevance feedback in order to capture different interaction patterns between a user and a target article. More specifically, the original OF-IDF weights are adjusted depending on whether the user clicked, read and liked, or read and did not like an article. Under this assumption, the user profile is changed as follows:
u = ∑ m ( α + S α ) + ∑ n ( β + S β ) + ∑ l ( γ + S γ )
u = ∑ m ( α + S α ) + ∑ n ( β + S β ) + ∑ l ( γ + S γ ) (23)
In Eq. ( 23
), the vectors S α
S α
, S β
S β
, S γ
S γ
represent the m
articles clicked, n
articles read and liked, and respectively, l
news read and not liked by the user. These vectors of OF-IDF weights are modified using parameters α
, β
, γ
, where the first two parameters are positive to illustrate the user’s interest in an article, while the last one is negative to capture negative feedback.
The semantic relatedness
model of Getahun et al. [ 60
] compares two articles
v i
v i
and v j
v j
using the cosine similarity of their vector representations v l
v l
comprising of concepts from an ontology and their corresponding weights:
v l = ( ⟨ c l
1 , w l
1 ⟩ , … , ⟨ c l
p , w l
p ⟩ ) , l ∈ { i , j }
v l = ( ⟨ c l 1 , w l 1 ⟩ , … , ⟨ c l p , w l p ⟩ ) , l ∈ { i , j } (24)
In comparison to item profiles of models such as CF-IDF (Eq. ( 8
)), in Eq. ( 24
) the total number of concepts appearing in an article’s profile is represented by the number of distinct concepts
p = | C S i ∪ C S j |
p = | C S i ∪ C S j |
in the sets denoting the two texts, C S i
C S i
and C S j
C S j
, respectively. The weight w i
w i
of concept
c i
c i
is based on its occurrence in the set of concepts C S j
C S j
of the other text. More specifically, if c i
c i
is contained in C S j
C S j
, then it receives a weight of w i = 1
w i = 1
, otherwise its weight is determined by its maximum enclosure similarity to concept
c j
c j
. Mathematically, this condition is expressed as follows:
w i = { 1 , if freq ( c i in CS j ) > 0
max j ( ES ( c i , c j ) ) , otherwise
w i = { 1 , max j ( ES ( c i , c j ) ) , if freq ( c i in CS j ) > 0 otherwise (25)
where
ES ( c i , c j ) =
| N ( c i ) ∩ N ( c j ) |
| N ( c i ) |
ES ( c i , c j ) = | N ( c i ) ∩ N ( c j ) | | N ( c i ) | (26)
The enclosure similarity between two concepts c i
c i
and c j
c j
represents the fraction of concepts from the semantic neighborhood of concept c i
c i
that also appear in the semantic neighborhood of concept c j
c j
. The advantage of this method is that it takes into account related concepts of a concept appearing in news, by utilizing its global semantic neighborhood.
The Ranked Semantic Recommendation ( RSR
) [ 78
] model is based on the assumption that reading an article containing a certain concept expands the user’s knowledge not only in that particular concept, but also in the concepts related to it. This notion is captured by assigning a rank to each concept from an ontology. For example, a user reading news about a concept represented by the class instance
Robinhood
might also be interested in his CEO Vladimir Tenev
or in the GameStop short squeeze
event. Since these instances are in a direct relation to Robinhood
, the ranks of all three should be increased. Similarly, if a user firstly reads an article containing instances Robinhood
and Elon Musk
, then accesses news about Open AI
, a related concept instance to Elon Musk
, but not to Robinhood
, the rank of Elon Musk
should be increased, while that of
Robinhood
should be decreased. Therefore, the rank of a concept aims to account for the user’s changing interests.
Each concept c i
c i
is associated with a set of related concepts r ( c i ) = { c i
1 , c i
2 , … , c i
k }
r ( c i ) = { c i 1 , c i 2 , … , c i k }
, and the union of all concepts related to those in the user profile can be expressed as R = ⋃ c u
i ∈ u r ( c u
i )
R = ⋃ c u i ∈ u r ( c u i )
. Hence, the extended user profile u R
u R
is obtained by extending the initial set of concepts extracted from the previously read articles with the set of related concepts, namely
u R = u ∪ R
u R = u ∪ R
.
Another assumption underlying RSR [ 78
] is that the more articles containing concept
c u
i
c u i
a user reads, the higher his interest in that concept. The weight w u
i
w u i
of concept
c u
i
c u i
is thus defined as the number of articles from the user’s reading history that contain the concept. RSR uses a rank matrix – rows contain concepts from the initial user profile and columns denote the concepts in his extended profile – to model the interaction between concepts and compute their importance for the user. The rank of a concept c u
i , j
c u i , j
from this matrix is obtained by weighting w u
i
w u i
using an experimentally determined constant value meant to capture the type of relationship between concepts:
r i j = w u
i × { + 1.0 if e j = c u
i
+ 0.5 if e j ≠ c u
i , e j ∈ r ( c u
i )
− 0.1 otherwise
r i j = w u i × ⎧ ⎩ ⎨ ⎪ ⎪ + 1.0 + 0.5 − 0.1 if e j = c u i if e j ≠ c u i , e j ∈ r ( c u i ) otherwise (27)
The final rank of every concept in the user’s extended profile, denoted
Rank ( e j ) = ∑ q
i = 1 r i j
Rank ( e j ) = ∑ q i = 1 r i j
, is computed as a sum of the values in the corresponding column in the rank matrix and stored in a vector v u
v u
.
A min-max normalization is applied to the extended user profile to ensure that the ranks are in the range [ 0 , 1 ]
[ 0 , 1 ]
, and thus, comparable between the user’s and article’s profiles. A news article, comprised from a set of concepts, is also represented as a vector of concept ranks v v
v v
, where a concept contained in the user’s extended profile and appearing in the unread article is assigned the same rank as in v u
v u
, while one not occurring in the target item has a rank of zero. Lastly, the extent to which an article is relevant to a user is computed as the ratio between the sum of concept ranks from the article’s representation and the sum of concepts ranks in the user’s profile:
sim ( v , u ) =
∑ r v ∈ v v r v
∑ r u ∈ v u r u
sim ( v , u ) = ∑ r v ∈ v v r v ∑ r u ∈ v u r u (28)
The Ranked Semantic Recommendation 2 ( RSR 2
) [ 55
] model improves RSR by considering, in addition to the concepts appearing in the unread news articles, also the concepts related to them. Following the previous example, this means that if a candidate news contains the concept instance Elon Musk
, the model will also use related concept instances such as Open AI
,
SpaceX
, Tesla, Inc.
, or Neuralink
to represent the article. Thus, the original article profile is extended by the set of related concepts, namely v E = v ∪ E
v E = v ∪ E
, where E = ⋃ c n
i ∈ v r ( c n
i )
E = ⋃ c n i ∈ v r ( c n i )
.
Another difference to RSR is that RSR2 uses different weight values to determine the concepts’ ranks. The rank of a concept in the extended article representation
v v E
v v E
is equivalent to the corresponding concept rank from the extended user profile v u
v u
, if it appears in it or is related to one of its concepts. Otherwise, a concept has a rank of zero. The final similarity measure between the extended article and user profiles is modified to incorporate these changes accordingly.
6.1.3. Summary
Non-neural, entity-centric news recommendation techniques are summarized in terms of three aspects:
– Profile representation.
Each model constructs two profiles, one representing the unread target article, and the other characterizing the user’s interests, as an aggregation of the articles from his reading history. CF-IDF uses concepts extracted from the news and contained in a domain ontology to represent articles. RSR and RSR2 also use ontological concepts, as well as concepts related to them in the ontology. In comparison, models such as SF-IDF or OF-IDF, use synsets of terms or concepts enriched with associated synonym sets from semantic lexicons to avoid ambiguity. Another approach, used by SF-IDF+, additionally takes into account relationships between synsets, by extending the original vector representation with concepts referred to by semantic relations characterizing the synsets from the initial profile. Lastly, Bing-SF-IDF+ further improves the technique by including named entities into the vector representations.
– Weighting scheme.
The majority of models discussed in this section employ a variant of the TF-IDF weighting scheme, modified to incorporate concepts or synsets instead of terms. SF-IDF+ refines the weighting model by assigning different weights to each semantic relation connecting a concept to its semantically related synset. In addition to using SF-IDF+ weights to measure the importance of concepts in a news article, the Bing-SF-IDF+ model computes Bing similarity scores for the user and item profiles based on the page rank-based PMI co-occurrence measure of the named entity pairs contained in the two profiles. In contrast, semantic context-aware techniques use weights in the range [ − 1 , 1 ]
[ − 1 , 1 ]
to denote the users’ likes and dislikes. Moreover, the semantic relatedness model defines concept weights in terms of semantic enclosure which considers the global neighborhood of a concept. The RSR frameworks compute ranks for each ontology concept based on the number of articles containing them and read by the user, as well as on how the concepts are related to each other in the user’s reading history.
– Similarity metric.
Cosine similarity is often employed to determine the preference of a user for an unread news article in context-aware models, as well as in models using a variant of the TF-IDF model. The latter category extends the similarity measure with the Bing similarity metric when named entities are taken into account through Bing page counts. Hybrid semantic context-aware models use a weighted combination of cluster-based cosine similarities to determine the news-user similarity. In contrast, RSR-based models compute the article relevance as the ratio of the sum of concepts ranks from the item and user profiles.
6.2. Path-based methods (non-neural)
The profiles of users and news articles in non-neural, path-based recommendation methods are represented using concepts or entities from a knowledge base. Similar to the models in the previous section, some of the recommendations approaches classified here generate latent representations of these concepts or entities using non-neural methods. However, in contrast to non-neural, entity-centric recommenders, path-based ones define the user-item and item-item similarities using metrics that take into account the distance between concepts and/or entities from the knowledge base.
6.2.1. Overall framework
The majority of methods in this category represent a news article as a set of tuples consisting of the concepts contained in an ontology and their corresponding weights. Formally, this can be written as
v = { ⟨ c n
1 , w n
1 ⟩ , … , ⟨ c n
p , w n
p ⟩ }
v = { ⟨ c n 1 , w n 1 ⟩ , … , ⟨ c n p , w n p ⟩ }
, where
c n
i ∈ O
, w n
i
is the weight of concept
c n
i ( 1 ⩽ i ⩽ p )
, and p
is the total number of concepts found in the article v
. The profile of a user u
is constructed by accumulating all the concepts that appear in the articles previously read by the user, denoted as u = { ⟨ c u
1 , w u
1 ⟩ , … , ⟨ c u
q , w u
q ⟩ }
, where w u
j
is the average weighting of concept c u
j
in the articles from the user’s reading history that contain concept c u
j
, and q
denotes the number of concepts in the articles read by the user. The recommendations are nearly always computed in a content-based, item-ranking fashion. We distinguish non-neural, path-based frameworks in terms of three aspects:
– Profile representation.
Different kinds of semantic information can be included in the users’ and items’ representations.
– Weighting scheme.
The concepts comprising the user and news profiles are weighted using different strategies to measure their importance.
– Similarity metric.
The similarity between two news articles is computed using several distance measures.
6.2.2. Representative models
In the following, we investigate six representative recommendation techniques for this category.
ePaper
[ 105
, 148
] weighs the ontology concepts denoting the user’s interests according to the user’s implicit feedback. More specifically, the weight of a concept
c u
i
is given by the number of clicks on articles containing the given concept relative to the total number of clicks in the user’s profile. The relevance of an item to a user is defined in terms of the hierarchical distance between the concepts from the associated profiles, which takes into account the amount of common and related concepts included in each profile, as well as the distance between them. Based on a 3-level ontology, ePaper relies on 1-hop (parent-child) and 2-hop (grandparent-grandchild) hierarchical relations between concepts [ 105
]. The relative position of related concepts from the user’s and the article’s profiles denotes their relationship in terms of specificity.
Three types of partial matches between concepts were defined by Maidel et al. [ 105
] based on hierarchical distance. A
perfect match
is obtained if the same concept appears in both profiles and at the same hierarchical level. For example, both the news and the user profile contain the concept ‘artificial intelligence’, found at level 1 in the ontology. However, if a concept occurs only in one of the profiles, while its parent or child is included in the other profile, a close match
is reached. In this case, one can further differentiate between cases when the user’s concept (e.g. artificial intelligence
) is more general than the article’s concept (e.g.
deep learning
), and those in which the user’s interest is more specific (e.g. user concept is graph neural networks
and item concept is deep learning
). Lastly, a weak match
occurs if the concepts from the two profiles are two levels apart in the hierarchy, such as the user being interested in graph neural networks
, whereas the article contains the concept
artificial intelligence
. Analogous to the previous match type, two cases are determined by the profile containing the more general concept.
A similarity score S i
assigns different weights based on the type of match of concept c w
1
to the corresponding concepts in the user’s profile. Lastly, the Item Similarity (IS) score, shown in Eq. ( 29
), determines how similar the target article is to the user’s interests, based on the number of concept matches (given by
S i
) and the concepts’ weights from the user profile, given by the number of clicks
N
on the items containing the concept [ 148
].
IS =
∑ p
i = 1 N i · S i
∑ q
j = 1 N j
A different approach is adopted in
Magellan
[ 45
], which uses a Weighted Term Frequency scheme to determine the importance of a candidate news article to a monitored domain. Magellan extracts named entities from news to represent the articles and operates on their corresponding concepts from an ontology. According to the weighting scheme, the importance of concepts is determined by their centrality and prestige [ 99
] in the ontology. The main assumption underlying the measure of centrality is that the more relations a concept has to other concepts, the higher is its importance in the given domain. Hence, the concept with the highest out-degree, namely the largest number of accumulative out-going connections, is considered the top-ranked individual. Subsequently, the importance of the remaining concepts depends on the distance, measured in the number of hops, and the strength of the relations w r
to the top-ranked concept, as given by the centrality weight
w centrality =
1
hops ×
w r
hops
.
The centrality score ensures that concepts with shorter and stronger connections to the top-ranked concept will be assigned higher importance than those situated further away in the ontology or having weaker relations. The centrality weight is complemented by the prestige of a concept in the ontology, a method that ranks the concepts based on their incoming relations. The more a concept is referred to via different relations by another concept (i.e. the larger its in-degree), the higher its prestige in the ontology. Consequently, the final importance score of a concept is computed as the product of centrality and prestige (denoted as rank in Eq. ( 30
)), weighted by a constant value α
assigned to the top-ranked concept:
w importance = α ×
w centrality
rank
The final weight w i
of concept i
is obtained by combining its importance in the ontology and frequency n i
in the news article, w = w importance × n i
. According to this weighting scheme, Magellan will assign higher scores to news articles which frequently contain entities with large importance in the ontology, whereas those which either contain few concepts or only named entities with low importance will be assigned a lower score.
Similar to SF-IDF, the Semantic Similarity ( SS
) recommendation model [ 26
] represents a news item using the WordNet synsets of the terms it contains, as shown in Eqs ( 10
) and ( 11
). Recommendations are generated by comparing the similarity of the synsets in the unread news article to the synsets of all the articles previously read by the user. For this purpose, firstly a vector containing all combinations of synsets from the target article and the union of synsets from the user profile is constructed as follows:
V = ( ⟨ s n
1 , s u
1 ⟩ , … , ⟨ s n
p , s u
q ⟩ ) , ∀ s n ∈ v , s u ∈ u
Furthermore, a subset is created from V
for all pairs of synsets sharing the same part-of-speech (POS):
W ⊆ V , ∀ ( s n , s u ) ∈ W : POS ( s n ) = POS ( s u )
where POS ( s n )
and POS ( s u )
denote the part-of-speech tag of synset s n
from the item’s profile, and synset s u
from the user’s profile, respectively.
The final similarity score of an unread article is given by the sum of all combinations’ similarity rank sim ( s n , s u )
relative to the total number of combinations | W |
, illustrated as follows:
sim S S =
∑ ( s n , s u ) ∈ W sim ( s n , s u )
| W |
The WordNet taxonomy constitutes a hierarchy of “is-a” relationships between its nodes which, in turn, constitute synsets. As such, Capelle et al. [ 26
] propose five semantic similarity measures to calculate the similarity rank
sim ( s n , s u )
for each combination of synsets in W
, namely the extent to which two synsets are semantically close. Three of the measures (Jiang and Conrath [ 82
]
sim J & R
, Resnik [ 135
] sim R
, Lin [ 97
]
sim L
) utilize the information content of a node, defined as
IC ( s ) = − log ∑ w ∈ S p ( w )
, where
p ( w )
denotes the probability of instance
w
of the synset to appear in the corpus. More specifically, this metric can be described as the negative logarithm of the sum of all probabilities of all the words w
from synset s
. Furthermore, they take into account the lowest common subsumer (
LCS
) between two nodes, which represents the lowest node dominating the pair [ 135
]. The three metrics are illustrated in Eqs ( 34
)-( 36
).
sim J & C ( s n , s u ) =
1
dist J & C ( s n , s u )
=
1
IC ( S n ) + IC ( s u ) − 2 × LCS ( s n , s u )
sim R ( s n , s u ) = IC ( LCS ( s n , s u ) )
sim L ( s n , s u ) =
2 × log p ( LCS ( s n , s u ) )
log p ( s n ) + log p ( s u )
, where p represents a probability.
The two remaining metrics, of Leacock and Chodorow [ 90
] sim L & C
, and of Wu and Palmer [ 184
] sim W & P
, shown in Eqs ( 37
)-( 38
), define the similarity based on the path length between nodes. The path length can refer to either the shortest path (denoted length
) between a pair of nodes or the maximum depth (denoted as
D
) from the least common subsumer to the top node in the hierarchy.
sim L & C ( s n , s u ) = − log
length ( s n , s u )
2 D
sim W & P ( s n , s u ) =
2 × depth ( LCS ( s n , s u ) )
length ( s n , s u ) + 2 × depth ( LCS ( s n , s u ) )
Similar to Bing-SF-IDF+, BingSS
[ 27
] extends the semantic lexicon-driven SS recommendation model by taking into account named entities. The semantic similarity formula from Eq. ( 33
) is modified to take into account only the set of synset pairs TOP β S S W
with the highest similarity in W
, as follows:
sim S S =
∑ ( s n , s u ) ∈ W sim S S ( s n , s u ) ∈ TOP β S S W
| TOP β S S W |
where β S S
constitutes a predefined positive integer, optimized on the test set, which indicates the top- β S S
similarities from the pairs of synsets in W
. This change is implemented to reflect the assumption that not all named entities occurring in an article are equally relevant for determining the user’s interests. For example, for news regarding the stock exchange changes of GameStop, the named entity
New York Stock Exchange
is less relevant for a user interested specifically in GameStop. The BingSS similarity measure introduced in Eq. ( 20
) is modified accordingly to take into account this assumption, as illustrated in Eq. ( 40
).
sim Bing =
∑ ( e n , e u ) ∈ V sim PMI ( e n , e u ) ∈ TOP β Bing V
| TOP β Bing V |
where TOP β Bing V
represents the set of top- β Bing
entity pairs with the highest similarity in V
(see Eq. ( 18
)), and β Bing
constitutes a predefined positive integer denoting the top- β Bing
similarities from pairs in the set V
.
Lastly, the Bing and the SS components are combined in the final BingSS similarity score using a weighted average with predefined weight α
:
sim B i n g S S = α × sim Bing + ( 1 − α ) × sim S S
OBSM
, the ontology-based similarity model proposed by Rao et al. [ 130
], uses a TF-IDF weighting scheme for the concepts in the user and news profiles. The similarity between two concepts c 1
and
c 2
found in the news depends on their ontological structures, represented in terms of the shortest distance d
among concepts in the ontology, the shortest distance δ
to their common ancestor closest to the root node, and the height H
of the ontology. This concept-concept similarity metric, illustrated in Eq. ( 42
), follows the assumption that two adjacent, more concrete concepts situated at a lower level in the ontology share more common information from their ancestors, and thus, have a higher likelihood to be similar than those found at a higher level. The preference for closer concepts is ensured by the term ( − log 2 H
d
2 H )
, which is negatively correlated with the concept distance d
. In turn, the weight
e δ
e δ + 1
will assign higher importance to concepts located at deeper levels in the hierarchy.
Csim ( c 1 , c 2 ) = { 1 , d = 0 or isSynonyms ( c 1 , c 2 )
e δ
e δ + 1
· ( − log 2 H
d
2 H ) , otherwise
The similarity between the profile of a target news article and user is computed in the following way [ 130
]:
sim ( u , v ) =
1
p
p
∑
i = 1
max 1 ⩽ j ⩽ q { Csim ( c n
i , c u
j ) × w i , j }
where p
is the number of profile concepts, and
w i , j =
2
1 + e k τ , with τ =
abs ( w n
i , w u
j )
max ( w n
i , w u
j )
According to Eq. ( 44
), two concepts c n
i
and c u
j
whose corresponding weights
w n
i
and w u
j
are relatively equal, will result in a higher confidence score w i , j
. In turn, this means that the two concepts are similarly important in their concepts sets, indicating that the target article might be of interest to the given user. Concepts with different weights in their associated sets are penalized using a smoothing factor k
which controls the sensitivity of the confidence function.
In contrast to the previous models, SED
, the entity shortest distance over knowledge graphs algorithm proposed by Joseph and Jiang [ 83
], defines item-item similarity as the shortest distance between the subgraphs consisting of named entities extracted from news articles. The approach is threefold [ 83
]. Firstly, all named entities contained in every news article are extracted and linked to the corresponding nodes in a knowledge graph. Secondly, in the subgraph generation phase, each news article is represented as a subgraph containing the linked nodes from the knowledge graph associated with the previously extracted named entities. These subgraphs are expanded with outgoing relations from the
L
-hop neighborhood of each node discovered using a breadth-first search strategy.
The shortest distance between two entities over the knowledge graph represents the shortest path length between the corresponding nodes, mathematically denoted as D ( e i , e j ) = min ( | p k | )
, where | p k |
is the length of path k
from the set of all paths between the entity pair
( e i , e j )
, namely p k ∈ P ( e i , e j )
. Based on this definition, the shortest distance between two articles’ subgraphs, S 1
and
S 2
, is computed according to Eq. ( 45
).
D ( S 1 , S 2 ) =
∑ e i ∈ S 1 min e j ∈ S 2 D ( e i , e j )
| S 1 |
Lastly, the similarity between the two articles is computed as the pair-wise shortest distance over the union of their subgraphs [ 83
], as shown in Eq. ( 46
).
ˆ D ( S 1 , S 2 ) =
D ( S 1 , S 2 ) + D ( S 2 , S 1 )
2
This method provides a symmetric average minimum row-wise distance which places higher importance on the entity pairs with the highest likelihood of co-occurrence in news article. Additionally, a weighted shortest distance between the articles could be used by weighting the edges of the subgraphs and computing the sum of all the weights of the traversed edges [ 83
]. For the weighted SED algorithm, different weighting schemes could be used, including the relation weighting scheme, which assigns edge weights based on the number of shared neighbors of two entity nodes from an article.
6.2.3. Summary
Non-neural, path-based knowledge-aware news recommender systems are summarized from the following perspectives:
– Profile representation.
Various types of representations are used to construct the profiles of users and news articles. On the one hand, ePaper, Magellan, and OBSM use ontological concepts, SS represents items and users in terms of WordNet synsets, while BingSS additionally considers named entities. On the other hand, SED represents profiles in terms of subgraphs consisting of named entities extracted from news articles.
– Weighting scheme.
Concepts in the item and user profiles are weighted to encode their importance. However, there is not one unique weighting scheme employed by all the models in this category. ePaper weights concepts based on the number of user clicks on articles containing them, while OBSM uses classic TF-IDF weights. Magellan weights concepts based on their importance in an ontology computed using social network measures and their frequency in news articles. SS-based methods assign weights based on the information content of nodes or the lengths of paths between pairs of nodes in a semantic lexicon. In contrast, SED does not represent the user or item profile in terms of concept sets, but as subgraphs of named entities from a knowledge graph.
– Similarity metric.
The majority of models previously discussed use a type of distance measure to directly calculate the similarity between two news articles. On the one hand, methods such as ePaper or OBSM focus on the hierarchical distance between the concepts contained in the items’ profile. The SS-based models use different functions that either take into account the information content of a node in the knowledge base, or the path lengths between nodes. On the other hand, SED views article similarity as the degree to which the subgraphs representing news articles overlap. In comparison, Magellan uses a combination of distance measure and term frequency to determine the importance of named entities from news articles and corresponding ontology concepts to a domain and to rank candidate articles accordingly.
6.3. Neural network-based methods
In recent years, the rapid advancements in the field of deep learning have also led to a paradigm shift in the domain of news recommendation. State-of-the-art knowledge-aware recommendation models combine latent representations of news articles, generated using neural networks, with external information contained in knowledge graphs, encoded by means of knowledge graph embeddings, defined below.
Definition 4.
Given a dimensionality k ≪ n
, the goal of
knowledge graph embedding
(KGE) is to project a knowledge graph G = ( V , E )
into a low-dimensional space, by learning k
-dimensional representations for all entities and relations in G
, which preserve the structural information of the original graph [ 20
, 170
].
6.3.1. Overall framework
Frameworks classified in this category generally use a knowledge distillation process to incorporate side information in their recommendations. Firstly, named entities are extracted from news articles using a named entity recognizer. Secondly, these are connected to their corresponding nodes in a knowledge graph using an entity linking mechanism. Thirdly, one or multiple subgraphs are constructed using the linked entities, their relations, and neighbors from the knowledge graph. Afterwards, the obtained graphs are projected into a continuous, lower-dimensional space to compute a representation for their nodes and edges. Thus, these models use both the structural and semantic information encoded in knowledge graphs to represent news. Figure 3
exemplifies this process.
Fig. 3.
Illustration of the knowledge distillation process used by neural-based recommendation models (reproduced from [ 170
]).
In contrast to models from the previous categories, the neural-based recommenders we reviewed for this survey predict the probability that a user will click on a target article, namely the click-through rate. We consider several factors underlying these recommendation models:
– Recommendation model input.
Usually, the input to the recommendation model consists of an unread news article and the user’s reading history. However, various elements, including textual information and knowledge entities can be combined to represent users and items.
– Knowledge graph embedding model.
Several models can be used to compute node embeddings for the knowledge graph entities [ 38
, 173
].
– Components of recommender system.
The systems’ architecture consists of multiple deep-learning models, each aiming to capture different aspects characterizing the news items, user’s preferences, and interactions among users and news.
– Aggregation of knowledge-level and text-level components.
Another distinguishing factor is constituted by the way in which the outputs of different components of the recommendation model are aggregated to predict the click-through probability for a candidate article.
6.3.2. Representative models
The architectures of 11 neural-based news recommendation frameworks are discussed in this section.
The Collaborative Entity Topic Ranking ( CETR
) [ 193
] model combines matrix factorization, topic modeling, and knowledge graph embeddings in a collaborative fashion to alleviate the data sparsity problem and the limitations of word-level topic models on very infrequent words appearing in news articles. The model joins together three modules, the first modeling the user’s reading behavior, the second performing entity-level topic analysis of news, and the last computing representations of the knowledge graph entities.
The user behavior component takes as input the user-news interaction matrix Y
, defined as follows:
Definition 5.
The user-item interaction matrix
Y = { y u v | u ∈ U , v ∈ V } ∈ R M × N
is defined according to the user’s implicit feedback y u v
, where:
y u v = { 1 if user u interacted with item v
0 otherwise
The user-item interaction matrix is factorized into a matrix U
of user features and a matrix V
of news latent features. The factorization method, a Bayesian Personalised Ranking (BPR) model [ 134
], uses a sigmoid function to characterize the probability of observing a triplet
( u , v , v ′ )
given the user and news matrices. Such a triplet denotes the scenario in which a user u
has read article
v
, but not v ′
. The two feature matrices are learned with a maximum likelihood function applied over all triplets in the user’s profile.
In the following step, topic analysis is conducted at the entity level, where entities belonging to the same topic are sampled from a Gaussian distribution [ 193
]. The third module learns knowledge graph embeddings with the TransR model [ 98
]. The probability of observing a quadruple
( h , r , t , t ′ )
, denoting the head entity h
being connected to tail entity t
, but not to
t ′
, by relation r
, is defined similarly to BPR. The three components are jointly trained by calculating the log-likelihood of seeing all triplets, entities, and quadruplets, given the user and news feature matrices, the distribution of topics over entities, and the embeddings of entities and relations from the knowledge graph.
DKN
, the deep knowledge-aware network proposed by Wang et al. [ 170
], was the first architecture to fuse neural network-based text-level and knowledge-level representations of news using an attention module. The input to the recommendation model is constituted by the user’s click history and one candidate news article. Each article t
is represented by its title. In turn, the article’s title is composed of a sequence of words,
t = [ w 1 , w 2 , … , w N ]
, and every word w
might correspond to an entity e
in a knowledge graph [ 170
]. The enrichment of textual information with external knowledge follows the knowledge distillation process from Fig. 3
. Wang et al. [ 170
] use not only direct knowledge graph correspondents of identified named entities to construct the subgraph, but also their one-hop neighbors to reduce sparsity and increase diversity among the extracted entities. This knowledge-level representation of news is further enhanced by taking into account the context of an entity, denoted as
context ( e )
, to increase the identifiability of entities after computing their embeddings.
Definition 6.
The context of an entity e
is defined as the set of its immediate neighbours in the knowledge graph [ 170
]:
context ( e ) = { e i | ( e , r , e i ) ∈ G ∨ ( e i , r , e ) ∈ G }
The inner-circle in Fig. 4
exemplifies this concept. DKN takes as input the embedding of GameStop short squeeze
to represent the entity, as well as its context, denoted by neighbors and associated relations, such as USA
(country), or Elon Musk
, Robinhood
, r/WallStreetBets
(participant).
Fig. 4.
Illustration of ripple sets of GameStop short squeeze
in Wikidata. The concentric circles indicate ripple sets with different hops. The fading blue signifies decreasing relatedness between the center and the neighboring entities (reproduced from [ 168
]).
One of the input elements to the recommendation model is constituted by the embedding of an entity’s context, defined in the following manner.
Definition 7.
The context embedding
of entity e
is defined as the average of the embeddings of its contextual entities [ 170
]:
ˉ e =
1
| context ( e ) | ∑ e i ∈ context ( e ) e i
The first level in DKN’s architecture is represented by a knowledge-aware convolutional neural network (KCNN), namely the convolutional neural network (CNN) framework proposed by Kim [ 85
] for sentence representation learning extended to incorporate symbolic knowledge in the text representations. Firstly, the entity embeddings
e i ∈ R k × 1
and the context embeddings
ˉ e i ∈ R k × 1
, obtained with TransD [ 80
], are projected from the entity to the word vector space, according to Eqs ( 50
) and ( 51
), using a hyperbolic tangent transformation function g
.
g ( e 1 : n ) = [ g ( e 1 ) g ( e 2 ) ... g ( e n ) ]
g ( ˉ e 1 : n ) = [ g ( ˉ e 1 ) g (
¯
e 2 ) ... g ( ˉ e n ) ]
Secondly, the matrices containing word embeddings w 1 : n
(pre-trained or randomly initialized), transformed entity
g ( e 1 : n )
and context g ( ˉ e 1 : n )
embeddings are aligned and stacked to obtain a multi-channel input
W = [ [ w 1 g ( e 1 ) g ( ˉ e 1 ) ] ... [ w n g ( e n ) g ( ˉ e n ) ] ] ∈ R d × n × 3
.
The word-aligned KCNN applies multiple filters of varying sizes to extract patterns from the titles of news, followed by max-over-time pooling and concatenation of features to obtain the final representation
e ( t )
of an article. Hence, the KCNN component is able to discover latent knowledge-level connections among news using extracted entities and common sense knowledge embedded in knowledge graphs.
Additionally, DKN employs an attention network to capture the diverse interests of users in different news topics by dynamically aggregating a user’s history according to the current candidate article [ 170
]. The second level of the DKN framework concatenates the embeddings of a target news t j
and an article t k
read by the user, feeding the resulting vector into a Deep Neural Network (DNN)
H
which computes the impact of the candidate news on the read article. The output of the attention network H
is normalized using a softmax function. This process is illustrated in Eq. ( 52
):
a t k , t j = softmax ( H ( e ( t k ) , e ( t j ) ) ) =
exp ( H ( e ( t k ) , e ( t j ) ) )
∑ N
k = 1 exp ( H ( e ( t k ) , e ( t j ) ) )
Given the normalized attention weights, a user i
’s embedding with respect to the target article t j
is represented by the weighted sum of the N i
embeddings of article titles from his click history:
e ( i ) =
N i
∑
k = 1
a t i
k , t j e ( t i
k )
Lastly, DKN [ 170
] predicts the click probability of user i
for news article t j
with another DNN G
that takes as input the final user embedding from Eq. ( 53
) and the article’s embedding, as
p i , t j = G ( e ( i ) , e ( t j ) )
.
The recommendation model of Gao et al.
[ 58
] learns semantic-level and knowledge-level representations of news by adjusting the DKN architecture to use a fine-grained word-level description of news, obtained with a self-attention mechanism, instead of a topic-level representation given by the KCNN component. The user’s click history and a candidate piece of news constitute the model’s input. The framework consists of four-level self-attention modules [ 58
]. Firstly, a word-level self-attention component computes the semantic-level and knowledge-level representation of articles using pre-trained embeddings of news tags and transformed pre-trained embeddings of entities extracted from a knowledge graph and their context, similar to DKN. The attention weight measuring the impact of each word in the news representation is computed as follows:
a 1 = softmax ( V 1 tanh ( W 1 w T
i + W ′
1 q T
i + b 1 ) )
where the subscripts of the trainable matrices denote the layer of the network and q i
are queries given by three keywords selected for each article. The word-level representation of news constitutes a weighted sum of its word embeddings w ′
1 : n = ∑ n
i = 1 a t
i w i
, whereas the entity-level e ′
1 : n
and context-level
ˉ e ′
1 : n
representations are computed in a similar manner.
Secondly, the item-level attention model computes the final representation of news article t k
, according to Eq. ( 55
), as a weighted sum of the different-level embeddings, where the weights are given by corresponding attention coefficients.
e ( t k ) = a word w ′ + a entity e ′ + a context ˉ e ′
The attention weights of words are calculated as shown in Eq. ( 56
), while those of entities and context can be computed analogously.
a word = softmax ( V 2 tanh ( W 2 w ′ + b 2 ) )
Thirdly, the user-level self-attention module computes the final representation of the user i
’s history e ( i )
with respect to the candidate news t j
as in Eq. ( 53
). However, in contrast to DKN, here the attention weight is computed as follows:
a t k , t j = softmax ( V 3 tanh ( W 3 e ( t i ) T + W ′
3 e ( t j ) T + b 3 ) )
Fourthly, the vector representation of the user and the target news article are combined using a multi-head attention module [ 163
] with ten parallel attention layers. Lastly, the output of the fourth module is passed through a fully connected layer to calculate the user’s probability of clicking the candidate article.
A different approach is constituted by
RippleNet
[ 168
], an end-to-end framework that propagates user preferences along the edges of a knowledge graph. RippleNet takes as input a candidate news article and the user’s historical set of interests V u
, which act as seeds in the knowledge graph. The main idea underlying the model is that of ripple sets S k
u
, namely sets of knowledge triples situated k
-hops away from the seed set V u
. The concepts of relevant entities and ripple sets are defined below.
Definition 8.
Giving the knowledge graph G
and the interaction matrix Y
, the set of k
-hop
relevant entities
for user u
is defined as:
E k
u = { e t | ( e h , r , e t ) ∈ G and e h ∈ E k − 1
u }
where k = 1 , 2 , … , H
and
E 0
u = V u = { v | y u v = 1 }
is the set of user
u
’s past interacted items.
Definition 9.
The k
-hop ripple set
of a user u
is the set of knowledge triples whose head entities are
( k − 1 )
-hop relevant entities E k − 1
u
:
S k
u = { ( e h , r , e t ) | ( e h , r , e t ) ∈ G and e h ∈ E k − 1
u }
where k = 1 , 2 , … , H
.
The user’s interests in certain entities are extended from the initial set along the edges of the knowledge graph, as shown in Fig. 4
. The further the hop, the weaker the user’s potential preference in the corresponding ripple set becomes since entities that are too distant from the user’s initial interests might introduce noise in the recommendations. This behavior is exemplified in Fig. 4
by the fading color of the concentric circles denoting ripple sets. The closer a neighboring entity is to the center seed, the more related the two are assumed to be. In practice, this is controlled by the number H
of hops considered [ 170
].
In the first step, RippleNet calculates the probability p i
that a news article is similar, in the space of relation r i
, to a head entity h i
from the user’s 1-hop ripple set S 1
u
. The relation type accounts for contextual similarities of entities, such as Elon Musk
and Vladimir Tenev
being similar when considering that they are both entrepreneurs, but having fewer similarities if only analyzing their connections with Stanford University. Mathematically, the relevance probability for each triple ( h i , r i , t i )
in S 1
u
of user u
is computed according to Eq. ( 60
) using the embeddings of the item v ∈ R d
, the relations R i ∈ R d × d
, and the entity
h i ∈ R d
:
p i = softmax ( v T R i h i ) =
exp ( v T R i h i )
∑ ( h , r , t ) ∈ S 1
u exp ( v T R h )
The 1-order response o 1
u
of user u
’s history to candidate news v
is defined as the sum of the embeddings t i ∈ R d
of tail entities from S 1
u
weighted by their corresponding relevance probabilities, as follows:
o 1
u = ∑ ( h i , r i , t i ) ∈ S 1
u p i t i
Equations ( 60
) and ( 61
) theoretically illustrate the preference propagation mechanism of RippleNet, through which the user’s interests are spread from the initial set V u
, along with the links of S 1
u
, to the set of 1-hop relevant entities E 1
u
. The preference propagation can be extended H
hops away from the initial seed set, by iteratively applying Eq. ( 61
) on the user u
’s H
ripple sets S i
u
. The final user preference distribution with regards to candidate article v
is computed by combining the responses of all H
orders:
u = ∑ H
i = 1 o i
u
. The click-through probability is then calculated using a sigmoid function applied to the embeddings of the user and the target news. In comparison to the previous methods, RippleNet not only incorporates external knowledge in its recommendations but also automatically identifies possible explanatory paths connecting news from the user’s click history to the candidate article.
An inward aggregation version of this model, denoted RippleNet-agg
, was later proposed by Wang et al. [ 169
] to extract high-order structural proximity information among entities in a knowledge graph. In comparison to the outward propagation model, this variant uses biases to aggregate and inject the ripple sets’ information in an entity’s representation. More specifically, the importance of a relation r i
to a user u
is measured using a scoring function π u
r i
= g ( u , r i )
applied to the user and relation embeddings. This weight aims to capture the relation-dependent user preferences, such as a reader being interested in technology news that contain the same entrepreneur
as previously clicked articles, while another being attracted by articles related to the same significant event
.
In RippleNet-agg, higher-order proximity information is captured by encoding the ripple sets in the final prediction function at the item-end, compared to the user-end, as it was the case in the original RippleNet model. To this end, the topological proximity structure of a news article v
is defined as the linear combination of its one-hop samples ripple set v u
S ( v ) = ∑ e ∈ S ( v ) ˜ π u
r v , e
e
, where
˜ π u
r v , e
e
represents the normalized user-relation score over all neighboring entities in v
’s ripple set.
Lastly, the representations of the entity v
and its neighborhood v u
S ( v )
are aggregated using an aggregation function
agg
, defined as:
agg = σ ( W · ( v + v u
S ( v ) ) + b )
Although the aggregation function in Eq. ( 62
) is represented by the sum operation followed by a nonlinear transformation σ
, this could be replaced by a concat
aggregation, which would concatenate instead of adding the two representations, or a neighbor − only
aggregation function, which would only consider the neighborhood representation.
In contrast to previous models, the Multi-task feature learning approach for Knowledge graph Recommendation ( MKR
) [ 172
] uses the knowledge embedding task to assist the recommendation one. The model is trained in an end-to-end fashion by optimizing the two components alternately, with different frequencies. The two components are connected by cross&compress units to learn high-order interactions between entities in the knowledge graph and items from the recommender systems sharing features in non-task-specific latent spaces. MKR aims to improve the generalization of predictions by using a multi-task learning environment.
MKR is composed of three modules. The recommendation component uses as input two raw feature vectors u
and v
of the user and article. The latent features of the user are extracted using an L
-layer multilayer perceptron (MLP) as shown in Eq. ( 63
), where M
is a fully-connected neural network layer:
u L = M L ( u )
The features of news article v
are computed using L
cross&compress units, as follows:
v L = E e ∼ S ( v ) [ C L ( v , e ) [ v ] ]
where S ( v )
denotes the set of entities corresponding to v
, [ C ( v , e ) ]
is a cross&compress unit, and suffix [ v ]
indicates the unit’s output.
The module outputs the probability of user
u
clicking on candidate news v
, computed using a nonlinear function which takes as input latent features of the user u L
and item v L
, combined with a predicting function f R S
, such as another MLP or inner product.
The goal of the KGE module is to learn the vector representation of the tail entity of triples in the knowledge graph. For a triple
( h , r , t )
, it firstly uses L
nonlinear layers to process the raw features of relation r
, using a variant of Eq. ( 63
), and cross&compress units to extract the latent feature vector of the head entity h
, with a modified Eq. ( 64
). The tail ˆ t
is predicted by feeding the concatenation of the feature vectors of the head entity h L
and relation r L
into a K
-layer MLP [ 172
]. Lastly, the score of the triple is calculated using the normalized inner product of the feature vectors of the real and the predicted tail representations.
The two task-specific modules are connected using cross&compress units which adaptively control the weights of knowledge transfer between the two tasks. The unit takes as input an article v
and a corresponding entity e
from the knowledge graph. The cross operation constructs a cross-feature matrix
C l ∈ R d × d
, by considering every possible pairwise feature interaction of their latent vector representations,
v L ∈ R d
and e L ∈ R d
, as follows:
C l = v L e T
L = [ v ( 1 )
L e ( 1 )
L … v ( 1 )
L e ( d )
L
... ...
v ( d )
L e ( 1 )
L … v ( d )
L e ( d )
L ]
Afterwards, the compress operation projects the cross features matrix back into the latent feature spaces R d
of items and entities in order to derive their vector representations for the following layer, as follows:
v l + 1 = C l w V V
l + C T
l w E V
l + b V
l = v l e T
l w V V
l + e l v T
l w E V
l + b V
l
e l + 1 = C l w V E
l + C T
l w E E
l + b E
l = v l e T
l w V E
l + e l v T
l w E E
l + b E
l
Although such units are able to extract high-order interactions between items and entities from the two distinct tasks, Wang et al. [ 172
] only employ them in the model’s lower layers for two main reasons. On the one hand, the transferability of features decreases as tasks become more distinct in higher layers. On the other hand, both item and user features, as well as entity and relation features blend together in deeper layers of the framework, which deems them unsuitable for sharing as they lose explicit association.
The Interaction Graph Neural Network ( IGNN
) [ 128
] aims to improve previous neural-based recommenders by enhancing the learning process of news and user representations with collaborative signals extracted from user-item interactions. This is achieved using two graphs: a knowledge graph for modeling news-news connections, and a user-item interaction graph.
The knowledge-based component jointly learns knowledge-level and semantic-level representations of news, similar to KCNN. More specifically, the embedding matrices of words, entities, and contextual entities are stacked before applying multiple filters and a max-pooling layer to compute the representation of news. In contrast to DKN, in IGNN the embeddings of entities and context, obtained with TransE [ 13
], are not projected into the word vector space before stacking. However, as observed by Wang et al. [ 170
], this simpler approach disregards the fact that the word and entity embeddings are learned using distinct models, and hence, are situated in different feature spaces. In turn, this means that all three types of embeddings need to have the same dimensionality in order to be fed through the convolutional layer. Nonetheless, this might be detrimental in practice, if the ideal vector sizes for the word and entity representations differ.
Higher-order latent collaborative information from the user-item interactions is extracted using embedding propagation layers that integrate the message passing mechanism of GNNs [ 128
] using the IDs of the user and candidate news as input. This strategy is based on the assumption that if several users read the same two news articles, this is an indication of collaborative similarity between the pair of news, which can then be exploited to propagate information between users and news. The propagation layers inherit the two main components of GNNs, namely message passing and message aggregation. The former passes the information from news t j
to user i
, as follows:
m i ← j =
1
√ | N ( i ) | | N ( j ) |
( W 1 e ( t j ) + W 2 ( e ( t j ) ⊙ e ( i ) ) )
where W 1 , W 2 ∈ R d ′ × d
, and
1
√ | N ( i ) | | N ( j ) |
is the Laplacian norm, defined using the 1-hop neighborhoods of user i
and article t j
, and representing the decay factor on the propagation edge between i
and t j
.
The latter component aggregates the information propagated from the user’s neighborhood with the current representation of the user, before passing it through a LeakyReLU transformation function, namely
e ( i ) ( 1 ) = ψ ( m i ← i + ∑ j ∈ N ( i ) m i ← j )
. High-order interactions are obtained by stacking multiple propagation layers, in order to expand the size of the neighborhood considered in the message passing step.
The KCNN results in a content-based representation of news and of users, where the latter is the result of a mean pooling function applied to the embeddings of the user’s previously read articles. Similarly, the k
propagation layers result in another
k
representations of user and news. Lastly, the inner product between the final user and news representations, obtained by concatenating the two kinds of embeddings, is used to determine the user’s preference for the candidate news.
In addition to using side information to extract latent interactions among news, the Self-Attention Sequential Knowledge-aware Recommendation system ( Saskr
) [ 33
] also considers the order in which users interact with the news. The sequence of interactions of a user with a group of news articles can reveal additional preferences, as it is generally assumed that users will read news deemed more relevant in the beginning of a session, and those in which they are less interested towards the end. Saskr combines sequential-aware with knowledge-aware modeling, both built as an encoder-decoder framework, to predict the article most likely to be clicked next by a user. The model’s input is constituted by a chronologically ordered sequence of L
items read by the user,
S t = ( S t − L , S t − L + 1 , … , S + t − 1 )
, where t
denotes the time step.
The encoder of the sequential-aware component of Saskr is composed of an embedding layer, followed by multi-head self-attention and a feed-forward network. The embedding layer projects an article’s body in a d
-dimensional latent space, by combining, for each piece of news i
, its article embedding Q i ∈ R d
and positional embedding P ∈ R L × d
. Equation ( 69
) shows the resulting embedding matrix E ∈ R L × d
.
E = [ Q S t − 1 + P 1
Q S t − 2 + P 2
...
Q S t − L + P L ]
The article’s embedding can be obtained in two ways. On the one hand, it can be computed as the sum of the pre-trained embeddings of its words, weighted by the corresponding TF-IDF weights, as
Q i = ∑ w t f i d f w j , i · w j
. On the other hand, it can be derived by stacking the embeddings of entities extracted from the text, namely the set entity ( i )
, as
Q i =
1
| entity ( i ) | ∑ e i ∈ entity ( i ) e i
.
These representations are then fed into a multi-head self-attention module [ 163
], to obtain the intermediate vector
M = MultiheadAtt s
encoder ( E , E , E )
. In turn, this intermediate representation functions as input for the fully-connected layers which compute the final sequential-aware encoding of the user’s interaction history:
C s = FFM s
encoder ( M ) = ReLU ( M W 1 + b 1 ) W 2 + b 2
where FFM
denotes the feed forward module. The attention and feed forward modules are stacked into B
blocks to capture deeper interactions.
Given the embedding C s
of the user’s interaction history, and the embedding
Q c d t
of candidate article i c d t
, the decoder predicts the sequence-aware recommendation score using Eq. ( 71
):
g s = FFM s
decoder ( MultiheadAtt s
decoder ( Q c d t , C s , C s ) )
The knowledge-aware module uses external knowledge from a knowledge graph to detect connections between news. The knowledge-searching encoder extracts entities from the body of articles and links them to predefined entities in a knowledge graph for disambiguation purposes. The set of identified entities is additionally expanded with 1-hop neighboring entities. The contextual entities are embedded using word embeddings pre-trained with a directional skip-gram model [ 150
]. The resulting contextual-entity embedding matrix C k
is used as input by the preference-interpreting decoder, which predicts the knowledge-aware recommendation score for candidate news i c d t
:
g k = FFM k
decoder ( MultiheadAtt k
decoder ( Q c d t , C k , C k ) )
The final recommendation score for candidate news article i c d t
is determined by aggregating the scores predicted by the two components, weighted by factor ω
which adjusts the contribution of each module, as g c d t = ω · g s + ( 1 − ω ) · g k
.
Liu et al. [ 100
] propose a Knowledge-aware Representation Enhancement model for news Documents ( KRED
) – a new method for creating knowledge-enhanced representations of news for multiple downstream tasks, such as news recommendation, news popularity prediction or local news detection, trained using a multi-task learning strategy. A document vector v d
, outputted by any natural-language understanding model and encoding a news article, constitutes the input to the KRED model. The framework encompasses three layers. As in previous models, entities extracted from the news articles are linked to their correspondents in a knowledge graph, and are, in this case, embedded using TransE [ 13
]. To take into account the contextual information of an entity, the authors employ the approach of Knowledge Graph Attention Network (KGAT) [ 174
] to compute the representation of an entity h
using the TransE embeddings of itself e h
and its 1-hop neighbors, as follows:
e N ( h ) = ReLU ( W 0 ( e h ⊕ ∑ ( h , r , t ) ∈ N ( h ) π ( h , r , t ) e t ) )
In Eq. ( 73
), π ( h , r , t )
represents the softmax normalized attention weights that adjust the amount of information propagated from a neighbor node to a given entity. The unnormalized attention coefficients π 0 ( h , r , t )
are determined using a two-layer fully connected neural network:
π 0 ( h , r , t ) = w 2 ReLU ( W 1 ( e h ⊕ e r ⊕ e t ) + b 1 ) + b 2
The next, context embedding layer encodes the dynamic context of entities from a news article, determined by their position, frequency, and category. The entity’s position in the article (i.e. in the title or body) is encoded using a bias vector
C ( 1 )
p h
, p h ∈ { 1 , 2 }
. While entities appearing in both the article’s body and title are considered more important, so are those occurring more often. The frequency of an entity is encoded by the vector
C ( 2 )
f i
. Lastly, a category encoding vector
C ( 3 )
t i
indicates the entity type t i
. The embedding of entity h
is thus enhanced in the following way:
e I h = e N ( h ) + C ( 1 )
p h
+ C ( 2 )
f i
+ C ( 3 )
t i
The entities’ representations are aggregated into a single vector in the information distillation layer, by means of an attention mechanism that takes into account both the context-enhanced entity vectors and the original embedding of an article to compute its final representation. More specifically, the attention weights
π 0 ( h , v )
, computed according to Eq. ( 76
), and then normalized using a softmax function, are used to weight the sum of entities from the same article to obtain its embedding e O h
, as per Eq. ( 77
).
π 0 ( h , v ) = w 2 ReLU ( W 1 ( e I h ⊕ v d + b 1 ) + b 2
e O h = ∑ h ∈ N ( v ) π ( h , v ) e I h
The knowledge-aware document vector
v k
is afterwards obtained by concatenating the entity and original document vectors and passing them through a fully connected feed-forward network. In contrast to DKN, KRED is not constrained by the type of document embedding model. Hence, it allows any state-of-the-art, pre-trained, or fine-tuned representation to be incorporated into the framework. Additionally, it is not restricted to short sequences of text, such as titles, but it can handle different types of data, including news bodies and metadata [ 100
].
In addition to injecting external knowledge into the recommendation model, the Topic-Enriched Knowledge Graph Recommendation System ( TEKGR
) [ 91
] improves items’ representation by exploiting the topical relations among the news. This is based on the assumption that even if two news share knowledge entities in which the user might be interested, they may belong to different topics, which are not all relevant for the reader. TEKGR, constructed of three layers, takes as input a user’s click history and a candidate article. News articles are represented by their titles.
Firstly, the KG-based news modeling layer is composed of three encoders and outputs a vector representation for each given article. The word-level news encoder learns news representations using their titles without considering latent knowledge features. The first layer of the encoder projects the titles’ sequence of words into a lower-dimensional space, while the bidirectional GRU (Bi-GRU) layer encodes the contextual information of a news title. Bi-GRU obtains the hidden state of an article by concatenating the outputs of the forward and backward gated recurrent units (GRUs) [ 91
]. This is followed by an attention layer which extracts more informative features from the vector representations by giving higher importance to more relevant words. Hence, the final representation of news article e ( t k )
is given by the weighted sum of the contextual word representations, where the weights are attention coefficients.
The knowledge encoder extracts topic information from the news titles through three layers [ 91
]. The concept extraction layer links each news title with corresponding concepts in a knowledge graph using an “is-a” relation. Afterwards, the concept embedding layer maps the extracted concepts to a high-dimensional vector space, while the self-attention network computes a weight for each word in the news title according to the associated concept and topic. For example, in the news title from Fig. 1
, Elon Musk
will have a higher attention weight in relation to the entrepreneur
, than with the
programmer
, concept. The layer’s output is then concatenated with the news embedding vectors obtained from the word-level encoder.
The third, KG-level news encoder firstly performs a knowledge distillation process. The resulting subgraph is enriched with 2-hop neighbors of the extracted entities, as well as with topical information distilled by the knowledge encoder [ 91
]. Therefore, not only are knowledge entities from the text disambiguated and their contextual information is taken into account but also adding topical relations among entities decreases data sparsity by connecting nodes not previously related in the knowledge graph. The topic and knowledge-aware news representation vector are computed with a graph neural network [ 171
]. The final news embeddings are obtained by concatenating the word-level and KG-level representations.
Secondly, the attention layer computes the final user embedding by dynamically aggregating each clicked news with respect to the candidate news. This step is accomplished as in DKN, by feeding the concatenated embedding vectors of the user’s click history and the candidate news into a DNN. Lastly, the user’s probability of clicking on the target article is computed in the scoring layer using the dot product of the user’s and article’s feature vectors.
CAGE [ 144 , 145 ]
(Context Aware Graph Embedding) is another framework based on neural networks which performs session-based news recommendation by building a knowledge graph of the articles for enriching its semantic meaning, and refining the article embeddings with the help of a graph convolutional network. Textual-level article embeddings are generated using pre-trained word embedding models, such as word2Vec [ 108
] or Glove [ 127
]. The representation of an article j
is a matrix of word vectors
V j
1 : n = ϕ ( w j
1 ) ⊕ ϕ ( w j
2 ) ⋯ ⊕ ϕ ( w j
n )
where w j
k
indicates the k
-th word in the article u
, and ϕ ( w u
k )
is the embedding of
w j
k
. A CNN is used to generate the final textual-level embeddings from the word vectors V j
1 : n
, namely
˜ V j
1 : n = σ ( W × ( z 1 ⊕ z 2 ⊕ , … , ⊕ z m ) + b )
, where z j = σ ( ˜ V j
1 : n ∗ k j + b j )
are the features of the CNN.
In the next step, the words w j
k
are disambiguated using entity linking to Wikidata, and a sub-knowledge graph is built from the Wikidata triples of the identified entities, as well as their one-hop neighbors, in order to mitigate sparsity issues and the lack of connection among entities. Semantic-level article embeddings are generated with TransE [ 13
] from the obtained sub-knowledge graph as
˜ e j
1 : n = ψ ( e j
1 ) ⊕ ψ ( e j
2 ) ⊕ ⋯ ⊕ ψ ( e j
n )
, where ψ ( · )
denotes the graph embedding model.
The textual-level and semantic-level article embeddings are concatenated and integrated with user features to obtain the final article embedding
˜ U = ˜ V j
1 : n ⊕ ˜ e j
1 : n ⊕ p
, where p
represents the one-hot encoding vector of the user’s attributes. In order to exploit neighborhood structural information for session-based recommendation, Sheu and Li [ 145
] construct an article-level graph, in which the articles compose the graph’s nodes and the pair-wise similarity of their embeddings are used as edge weights. A two-layer graph convolutional network (GCN) [ 86
] is used to compute the article embedding of sessions s
according to Eq. ( 78
):
H ( l + 1 ) = σ ( ˆ D − 1 / 2 ˆ A ˆ D − 1 / 2 H ( l ) ) W ( l )
where H ( l ) ∈ R N × D
denotes the input of the l
-th layer, ˆ A
is the adjacency matrix with identity matrix, and ˆ D
is a degree matrix. The refined article embedding is denoted by X = H ( 2 )
. GRUs are used for generating session embedding based on the corresponding sequential information. Here final session embedding is given by ˆ h t
. Finally, CAGE is trained to maximize the similarity between user’s session and the next-click article actually read by user (i.e. positive samples
item + ∈ U +
, where U +
is the set of articles that the user has read) and to minimize the similarity between session and articles that are not read by user (i.e. negative samples item − ∈ U −
, where
U +
is the set of articles that the user has not read). The relevance scoring function is defined as
Rel ( session , item ) = φ ( h t ⊕ item )
, where item = item + ∪ item −
, and φ
denotes a neural network with several fully connected layers. The posterior probability of clicking a candidate news article given the current session embedding ˆ h t
is given as follows:
P ( item + | ˆ h t ) =
exp ( γ Rel ( ˆ h t , item + ) )
∑ ∀ item ∈ Y ′ exp ( γ Rel ( ˆ h t , item ) )
, where γ is a smoothing factor, and U ′ = item + ∪ U −
6.3.3. Summary
Neural-based news recommendation systems are summarized by focusing on four distinguishing aspects:
– Recommendation model input.
These methods use the user’s news interaction history and a candidate article as input. The user’s interaction history is most often represented by previously clicked items. In such cases, the user profile is created by aggregating the representations of the individual articles from the click history. In contrast, CETR uses a user-item interaction matrix to represent the connection between users and news, and to generate collaborative recommendations. Similarly, RippleNet computes recommendations using the matrix of implicit feedback and a knowledge graph. Furthermore, the majority of models use a combination of word-level and entity-level representations of articles, based usually on their titles. The entities directly extracted from the news articles are further enriched with contextual information from the knowledge graph, in the form of k
-hop neighbors, where the maximum number of hops considered represents one of the model’s hyperparameters. Furthermore, Saskr is the only model to take into account the order in which a user interacts with a sequence of news articles.
– Knowledge graph embedding model.
Several approaches for embedding knowledge graph entities have been identified in the surveyed frameworks. Recommenders such as CETR, DKN, IGNN, KRED, or CAGE use TransE [ 13
], TransH [ 178
], TransR [ 98
], or TransD [ 80
] to compute knowledge graph embeddings. MKR uses a combination of MLP and cross&compress units, while Saskr embeds knowledge entities with pre-trained word embeddings. More recently, TEKGR adopts a GNN for deriving entity embeddings.
– Components of recommender system.
With the exception of CETR, which uses a combination of matrix factorization, topic analysis, and KGE models, the other systems are based on various combinations of neural networks. MKR uses a combination of MLPs and cross&compress units to train two components for the tasks of recommendation and knowledge graph embedding, while IGNN fuses KCNN for content-based representation of news with a message-passing GNN that captures collaborative signals among the news. CAGE combines a CNN for textual-level embeddings with a GCN to compute refined article representations. All the remaining models use a type of attention mechanism. For example, DKN combines KCNN used for news representation with a DNN-based attention layer. Gao et al.’s model [ 58
] incorporates only self-attention modules at all three levels – word, item and user – and employs another multi-head attention layer followed by a fully-connected layer for the final prediction. Similarly, Saskr is composed only of multi-head self-attention and fully connected layers. TEKGR and KRED combine attention modules with different types of GNNs. KRED uses a KGAT to aggregate the embeddings of an entity with those of its neighbors, followed by the attention mechanism of the Transformer [ 163
] used for assigning different weights for each entity and for computing the article’s final embedding. TEKGR combines attention with Bi-GRU in the word-level encoder, and with KGE in the knowledge encoder. Additionally, it incorporates a GNN in the KG-level news encoder.
– Aggregation of knowledge-level and text-level components.
As previously observed, the attention mechanism is widely used in models such as DKN, KRED, or TEKGR, to dynamically aggregate the outputs of different model components or the representations of individual modules at intermediate steps in the framework. A simpler strategy is adopted in IGNN, where the content-based and collaborative representations of news and users are concatenated before computing the final prediction. In comparison, MKR uses cross&compress units at the lower levels of its model to transfer similar latent features between the two task-specific components.
7. Evaluation approaches
This section analyses approaches used for evaluating the surveyed knowledge-aware news recommender systems, as well as potential limitations concerning the reproducibility and comparability of experiments.
7.1. Evaluation methodologies
The type of evaluation methodology depends on the target function of the recommendation models and the user data. In this context, the surveyed recommender systems were typically evaluated either through offline experiments based on historical data, through online studies on real-world websites, or in laboratory studies. Frameworks based on an item-ranking target function usually use an online setting or laboratory experiment. In these scenarios, participants are asked to annotate news articles recommended to them by the model based on their relevance to the user’s profile. In turn, the user profile is either created during the experiment or predefined and assigned to the participants by the evaluators. Once the annotations are obtained, the performance of the model is evaluated by comparing the predicted recommendations against the truth values provided by the annotators. In contrast, systems that target the click-through rate are evaluated through experiments in an offline setting, using data comprising of logs representing users’ historical interactions with sets of news.
Table 6
provides an overview of evaluation settings in terms of datasets and metrics used. As it can be observed there, all models are evaluated using different types of information retrieval accuracy measures, such as precision, recall, F1-score, or specificity. The performance of some of the more recent, neural-based systems is also evaluated in terms of rank-based measures, such as Normalized Discounted Cumulative Gain, Hit Rate, or Mean Reciprocal Rank. Generally, these metrics are computed at different positions in the recommendation list to observe the recommender’s performance based on the length of the results list. Moreover, for non-neural, entity-centric methods, the authors use statistical hypothesis tests, such as the Student’s t
-test, to measure the significance of the experimental results.
Table 6
Overview of evaluation settings. We list the model’s category and abbreviated name, datasets used, and reported evaluation metrics and setup information. The abbreviations used in the table are the following: Eval. = Evaluation, Acc = Accuracy, P = Precision, R = Recall, F1 = F1-score, NDGC = Normalized Discounted Cumulative Gain, RMSE = Root Mean Square Error, MAE = Mean Absolute Error, ROC = Receiver Operating Characteristic, PR curves = Precision-Recall curves, AUC = Area Under the Curve, NDPM = Normalized Distance-Based Performance measure, HR = Hit Rate, MRR = Mean Reciprocal Rank, Kappa = Kappa statistics, Student’s t
-test = One-tailed two-sample paired Student t
-test, ESI-RR = Expected Self-Information with Rank and Relevance-sensitivity [ 56
], EILD-RR = Expected Intra-List Diversity with Rank and Relevance sensitivity [ 162
], PROCS = processing steps, DS = data split, PARAMS = parameters, All available = PROCS + DS + PARAMS + CODE
Category Model Dataset(s) Metric(s) Eval. setup information
NNECM Semantic aware context recommendation [ 21 , 23 ]
News@hand P@K PROCS, DS
Social tags enriched recommendations [ 24 ]
News@hand Relevance PROCS, DS
Semantic relatedness [ 60 ] Unknown source P, R, F1 –
RSR [ 78 ] Unknown source Acc, P, R, Spec –
CF-IDF [ 64 ] Reuters ROC, PR curves, Kappa DS
Hybrid context-aware recommendation [ 23 ]
News@hand P@K PROCS, DS
RSR 2 [ 55 ] Unknown source Acc, P, R, Spec DS
SF-IDF [ 26 ] Reuters Acc, P, R, F1, Spec,
t -test
DS
SF-IDF+ [ 112 ] Reuters Acc, P, R, F1, Spec,
t -test
DS, PARAMS
Bing-SF-IDF [ 71 ] Reuters Acc, P, R, F1, Spec, Kappa DS, PARAMS
Bing-SF-IDF+ [ 28 ] Reuters Acc, P, R, F1, Spec, Kappa DS, PARAMS
Agarwal and Singhal [ 2 ] BBC, CNBC, Times of India P, R, F1 PROCS, PARAMS
OF-IDF [ 133 ] News database [ 72 ] P, R, F1, runtime DS
CF-IDF+ [ 40 ] Reuters P, R, F1, ROC, AUC, Kappa PROCS, DS, PARAMS
Bing-CF-IDF+ [ 17 ] Reuters P, R, F1, ROC, Kappa PROCS, DS, PARAMS
Bing-CSF-IDF+ [ 161 ]
Reuters F1, Kappa, Student’s
t -test
PROCS, DS
NNPM ePaper [ 105 ] The Jerusalem Post NDPM, MAE PROCS, DS, PARAMS
Magellan [ 45 ] Unknown source Acc, R –
SS [ 26 ] Reuters Acc, P, R, F1, Spec,
t -test
DS
BingSS [ 27 ] Reuters Acc, P, R, F1, Spec DS, PARAMS
OBSM [ 130 ] New York Times, Sina News P, R, F1 DS
Kumar and Kulkarni [ 88 ]
CNN news R PROCS, DS, PARAMS
Werner and Cruz [ 179 ] Unknown source P, R, F1 PROCS, PARAMS
BKSport [ 117 ] Sky Sports, ESPN, Yahoo Sports P PROCS, DS, PARAMS
SED [ 83 ] CNREC P, R, F1 PROCS, DS, PARAMS
Table 6
(Continued)
Category Model Dataset(s) Metric(s) Eval. setup information
NM CETR [ 193 ] Hupu News R@K PROCS, DS, PARAMS
Colombo-Mendoza et al. [ 35 ]
Unknown source P, R, F1 PROCS
DKN [ 170 ] Bing News F1, AUC All available
Gao et al. [ 58 ] Unknown source AUC,
NDCG@K DS, PARAMS
RippleNet [ 168 ] Bing News P@K ,
R@K ,
F1@K , AUC, Acc
All available
RippleNet-agg [ 169 ] Bing News P@K ,
R@K ,
F1@K , AUC, Acc
All available
MKR [ 172 ] Bing News Acc, AUC,
P@K ,
R@K
All available
IGNN [ 128 ] DC, Adressa R@K ,
NDCG@K PROCS, DS, PARAMS
Saskr [ 33 ] Eastday Toutiao HR@K , MRR PROCS, DS
KRED [ 100 ] Microsoft News AUC,
NDCG@K ,
HR@K , ACC, F1-macro
All available
TEKGR [ 91 ] Bing News, Adressa F1, AUC PROCS, DS, PARAMS
KCNR [ 176 ] Sogou News R@K ,
NDCG@K PROCS, DS, PARAMS
KG-RWSNM [ 188 ]
Weibo AUC, P, R, F1 PROCS, PARAMS
MUKG [ 152 ] Bing News AUC, Acc,
P@K ,
R@K
PROCS, DS, PARAMS
CAGE [ 145 ] Adressa HR@K ,
MRR@K ,
HR@K ,
ESI-RR@K ,
EILD-RR@K
PROCS, DS, PARAMS
7.2. Evaluation datasets
In comparison to the relatively uniform usage of evaluation metrics, the type of datasets used for evaluation varies significantly among recommender systems. The majority of non-neural models can be clustered into two groups, depending on the dataset used for their evaluation. As shown in Table 6
, semantic-aware context recommenders are evaluated using the
News@hand
architecture described in [ 22
]. Most of the remaining models are incorporated in the Hermes News Portal [ 54
]. The authors of a few of the path-based, non-neural recommender systems construct their own datasets using news articles collected from websites such as the New York Times, or Sina News, 16 16
CNN, 17 17
Sky Sports, 18 18
ESPN, 19 19
or Yahoo Sports. 20 20
Joseph and Jiang [ 83
] developed CNREC 21 21
for evaluating SED. CNREC is a dataset providing articles similarity and annotations for pairs of items showing the extent to which they are considered a good recommendation.
Table 7
Overview of evaluation datasets. We list the model’s category and abbreviated name, the dataset’s source, language, time frame, as well as the number of users, items, and interactions. An entry annotated with “*” denotes that the statistics were approximated by us based on the data provided by the authors. The abbreviations used in the table are the following: # = number of, N/A = not applicable
Category Model Data source Language Time frame #Users #Items # Logs/Interactions
NNECM Semantic aware context recommendation [ 21 , 23 ] BBC, CNN, New York Times, Washington Post English 01/01/2008-01/03/2008 16 9,698 N/A
Social tags enriched recommendations [ 24 ] BBC, CNN, New York Times, Washington Post English 01/01/2008-01/03/2008 20 9,698 N/A
Semantic relatedness [ 60 ] CNN, BBC, USA Today, L.A. Times, Reuters English Unknown N/A 158 N/A
Synthetic data Unknown N/A N/A 100 N/A
RSR [ 78 ] Unknown Unknown Unknown 5 Unknown 1500 *
CF-IDF [ 64 ] Reuters English Unknown 19 100 1900 *
Hybrid context-aware recommendation [ 23 ] BBC, CNN, New York Times, Washington Post English 01/01/2008-01/03/2008 20 9,698 N/A
RSR 2 [ 55 ] Unknown Unknown Unknown 5 300 1500 *
SF-IDF [ 26 ] Reuters English Unknown 19 100 1900
SF-IDF+ [ 112 ] Reuters English Unknown N/A 100 N/A
Bing-SF-IDF [ 71 ] Reuters English Unknown N/A 100 N/A
Bing-SF-IDF+ [ 28 ] Reuters English Unknown N/A 100 N/A
Agarwal and Singhal [ 2 ] BBC, CNBC, Times of India Unknown Unknown Unknown Unknown Unknown
OF-IDF [ 133 ] Unknown Unknown 2010 33 1823 3600
CF-IDF+ [ 40 ] Reuters English Unknown N/A 100 N/A
Bing-CF-IDF+ [ 17 ] Reuters English Unknown N/A 100 N/A
Bing-CSF-IDF+ [ 161 ]
Reuters English Unknown N/A 100 N/A
NNPM ePaper [ 105 ] The Jerusalem Post English 4 days 57 Unknown 4,731 *
Magellan [ 45 ] Unknown Unknown 09/2010-01/2011 N/A Unknown N/A
SS [ 26 ] Reuters English Unknown 19 100 1900
BingSS [ 27 ] Reuters English Unknown N/A 100 N/A
OBSM [ 130 ] New York Times English 2006-2007 581 6,000 232,400 *
Sina News Chinese Unknown 581 Unknown 232,400 *
Kumar and Kulkarni [ 88 ]
CNN English Unknown Unknown Unknown Unknown
Werner and Cruz [ 179 ]
Unknown Unknown Unknown 10 70 700 *
BKSport [ 117 ] Sky Sports, ESPN, Yahoo Sorts English Unknown Unknown 100 Unknown
SED [ 83 ] Unknown English 25/08/2014-28/08/2014 N/A 300 N/A
Table 7
(Continued)
Category Model Data source Language Time frame #Users #Items # Logs/Interactions
NM CETR [ 193 ] Hupu News Chinese Unknown 3,118 9,684 132,713
Colombo-Mendoza et al. [ 35 ]
Bolsa de Madrid Spanish Unknown 10 20 200 *
DKN [ 170 ] Bing News Unknown 16/10/2016-11/08/2017 141,487 535,145 1,025,192
Gao et al. [ 58 ]
Unknown Unknown 19/03/2018-31/03/2018 26,224 13,285 1,498,862
RippleNet [ 168 ] Bing News Unknown 16/10/2016-11/08/2017 141,487 535,145 1,025,192
RippleNet-agg [ 169 ] Bing News Unknown 16/10/2016-11/08/2017 141,487 535,145 1,025,192
MKR [ 172 ] Bing News Unknown 16/10/2016-11/08/2017 141,487 535,145 1,025,192
IGNN [ 128 ] DC Unknown Unknown 10,000 6,385 116,225
Adressa Norwegian 2017 640,503 20,428 3,101,991
Saskr [ 33 ] Eastday Toutiao Chinese 30/10/2018-13/11/2018 6960 108,684 861,996
KRED [ 100 ] Microsoft News Unknown 15/01/2019-28/01/2019 665,034 24,542 1,590,092
TEKGR [ 91 ] Bing News Unknown 16/10/2016-11/08/2017 141,487 535,145 1,025,192
Adressa Norwegian 2017 561,733 11,207 2,286,835
KCNR [ 176 ] Sogou News Chinese 19/03/2019-26/03/2019 91,924 197,649 2,927,430
31,738 41,012 1,300,380
KG-RWSNM [ 188 ]
Weibo Unknown 28/09/2012-29/10/2012 1,776,950 Unknown Unknown
MUKG [ 152 ] Bing News Unknown 16/10/2016-11/08/2017 141,148 535,145 1,025,192
CAGE [ 145 ]
Adressa Norwegian 2017 314,000 13,000 2,648,000
The datasets used to evaluate neural-based frameworks consist of user interaction logs gathered from websites such as Bing News, 22 22
Microsoft News, 23 23
Hupu, 24 24
Eastday Toutiao, 25 25
Sogou News, 26 26
or the Weibo dataset [ 192
]. An exception is constituted by IGNN, TEKGR, and CAGE, evaluated on the different subsets or versions of the Adressa dataset. Adressa [ 65
] is an event-based dataset comprising of click log data collected from a Norwegian news portal. Although the Adressa dataset is often used in evaluating deep learning-based news recommender systems [ 73
, 74
, 122
, 197
], it is not used by any other of the surveyed knowledge-aware models.
As it can be further observed in Table 7
, which summarizes the statistics of the used evaluation datasets, the number of users and items contained in these datasets varies widely. Non-neural models are evaluated on small datasets, usually with less than 1000 articles, with the exception of the semantic contextualization systems, tested with nearly 10,000 items. In contrast, neural-based methods are mostly evaluated on over 1 million click logs from more than 100,000 users and items.
Another critical finding is that in many cases, datasets are not described clearly enough. In a fourth of the cases, the data source is not specified. Moreover, the language of the dataset is rarely mentioned explicitly. While the language can easily be deduced from monolingual news websites, this does not hold true for international news platforms, leading to an unknown language in more than half of the cases.
7.3. Reproducibility and comparability of experiments
Table 6
also lists the type of information provided by each model with regards to the evaluation setup. Replicating experiments requires not only access to the data used, but also knowledge of how the data was split and processed for training and evaluation, and which values were used for the different parameters and hyperparameters of the model. Moreover, differences in the models’ implementation, especially of neural-based models, can further influence the results obtained when reproducing experiments. Hence, access to the original implementation constitutes an important factor for the comparability and reproducibility of results.
However, as it can be observed in the last column of Table 6
, only 5 out of the 40 surveyed papers provide all this information. For both sub-categories of non-neural models, generally only the data split and some of the parameters or processing steps are specified. Even when some processing steps are explained in the paper, not enough details are provided regarding how procedures such as named entity recognition or entity linking were performed. Moreover, systems in these categories each propose their own evaluation setups, without following a uniform procedure.
In contrast, most papers describing a neural-based framework offer extensive details regarding their evaluation settings and model architecture. This phenomenon could be explained in two ways. On the one hand, since all neural-based models are deep learning architectures, hyperparameters play a central role in their performance. On the other hand, most of the approaches in this family have been published in the recent past, and there has been a trend in the recent years in the academic community to make implementation details available when publishing a research paper in order to facility reproducibility.
Nonetheless, important aspects which would increase the comparability of experiments are still neglected in some works. Often, the entity extraction and linking processes are not thoroughly explained, meaning that if no implementation details are available, it would be impossible to reproduce the exact steps of the original experiments. Nonetheless, all the previously discussed knowledge-aware news recommender systems use a form of named entity recognition and linking in order to identify entities and concepts in the news articles and to map them to a knowledge base. However, almost none of the papers explicitly mention how these steps are performed and implemented. Other important steps required by any news recommender system, such as general text pre-processing, which can heavily influence the data representation, and ultimately, the generated recommendations, are also not discussed. In addition to the recommendation module itself, such steps constitute important dimensions that may differ between systems, and in turn, choices in their design and implementation may lead to great differences in performance. In Saskr, for example, the authors offer few details on the construction of the news-specific knowledge graph used, and no specification of the news data source.
Table 8
Overview of evaluated features and components. We report the model’s category and abbreviated name, the features evaluated and the components evaluated during an ablation study, if one was conducted. The abbreviations used in the table are the following: dim. = dimension, emb. = embedding, init. = initialization, # = number of
Category Model Eval. feats. Ablation study
NNECM Semantic aware context recommendation [ 21 , 23 ]
– model components
Social tags enriched recommendations [ 24 ]
– –
Semantic relatedness [ 60 ]
– –
RSR [ 78 ] threshold value –
CF-IDF [ 64 ] threshold value –
Hybrid context-aware recommendation [ 23 ]
– model components
RSR 2 [ 55 ] – –
SF-IDF [ 26 ] – –
SF-IDF+ [ 112 ] – –
Bing-SF-IDF [ 71 ] threshold value –
Bing-SF-IDF+ [ 28 ] threshold value –
Agarwal and Singhal [ 2 ]
OF-IDF [ 133 ] – –
CF-IDF+ [ 40 ]
Bing-CF-IDF+ [ 17 ] threshold value, Bing similarity parameters –
Bing-CSF-IDF+ [ 161 ] threshold value, Bing similarity parameters –
NNPM ePaper [ 105 , 148 ] matching parameters, #user ratings, user profile init., concept weights –
Magellan [ 45 ] – –
SS [ 26 ] – –
BingSS [ 27 ] threshold value, Bing similarity parameters –
OBSM [ 130 ] – –
Kumar and Kulkarni [ 88 ]
vector dim. –
Werner and Cruz [ 179 ]
– similarity metric, recommendation algorithm
BKSport [ 117 ] – semantic similarity, content similarity
SED [ 83 ] length expansion radius, entity screening, context words, edge weighting schema, distance measure, disconnected nodes penalty –
Table 8
(Continued)
Category Model Eval. feats. Ablation study
NM CETR [ 193 ]
– –
Colombo-Mendoza et al. [ 35 ]
– network-based feature learning algorithm, similarity metric
DKN [ 170 ] word & entity emb. dim., #filters, window size knowledge & attention component, KGE model, transformation function
Gao et al. [ 58 ] user profile length, #keywords –
RippleNet [ 168 ] ripple set size, #hops, emb. dim. regularization weight –
RippleNet-agg [ 169 ] aggregator, ripple set depth, neighbourhood sampling size, emb. dim. –
MKR [ 172 ] KG size, RS training frequency, emb. dim. cross&compress units, multi-task learning
IGNN [ 128 ] emb. dim., #emb. propagation layers emb. propagation layers
Saskr [ 33 ] emb. layer init., article emb. strategy, sequence length, #targets, weight factor –
KRED [ 100 ] base document vector, training strategy layers (incl. knowledge component)
TEKGR [ 91 ] #hops encoder types
KCNR [ 176 ] user’s click history length preference prediction module, k -hop neighbour information
KG-RWSNM [ 188 ]
– social network component, entity information
MUKG [ 152 ]
– data sparsity, recommender system module
CAGE [ 145 ] entity emb. dim. KGE model, KG removal
Another significant factor to be considered in the evaluation and comparison of recommender systems is how different model features and components affect its performance. All of the surveyed papers compare their knowledge-aware news recommendation models against baselines which do not incorporate side information in order to illustrate the gains of a knowledge-enhanced system. In addition to evaluating a model against baselines and state-of-the-art systems, it is also necessary to understand the effect of different features and modules on the recommender’s performance. To this end, the choice of knowledge resource is critical for a knowledge-aware model. However, none of the papers compare their model’s performance using different knowledge bases to determine the extent to which the resource itself influences results.
As it can be seen in Table 8
, only 6 out of 16 papers describing non-neural, entity-centric systems evaluate their model’s parameters. In these cases, the threshold values determining which articles are suggested to the user are empirically tested. In the case of non-neural, path-based recommenders, only the authors of ePaper [ 105
], BingSS [ 27
], Kumar and Kulkarni [ 88
] and SED [ 83
] evaluate the influence of different parameters or user profile initialization on the model’s performance. In comparison, the evaluation of neural-based systems involves parameters sensitivity analysis, as well as experiments with different initialization, training or embedding strategies. Such extensive experiments could also be influenced by the type of models, since neural network architectures comprise of several components, and are more sensitive to hyperparameters and design choices than models from the first two categories.
An additional finding is that few works perform an ablation study to determine the contribution of each component to the overall system. In the case of semantic-aware context recommenders, the authors analyze variants of the model obtained by removing either the contextualization of user preferences, the extension of user and news profiles, or both. Werner and Cruz [ 179
] investigate different similarity metrics and recommendation techniques, while BKSport’s authors examine the performance of the recommender when taking into account only semantic similarities, only content similarities, or both. Colombo-Mendoza et al. [ 35
] similarly experiment with two network-based feature learning algorithms and different similarity metrics. Wang et al. [ 170
] remove not only the knowledge component during the ablation study, but also experiments with different types of knowledge graph embedding models. Additionally, DKN’s performance was tested using different transformation functions, as well as with and without the attention module. The authors of MKR evaluate the contribution of its cross&compress units by replacing them with different modules, while those of IGNN examine the effectiveness of the embedding propagation layers by comparing different model variants which use them either to enhance the news, the user, or both representations. Lee et al. evaluate the improvements of using side information in TEKGR by analyzing the effect of its KG-level and knowledge encoders. Similarly, KRED’s authors conduct an ablation study in which they remove each of KRED’s entity representation, context embedding and information distillation layers. KCNR’s performance is analyzed with and without the user preference prediction module, and the influence of the preference propagation in the knowledge graph by considering different k
-hop neighbor information. KG-RWSNM’s authors perform an ablation study on the impact of the social network information, while MUKG’s recommender performance is examined given varying degrees of data sparsity. Lastly, Sheu and Li [ 145
] examine CAGE’s performance without the knowledge graph or with different knowledge graph embedding models.
7.4. Summary
Overall, this investigation of evaluation approaches shows that there is no unified evaluation methodology to produce comparable experiments. Moreover, the datasets used for evaluation are freely chosen by the authors, and there is no clear benchmark set of datasets used by all the systems. Although an effort has been made in recent years to provide more details on the evaluation setup, model architectures and choice of parameters, there is often still too little information specified for critical processing steps. In conclusion, we argue that only some of the most recent, neural-based approaches could be replicated given the available data, whereas the remaining methods cannot be reproduced in accordance to the original implementations. In this context, knowledge-aware news recommendation models lack reproducibility and comparability, standards which have been strongly encouraged in other fields of machine learning.
8. Open issues and future directions
Existing works have already established a strong foundation for knowledge-aware news recommender systems. In this section, we firstly discuss which fundamental challenges of news recommendation have already been addressed by knowledge-aware models, then identify and elaborate on several open issues in the field, and propose promising research directions.
In addition to general challenges for recommender systems, such as the cold-start, data sparsity, personalization, diversity, or privacy issues [ 143
], news recommenders systems face additional domain-specific challenges, as explained in Section 2
. Data sparsity and cold-start problems have clearly been addressed by the injection of external information from a knowledge base into the recommendation module, as such information enriches the initial data available about items and users. Similarly, the
news consumption behavior and the lack of explicit feedback
have also been tackled by enriching initial user profile information gathered from click logs of read news articles with related information about entities or concepts identified in the respective articles and contained in a knowledge base. Although
recommendation diversity
has been explicitly addressed only in one of the discussed models, using knowledge graphs to extract knowledge-level connections between news can improve diversity compared to solely text-based recommenders by taking into account relations between news that stem from second or third-order related neighbors of extracted entities.
However, the backbone of knowledge-aware recommender systems is represented by the recognition and disambiguation of named entities in the articles, a plain task for humans, but difficult for automatic systems. While knowledge representations obtained from identified entities in the text have been claimed to provide a solution for many shortcomings of traditional recommender systems, this is only true if such entities have been firstly disambiguated correctly and knowledge about them has been created and stored in knowledge bases. In turn, this passes the problem to the entity linking and knowledge graph construction components, which are most often not thoroughly discussed by the existing works, as shown in Section 7.3
. Moreover, these components themselves are being subjected to the same challenges of resolving ambiguities and discovering knowledge-level connections as a knowledge-unaware recommender system. If such knowledge is extracted automatically, the problem is pushed further down the pipeline, whereas if human experts are involved, the challenge becomes how to create structured knowledge in the face of the high churn of the news domain. Overall, these problems have not been tackled in the existing literature, although they pose significant problems for deploying a high-performing system as an effective solution in the real world. Therefore, we strongly believe that future research should not only be concerned with achieving increased performance on benchmark datasets while ignoring the additional challenges that a real-world application of the recommender system would pose, but should instead also try to address these open questions.
Several challenges have only been partly addressed by the surveyed works. For example, recommenders that construct user and item profiles based on ontological concepts take into account a smaller amount of data than those that use the full-text of news articles. Therefore, computations are faster and the negative effect of the large volume of data characterizing news recommendations is diminished. However, as it will be explained in Section 8.2
, it remains unclear what is
the impact of utilizing complete, large-scale knowledge graphs
as side information. Similarly, the issue of
sequential news consumption
has only been addressed by Saskr and CAGE, although it constitutes an important characteristic of news recommendation in general which has already been addressed by non-knowledge-aware recommenders [ 4
, 125
, 197
].
Nevertheless, a large number of news-specific challenges are not yet tackled by knowledge-aware news recommender systems. Issues related to the
fairness of recommendation
, such as over-specialization and bias or fake news, which constitute central challenges and avenues for research nowadays are not addressed in any of the surveyed papers. Similarly, neural knowledge-aware recommenders focus on
the short-term interests of users
and do not take into consideration their long-term preferences. Lastly, the influence of using knowledge bases, which often might not be frequently updated, on the timely recommendation
of news with short shelf lives has so far not been investigated.
In the remainder of this section we elaborate on the identified open issues and propose future research directions.
8.1. Comparability of evaluations
Zhang et al. [ 194
] have observed that the entire field of recommender systems lacks a unified evaluation methodology or benchmark datasets, which are common, e.g. in the domains of computer vision or natural language processing to ensure a fair comparison of models. A similarly troubling finding with regards to the reproducibility of research published in the area of recommender systems has been discussed by Dacrema et al. [ 37
]. The authors compared numerous works published in recent years at prestigious conferences in the domain of neural, collaborative filtering-based recommendation approaches and found that less than a half could be reproduced. Moreover, the majority of the proposed methods were equally good or even outperformed by simpler methods, due to methodological issues such as the choice of baselines, propagation of weak baselines, or the poor tuning of these baselines [ 37
].
The findings of Section 7.3
have shown that currently, knowledge-aware news recommender systems also hardly produce comparable experiments. While neural-based methods have a higher degree of reproducibility, the other models do not provide enough details on their evaluation methodology in order to be accurately replicated and verified. Another important observation is that none of the deep learning models have been compared against recommenders from the non-neural approaches. Nonetheless, comparability of evaluations is essential for benchmarking different models, which in turn, drives advancements in the field. Therefore, we argue that the field of knowledge-aware news recommender systems needs a stricter and more unified evaluation approach, including common benchmark datasets, clear processing steps, unification of evaluation metrics, usage of comparable resources and hyperparameters of pre-trained models, and ablation studies.
Need for Benchmark Datasets.
As it is common in other fields of machine learning, we believe that a set of benchmark datasets is needed to compare and contrast news recommenders. Such datasets should address all downstream tasks in the field of news recommendation, such as click-through rate or popularity prediction. Moreover, benchmark datasets should cover a wide range of sizes. Since scalability constitutes a key factor for a good news recommender, evaluating models on datasets of various sizes would prove to what extent a system could be used in real-world scenarios. Furthermore, benchmark datasets should have clearly defined splits for training, testing, and validation. This requirement is necessary to prevent each author from creating randomized test splits, which cannot be replicated. Wu et al. [ 182
] have recently constructed MIND, a large-scale dataset for news recommendation containing click logs of 1 million users on English articles from Microsoft News. Similar efforts have already been conducted in other fields. Datasets such as MNIST or ImageNet in computer vision, or SQuAD in natural language processing, are already widely used for comparing models in their respective domains. With the creation of Open Graph Benchmark, the GNN community has recently undertaken a similar effort in creating a set of benchmark datasets from varying domains and sizes [ 75
]. Lastly, we have shown in Section 7.3
that the surveyed recommender systems cannot be accurately reproduced and faithfully compared to each other, partially due to the wide range of different knowledge graphs and similar resources used, as well as to the lack of information regarding the construction, processing, and usage of such external resources. In this context, a standard benchmark dataset should also contain a range of knowledge resources, such as knowledge graphs and ontologies, in order to truly allow for a full and fair comparison of knowledge-aware news recommender techniques.
Ensure Reproducibility.
In addition to evaluating on the same datasets, with the same data splits, it is necessary to establish a stricter criterion for describing the evaluation methodology in order to ensure replicability of experiments. This means that detailed information of all processing steps, from general text pre-processing, to named entity recognition and linking, or the creation of news-specific knowledge graphs, should be provided to ensure that the experimental setup can be accurately reproduced at all steps. Moreover, underlying assumptions should be clearly stated, and all design choices regarding the hyperparameter optimization strategy should be reported. In case benchmark datasets are not used, the datasets on which the experiments are performed should be made publicly available. Lastly, as suggested in [ 37
], the source code of all proposed models, including baselines, should be published using persistent repositories and ensuring that the reproduction steps are easy to follow by other users (e.g. software requirements, scripts for executing all steps of the pipeline and experiments are readily available).
Unification of Evaluation Metrics.
The majority of papers already use the same information retrieval and rank-based metrics to evaluate their models. Nevertheless, every model should be evaluated using the same set of measures, which requires standardizing a set of evaluation metrics for each downstream application. Additionally, if the metrics consider the position of a recommendation in the results list, the same set of ranks should be applied throughout all modes being benchmarked.
Usage of Comparable Resources and Hyperparameters of Pre-trained Models.
When comparing models against each other, authors should use the same external resources in as far as possible given the recommendation framework. For example, the same knowledge graph or ontology should be used to ensure that the knowledge resource itself does not influence the results on the downstream task. Similarly, in case pre-trained models, such as word or knowledge graph embeddings, are used, the same parameters (e.g. dimension of embedding vector) should be used by all analyzed models.
Ablation Studies.
Furthermore, ablation studies should be performed for each newly proposed model to investigate the contribution of each component to the whole system. While this holds true for any recommender system, for knowledge-aware techniques it is essential to test the influence of the knowledge component, as done, for example, in DKN’s evaluation. Another interesting experiment would be to investigate the effect of the knowledge resource itself on the recommender’s performance, by injecting external knowledge, for example, from different knowledge graphs [ 166
].
As discussed above, while natural language processing methods, in particular entity recognition and linking, play a crucial role in processing new texts, their effect is rarely documented. In the realm of ablation studies, we would encourage to investigate those effects more thoroughly (e.g. by exploiting different entity linking methods), and to also investigate interaction effects between the natural language processing methods, recommendation methods, and the knowledge resource used.
Overall, all these steps would ensure that models are not only fairly and transparently compared against each other without great variations in parameter settings, but would also indicate whether the improvement of a new model over the state-of-the-art results is determined by the system’s architecture, or simply, by a better-tuned set of hyperparameters. Similar studies that can serve as an example for the field of news recommendation have been conducted for graph neural networks [ 48
] or knowledge graph embeddings [ 138
].
Lastly, we believe that a comparison between non-neural and neural-based knowledge-aware news recommender systems is needed to compare and understand the strengths and weaknesses of all existing approaches for incorporating external knowledge into news recommendations.
8.2. Scalability of news recommenders
The continuously increasing amount of news published daily, as well as the growing number of online news readers and their desire to receive news content in a timely manner [ 132
] constitute a constant challenge for any news recommender system, which requires scalability in order to be applied in real-world scenarios. Several techniques, ranging from fast clustering to dimensionality reduction, have been proposed to address the scalability issue. For example, Li et al. [ 93
] proposed a scalable news recommender system which firstly clusters news articles based on their content in order to reduce the amount of similarity computations required for personalized recommendation. A combination of three approaches has been adopted by Das et al. [ 39
] to improve the scalability of a recommender system dealing with millions of users and articles from Google News. A MinHash-based user clustering algorithm and Probabilistic Latent Semantic Indexing [ 70
], both adapted for large-scale dataset scalability using the MapReduce framework [ 41
], were employed by Das et al. [ 39
] to cluster dynamic news datasets. These methods were combined with an item covisitation technique for extracting user-item relations to generate personalized news recommendations.
However, the injection of external information in the recommender systems further enlarged the scale of the datasets that need to be processed by the model, particularly in the case of frameworks using knowledge graphs as side information. As shown in Sections 6.2
and
6.3
, such models obtain scalability using subgraphs, constructed by sampling fixed-sized neighborhoods. While this approach ensures that the recommendation model scales arbitrarily regardless of the size of the full graph, by not considering the entire graph at once, it is possible to ignore relevant neighbors of a node when gathering its contextual information. Hence, the sampling strategy used for defining a node’s neighborhood during subgraph construction influences the efficiency of the model. Overall, it can be concluded that knowledge-aware news recommender systems ensure scalability by sacrificing knowledge graph completeness. In this context, a promising research direction would be to investigate how to balance scalability and knowledge graph completeness in each downstream application scenario. To this end, we believe that an analysis of the effect of sampling strategy and neighborhood size on the robustness of the system and quality of the recommendations, as performed in [ 169
], should be conducted for a larger variety of recommenders.
8.3. Explainability of recommendations
Providing explanations for the results generated by a recommender system helps users to understand why a certain item has been recommended to them by the model. In turn, this can increase the users’ trust in the system. For example, LISTEN, a model designed to explain rankings generated by a news recommendation model [ 158
], explains the ranking of recommendations by identifying the most important features contributing to the current ranking and providing them to the user in a human interpretable form. The importance of features is determined by disrupting their values, one at a time, and observing how the change affects the ranking. In this case, a significant feature value will substantially change the ranking [ 158
].
Although the workings and outputs of deep learning-based recommender systems are intricate and often not easily interpretable by non-expert users, attention mechanisms have recently alleviated the lack of interpretability of neural models. Attention weights not only provide insights into the inner functioning of a system but also serve as explanations for which features in a user’s or item’s profiles have contributed to the model’s recommendation. In this context, the Dynamic Explainable Recommender was designed by Chen et al. [ 32
] to increase the accuracy of user modeling by taking into account the dynamic nature of user’s preferences, while providing recommendation explanations. More specifically, the model utilizes time-aware gated recurrent units to encode the user’s dynamic preferences and sentence-level convolutional neural networks to represent items based on the information captured in their reviews. The review information of different items is combined using a personalized attention mechanism, which learns the relevant pieces of information from a review according to the user’s current preferences, thus being able to explain the generated recommendations tailored to the user’s current state [ 32
]. A different approach for balancing the accuracy and explainability of recommendations was adopted by Gao et al. [ 57
], who built a rating prediction model using an attentive multi-view learning framework based on an explainable deep hierarchy. An attention mechanism connects adjacent views denoting different levels of features representing a user’s profile. Personalized explanations are generated from these multi-level features using a constrained tree node selection solved with dynamic programming [ 57
].
Incorporating knowledge graph information into recommender systems has been used not only to improve recommendation accuracy, but also to increase the explainability of results, as paths capturing user-items interactions in the knowledge graph could illustrate which semantic relations and entities contribute to a particular recommendation given the input user profile [ 76
, 175
, 186
]. As such, reasoning over the knowledge graph can reveal possible user interests and provide explanations for why a certain article has been recommended to the reader. Another means of using a knowledge graph to provide users with human-readable explanations for a recommender’s prediction was proposed by Ma et al. [ 104
]. Their method learns inductive rules from an item-centric knowledge graph, which encodes items associations in the form of multi-hop relational patterns. The induced rules are incorporated in the recommendation module to address the cold start problem and provide explainability.
A growing number of recent news recommenders employ graph neural networks as components in the framework. However, these deep learning models are often seen as black-box models, whose interpretability is concealed to regular users. The GNNExplainer proposed by Ying et al. [ 190
] is a model-agnostic approach for explaining predictions of any GNN-based model. The method takes as input a trained GNN and a prediction and generates an explanation in the form of a compact subgraph of the input graph and a small subset of node features with the highest impact on the given prediction. Computing explanations require optimizing the subgraph structure, such that its mutual information with the GNN’s prediction is maximized. Given the increasing usage of graph neural networks in news recommender systems, the GNNExplainer could be used to provide explanations for knowledge-aware news recommendations.
Hitherto, to the best of our knowledge, an explainable knowledge-aware news recommender system has not yet been designed. Providing explanations for online news readers remains thus an open problem. Therefore, we believe this is a noteworthy avenue which should be explored in future research.
8.4. Fairness of recommendations
Nowadays, news recommender systems have an increasing influence over people’s lives, by controlling which articles a reader is exposed to. This has raised concerns about biases that might be amplified by such systems. Yao and Huang [ 189
] identified two types of biases inherent in recommender systems, namely observation bias, and population imbalance bias.
Observation bias is determined by feedback loops that prevent the model from learning how to predict items that are dissimilar to the previously recommended or consumed ones [ 51
]. Content-based recommenders generate suggestions that are similar to the ones in the user’s history, while collaborative filtering systems recommend items liked by similar users. In both cases, the model learns to make predictions based on its past actions, since users cannot provide feedback for items that are not recommended to them, thus reinforcing the recommender’s algorithmic behavior [ 51
]. In the context of news recommendation, observation bias has given rise to the hypothesis that readers become trapped inside filter bubbles – states in which they are exposed only to the news that supports or amplify their opinions [ 123
]. In turn, this might lead, in the long run, to opinion polarization and self-radicalization of individuals through online media [ 119
].
Bias stemming from imbalanced data is a systematic bias caused by societal or historical discrimination, which occurs when different categories of users are represented in unequal proportions in the data used for training a recommender system [ 189
]. For example, population imbalance bias would occur if a recommender would suggest technology news mainly to men and cooking articles to women.
Several techniques have been designed for fair recommender systems in general. For example, Beutel et al. [ 8
] proposed using pairwise comparisons as a metric for measuring the ranking fairness of a recommender system. Moreover, they introduce a pairwise regularization method to improve the model’s fairness property during training. Burke et al. [ 19
] identify multiple stakeholders of a recommender system and distinguish between different types of fairness depending on the corresponding stakeholder group, namely consumer-centered, provider-centered, or both. The authors propose using the concept of balanced neighborhoods combined with a sparse linear model to obtain a desirable trade-off between fairness of results and personalization of recommendations [ 19
].
Wu et al. [ 181
] proposed using decomposed adversarial learning and orthogonality regularization to diminish unfairness caused by the biases of sensitive user attributes, such as gender, in news recommendation. More specifically, during training, the model learns two types of user embeddings: bias-aware ones that capture biases encoded in sensitive attributes describing the user’s behaviors, and bias-free ones that capture attribute-independent information related to the user’s interests. Adversarial learning is used to ensure that the bias-free embeddings do not contain information from the sensitive user attributes, while orthogonality regularization ensures that the two types of representations are orthogonal to each other. Lastly, fairness-aware news recommendations are computed using only the bias-free user embeddings [ 181
].
Symeonidis et al. [ 156
] propose a popularity-based and a distance-based novelty-aware matrix factorization technique to address the problem of filter bubbles created by recommender systems. Novelty-aware matrix factorization introduces in the classic regularized matrix factorization model a soft constraint that controls how new items are being recommended. In the popularity-based recommendation setting, the novelty of an item is defined as the inverse of its popularity, with items being more novel the fewer people are aware of them. In the case of distance-based recommendations, an item is considered novel if the topic category to which it belongs does not comprise many other items with which the user has already interacted in the past [ 156
]. However, this approach focuses on systems based on matrix factorization, which are not used by knowledge-aware news recommender systems, as discussed previously.
In the field of news recommendation, Gharahighehi et al. [ 61
] address the news recommendation task from a multi-stakeholder perspective and adopt a hypergraph learning method in order to take into account multiple stakeholders and counteract the negative effect of popularity bias on the recommendations. The stakeholders involved in the news recommendation scenario and their interactions are modeled by means of a hypergraph, thus enabling the direct computation of the relatedness between different stakeholders, represented as vertices of the hypergraph. Moreover, the authors introduce a temporal-aware learning approach which dynamically updates the weights given to the different stakeholders in order to increase recommendation fairness [ 61
].
However, these methods have been developed for traditional recommender systems and do not consider biases that might stem from the knowledge resource used as side information. Moreover, none of the surveyed models investigates whether filter bubbles arise when using external knowledge resources for recommendations. Hence, given the importance of these topics, investigating how fairness can be incorporated into knowledge-aware news recommender systems, as well as examining if filter bubbles are created and how their effect can be diminished, represent promising directions for future works in this field.
Another related problem is that of fake news, which can be propagated by recommender systems using news data whose credibility has not been verified. In this context, numerous fake news detection algorithms have already been proposed [ 103
, 164
, 165
]. Additionally, knowledge graphs can also be used to detect whether the news is fabricated [ 46
, 121
, 157
]. Nonetheless, none of the surveyed works is concerned with the potential propagation of fake news by the recommender system or ways to mitigate it. Therefore, we conclude that incorporating a fake news detection module, potentially based on knowledge graphs, represents an important avenue for research that would contribute to reducing the spread of fake news and misinformation by knowledge-aware news recommendation algorithms.
8.5. Multilingual and multi-modal news recommendation
Today, online news comes in various shapes. Next to online newspapers, internet users increasingly consume their news in the form of podcasts or videos, most often using a mix of text, audio, and video modalities [ 116
]. Given that observation, multi-modal recommendation methods are likely to gain more traction but are rarely observed so far [ 132
]. Here, knowledge-based recommenders would be an interesting opportunity, since knowledge-based content representations and multi-modal knowledge graphs [ 102
] could be used to form links between news present in different modalities. Moreover, given the strong trend of neural recommendation methods in the field, multi-modal embedding models [ 115
, 159
] could be an interesting pathway towards developing such recommendation techniques [ 153
].
Multi-lingual news consumption is also quite frequent. According to a study from 2014, 36% of all internet users in the European Union “frequently” and even 81% “occasionally” consume news and information online in more than one language [ 42
]. While many knowledge graphs are inherently multi-lingual, and the use of identifiers for concepts and entities can help to bridge the gap between documents in different languages, all of the approaches surveyed in this document are monolingual. Like multilingual neural language models can be applied to the task of cross-lingual news recommendation [ 180
], we also foresee the development of knowledge-based multi-lingual news recommenders.
8.6. Multi-task learning for recommendation
Multi-task learning [ 29
] is a transfer learning-based paradigm which aims to exploit similarities across different tasks in order to improve the generalization performance of a model. The model is trained for multiple related tasks in parallel and domain-specific information is transferred between tasks to prevent overfitting on a single downstream application [ 195
]. This approach has proven successful in numerous applications, ranging from computer vision to speech recognition and natural language processing [ 137
].
Multi-task learning has also been employed by recommender systems from different domains [ 118
]. In the case of recommender systems using knowledge graphs as side information, the quality of recommendation might be negatively affected by missing facts in the knowledge graph as the user’s preferences may be ignored if they are not captured by existing entities and relations. Recent works have shown that jointly learning a model for both recommendation and knowledge graph completion can result in improved recommendations [ 25
, 96
]. Similarly, in the field of knowledge-aware news recommendation, Wang et al. [ 172
] have used this paradigm to jointly train a model for the tasks of news recommendation and knowledge graph embedding, while Liu et al. [ 100
] jointly trained a knowledge-aware representation enhancement model for news documents on a variety of tasks, ranging from item recommendation to local news prediction.
Taking into account the advantages of the multi-task learning paradigm, we believe that utilizing transfer knowledge from tasks such as entity classification or link prediction for knowledge-aware news recommendation is a promising direction to pursue in the future.
8.7. Sequential and timely recommendations
Readers consume news in sequences and prefer updates about ongoing and developing stories, rather than repeated or highly similar articles. Taking into account sequential dependencies between articles has been addressed in news recommendation generally by means of recurrent neural networks (RNNs) [ 125
]. More recent approaches combine RNNs with attention modules. For example, Zhu et al. [ 197
] use an attention-based RNN as a sequential information extractor that can automatically model the dynamic history sequential features used to represent a user’s clicked articles, while Bai et al. [ 4
] use a combination of RNNs and attention to build a sequence-aware, user-based collaborative filtering recommender system. However, knowledge-aware sequential news recommender systems have been rarely proposed so far. In this context, we believe that enhancing existing sequential news recommenders with side information from a knowledge base is an interesting research avenue towards tackling this problem.
In addition to consuming articles sequentially, readers prefer recent and up-to-date news. Not only does an article’s relevance diminish over time, but the news is constantly updated and superseded by more popular pieces of information. In turn, this means that recommendations that are based not only on the text content of news, but also on knowledge entities and side information, need to ensure the timeliness of the information contained in external knowledge bases. However, many large knowledge graphs quickly become outdated and do not contain the latest information about world events [ 50
].
In this context, one approach to address this issue is the inclusion of temporal constraints to model the limited validity of knowledge base items determined by the dynamic nature of events described in the news. Among the existing recommender systems, the ones included in the Hermes News Portal [ 17
, 26
–
28
, 40
, 55
, 64
, 71
, 112
, 161
] support knowledge base updates. More specifically, the Hermes framework not only provides the functionality for specifying temporal constraints of news items, but it also incorporates updates to the knowledge base based on event rules, meant to reflect changes of real-world events [ 53
]. A similar strategy of updating the ontology used for recommendation is adopted in Magellan [ 45
], in which erroneous statements or outdated facts are removed from the ontology if the lifespan of the corresponding relations in the ontology – updated with every repetition in a news story – are not refreshed for a certain period of time. Another technology that could be adopted by news recommenders based on ontologies is tOWL [ 109
], namely an extension of the OWL Description Logic language used to model ontologies. tOWL enables temporal representations through the introduction of time points and relations between them, as well as timeslices that can represent complex temporal aspects, such as process state transitions [ 109
].
Furthermore, we encourage a shift from static towards temporal knowledge graphs that capture temporal dynamics of entities and the relations [ 81
] between them. This could help knowledge-aware news recommenders overcome the problem that the validity of any facts contained in static knowledge graphs is constrained to a specific time period. Temporal knowledge graphs have gained traction in the latest years in the field of recommender systems. For example, Xiao et al. [ 187
] proposed a temporal knowledge graph, which is incrementally constructed from user-item interactions and related auxiliary information, and used for recommendation. Similarly, Mezni [ 107
] leverages a temporal knowledge graph to build a time-aware recommender system for service recommendation. Therefore, we believe that using temporal knowledge graphs is not only a potential solution to ensure the timeliness of external data injected in the recommendation module, but also a highly promising direction for future research in the field of knowledge-aware news recommendation.
8.8. Changing user preferences
In addition to preferring timely news, readers also have preferences that evolve over time. On the one hand, short-term preferences are determined by current trends, popularity, and context of certain news and events, such as the local elections in a country. On the other hand, long-term preferences evolve more slowly and are motivated by socio-economic and personal factors, such as an interest in climate change [ 67
]. However, as it can be observed from Section 6.3
, neural knowledge-aware news recommender systems learn single representations of users that do not differentiate between the two types of user interests. In turn, this can be detrimental for the generated recommendations, as users might not only want to see news regarding the latest events, but also read articles related to their long-term interests.
The LSTUR model proposed by An et al. [ 3
] takes into account both kinds of preferences when constructing user profiles. More specifically, long-term representations are given by the embeddings of user IDs, while short-term preferences are captured from the users’ recently browsed news using a GRU. The two representations can either be concatenated to obtain the final user representation, or the long-term user representation can be used to initialize the hidden state of the GRU network for the short-term representation module [ 3
].
Another approach has been proposed by Hu et al. [ 73
]. Their model, GNewsRec, uses a GNN on a heterogeneous user-news-topic graph to learn the user’s long-term interest encoded as high-order relationships between users, items, and topics in the graph. To capture the short-term user preferences, the authors employ an attention-based long short-term memory [ 69
] on the user’s reading history.
Given the existing research already conducted to account for changing user interests in news recommendation, we believe that incorporating techniques that are able to differentiate between short-term and long-term user preferences in knowledge-aware news recommenders is a pathway worth pursuing to ensure diversity of recommendations and user satisfaction.
9. Conclusion
In this survey paper, we have extensively reviewed knowledge-aware news recommender systems. We propose a new taxonomy for classifying existing recommenders, based on how the latent representations are generated for the users’ and articles’ profiles using concepts and entities from a knowledge base, as well as on the type of similarity metric used. According to the classification scheme, we categorize knowledge-aware news recommender systems into non-neural and neural-based frameworks, with the former category further divided into entity-centric and path-based methods. Representative models from each category are summarized and thoroughly analyzed. Moreover, we discuss and compare evaluation approaches used by existing publications and identify limitations in terms of comparability and reproducibility of experiments. Lastly, we identify and examine open issues in the field and propose future research directions that could drive progress in this domain. We hope this survey can serve as a comprehensive overview of knowledge-aware news recommender systems, clarifying key aspects of the field and uncovering open problems and corresponding promising directions to pursue in future studies.
Notes
1 https://dblp.dagstuhl.de/
2 https://dl.acm.org/
3 https://ieeexplore.ieee.org/
4 https://www.sciencedirect.com/
5 https://link.springer.com/
6 https://www.webofscience.com/
7 https://www.zotero.org/
8 The corresponding spreadsheets for both phases are available at:
https://docs.google.com/spreadsheets/d/11NxjctjgQ5sAbbA2g2vKgqyUigg4t6S_H98-VsHJDWQ/edit?usp=sharing
.
9 https://iptc.org/standards/newscodes/
10 https://developers.google.com/freebase
11
https://www.wikidata.org/wiki/Wikidata:Statistics
12 https://wikidata-todo.toolforge.org/stats.php
13
https://www.dbpedia.org/resources/knowledge-graphs/
14
https://wordnet.princeton.edu/documentation/wnstats7wn
15 The Bing similarity is comparable to the Normalized Google Distance [ 34
].
16 http://news.sina.com.cn
17 http://edition.cnn.com/services/rss
18 http://www.skysports.com
19 http://www.espnfcasia.com
20 http://sports.yahoo.com/
21
https://github.com/kevinj22/CNRec/blob/master/CNRec.zip
22 https://www.bing.com/news
23 https://news.microsoft.com
24 https://www.hupu.com
25 http://mini.eastday.com/
26 https://www.news.sogou.com
Acknowledgements
The work presented in this paper has been conducted in the ReNewRS project, which is funded by the Baden-Württemberg Stiftung in the Responsible Artificial Intelligence program. The publication of this article was funded by the Ministry of Science, Research and the Arts Baden-Württemberg and the University of Mannheim.
Acronyms
Bi-GRU
Bidirectional Gated Recurrent Unit, 36
BPR
Bayesian Personalised Ranking, 29
CNN
Convolutional Neural Network, 29, 37, 38
CTR
Click-Through Rate, 11
DNN
Deep Neural Network, 30, 37, 38
GCN
Graph Convolutional Network, 37, 38
GNN
Graph Neural Networks, 8, 13, 14, 34, 38, 47, 49, 52
GNN-KADR
Graph Neural Network-based Knowledge-Aware Deep Recommender, 8
GRU
Gated Recurrent Unit, 36, 37, 52
KB
Knowledge Base, 10, 11
KCNN
Knowledge-aware Convolutional Neural Network, 29, 30, 34, 38
KG
Knowledge Graph, 9, 11, 36-38, 43
KGE
Knowledge Graph Embedding, 27, 33, 38
MLP
Multilayer Perceptron, 33, 38
PMI
Point-Wise Mutual Information, 20
POS
Part-Of-Speech, 24
RNN
Recurrent Neural Network, 51
TF-IDF
Term Frequency-Inverse Document Frequency, 16, 18, 19, 22, 23, 27, 35
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Adverse childhood experiences and resilience among adult women: a population-based study | medRxiv
medRxiv - The Preprint Server for Health Sciences
Adverse childhood experiences and resilience among adult women: a population-based study
View ORCID Profile Hilda Björk Daníelsdóttir , Thor Aspelund , Edda Björk Þórðardóttir , Katja Fall , View ORCID Profile Fang Fang , Gunnar Tómasson , Harpa Rúnarsdóttir , Qian Yang , Karmel W. Choi , Beatrice Kennedy , Thorhildur Halldorsdottir , Donghao Lu , Huan Song , Jóhanna Jakobsdóttir , Arna Hauksdóttir , Unnur Anna Valdimarsdóttir
doi: https://doi.org/10.1101/2021.07.05.21260008
Now published in eLife doi: 10.7554/eLife.71770
Abstract
Full Text
Abstract
Adverse childhood experiences (ACEs) have consistently been associated with elevated risk of multiple adverse health outcomes, yet their contribution to coping ability and psychiatric resilience in adulthood is unclear. Participants were 19,613 women in the Icelandic Stress- And-Gene-Analysis cohort with complete data on 13 ACEs measured with the ACE-International Questionnaire. Self-reported coping ability was measured with the Connor-Davidson Resilience Scale and psychiatric resilience was operationalized as absence of psychiatric morbidity. Compared to women with 0 ACEs, women with ≥ 5 ACEs had 33% lower prevalence of high coping ability (PR=0.67, 95% CI 0.60,0.74) and 56% lower prevalence of high psychiatric resilience (PR=0.44; 95% CI 0.41,0.48). Specific ACEs including emotional neglect, bullying, sexual abuse and mental illness of household member were consistently associated with reduced adult resilience. We observed only slightly attenuated associations after controlling for adult socioeconomic factors and social support in adulthood, indicating that adult resilience may be largely determined in childhood.
Introduction
Exposure to adverse childhood experiences (ACEs), including child abuse, neglect and growing up in dysfunctional households, is associated with elevated risk of a wide range of physical and mental health problems across the life course (Anda et al., 2006;Bellis et al., 2015;Hughes et al., 2017;Petruccelli, Davis, & Berman, 2019). The results from a recent meta-analysis (Hughes et al., 2017) suggest that the adult health outcomes most clearly associated with ACEs include problematic alcohol consumption and substance use, violence, and mental illness. However, there is great variation in long-term outcomes of children exposed to ACEs, and many children remain healthy despite excessive ACE exposure. Importantly, it has been documented that a substantial proportion of individuals exposed to ACEs do not develop mental illness in adulthood (Green et al., 2010;Kessler et al., 2010), but instead exhibit resilience (DuMont, Widom, & Czaja, 2007;Holmes, Yoon, Voith, Kobulsky, & Steigerwald, 2015).
Resilience is generally conceptualized as maintained mental health or positive adaptation despite trauma exposure (Choi, Stein, Dunn, Koenen, & Smoller, 2019;Kalisch et al., 2017;Luthar, Cicchetti, & Becker, 2000). The two most widely used approaches to operationalize the concept define resilience as perceived coping abilityreflecting a stable tendency to cope effectively with stress and adversity (Campbell-Sills & Stein, 2007;Connor & Davidson, 2003), and as psychiatric resiliencereflecting an empirically derived outcome, such as the absence of PTSD or other psychiatric disorders among individuals exposed to adversity (Nishimi, Choi, Cerutti, et al., 2020; Sheerin, Stratton, Amstadter, The VA Mid-Atlantic Mental Illness Research, Education, Clinical Center (MIRECC) Workgroup., & McDonald, 2018). The different resilience definitions are not mutually exclusive, but rather complementary and may capture different underlying dimensions of resilience (Choi et al., 2019;Fisher & Law, 2021;Sheerin et al., 2018).
Only a handful of previous studies have addressed the association between ACEs and adult resilience. Childhood maltreatment, variously defined, has been negatively associated with psychiatric resilience (McGloin & Widom, 2001;Mersky & Topitzes, 2010;Topitzes, Mersky, Dezen, & Reynolds, 2013;Williams, MacMillan, & Jamieson, 2006) and perceived coping ability (Campbell-Sills, Forde, & Stein, 2009; Nishimi, Choi, Davis, et al., 2020) in adulthood. However, most studies have focused solely on childhood maltreatment or included only a small number of ACEs. Therefore, to date, little is known about the association between cumulative ACE exposure and adult resilience, and whether specific ACE types are to a varying extent associated with resilience.
Leveraging a large nationwide study of Icelandic women, we aimed to investigate the association between the cumulative number of a broad spectrum of ACEs and two distinct measures of adult resilience, i.e. perceived coping ability and an outcome-based measure of low psychiatric morbidity.
Material and Methods
Study sample
In this study, we utilized data from the Stress-And-Gene-Analysis (SAGA) cohort, a population-based study in Iceland on the impact of trauma on women’s health. All 18 to 69-year-old Icelandic speaking women residing in Iceland with an identifiable address or telephone number (n≈104,197), were invited to participate in the study from March 2018. Data collection continued until July 1 st2019, yielding a total of 30,372 participating women (30% of eligible women). Since trauma exposure is intrinsic to psychiatric resilience, the analytic sample was restricted to women reporting a worst traumatic event at some point during their lifetime (see description of PCL-5 below). In addition, women who had missing or incomplete data on ACEs (n=2939), perceived coping ability (n=511), and/or psychiatric resilience (n=4737), were excluded, which resulted in a final study population of 19,613 women (Supplementary Figure 1).
Measures
Adverse childhood experiences (ACEs)
ACEs were measured with a modified version of the Adverse Childhood Experiences International Questionnaire (ACE-IQ) developed by the WHO (‘WHO | ACE-IQ’). The instrument consists of 30 items assessing how often individuals were exposed to the following 13 ACEs during the first 18 years of their life: emotional neglect, physical neglect, emotional abuse, physical abuse, sexual abuse, domestic violence, living with a household member who abuses drugs and/or alcohol, living with a household member who is mentally ill or suicidal, incarceration of a household member, parental death or separation/divorce, being bullied, witnessing community violence, and exposure to war/collective violence. For an overview of included items and their response options see Supplementary Table 1. The recommended frequency scoring system (‘WHO | ACE-IQ’), which takes into account the level of exposure for each ACE, was used to generate three types of exposure variables: 1) a continuous ACE-IQ total score ranging from 0 to 13, reflecting the number of ACEs participants were exposed to; 2) the total score was categorized (0, 1, 2, 3-4 and ≥ 5 ACEs) based on the distribution of the sample; 3) binary variables for each individual ACE type (described above), coded as 0 (unexposed) and 1 (exposed).
Perceived coping ability
Perceived coping ability was assessed with the 10-item version of the Connor-Davidson Resilience Scale (CD-RISC-10) (Campbell-Sills & Stein, 2007). The scale has demonstrated good reliability and validity (Campbell-Sills & Stein, 2007). All items were answered on a 5-point scale ranging from 0 (not true at all) to 4 (true nearly all the time). Items were summed to create a total score ranging from 0 to 40 with a higher score indicating higher levels of perceived coping ability. As there is no standardized cut-off for the CD-RISC, the total scores were divided into quintiles (for more details see Supplementary Materials), and a binary variable was created where the highest quintile was used to define a high level of perceived coping ability (i.e. resilience, CD-RISC score ≥ 35).
Psychiatric resilience
Consistent with previous literature (Choi et al., 2019; Nishimi, Choi, Davis, et al., 2020;Stein et al., 2019) psychiatric resilience was defined as absence of or low psychiatric morbidity among women exposed to lifetime trauma, i.e. total sum of the inverse number of above-threshold symptom levels on PTSD, trauma-related sleep disturbances, binge drinking, depression, and anxiety.
The PTSD Checklist for DSM-5 (PCL-5) is a 20-item valid instrument that assesses symptoms of PTSD in the past month according to the DSM-5 (Blevins, Weathers, Davis, Witte, & Domino, 2015;Bovin et al., 2016;Weathers et al., 2013;Wortmann et al., 2016). Before answering the PCL-5, participants reported their lifetime exposure to potentially traumatic events assessed with the Life Events Checklist for DSM-5 (LEC-5). Participants were asked to determine the worst traumatic event they had experienced and answer the PCL-5 according to the worst selected trauma. A clinical cut-off score of ≥33 was used to indicate probable PTSD (Weathers et al., 2013). The Pittsburgh Sleep Quality Index Addendum for PTSD (PSQI-A) is a 7-item valid questionnaire designed to assess the frequency of disruptive nocturnal behaviours common in individuals with PTSD (Germain, Hall, Krakow, Katherine Shear, & Buysse, 2005). A clinical cut-off score of ≥4 was used to discriminate between participants with and without trauma-related sleep disturbances (Germain et al., 2005). Binge drinking was defined as having 6 or more units of alcohol on a single occasion (one unit corresponds to a single measure of spirits) at least once a month during the last year (Bush, Kivlahan, McDonell, Fihn, & Bradley, 1998). The widely used Patient Health Questionnaire (PHQ-9) (Kroenke, Spitzer, & Williams, 2001) and Generalized Anxiety Disorder Scale (GAD-7) (Kroenke, Spitzer, Williams, & Löwe, 2010;Löwe et al., 2008;Spitzer, Kroenke, Williams, & Löwe, 2006) were used to measure the presence of depression and anxiety symptoms, respectively, during the past two weeks. The standard cut-off score of ≥10 was used, indicating clinically relevant depression and anxiety (Kroenke et al., 2001;Spitzer et al., 2006).
Binary variables were created indicating whether an individual met the clinical cut-off for symptoms of each disorder above (0=no, 1=yes). The psychiatric resilience phenotype was derived by summing together the binary variables and reversing the score which resulted in a total score ranging from 0 to 5 where higher scores indicate greater psychiatric resilience in these trauma-exposed women. In addition, we created a binary variable where endorsement of 0 on all measures indicated high psychiatric resilience.
Covariates
Variables with a conceptual rationale for being associated both with ACEs and perceived coping ability or psychiatric resilience were considered as covariates. These included age (at responding), childhood deprivation, as well as educational level, employment status, civil status and current monthly income at responding. In addition, current perceived social support, measured with the Multidimensional Scale of Perceived Social Support (MSPSS) (Zimet, Dahlem, Zimet, & Farley, 1988), and perceived happiness, measured with a 10-point visual digital scale, were included in additional analyses. For more detailed description of covariate assessment, see the Supplementary Materials.
Statistical analysis
Descriptive characteristics were compared using Chi-square tests for categorical data and ANOVAs for continuous data.
Rank order correlations were used to determine i) the correlation between perceived coping ability and psychiatric resilience, ii) correlations between perceived coping ability and different measures of psychopathology (PHQ-9, GAD-7, PCL-5, PSQI-A, binge drinking) used to derive psychiatric resilience, and iii) correlations between different ACE subtypes.
We used linear regression models assuming normally distributed errors and log-linear Poisson regression models with robust error variance to determine the associations between ACEs and perceived coping ability and psychiatric resilience, as continuous and binary outcomes (high perceived coping ability/ high psychiatric resilience), respectively. In all analyses, we adjusted for age and childhood deprivation (model 1) and then additionally for adult educational level, civil status, employment level and income (model 2).
We ran all models with ACE-IQ as a continuous predictor and as a categorical predictor where we compared resilience levels of unexposed women (0 ACEs) to resilience levels of those who had been exposed to increasing number of ACEs (1, 2, 3-4 and ≥ 5 ACEs). In addition, we carried out stratified analyses to assess whether the association between ACEs and resilience differed by levels of perceived social support (linear models). Furthermore, because parental separation/divorce is a common childhood experience, we carried out a sensitivity analysis excluding this item from the ACE-IQ score and re-ran the linear models. Finally, to preclude whether a particular response style influenced the observed associations between ACEs and resilience, we excluded women who scored low or high on happiness (10% top/bottom scores) and re-ran the linear models.
To determine the independent associations of specific types of ACEs with resilience, we ran analyses on perceived coping ability and psychiatric resilience for each of the 13 ACEs. We first examined each ACE type separately while adjusting for covariates, and then re-ran the analyses with all ACE subtypes entered simultaneously into the model, as ACEs frequently co-occur (Radford, Corral, Bradley, & Fisher, 2013).
Standardized regression coefficients were reported from all linear regression analyses and prevalence ratios (PR) were reported from the Poisson regression analyses. All statistical analyses were performed using R (version 3.6.1).
Results
Characteristics of the sample
Descriptive statistics of the study population are presented inTable 1. Overall, about 22% of participants reported no ACEs and 17% reported five or more ACEs. Middle aged women had on average higher scores on the ACE-IQ than younger or older women. Women with higher ACE scores were more often single or widowed, less educated, unemployed, had lower income and were more likely to report childhood deprivation and low perceived social support (Table 1. Bivariate associations
Table 1.
Descriptive characteristics of the study population by number of adverse childhood experiences (ACE-IQ) (n = 19,613)
Both perceived coping ability and psychiatric resilience were consistently associated with increased age, higher educational level, being in a relationship or married, being employed, higher income, lower childhood deprivation and higher perceived social support (Table 2). The two resilience measures were moderately correlated (r s=0.45). Perceived coping ability was moderately negatively correlated with each of the measures used to derive the psychiatric resilience phenotype (i.e. symptoms of depression, anxiety, PTSD, and trauma-related sleep disturbances) but weakly correlated with binge drinking (Supplementary Table 2). The 13 ACE subtypes were weakly to moderately correlated with each other (r sranging from 0.05 to 0.46), with emotional abuse showing the strongest correlation with other ACEs (Supplementary Table 3).
Table 2.
Distribution of perceived coping ability (CD-RISC) and psychiatric resilience scores by sociodemographic characteristics
Bivariate associations
Both perceived coping ability and psychiatric resilience were consistently associated with increased age, higher educational level, being in a relationship or married, being employed, higher income, lower childhood deprivation and higher perceived social support (Table 2). The two resilience measures were moderately correlated (r s=0.45). Perceived coping ability was moderately negatively correlated with each of the measures used to derive the psychiatric resilience phenotype (i.e. symptoms of depression, anxiety, PTSD, and trauma-related sleep disturbances) but weakly correlated with binge drinking (Supplementary Table 2). The 13 ACE subtypes were weakly to moderately correlated with each other (r sranging from 0.05 to 0.46), with emotional abuse showing the strongest correlation with other ACEs (Supplementary Table 3).
Associations between ACEs and resilience
Linear models revealed that exposure to one or more ACEs (relative to 0 ACEs) was associated with attenuated perceived coping ability and psychiatric resilience in a dose-dependent manner (Table 3); every 1 SD unit increase in ACE-IQ scores was associated with lower levels of perceived coping ability (β=-0.14; 95% CI -0.15,-0.12) and psychiatric resilience (β=-0.28; 95% CI -0.29,-0.26) in the fully adjusted model. Associations between ACEs and perceived coping ability and psychiatric resilience were observed across levels of social support but were slightly stronger among women with low social support (Supplementary Table 4). Sensitivity analyses showed that the associations remained evident when excluding parental separation/divorce from the ACE-IQ score (Supplementary Table 5), and when excluding women with top/bottom 10% happiness values (Supplementary Table 6).
Table 3.
Associations between the number of ACEs and perceived coping ability (CD-RISC) and psychiatric resilience (β and 95% CI)*
Poisson models revealed that compared to women with 0 ACEs, women with ≥ 5 ACEs had a lower prevalence of high perceived coping ability (PR=0.67, 95% CI 0.60,0.74), and high psychiatric resilience (PR=0.44, 95% CI 0.41,0.48) in the fully adjusted model (Table 4). Every unit increase in the ACE-IQ scores was associated with lower prevalence of high perceived coping ability (PR=0.94, 95% CI 0.92,0.95) and high psychiatric resilience (PR=0.87, 95% CI 0.86,0.88).
Table 4.
Prevalence Ratios (with 95% CI) of high perceived coping ability (CD-RISC ≥ 35) and high psychiatric resilience (absence of psychiatric morbidity) in relation to the number of ACEs
ACE subtypes were associated with lower levels of perceived coping ability and psychiatric resilience (Supplementary Figure 2) as well as lower prevalence of high psychiatric resilience and high perceived coping ability except for physical neglect- and abuse, parental death or separation/divorce, and community- and collective violence (Supplementary Figure 3). After mutual adjustment for all ACE subtypes, we found that emotional neglect, being bullied, sexual abuse, and growing up with a mentally ill household member had consistent associations with both resilience measures, both in linear models (Figure 1) and Poisson models (Figure 2). Associations were also suggested for emotional abuse, domestic- and community violence with psychiatric resilience in the full model while associations for other ACEs were substantially attenuated (Figures 1and2).
Figure 1.
Associations between different types of ACEs and perceived coping ability (A) and psychiatric resilience (B) (β and 95% CI). Models were corrected for age, childhood deprivation, educational level, civil status, employment status, income and mutually adjusted for other ACEs. *Coefficients are standardized. Figure 2. Prevalence Ratios (with 95% CI) of high perceived coping ability (A) and high psychiatric resilience (B) in relation to individual ACEs. Models were corrected for age, childhood deprivation, educational level, civil status, employment status, income and mutually adjusted for other ACEs.
Figure 2.
Prevalence Ratios (with 95% CI) of high perceived coping ability (A) and high psychiatric resilience (B) in relation to individual ACEs. Models were corrected for age, childhood deprivation, educational level, civil status, employment status, income and mutually adjusted for other ACEs.
Discussion
In a large nationwide study of Icelandic women, a comprehensive measure of 13 adverse childhood experiences (ACEs) was negatively associated with two distinct measures of resilience in adulthood in a dose-dependent manner. Indeed, women who endorsed five or more ACEs had 33% lower prevalence of high perceived coping ability and 56% lower prevalence of high psychiatric resilience compared to women who endorsed 0 ACEs. In addition, specific ACEs including emotional neglect, bullying, sexual abuse and growing up with a mentally ill household member were strongly associated with attenuated adult resilience.
To our knowledge, the present study is the first to consider a wide range of ACEs in relation to adult resilience, and to address their association with two distinct resilience measures. Overall, our results are in line with previous studies examining the association between childhood maltreatment and adult resilience (Campbell-Sills et al., 2009;McGloin & Widom, 2001;Mersky & Topitzes, 2010; Nishimi, Choi, Davis, et al., 2020;Topitzes et al., 2013;Williams et al., 2006). However, the existing evidence base is limited by relatively small sample sizes, consideration of only few ACEs (Campbell-Sills et al., 2009;McGloin & Widom, 2001; Nishimi, Choi, Davis, et al., 2020;Williams et al., 2006), and/or the use of composite measures of childhood adversity (Mersky & Topitzes, 2010;Topitzes et al., 2013).
Our results indicating a dose-response relationship between the cumulative number of ACEs and attenuated adult resilience is consistent with a recent cross-sectional study byNishimi et al. (2020)who observed a similar pattern between four ACEs (emotional abuse, physical abuse, sexual abuse, and witnessing domestic violence) and perceived coping ability, as measured with the CD-RISC. We have now extended these findings to psychiatric resilience as an outcome, and further demonstrated this pattern for a broad set of ACEs in a large nationwide study representing 30% of the Icelandic female population. Furthermore, our results suggest that all ACE subtypes are associated with perceived coping ability and psychiatric resilience. However, when mutually adjusting for other ACEs, only emotional neglect, sexual abuse, being bullied and growing up with a mentally ill household member were consistently associated with both resilience measures.
In line with previous literature (Nishimi, Choi, Cerutti, et al., 2020;Sheerin et al., 2018), we found that self-assessed coping ability and outcome-based psychiatric resilience were only moderately correlated with each other, indicating these may reflect different patterns of adaptive functioning following adversity. Collectively, our research adds to the growing literature on the nature of resilience as a construct. The associations between ACEs and adult resilience were independent of age, childhood deprivation and, importantly, other adult socio-demographic factors (i.e. educational level, civil status, employment level and income), suggesting that ACEs affect resilience over and above these potential mediating variables. In fact, effect sizes only diminished slightly when we additionally adjusted for adult socio-demographic factors, which indicates that adult characteristics such as education and employment level do not compensate for the deleterious impact of ACEs on adult resilience. This suggests that adult resilience may largely be determined in childhood and that situational factors in adulthood (e.g. high social support) only marginally buffer the association between ACEs and adult resilience.
The main strengths of the study include the population-based design and large sample size of the SAGA cohort, which represents the Icelandic adult female population in terms of distribution of age, residence, education and income (‘Preliminary findings of the Stress- And-Gene-Analysis Cohort’). The wealth of measures in the SAGA cohort baseline assessments made it possible to derive two types of resilience measures and examine a wide range of ACEs and take into account important covariates all of which have been limited in previous studies (Arseneault et al., 2011;Bellis et al., 2017;Copeland et al., 2018). However, our study also has several limitations. First, the cross-sectional nature of our data does not allow us to make any inferences about the directionality of the studied associations. Second, we cannot rule out that the observed association between ACE growing up with a mentally ill household member and resilience, is due to a genetic predisposition for psychopathology rather than the experience itself. Future genetically informative studies will need to examine the extent to which this association is confounded by genetic factors. In addition, ACEs were retrospectively reported and thus may be subject to recall bias. However, previous studies have shown acceptable validity for retrospective assessments of ACEs (Hardt & Rutter, 2004;Reuben et al., 2016;Widom & Morris, 1997;Widom & Shepard, 1996) although they may be influenced by current mental health status or response style (Reuben et al., 2016). Yet, the similar results obtained from our sensitivity analyses excluding individuals with extreme values on the happiness assessment, reduce concerns that our results are due to a particular response style. Finally, our results are based on an exclusively female sample, therefore, future studies should explore whether there are qualitative differences in how ACEs relate to adult resilience among men.
In conclusion, in a large nationwide-representative female population, we observed a strong association between cumulative exposure of ACEs and two distinct measures of adult resilience. Specific ACEs, including exposure to emotional neglect and bullying, sexual abuse, and growing up with a mentally ill household member were consistently associated with attenuated adult resilience. If these findings are confirmed through prospective designs, there may be huge societal benefits of prevention strategies targeting the protection of children against traumatic occurrences and their consequences. Future research is needed to address how children exposed to ACEs can be supported to reduce risks of compromised adult resilience and health inequalities.
Data Availability
The data used in this study are compiled in the SAGA cohort and are available for review on site, on request. The use of these data is in accordance with the Icelandic law and with permission of the Icelandic Bioethics Committee. Therefore, the authors cannot make the dataset publicly available. On the other hand, interested researchers can obtain data access upon approvals by Icelandic Bioethics Committee (https://www.vsn.is/en) and by contacting the corresponding author.
Declaration of interest
None.
Ethics
The study was approved by the National Bioethics Committee (NBC number: 17-238) and all participants gave informed consent before participation.
Funding
This work was supported by research grants from the Doctoral Grants of the University of Iceland Research Fund (HBD, 2020), European Research Council (UAV, grant number 726413), and the Icelandic Center for Research (Grant of excellence; UAV, grant number 163362-051).
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Evaluation Summary:
This is one of the larger studies investigating the impact of adverse experiences during childhood on adult psychological and psychiatric resilience. Using data from an ongoing cohort study on Icelandic women, Daníelsdóttir and colleagues reported that in the face of accumulated adverse childhood events the prevalence of resilience declines, which supports earlier studies suggesting that resilience is not invincibility. Although the data are limited to women within gender binarism and the operationalization of resilience concept could be improved, the quality of the data, (e.g., sample size), justifies the authors' conclusion that the one way to improve resilience in adulthood lies in facilitating the quality of life in childhood. This paper has the potential to make an important contribution to raising awareness of the adverse childhood experiences and their impact on resiliency, which is of interest to those working on childhood adversity and resilience.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)
Reviewer #1 (Public Review):
This important research supports the idea that adverse experiences during childhood can have lasting impact on people through to adulthood. This study has some important strengths, including the relatively large sample size and population-based sample, although is limited in that the data reported here were collected at only one point in time and relied on the memory of participants for collecting data. The research has important implications for health and social policy in protecting the interests of children, particularly those who are vulnerable and at greater risk of adverse experiences during childhood.
Reviewer #2 (Public Review):
Hilda Björk Daníelsdóttir et al. demonstrated the relationship between adverse childhood experiences (ACEs) and adult resilience, measured as perceived coping ability and psychiatric resilience. While this was already done for specific single types and subsets of ACEs, no study so far could show these associations for the full spectrum of all ACEs.
The large dataset of Icelandic women from the ongoing Stress-And-Gene-Analysis (SAGA) cohort gives the opportunity for an in-depth analysis, controlling for sociodemographic variables like age group, income, civil status and additionally, childhood deprivation, perceived social support, sleep quality, binge drinking and traumatic events. Furthermore, the authors could provide information about correlations (if present) between ACEs as well as between perceived coping ability, psychiatric resilience and between perceived coping ability and different tools to obtain the mental health status.
Overall, the paper is well-structured, only descriptive data and associations of the main outcomes are reported as tables within the paper whereas all further results are presented within the supplement. Additionally, the statistical methods like Chi-square tests, rank order correlations and linear models are well known, which additionally is helping to address the paper to a wider audience. The large dataset allowing control for many variables and their possible correlations as well as for correlation between all ACEs, reducing "noisy" effects of small sample sizes.
In the end, the authors succeed identifying the relationship between women without ACEs versus women with one or more ACEs as well as the cumulative effects of ACEs on adult resilience. In addition to the importance of the unique results, the paper it is not too "technical" and well written. Therefore, the paper has the potential to communicate the results outside of the "academic sphere" without too many changes in the main text. In this way, it can make an important contribution to raising awareness of the topic in public.
Reviewer #3 (Public Review):
Daníelsdóttir and colleagues, using data from an ongoing cohort study of Icelandic women with the objective of studying the associations of ACEs with two measures of adult resiliency: an established questionnaire measure of psychological resilience and a measure based on psychiatric outcomes. One of the key findings of this study was that there was that resilience decreased as ACEs accumulated.
Strengths: The data they used are from nearly 20000 women exposed to at least one traumatic event and complete data on outcomes and exposures. In addition to this large data set, this study had a large number of ACEs. Having a validated measure of psychological resilience is another strength of this study.
Weaknesses: The authors were not very successful in conceptualising resilience. Although Connor-Davidson scale is well known and can be introduced as such, in this paper there is a new outcome-based measure was introduced, which require laying a strong foundation on the concept of resilience. Not engaging with literature on resilience from the likes of Garmezy, Rutter, Masten, Werner, and others might have contributed to the conceptual weakness. An example might be that the authors refer to Connor- Davidson measure as perceived coping ability while the original authors meant their scale as a measure of psychological resilience in the face of perceived stress.
Although operationalisation of resilience varies, there is a common understanding that resilience is flourishing despite adversity. In this conceptualisation, establishing the role of an exposure as adversity is of paramount importance. In this paper, the psychiatric resilience is operationalised as reduction of psychiatric morbidity in the presence of trauma. However, the role of childhood events as adversities for the psychiatric morbidity cannot be established in this data where everyone has faced at least one trauma, thus leading to the absence of a counterfactual.
| https://www.medrxiv.org/content/10.1101/2021.07.05.21260008v1.full |
PET/CT and WB MRI for Staging and Response in CRPC Patients Receiving Enzalutamide - Full Text View - ClinicalTrials.gov
PET/CT and WB MRI for Staging and Response in CRPC Patients Receiving Enzalutamide
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
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ClinicalTrials.gov Identifier: NCT02814968 Recruitment Status :
Completed First Posted : June 28, 2016 Last Update Posted : April 14, 2022
Sponsor:
The European Uro-Oncology Group
Collaborator:
Centre for Human Drug Research, Netherlands
Information provided by (Responsible Party):
The European Uro-Oncology Group
Study Details
Study Description
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
The aim of the study is to assess the clinical utility of 18F-fluoro-deoxyglucose Positron Emission Tomography (PET)/Computed Tomography (CT) and Whole Body Magnetic Resonance Imaging (MRI) versus conventional bone scan and prostate-specific antigen (PSA) measurements in response prediction to treatment with Enzalutamide in castration-resistant prostate cancer patients.
The study will assess how these 2 imaging modalities perform compared to traditional serial PSA measurements and bone scan in assessing metastatic tumour load, progressive disease and response to treatment with Enzalutamide in castration-resistant prostate cancer patients.
In addition measurements of serially collected circulating tumour cell (CTC) samples, cell-free tumour DNA and RNA will be performed in order to evaluate their predictive value in terms of response measurement.
Condition or disease Intervention/treatment Phase Prostate Cancer Metastatic Drug: Enzalutamide Device: 18-FDG PET/CT Device: Whole body MRI Device: Bone scan Phase 2
Detailed Description:
Castration-resistant prostate cancer patients eligible for 2nd line hormonal treatment will undergo treatment with Enzalutamide (XTANDI). Subjects will receive 1dd 160 mg Enzalutamide orally continuously until progressive disease occurs.
All subjects will undergo 18F-FDG PET/CT scans at baseline, 2 weeks, 2 and 6, 9 and 12 months after starting androgen receptor-directed treatment. All subjects will undergo Whole Body MRI at baseline, 6, 9 and 12 months. Bone scans will be performed at baseline, 3 months, 6 and 12 months. PSA will be measured at baseline and every 4 weeks thereafter until at 12 months. CTC counts and characteristics will be measured at baseline and during Enzalutamide treatment.
Study Design
Layout table for study information Study Type : Interventional
(Clinical Trial) Actual Enrollment : 66 participants Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment Official Title: A Phase 2, Open-label, Single-arm, Efficacy and Imaging Study of Oral Enzalutamide in Chemo-Naïve Patients With Progressive Prostate Cancer Who Have Failed Androgen Deprivation Therapy (Castration-resistant Prostate Cancer Patients) Study Start Date : February 2015 Actual Primary Completion Date : June 2020 Actual Study Completion Date : December 2020
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics: Prostate cancer
MedlinePlus related topics: Prostate Cancer
Drug Information available for: Enzalutamide
U.S. FDA Resources
Arms and Interventions
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Arm Intervention/treatment Experimental: Single arm Subjects will receive 1 dd 160 mg Enzalutamide orally continuously until progressive disease occurs. Serial PSA measurements, PET/CT scans, Whole Body MRI, bone scans will be performed to assess metastatic tumour load, progressive disease and response to treatment. Drug: Enzalutamide Other Name: Xtandi Device: 18-FDG PET/CT Device: Whole body MRI Device: Bone scan
Outcome Measures
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Primary Outcome Measures
:
Progression-Free Survival (PFS) at 6 months [ Time Frame: 6 months ]
Defined as the time from the date of randomization to the date of radiological progression or death (patients will be followed beyond the fixed time point of 12 months for continued response cq recurrence, but 12 month is the last fixed primary endpoint assessment). Radiological progression is defined by any of the following criteria:
Soft tissue lesions: Progressive disease on 18F-FDG PET/CT or MRI by RECIST 1.1. Bone or bone marrow lesions: Progressive disease on PET/CT or MRI as evidenced by new lesions or an increase in size of 25% of the sum of target lesions.
Conversion of the 18F-FDG PET signal of the metastases at 2 weeks, 2 or 6 months compared to baseline PET which by comparing it to PFS at 6 and 12 months may be an indicator or drug response. Radiological PFS at 6 months will be compared to a) PET signal conversion and to b) PSA measurements, and changes in number of lesions on the bone scan (conventional work up).
Progression-Free Survival (PFS) at 12 months [ Time Frame: 12 months ]
Defined as the time from the date of randomization to the date of radiological progression or death (patients will be followed beyond the fixed time point of 12 months for continued response cq recurrence, but 12 month is the last fixed primary endpoint assessment). Radiological progression is defined by any of the following criteria:
Soft tissue lesions: Progressive disease on 18F-FDG PET/CT or MRI by RECIST 1.1. Bone or bone marrow lesions: Progressive disease on PET/CT or MRI as evidenced by new lesions or an increase in size of 25% of the sum of target lesions.
Conversion of the 18F-FDG PET signal of the metastases at 2 weeks, 2 or 6 months compared to baseline PET which by comparing it to PFS at 6 and 12 months may be an indicator or drug response. Radiological PFS at 12 months will be compared to a) PET signal conversion and to b) PSA measurements, and changes in number of lesions on the bone scan (conventional work up).
Secondary Outcome Measures
:
Biochemical (PSA) response defined as prostate-specific antigen (PSA) nadir. [ Time Frame: 12 months ]
Response as PSA nadir.
PSA progression. PSA kinetics measured by PSA doubling time (regular PSA measurements). [ Time Frame: 12 months ]
PSA doubling time
Progression of bone lesions detected with bone scan according to Prostate Cancer Working Group 2 (PCWG2) criteria. [ Time Frame: 6 and 12 months ]
Progression of bone lesions
Radiologically confirmed spinal cord compression or pathological fracture due to malignant progression. [ Time Frame: 6 and 12 months ]
Radiological assessment of spinal cord compression or pathological fracture
Occurrence of Symptomatic Skeletal Events (SSE) evaluated by combination of clinical and radiological assessments [ Time Frame: 12 months ]
Assessment of external beam radiation therapy to relieve skeletal pain, occurrence of a new symptomatic pathologic bone fracture, spinal cord compression, tumour-related orthopedic surgical intervention or change of anti-neoplastic therapy to treat bone pain
Number of participants with change in CTC measurements correlated to radiological PFS. [ Time Frame: 6 and 12 months ]
Assessment of radiological PFS
Percent change from baseline in serum concentration of circulating testosterone (T). [ Time Frame: 12 months ]
Change in circulating testosterone
Percent change from baseline in serum concentration of dihydrotestosterone (DHT). [ Time Frame: 12 months ]
Change in serum concentration of dihydrotestosterone
Percent change from baseline in serum concentration of sex hormone binding globulin (SHBG). [ Time Frame: 12 months ]
Changes of SHBG
Percent change from baseline in serum concentration of androstenedione (A). [ Time Frame: 12 months ]
Changes of androstenedione from baseline
Number of participants with changes in biomarkers of bone turnover correlated to PSA. [ Time Frame: 12 months ]
Changes in biomarkers
Number of participants with adverse events (AEs) and serious adverse events (SAEs) leading to treatment discontinuation. [ Time Frame: 6 and 12 months ]
Assessment of AE and SAEs
Time to symptomatic progression (including death due to prostate cancer). [ Time Frame: 12 months ]
Time to progression
Time to initiation of salvage systemic therapy, including chemotherapy, or palliative radiation. [ Time Frame: 12 months ]
Time to chemotherapy or palliative radiation.
Quality of life measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. [ Time Frame: 6 and 12 months ]
Quality of life assessment
Quality of life measured by the EuroQol 5-Dimension QoL Instrument (EQ-5D). [ Time Frame: 6 and 12 months ]
Quality of life assessment
Changes in Karnofsky score [ Time Frame: 6 and 12 months ]
Changes in Karnofsky score
Changes in visual analogue scale (VAS) for tumour-related pain. [ Time Frame: 6 and 12 months ]
Pain changes from baseline (QoL)
Changes in bone mineral density (BMD) as measured by Dual-energy X-ray absorptiometry (DXA) scan. [ Time Frame: 6 and 12 months ]
Bone mineral density changes
Eligibility Criteria
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Layout table for eligibility information Ages Eligible for Study: 18 Years and older (Adult, Older Adult) Sexes Eligible for Study: Male Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:
Male aged 18 years or older;
Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features;
Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy;
Three consecutive rises of PSA, 1 week apart, resulting in two 50% increases over the nadir, with PSA of at least > 5 ng/mL but preferably >10 ng/mL;
Progressive disease as defined by rising PSA levels plus by evidence of progressive and measurable soft tissue or bone disease by 18F-FDG PET/CT, Whole Body MRI or both;
Castrate serum levels of testosterone < 50 ng/dL or < 1.7 nmol/L;
Anti-androgen withdrawal for at least 6 weeks for bicalutamide, nilutamide or flutamide for at least 6 weeks;
No prior treatment with cytotoxic chemotherapy;
Eastern Cooperative Oncology Group (ECOG) score 0-2;
A life expectancy of at least 12 months;
Written informed consent.
Exclusion Criteria:
Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrolment;
Known or suspected brain metastasis or active leptomeningeal disease;
History of another malignancy within the previous 5 years other than curatively treated non melanomatous skin cancer;
Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2.5 times the upper limit of normal at the Screening visit;
Creatinine > 177 µmol/L (2 mg/dL) at the Screening visit;
Hemoglobin <6 mmol/L, White blood cells < 4.0 x10^9/L, platelets < 100 x 10^9/L;
History of seizure or any condition that may predispose to seizure. Also, history of loss of consciousness or transient ischemic attack within 12 months of enrolment (Day 1 visit);
Contra-indication for MRI (e.g. pacemaker).
Contacts and Locations
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02814968
Locations
Layout table for location information Netherlands Leiden University Medical Center Leiden, Netherlands, 2333 ZA
Sponsors and Collaborators
The European Uro-Oncology Group
Centre for Human Drug Research, Netherlands
Investigators
Layout table for investigator information Study Chair: Susanne Osanto, MD PhD The European Uro-Oncology Group (EUOG)
The European Uro-Oncology Group
Layout table for additonal information Responsible Party: The European Uro-Oncology Group ClinicalTrials.gov Identifier: NCT02814968 History of Changes Other Study ID Numbers: EudraCT Number 2014-001161-27 First Posted: June 28, 2016 Key Record Dates Last Update Posted: April 14, 2022 Last Verified: February 2021
Keywords provided by The European Uro-Oncology Group:
Castration-resistant prostate cancer Enzalutamide Imaging PET/CT Whole body MRI Circulating tumour cells Cell-free tumour DNA
Additional relevant MeSH terms:
| https://clinicaltrials.gov/ct2/show/NCT02814968 |
(PDF) Director identity in pre and post-crisis Iceland: effects of board life stage and gender
PDF | Purpose – The purpose of this paper is to examine how directors’ roles and social identities are shaped by gender and board life stage, using pre-... | Find, read and cite all the research you need on ResearchGate
Director identity in pre and post-crisis Iceland: effects of board life stage and gender
October 2015
Gender in Management 30(7):572-594
DOI: 10.1108/GM-07-2015-0064
Authors:
Susan Vinnicombe
Abstract and Figures
Purpose
– The purpose of this paper is to examine how directors’ roles and social identities are shaped by gender and board life stage, using pre- and post-crisis Iceland as the setting. Recent theoretical work suggests the importance of directors’ monitoring and resource provision roles at certain board life stages; however, there is limited empirical evidence of directors’ identification with these roles as well as social role identification as a member of the board.
Design/methodology/approach
– The authors contribute empirical evidence from interviews with 23 corporate directors in Iceland on individual identification with the director role of monitoring and resource provision, relational identification with the CEO role and social identification as a member of the board.
Findings
– Prior to the crisis, male directors identified more strongly with resource provision and with their social roles and less strongly with monitoring roles. Compared to their male counterparts, pre-crisis female directors identified more strongly with monitoring and did not identify with their social roles. After the crisis, mature boards’ male director role identities were little changed; male directors continued to identify with resource provision and social identification, rather than monitoring, roles. Compared to pre-crisis, post-crisis female directors described greater identity with their resource provision roles and reported that male directors resented their attempts to fulfill their monitoring roles. In post-crisis, newly formed diverse boards, male and female directors reported very similar role identities which reflected balanced monitoring and resource provision roles, for example providing the board with ethical individual identities and unblemished reputations. The findings of this paper indicate that board composition and life cycle stage might have more impact on director identity than a pre- or post-crisis setting. These findings suggest implications for theory, practice and future research.
Originality/value
– This paper provides further empirical evidence of the roles male and female directors identify with on corporate boards. Its originality lies in the context of the board work in terms of newly formed and mature boards, before and after the financial crisis, with differing gender composition (male-dominated and gender-balanced boards).
Iceland: per cent Female board members, GDPPC, and Consumer Confidence …
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Gender in Management: An International Journal
Director identity in pre- and post-crisis Iceland: effects of board life stage and
gender
Thoranna Jonsdottir Val Singh Siri T erjesen Susan Vinnicombe
Article information:
T o cite this document:
Thoranna Jonsdottir Val Singh Siri T erjesen Susan Vinnicombe , (2015),"Director identity in pre- and
post-crisis Iceland: effects of board life stage and gender", Gender in Management: An International
Journal, Vol. 30 Iss 7 pp. 572 - 594
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women’s odds of corporate board directorships", Gender in Management: An International Journal,
Vol. 30 Iss 7 pp. 523-550 http://dx.doi.org/10.1 108/GM-07-2015-0063
Val Singh, Sébastien Point, Y ves Moulin, (2015),"French supervisory board gender composition and
quota threat: changes from 2008 to 2010", Gender in Management: An International Journal, Vol. 30
Iss 7 pp. 551-571 http://dx.doi.org/10.1108/GM-07-2015-0065
Elena Doldor, Susan Vinnicombe, (2015),"W omen’s pathways to the boardroom", Gender in
Management: An International Journal, Vol. 30 Iss 7 pp. - http://dx.doi.org/10.1 108/GM-07-2015-0062
Director identity in pre- and
post-crisis Iceland: effects of
board life stage and gender
Thoranna Jonsdottir
School of Business, Reykjavik University, Reykjavik, Iceland
Val Singh
International Centre for Women Leaders,
Craneld School of Management, Craneld University, Bedford, UK
Siri Terjesen
Department of Management and Entrepreneurship,
Kelley School of Business, Indiana University, Bloomington, Indiana, USA
and School of Economics and Management, Lund University,
Lund, Sweden, and
Susan Vinnicombe
International Centre for Women Leaders, School of Management,
Craneld University, Bedford, UK and Simmons College,
Boston, Massachusetts, USA
Abstract
Purpose – The purpose of this paper is to examine how directors’ roles and social identities are shaped
by gender and board life stage, using pre- and post-crisis Iceland as the setting. Recent theoretical work
suggests the importance of directors’ monitoring and resource provision roles at certain board life
stages; however, there is limited empirical evidence of directors’ identication with these roles as well as
social role identication as a member of the board.
Design/methodology/approach – The authors contribute empirical evidence from interviews with
23 corporate directors in Iceland on individual identication with the director role of monitoring and
resource provision, relational identication with the CEO role and social identication as a member of
the board.
Findings – Prior to the crisis, male directors identied more strongly with resource provision and with
their social roles and less strongly with monitoring roles. Compared to their male counterparts,
pre-crisis female directors identied more strongly with monitoring and did not identify with their
social roles. After the crisis, mature boards’ male director role identities were little changed; male
directors continued to identify with resource provision and social identication, rather than monitoring,
roles. Compared to pre-crisis, post-crisis female directors described greater identity with their resource
provision roles and reported that male directors resented their attempts to fulll their monitoring roles.
In post-crisis, newly formed diverse boards, male and female directors reported very similar role
identities which reected balanced monitoring and resource provision roles, for example providing the
board with ethical individual identities and unblemished reputations. The ndings of this paper
indicate that board composition and life cycle stage might have more impact on director identity than a
pre- or post-crisis setting. These ndings suggest implications for theory, practice and future research.
Originality/value – This paper provides further empirical evidence of the roles male and female
directors identify with on corporate boards. Its originality lies in the context of the board work in terms
The current issue and full text archive of this journal is available on Emerald Insight at:
www.emeraldinsight.com/1754-2413.htm
GM
30,7
572
Received 30 July 2014
Revised 17 May 2015
3 June 2015
Accepted 5 June 2015
Gender in Management: An
International Journal
Vol. 30 No. 7, 2015
pp. 572-594
© Emerald Group Publishing Limited
1754-2413
DOI 10.1108/GM-07-2015-0064
Downloaded by Indiana University Bloomington At 10:11 01 October 2015 (PT)
of newly formed and mature boards, before and after the nancial crisis, with differing gender
composition (male-dominated and gender-balanced boards).
Keywords Gender, Directors, Economic change
Paper type Research paper
Introduction
Good corporate governance is crucial to the effective and ethical functioning of large
corporations. Individual board directors play two key roles, as:
(1) monitors of the rm’s nances, conduct, strategic direction and CEO on behalf of
shareholders; and
(2) resource providers, via human capital and social capital, of advice, legitimacy
and access to additional individuals and resources ( Demb and Neubauer, 1992 ;
Hillman and Dalziel, 2003 ).
Despite the vast literature on boards of directors’ roles and responsibilities, we know
very little about the inner workings of corporate boards ( Finkelstein et al. , 2009 ; Huse
et al. , 2011 ). One particularly critical knowledge gap concerns how directors specically
identify with their monitoring and resource provision roles and how these relate to
directors’ social identities on the board.
Directors on corporate boards fulll two distinct functions. Building on agency
theory, they serve a monitoring function that ensures the alignment of management and
shareholder interests ( Fama and Jensen, 1983 ). Building on resource dependency theory,
directors fulll a resource provision function ( Pfeffer and Salancik, 1978 ). Monitoring
activities include analysis of strategy implementation, succession planning, evaluations
of top executives and general oversight of top management. Directors, by virtue of their
expertise (human capital) and connections (social capital), provide advice, legitimacy,
communication channels and access to elite networks ( Hillman and Dalziel, 2003 ).
An emerging body of theory suggests that the strength of directors’ social
identication with the CEO and the board in general inuences the extent to which they
engage in monitoring and resource provision ( Hillman et al. , 2008 ). Furthermore,
directors’ identities strongly shape their behavior during organizational crises ( Withers
et al. , 2012 ). Scholars have called for empirical tests of director identity ( Cannella et al. ,
2015 ), including in times of crisis. As most corporate governance research relies on
externally available data, such as annual reports, nancial results and director
biographies, researchers such as Bilimoria and Huse (1997) , Huse (2005) called for work
that directly accesses these elite subjects and provides an in-depth analysis to better
understand how directors enact their roles.
The global economic crisis is a particularly salient context for the study of director
roles, especially with respect to changing board demographics. The 2001 Enron asco
and subsequent banking scandals led to greater demands for better corporate
governance, including the appointment of more women to corporate boards ( Higgs,
2003 ). Despite many national corporate governance codes with “comply or explain”
policies to promote women to directorships, the boards of directors of most large
corporations around the world remain male dominated ( Catalyst, 2015 ), and
consequently, most governance research focuses on male-dominated boards ( Pye, 2000 ;
Arfken et al. , 2004 ; Adams et al. , 2015 ). A growing body of research investigates female
573
Effects of
board life
stage and
gender
perspectives on boards of directors ( Terjesen et al. , 2009 for a literature review) and nds
that a non-token share of female directors function differently from their all-male or
token female counterparts ( Konrad et al. , 2008 ; Huse et al. , 2009 ; Nielsen and Huse, 2010a ,
2010b ; Hafsi and Turgut, 2012 ).
This study responds to the above calls by investigating: How do directors identify
with their individual roles and social identities as board members? How are directors’
identities shaped by gender and membership on mature, male-dominated or newly
constituted, gender-balanced boards? We address these questions with data from 23
face-to-face interviews with Icelandic directors in settings before and after the 2008
crisis. We begin by describing the Icelandic context and reviewing the relevant
theoretical literature. Next, we outline our data and methodology and present our
ndings, suggesting eight propositions. We discuss the study’s contribution to theory
and practice and outline limitations and suggestions for further research.
The Icelandic context: crisis and corporate governance
Iceland’s small economy of 320,000 inhabitants and approximately 30 listed companies
came to global attention in September 2008 with the collapse of country’s three major
banks (Glitnir, Landsbanki and Kaupthing). Prior to the crisis, Icelandic banks engaged
in extremely risky speculation that involved considerable conicts of interest due to
lending to owners and related parties ( Sigurjonsson and Mixa, 2011 ; Vaiman et al. , 2011 ).
Although activities greatly expanded bank balances and contributed signicantly to
Iceland’s macroeconomic book which peaked in 2007, the speculation introduced serious
systematic risk. The Financial Supervisory Authorities and the Central Bank failed to
detect this risk and the banks were not required to deleverage. Furthermore, the banks
failed to secure their liquidity in foreign currency and engaged heavily in purchasing
their own shares to keep the stock prices up. The rapid loss of liquidity and market
funding resulted in the collapse of all three major banks in Iceland during the second
week of October 2008 ( Baldursson and Portes, 2013 ).
After the crisis, the Icelandic economy experienced dramatic falls in national
currency, gross domestic product (GDP) and consumer condence. The Icelandic stock
exchange’s market capitalization decreased by 90 per cent due to companies going
bankrupt or being de-listed. Consequently, most large Icelandic companies faced
extreme difculties and often entire boards were reconstructed, especially in the
nancial sector. Iceland is considered to have experienced the world’s greatest modern
crisis ( Sigurjonsson and Mixa, 2011 ); however, the Icelandic case has not been examined
in prior studies of crisis and corporate governance ( van Essen et al. , 2013 ).
Prior to the crisis, women occupied less than 10 per cent of the board seats of the
largest 100 companies and none of Iceland’s largest 50 companies had more than one
female director on the board. Discussions on the scarcity of women on corporate boards
had started in 2004; however, business sector leaders did not consider the issue pressing
( Jonsdottir, 2008 ). Norway was the rst country to introduce gender quotas for corporate
boards, in 2003 for private companies and 2006 in public companies, followed by Spain
in 2007 ( Terjesen et al. , 2014 ). Subsequently, the introduction of gender quotas in Iceland
was debated; however, the idea of a quota was not well received until after the crisis. On
March 4, 2010, a bill was passed that came into effect in September 1, 2013, requiring
both publicly owned companies and public limited companies with more than 50
employees to compose their boards of at least 40 per cent of either gender ( Fichtl, 2013 ).
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The new legislation generated very little public debate, and by the end of 2013, most
large companies had fullled the quota requirement. Following the crisis, a number of
boards were reformed, resulting in the largest shares of female directors ever witnessed
in Iceland. For example, in the spring of 2009, women comprised 40, 60 and 100 per cent
of the newly formed boards of the three largest banks. It is interesting to note that these
female appointments pre-dated Iceland’s mandatory quota for at least a 40 per cent
share of women. Iceland’s female board members have been described as the “heroines
of Reykjavik” by the media ( Carlin, 2012 ) for their role in rebuilding Icelandic rms and
the economy. Certainly, Iceland’s GDPPC and consumer condence gradually increased
over time. Figure 1 depicts Iceland’s percentage of female board members, GDPPC and
consumer condence for the 2003-2012 period.
Icelandic boards range in size from three to nine directors, with ve as the most
common size, and are hence much smaller than their American and British counterparts
which average about 9-10 members. Icelandic boards consistent only of independent
(non-executive) directors. Furthermore, in contrast to other national corporate
governance models, the CEO is generally not a formal member of the board but attends
and participates in board meetings. Icelandic corporate law prohibits the dual CEO/
Board Chair role, which is commonly found in corporate governance systems around the
world. Icelandic boards commonly met 10-14 times a year before the crisis. In the months
following the crisis, boards met as often as two or three times per week. By contrast,
most American, British, European and Asian boards of publicly traded rms meet
between four and twelve times a year.
Theoretical background
Social identity theory
Social identity theory focuses on the social categories of identities, for example, as based
on organizational or social memberships. Individuals use social identity to perceive
themselves in relation to categories or groups of other people in particular contexts
( Tajfel and Turner, 1986 ), drawing on prototypes of the group member role and
behavior. Individuals identify with membership of the group to varying degrees,
depending on their emotional attachments to the group and the context. At any one time,
individuals may have many group memberships with varying strengths of
Figure 1.
Iceland: per cent
Female board
members, GDPPC,
and Consumer
Condence
575
Effects of
board life
stage and
gender
identication. For example, a female director may be more aware of her membership of
the female category in a context where she is the only woman (e.g. on a corporate board)
than of her actual membership as a director on that board. Furthermore, others’
perceptions of an individual’s social identity will depend on their own categorization
processes and strengths of identication with the group membership and the salience of
the context.
Identity in the corporate board setting
An important and under-examined context for examining individuals’ role identity and
social identity is the corporate board, where directors are expected to identify both in
terms of roles and social groups ( Hillman et al. , 2008 ). Hillman et al. ’s (2008) early
theoretical work suggests that independent directors may provide varying levels of
monitoring and resource provision based on ve role identities: as organizational
member, director, CEO, shareholder and customer or supplier. Thus, Hillman et al.
(2008) suggest that individuals who strongly identify with the board member role are
more likely to be concerned with personal reputation and, hence, will actively monitor
and provide resources to their boards. In contrast, a director who is also a CEO of
another rm may be less reluctant to criticize in the boardroom, due to empathy for the
CEO’s position and a high level of discomfort with close scrutiny when he/she is the
CEO. In this paper, we look at how directors identify with being on members of the board
and specically with being a CEO.
A second branch of theorizing examines organizational decline and crisis, suggesting
that individuals’ roles also map to context, such that in an organizational crisis,
individuals who identify with director roles are more likely to be concerned with their
exit and reputation, while individuals who identify as CEOs or shareholders will be
more likely to seek to ensure the rm’s survival ( Withers and Hillman, 2008 ). A recent
extension by Withers et al. (2012) considers that strong identity with a particular role, for
example as a CEO, will delay the onset of proactive monitoring. Taken together, this
work suggests the importance of empirically examining director identity in a context.
While the context in Withers and Hillman’s (2008) study was an organizational
turnaround, the context in this paper is the nancial crisis in Iceland and the
restructuring of a number of boards to become gender balanced.
Corporate board director responsibilities: board life cycle stages and gendered
perspectives
Corporate directors have multiple sets of responsibilities, including monitoring
managers on behalf of the owners and shareholders, giving advice, conferring
legitimacy and facilitating connections to resources based on social capital ( Zahra and
Pearce, 1989 ; van Ees et al. , 2009 ). Extant research generally views boards as
homogeneous groups that perform generic functions and does not differentiate among
organizational contexts or between individual and group behavior ( Pye, 2004 ).
One particularly salient organizational context is the life cycle stage of the board.
Mature board cultures may be characterized by path-dependent experiences and
long-standing relationships among members and a sense of tradition. By contrast,
newly constituted boards are not bound by administrative history and inertia, and
members may perceive more opportunities for fresh and non-traditional perspectives on
their board work and their identities and roles associated with the board.
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A second component of organizational context is gender and concerns the share of
female directorships, including whether these women directors are tokens (i.e. less than
15 per cent, Kanter, 1977 ) on their boards. Prior research suggests that critical mass,
rather than absolute numbers of women, inuences board dynamics and leads to
women’s voices being heard and outcomes, such as increased innovation ( Torchia et al. ,
2011 ). Higher proportions of women directors enhance board development activities, as
women contribute greater levels of preparation ( Nielsen and Huse, 2010a ). When female
directors’ share is higher, female directors are more likely to believe that they monitor
and control, express their views and have a high level of inuence in the boardroom
( Elstad and Ladegard, 2010 ). Other gendered aspects of director responsibilities relate to
women’s challenges, even after becoming directors, to demonstrate their legitimacy
( Hillman et al. , 2000 ; Westphal and Milton, 2000 ). Furthermore, women directors’
specic boardroom roles may include advocating for women’s issues, such as balancing
work/family needs and other “soft issues” ( Burke, 1997 ).
Taking the above into consideration, we probe our data for board life cycle and
gendered perspectives on director roles in a pre- and post-crisis setting.
Data and methodology
We chose a qualitative approach to gain an in-depth understanding about directors’
interpretations of their responsibilities as well as their role identication. We sought to
gain insight into the individuals’ experience as board members and how they thought
about their roles and how they acted to fulll them. Interviews were semi-structured and
followed a protocol which was identical for all interviews both in the pre- and post-crisis
setting. When analyzing the data, we looked for patterns of similarities and differences
across individuals and sub-groups. While the generalizability of our ndings is very
limited, the semi-structured approach enabled us to uncover thoughts and ideas that
might not have emerged in a more structure setting.
Sample
We conducted in-depth interviews with 12 women and 11 men who collectively held
directorships in 50 of Iceland’s largest companies (by revenue in 2005). For the rst
study, we selected mature boards with at least one female member, as it turned out none
of the boards of the 50 largest companies had more than one female at the time; hence,
our boards had only one female. Boards in the second study also had at least one female
director and could be identied as either mature or newly constructed. The rst wave of
interviews, collected from November 2006 to April 2007, included ve males and six
females from six focal boards. These rms were predominantly in the nancial and
investment sector, but also included transport, high-technology manufacturing and
retail. All pre-crisis male director interviewees had mostly served on all-male boards, the
focal board being an exception. The pre-crisis female director interviewees were always
the only female directors on their boards.
The second wave of interviews was conducted after the 2008 crisis, from March to
May 2009, and included 12 independent directors (6 women, 6 men) from 5 of Iceland’s 50
largest rms. Two boards were selected because they had gender balance and were
newly constructed, which was a consequence of the crisis and the need to build a
completely new organization. The other three boards were chosen based on women
577
Effects of
board life
stage and
gender
directors’ positions as a minority or token on these mature entities and, thus, resembled
the gender composition of the focal boards in the rst wave of the study.
Table I provides an overview of the participants. As shown, female directors were
generally younger and had less business and board experience than their male
counterparts. However, among the newly constituted boards, female directors had
more business experience than their male counterparts and similar levels of board
experience. Across all boards, male and female directors possessed generally high levels
of education.
Interviewees were asked not only to keep their focal board in mind, but also to reect
on their extensive general board experience which altogether covered the boards of more
than 50 of Iceland’s largest 100 companies. Many interviewees were personally
acquainted with the co-author who conducted the interviews. We believe that high levels
of trust between interviewer and interviewee led to greater access and willingness to
share information.
Interviews
Our in-depth, semi-structured interviews were conducted at the ofce of either the
interviewer or the interviewee and followed the interview protocol in Appendix 1 . This
protocol was designed to elicit directors’ interpretation of their roles on the board and
explicitly asked interviewees to describe the nature and importance of informal
relationships in their board roles, which provided the basis for our coding on social role
identity. The protocol served as a checklist of themes or points of discussion to ensure
that relevant topics were covered with additional questions as needed. Interviews were
conducted in Icelandic, the native language of the interviewer and interviewees, and
recorded and transcribed in Icelandic and then translated into English by the
interviewer who was mindful of getting the tone and context across; however,
translation might cause lack of accuracy of the data. Each interview lasted
approximately 60 minutes.
Design and analytical approach
The interview design reects calls for clarity in the level of analysis in board studies
( Pye, 2004 ) by focusing on the individual’s identication with the director and social
roles. The research design followed a social constructionist approach, drawing on
respondents’ thoughts, experiences and interpretations, as they constructed their own
realities of their board roles during the interviews. The directors’ responses are
reinterpreted by the researchers to make sense of the underlying identication with
director and board roles ( Berger and Luckmann, 1966 ). We viewed our task as not to
gather facts and measure how often events or patterns occur to be able to generalize to
a larger population but rather as to gain depth and understanding of a particular context
( Easterby-Smith et al. , 2002 , p. 30).
As qualitative data analysis is prone to biases due to the researchers’ expectations
and preconceived ideas ( Easterby-Smith et al. , 2002 ), we took steps to limit these biases
by keeping an open mind and systematically analyzing the data. We imported the text
into NVivo to identify and structure emerging concepts and themes. This process
followed Easterby-Smith et al. (2002 , pp. 123-124) and involved interactive rounds of
analysis.
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Table I.
Interview
participants
Gender Age Education
No. of years
on focal board
No. of board
directorships at
time of interview
Board
experience
Business
experience
CEO at time
of interview
Pre-crisis interviews
Male-dominated M 59 Masters 15 6 High High Yes
M 44 Masters 4 1 Medium High Yes
M 44 High school 1 3 High High Yes
M 58 High school 1 2 High High No
M 49 Masters 1 3 High High No
F 52 Undergraduate 17 3 High High Yes
F 47 Masters 4 1 Medium High No
F 39 Masters 1 1 Low Low No
F 46 Undergraduate 1 1 Low Medium No
F 50 Masters 1 2 Medium High No
F 38 Masters 1 2 High Medium No
Post-crisis interviews
Male-dominated M 57 Undergraduate 10 5 High High Yes
M 63 Undergraduate 3 5 High High Yes
M 52 Masters 1 3 High High Yes
F 44 Masters 2 3 Medium High No
F 59 Undergraduate 2 2 Medium High No
F 48 Masters 1 2 High High Yes
Balanced M 54 Masters 1 1 Medium medium No
M 55 PhD 1 1 Low Low No
M 53 Masters 1 2 High High No
F 55 Undergraduate 1 3 High High Yes
F 45 Masters 1 1 Medium medium Yes
F 44 PhD 1 1 Low low No
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Effects of
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stage and
gender
We initiated the analysis with several deep readings of the transcripts and began by
informally identifying issues in the existing literature and then extended these ideas.
For example, as well as the director role interpretation coding theme, we identied
another strong theme relating to the director role identication process and the social
role identity of being a board member. We returned to the literature on director identity
to build up coding labels below those headings. We undertook several rounds of coding
in NVivo, reorganizing themes and coding. We revisited the interview data as a validity
check, in consultation with key literature. The emerging conceptual structure on
director identication was reviewed and adjusted based on iterative discussions among
the authors.
Findings
We report the ndings according to the themes we identied during the analysis of the
interviews. Taking advantage of the qualitative nature of the study, we construct our
propositions based on the themes and constructs emerging from the data.
Identication with the director role as monitors
Pre-crisis. In the pre-crisis setting, none of the male directors brought up the monitoring
role as one of their primary functions on the board. Only one male director commented
on his agency role as being a monitor of management actions but said he was not going
to check the nancial statements:
I cannot get bothered with the numerical details; it’s a kind of common sense that you have to
have and a broad overview. M4 (Mature Board, non-CEO)
In contrast to the male directors, all of the female directors described their key role as
monitoring. The female directors reported that they asked critical questions, challenged
managers, made them “justify things to themselves”, “dragged the board members
back” and requested explanations. The female directors also commented that this
monitoring role took courage, was not well received by other members and was not done
by other (all male) board members. According to the female directors, “political skill”
was needed to monitor and “you do have to pick and choose a bit” about what and when
to question other board members. This indicates that while the female directors
expressed a strong interest in their monitoring roles, they had to take care of not being
too vocal to avoid the risk of being criticized by their male counterparts:
P1 . In pre-crisis mature male-dominated boards, female directors are more likely
than male directors to identify with their monitoring roles.
Post-crisis. In general, the male directors on mature boards, similar to their counterparts
on the pre-crisis mature boards, did not relate to the monitoring role. The only male
director from a mature board to describe questioning as important commented on the
issue very late in the interview and in the context that the boards should do more
questioning and that questioning was not the norm:
I am quite sure that critical questioning by board members has been severely lacking. You
don’t need to ght like cats and dogs, I just mean that solid, well-worded and critical questions
that experienced people have the cleverness to ask - and review things in that manner. TM2
(Mature Board, CEO)
GM
In contrast, the male directors sitting on the new gender-balanced boards strongly
identied with their monitoring role.
As they reported in the pre-crisis interviews, female directors on mature boards
commented, without prompting, on the critical monitoring aspect of their role as a
director. According to one female, “one of the board’s main roles is to review the
nancials”. All of the female directors on mature boards indicated that questioning,
from female directors in particular, was still generally not welcomed by their male
counterparts. One female director who was also a CEO stated, “we have to learn that
asking questions is not being annoying”. Another experienced female director reported
that she felt “it was like at school where someone is afraid to ask, and if she did, then ‘Oh
dear, why is she asking so much?’” This director added that “people sometimes took the
questioning as personal”, rather than as a disciplined component of board processes.
Another female director commented on the males’ negative reactions to her monitoring
role:
Sometimes it is like you are being excessively ofcious, but I choose to look at it in a way that
you are trying to improve the operations and point to things that can be improved […] and you
are not always looking for someone to blame, you are trying to help people to manage their
affairs properly. TF2 (Mature Board, non-CEO)
One female director of a mature board suggested that the willingness or motivation to
question critically might be gender-related:
Well, because men tend to be more eager to make statements, they act as if they have the
complete view. While the women sort of work their way toward the information – the men
make the statements, they claim they know things for a fact right from the start and then
perhaps back off if there is a need to support their statements, while women sort of come from
the other side and work their way toward the statement by questioning. F2 (Mature Board,
non-CEO)
Female directors on new gender-balanced boards dened their key roles as monitoring,
in asking critical questions and improving board performance. These female directors’
responses indicated their personal condence in their roles as monitors, as illustrated by
the following quotations:
What is really important to me is to ask a lot – I consider it to be one of my main duties to ask
until I understand it, so I can make my decision with a certain level of condence, so I can be
certain that the right things are being done, and it really applies to the entire board, everybody
asks a lot. NF1 (New Board, CEO)
I would say I ask more questions because I have made a point of doing so, yes. Perhaps it is just
the experience and maturity that has taught you that you know when to ask, and you are just
past a certain barrier and just ask. You are no longer prepared to just follow the group, so I
think it is more that. NF2 (New Board, CEO)
Male directors on new gender-balanced boards described role identications that were
similar to the female directors, namely, as “critical” directors “probing and striving for
better board practices”. Male board directors also mentioned monitoring that the law
was being obeyed and that nancial results were closely scrutinized. None of the new
board male directors were CEOs, and perhaps because of this lack of identity with the
CEO role, they were willing to question the CEO and nancial matters, fullling their
agency role. This nding is in sharp contrast to that of male directors on mature boards
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Effects of
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stage and
gender
who focused far more on their resource provision roles than their duty to engage in
monitoring roles:
P2 . In post-crisis boards, male directors on new gender-balanced boards and female
directors on both new gender-balanced and mature male-dominated boards are
more likely than male directors on mature male-dominated boards to identify
with their monitoring roles.
Identication with the director role as resource providers
Pre-crisis. All of the male directors identied with their key roles of bringing strategic
resources to the boardroom. The ve male directors, including three CEOs, saw
themselves as bringing their long-standing experience, judgment and “big picture
vision” as directors to the table. Examples of this emphasis on the resource provision
role include:
As time goes by and the maturity and experience increase, you see things more with the eyes
of a “wise old man”. M3 (Mature Board, CEO)
I have extensive experience. […]. I think an old nose like mine can very well sniff out the pros
and cons of particular matters. M1 (Mature Board, CEO)
By contrast, female directors, including one who was a CEO, described themselves as
“there to support and provide specialist assistance”, mainly to the CEO. These female
directors were modest and did not claim to be wise or vastly experienced, although their
pre-board education was comparable to their male counterparts. One female director
shared that she brought a “more simplied view” of issues to the board. Taken together,
female directors did not explicitly mention their roles as resource providers:
P3 . In pre-crisis mature boards, male directors are more likely than female directors
to identify with their resource provision roles.
Post-crisis. Following the crisis, all female and male directors on mature male-dominated
and newly formed gender-balanced boards revealed the importance of their resource
provision roles. Compared to the male directors, female directors were more explicit in
identifying these strategic resources. For example, two female CEOs emphasized the
need to manage their personal reputations as directors, based on their previous actions
and involvement. The following interviewee excerpts are illustrative:
You have to have some principles that you stick to and not be willing to compromise or sell
your reputation. TF3 (Mature Board, CEO)
You are attaching your name in a very different manner than if you were an employee of the
owner. You become more alert that you need to deliver and take care of your reputation, so
often outsiders approach things more formally, have more formal minutes and so on, if you are
going to attach your name to it. NF2 (New Board, CEO)
On mature boards, directors’ resources included human capital, such as business
experience and education, and social capital, such as linkages to external networks. Two
male and two female directors reported that their appointments were due to their
business experience and relationships with previous owners. One female director noted
that her “nance and business turnaround experience, as well as my degree” were
sought by those appointing her to the board. Another female director shared that she
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had been the board secretary but had recently been appointed as a director because of
that knowledge acquired in that earlier role.
On new gender-balanced boards, where all directors had only one year of experience,
male and female directors also shared similar, resource provision-related views as to
why they had been appointed. Directors identied key factors as based on their
“unblemished reputations”, which provided legitimacy to the board which was
“desperately needed”. One male director felt that he was selected based on “being known
to an Icelandic Minister, distant from the crash, and some earlier board experience”.
Another male director with an academic background was told that “he had a good
reputation with operational and nancial experience”. Another male director described
his resource as being known as independent, professional and not politically afliated
through his participation in public debates and writings:
I am there on the board of the bank and there is no one who can tell me how to act […] no one,
no one!!! I don’t take any instructions or messages about how I should deal with matters; I am
completely free and independent. And the party that appointed me has not made any gestures
in that direction, anyway I wouldn’t attend to it - and if they tried to I would just immediately
walk away. NM1 (New Board, non-CEO)
A female CEO sitting on a new board emphasized her honesty and moral standards and
that she was “someone not associated with those who had brought the country to its
knees”. She shared:
I at least think that he wanted someone who was honest and had never been involved in
something dubious or dishonest so you could doubt the moral standards of the person […] And
that I am not connected to any of the big business circles that were in the playing eld, so I
should be in a neutral position. NF1 (New Board, CEO)
Several new board directors reported taking on their director roles as “rather a duty that
you perform as a citizen”. One male academic saw his directorship as a service, because
the pay was limited and the board role required one day a week. A female director added
that while she had “no great interest in becoming a director of a bank, it was the socially
responsible thing to do” and that “everyone needed to lend a hand”:
P4 . In post-crisis boards, male directors and female directors strongly identify with
their resource provision roles, regardless of whether the board is a mature
male-dominated one or a newly established gender-balanced board.
Identication with the CEO role
Pre-crisis. In our pre-crisis sample, three of the ve male directors were CEOs themselves
and mentioned their role as director in relation to their role as CEO. One non-CEO male
illustrated an exception and described monitoring of the CEO as an important task for
the board as a whole and as his individual role:
Well, we the board, we hire the CEO, we approve the corporate strategy the CEO suggests, we
have an opinion on how the company can work, we provide the discipline […]. I make it my
concern to look at how the CEO presents matters, and I’m thinking is he doing the right thing
[…] I’m trying to get a feeling for if the guy is blufng, not intentionally, it’s just, is he living
up to standards, is he making sense, is it working? M4 (Mature Board, non-CEO)
Two male directors commented that CEOs need to trust board members and consult
with them, but “condentially”, as at that level “there are lots of things you don’t want
583
Effects of
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stage and
gender
to elaborate on just anywhere”. Of the six female directors, only one was also a CEO.
While one female director spoke of the “great sounding board”, two other women
extensively discussed their roles as “support” to the CEO as the reason for their
appointments, thus not really identifying with the “directing” aspects of their director
roles.
Our data on male directors’ perceived roles reveal that few prioritized the role of
monitoring the CEO. This reluctance to question management, including the CEO, is in
contrast to their non-CEO female peers who, as described earlier, identied strongly
with the monitoring role. Individuals who identify with the CEO role (i.e. those directors
who are also CEOs of other rms) are likely to ask fewer questions of executive
management, believing it to be the CEO’s area of responsibility, and trust that “what
needs to be done will be done”. Taken together, we propose:
P5 . In pre-crisis mature male-dominated boards, male directors who are also CEOs
are more likely than non-CEO directors to identify with the CEO role and to
demonstrate a reluctance to challenge the CEO.
Post-crisis. Following the crisis, both male and female directors on new gender-balanced
boards – whether or not they were also CEOs outside the focal boards – shared the view
that a key part of the role was to monitor the CEO and the nances. However, on mature
male-dominated boards, the male directors, all of whom were CEOs, were still less
involved in their monitoring role, with only one male director mentioning the CEO
monitoring role briey when prompted. By contrast, the one female director who was
also a CEO and sat on a mature board was very emphatic about the directors’ need to be
able to:
[…] question without negativity, especially about the key nancial results […] if the right
structures and processes were in place, then any problems should be highlighted in time for
remedial action.
Taken together, we observed gender differences between directors on mature male-
dominated boards and gender similarities between directors on new gender-balanced
boards. Through their lower concern for monitoring, male directors’ behavior on mature
male-dominated boards pre- and post-crisis indicates their stronger identication with
the CEO of the focal company:
P6 . In post-crisis boards, male directors on mature male-dominated boards are more
likely than male directors on new gender-balanced boards and female directors
on mature male-dominated boards and new gender-balanced boards to identify
with the CEO role and to demonstrate a reluctance to challenge the CEO.
Identication with the social role as board member
Social role identity concerns identication with membership of a group that has certain
dening characteristics, including norms and behaviors, which are typical of the group.
Here, we are concerned with how directors perceive themselves as members of their focal
boards rather than as individual directors.
Pre-crisis. Prior to the crisis, the male directors emphasized the importance of
establishing and developing informal and personal relationships with their fellow board
members and considered this to be a crucial part of being effective as a director. One
male director described himself as a member of “the forum that creates the drive”. The
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male directors also reported informal communication several times a week. According
to one director:
I think it does matter that men know one another; they’re not simply sitting there with a
straight back and a straight tie but that they can share social moments together. M1 (Mature
Board, CEO)
In sharp contrast, female directors reported very low levels of informal relationships
with fellow board members. The following quotations illustrate that female board
members did not seem to have an equal amount of interaction with their boards before
the crisis:
There are basically no interactions between board meetings unless there is an issue that needs
attention, maybe a phone call or two. F1 (Mature Board, CEO)
I’m on good terms with [two of the board members] but that relationship is limited to the board
meetings […]. I do know, however, that they are active between meetings and keep in touch. F3
(Mature Board, non-CEO)
One male director described being a member of the sub-group that is “a relatively tight
nucleus that makes the big decisions, important in a big board, where informal meetings
are held on the phone, in the evenings or weekends”. According to this male director,
membership in this group means that “your views are considered valid – whether you
are in the group that is really pushing things forward”.
These pre-crisis male directors’ comments were consistent with the view that being a
director is a signal of being a trusted member of a board and also that trust is an outcome
of the social relationships between board members. Male directors described this trusted
membership as something that had been built up over time and which helped to predict
the behavior of other board members. As one male director shared:
Yes, it [trust] is absolutely a fundamental. And of course in this group men have worked
together for a long time […] we know each other well, and you have to trust these people you’re
working with, it’s all about that. M2
Despite possessing similar years of board tenure (i.e. just over four years) to their male
counterparts, female directors described having to undertake activities to acquire trust
from their fellow board members. Several female directors shared stories having to build
credibility as a useful and consistent contributor and board member, as the following
quotation illustrates:
To build credibility you need to show consistency in behavior, I would say, so people know
where you are coming from and know what type of person you are. F2
Only female directors described themselves as needing to “facilitate a good atmosphere
in the boardroom” and reected on the masculine culture of the boardroom. Two female
directors portrayed themselves as “diplomats”, while another female director focused on
how her role involved “rebuilding what had been demolished”. Taken together, female
directors’ gender identity as the sole woman on the board may have taken precedence
over their board member identities such that they did not strongly identify with the
social role:
P7 . In pre-crisis mature male-dominated boards, male directors are more likely than
female directors to identify with the social role of being a board member.
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Effects of
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Post-crisis. Following the crisis, informal relationships were regarded as important by
male directors on male-dominated mature boards, and thus, there is no change from the
pre-crisis interviews in which male directors identied strongly with the social role of
board members and dened informal relationships as a prerequisite of trust and
effectiveness. One male CEO said that “there were lots of interactions between meetings
on all of the boards” that he sat on. Another CEO said that “in a small country like
Iceland, the board members know each other and naturally meet and talk about board
matters”; however, he added that on larger boards, this could lead to a “need to tighten
up processes and keep things more responsible and orderly”. These quotations suggest
that male directors on mature boards strongly identify with their social role as members
and consider themselves to be part of an extensive network of directors with signicant
activity and inuence.
One of the three female directors on mature boards explained how she gradually
became part of the board dialogue, and how her knowledge and contacts limited the
possibility that she might be marginalized:
I think you need to be involved in the dialogue. And I would say – you don’t dive into it in the
rst meeting of a new company or a new board. It sort of comes gradually, you just interact, but
I am fortunate to know the company and its operations well, so that helps. You also often try
to have conversations before the meeting. That is a part of it. TF1 (Mature Board, non-CEO)
Another female director (also a CEO) commented that on her mature board, there was
“too little interaction between board members outside the Chairman/CEO relationship”.
She felt that “delicate issues and warning signs could be dealt with earlier if informal
relationships were there”.
On new gender-balanced boards, female directors again reported that they had few
informal relationships with other directors; however, the female CEO did not consider
this to be highly important:
Sometimes it matters, but often it can be quite sufcient to attend meetings and prepare –
because there is a lot of open discussion and it is really the case that we can discuss matters in
full at the meetings. NF1 (New Board, CEO)
Interestingly, male directors on new boards also did not report that informal
relationships played an important role. One said that “occasionally there would be
e-mails, but that was the exception rather than the rule”. Another new male board
director stated that “people might make phone calls on something specic, but it was not
often”. However, one of the new board male directors talked about communication
between board meetings, as members got to know each other better:
I didn’t know everybody, but now people have gotten acquainted and can have a chat two and
two between meetings, so there has been created a sense of rapport people can read each other
sort of […] is that OK or should we have it like that? NM1 (New Board, non-CEO)
P8 . In post-crisis boards, male directors on mature male-dominated boards are more
likely than male directors on new gender-balanced boards and female directors
on mature male-dominated and new gender-balanced boards to identify with the
social role of board member.
Our ndings are summarized in Table II .
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Table II.
Summary of ndings
Pre-crisis, mature, male-dominated boards Post-crisis, mature, male-dominated boards Post-crisis, new gender balanced boards
Individual identication as
director (monitor and resource
provision roles)
“Wise”, older male directors play a resource
provision, rather than a monitoring, role
Female directors do not identify with a
resource provision role
Female directors perceive themselves in a
specialist support role
Female directors identify strongly with
monitoring roles, but are frustrated by male
directors’ response to their monitoring
Male and female directors identify with resource
provision roles
Male directors do not identify strongly with
monitoring roles
Female directors identify strongly with
monitoring roles, but are still somewhat
frustrated by male directors’ responses to this
monitoring
New directors have diverse backgrounds
and are well-educated, not tarnished by
scandal, socially responsible, but mostly
inexperienced as directors
All directors identify with both resource
provision and monitoring roles
Monitoring is actively encouraged
Relational identication with
CEO role
Male directors identify with resource role,
and are reluctant to closely monitor the
CEO particularly where they are CEOs
Female directors strongly identify with the
monitoring role
All directors identify with the resource
provision role and monitoring role, although
males did less monitoring than females
All directors identify with both resource
provision and monitoring roles
Relational identication as board
member
Male directors view informal relationships
as crucial for trust and success
“Old boys network” where women feel
excluded from informal decision-making
Male directors view their success in terms
of corporate results
Female directors require afrmation from
the board regarding their performance and
are directors “on approval”
Female directors play a “diplomat” role and
conform to gender stereotypes
Informal relationships and networking mainly
occurs among male directors
Female directors suggest that informal
relationships might help to uncover delicate
issues and spotlight warning signs
Very limited, nascent efforts at informal
relationships and networking; however,
limited importance is placed on these
Decisions are mainly taken in boardroom
and not in advance conversations
Female directors are condent in their
roles
The board is a “new experience” for all
due to the diversity of genders and
backgrounds
587
Effects of
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Discussion
This study examined how directors’ identities may be shaped by the gender
composition of the board and by board life cycle stage. While pre- and post-crisis
settings had little effect on members of mature male-dominated boards, we found
evidence of effects on newly established gender-balanced boards. With respect to
director role identity, we uncovered gender differences within the mature
(male-dominated) board director group, although these were strongest pre-crisis, when
males did not identify with the monitoring role and females did not identify with the
resource provision role. However, post-crisis, new directors were very clear on how their
unblemished reputations and lack of connections to the wrong-doers added legitimacy
to their boards. In terms of relational identity with the CEO role, we found that male
directors who were CEOs identied strongly with this role and were less reluctant to
identify with their monitoring role. We also uncovered gender differences in the social
identity of board members across the pre- and post-crisis mature boards, where women
seemed to be “directors on approval” on these male-dominated boards. On new
gender-balanced boards, a cohort effect seemed to be taking place, as there was
increasing group cohesion and fewer gender differences in directors’ identication with
their roles.
Our study offers implications for several relevant theoretical perspectives. First, with
respect to director role identity ( Hillman et al. , 2008 ; Withers and Hillman, 2008 ; Withers
et al. , 2012 ), we extend theoretical research by contributing empirical qualitative
evidence on directors’ individual identication with director monitoring and resource
provision roles, the CEO role and social identication as board members. We also
provide an important gendered perspective on these roles. Taken together, our ndings
highlight different outcomes for male and female directors on mature and new boards
before and after the crisis. That is, mature boards’ male directors’ role identities change
very little after a crisis and continue to focus on resource provision and social
identication; however, post-crisis female directors identify more with their resource
provision roles and describe male directors as resenting the female directors’ attempts to
fulll monitoring roles. Furthermore, among newly formed diverse board members,
both male and female directors identify with their balanced monitoring and resource
provision roles. Our results are consistent with theory suggesting that directors who
identify strongly with their roles will take these roles seriously so as to protect their
external identities and future directorships ( Hillman et al. , 2008 ; Withers et al. , 2012 ).
Furthermore, with respect to mature strong identity with the CEO role, we nd that male
directors who are CEOs are less likely to perform their monitoring tasks, consistent with
Withers et al. (2012) .
Second, we extend earlier work on tokenism theory and the critical mass of women on
boards ( Torchia et al. , 2011 ; Nielsen and Huse, 2010a , 2010b ; Elstad and Ladegard, 2010 ).
We elaborated on this work by considering how token status and female ratios may be
considered in light of board life stage and crisis context. Although none of the 12 female
directors mentioned the effect of multiple women on board, the different gender
proportions of the mature and new boards could be an explanatory factor for some of
the differences. Pre-crisis gender differences persisted in the post-crisis period on
mature, male-dominated boards. Our different ndings among post-crisis boards may
be explained by a mix of balanced gender diversity, the new board effect and, to some
extent, the crisis context.
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Third, our ndings offer some empirical support for the glass cliff theory ( Ryan and
Haslam, 2007 ), which suggests that women are often promoted into precarious
leadership positions. Certainly, immediately following the crisis, substantial numbers of
women were named to the boards of Iceland’s largest rms. These women carried the
burden of turning around their rms and uplifting a nation from severe economic,
nancial and moral crises. There were few female CEOs of Icelandic rms following the
crisis, demonstrating a continued scarcity of female CEOs ( Oakley, 2000 ). The nding,
consistent with Norwegian research, is that the signicant growth of female directors
was not accompanied by a growing share of female CEOs ( Sørensen, 2013 ).
Our ndings also offer implications for practice. First, retrospective analyses of
Iceland’s crisis suggest that its drivers included a lack of corporate governance
transparency and close scrutiny of rms, particularly among banks ( Sigurjonsson and
Mixa, 2011 ; Vaiman et al. , 2011 ). Indeed, our pre-crisis interviews illustrate a lack of close
monitoring by males who at that time constituted 95 per cent of Iceland’s board seats.
The limited monitoring, particularly on boards of companies in the nancial sector, may
have contributed signicantly to the crisis.
Second, our data indicate that female directors may require some level of afrmation
of their value to the board group. Our pre-crisis sample of female directors emphasized
the importance of being well-prepared for board meetings, a result consistent with
Nielsen and Huse (2010a) . In our sample, male directors did not discuss the importance
of seeking afrmation. Taken together, our ndings indicate that female directors on
mature male-dominated boards generally assessed their own contribution through the
feedback they received from fellow board members and that male directors assessed
their contributions through corporate results. This suggests that the female directors on
mature male-dominated boards identied themselves as “members on approval”. Given
Nielsen and Huse’s (2010b) nding that male directors were negative about women’s
contribution to decision-making, and particularly when the female directors had
professional backgrounds which were dissimilar to their own, it may be that the female
directors in our pre-crisis study, only one of whom was a CEO, seemed to be protecting
themselves from negative evaluations by their male colleagues by preparing
extensively and assessing their contributions by feedback from male directors. After the
crisis, both male and female directors on new boards described being successful in their
role in terms of corporate results, although females on mature boards did not comment
on this. The new board females reported feeling comfortable and condent in their
membership of the board. New boards had a critical mass of women and an open culture
that allowed all board members to contribute.
Interestingly, none of the 12 female directors before or after the crisis mentioned that
she brought women’s issues (such as work–life balance, masculine culture in the
workplace or supporting women employees’ careers) to the notice of the board, as
suggested by Burke (1997) . This indicates that female directors did not identify as being
a “female champion”. This nding, which is inconsistent with Burke (1997) , likely
reects female directors’ concerns that they were “on approval” and that they should
focus on the immediate director roles.
Our data indicate that post-crisis boards were increasingly gender diverse. A large
body of prior research establishes that greater levels of diversity in decision-making
groups can lead to higher-quality decisions, as people bring in diverse skills and
knowledge and contribute realistic and complex perspectives, as long as there is time for
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discussion ( Milliken and Martins, 1996 ). Furthermore, group tenure is also related to
greater cohesion and individual integration. Our sample may be subject to a “cohort
effect”, as new members join a unit and initiate similar individual and social
identication processes that involve setting up of formal and informal structures, such
as communication and networking routines.
Finally, our ndings suggest that boards comprising mostly male CEOs or ex-CEOs
may risk identifying too strongly with the CEO role and, thus, engage in limited
monitoring. Although director board demographic turnover is quite low, there is a
steady increase in female directors in Iceland and elsewhere around the world, brought
on by mandatory quotas and “comply or explain” codes. New board chairs have the
opportunity to create a positive and inclusive culture, allowing all board members to
make contributions, while mature board chairs must take proactive steps, such as
individual and collective board member training, to change the culture.
Conclusion
Before concluding, we wish to acknowledge several limitations of our study that are in
summary on one hand based on context and the other on the methodology. First, Iceland
is a very small country with a very small business community. In addition, Iceland
experienced an extremely severe crisis, unrivalled in any other developed or developing
country in modern times. Furthermore, Iceland has a rather unique set of corporate
governance codes, for example, prohibiting the CEO from being Chair or even sitting on
the board. It is therefore possible that our results are not generalizable to other countries.
Future research should examine directors’ roles in other countries and provide country
comparative analyses. Second, while we claried the role of board life cycle stage and
gender, future research should examine other possible explanatory factors, such as
directors’ specic background experience in a particular industry or political afliation.
Third, we realize that the methodology and very limited sample size in this study limits
the ability to generalize from our ndings. The propositions we offer can be used in
different contexts to further validate the constructs of our ndings.
In addition to the suggestions based on limitations, we outline several promising
directions for future research. First, as a follow-up to this initial study of director
behavioral in a crisis, future work could examine the actual tasks that post-crisis board
directors undertake to shore up their rms and also to protect their public reputations.
Second, our study identies vast changes in board composition in a short period. While
these changes were independent of mandatory quotas and “comply or explain” codes,
these new institutions are signicantly changing the landscape of corporate governance
in terms of director demographics and should be explicitly examined. There is early
evidence that the new Icelandic quotas are effective in bringing women onto boards
( Ólafsdóttir, 2015 ) and in changing the selection processes of boards ( Arnardóttir et al. ,
2015 ). A third promising direction for future research involves the potential for role
conict and necessitates close observation of how directors seek to mitigate this conict.
This could be achieved by further examining actual boardroom interactions and how
directors enact their roles in these groups. A nal promising direction could examine the
extent to which the discourse about director identities and processes around boards
reects theoretical perspectives, such as utility, justice, social capital and institutions
( Seierstad, 2015 ; Terjesen and Sealy, 2015 ).
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Appendix 1. Protocol for pre-crisis and post-crisis interviews
Please keep a particular focal board in mind; however, you are encouraged to compare and
contrast this focal board experience to other boards that you have served on:
(1) Can you tell me about other boards you sit on?
(2) Why were you asked to serve on this particular board?
(3) How would you describe your role or purpose as a board member on this board?
(4) Can you describe how you would behave and interact in a typical board meeting?
(5) To whom or what do you feel accountable as a director? Why?
(6) Can you describe your relationships with other board members?
(7) What do you think is your greatest contribution to this board?
(8) Anything else you would like to share or comment on?
... Women are on average less aggressive, competitive, self-interested, and overconfident, and more altruistic, cautious, communal, fair, objective, conservative, and responsible. These traits enable them to monitor more intensely relative to men, and FP studies identify that women on boards improve board monitoring (Adams & Ferreira, 2009;
Jonsdottir et al., 2015;
Zalata et al., 2019). 3 RDT identifies benefits from female representation on boards due to stronger links with the membership and a capacity to build better trust relationships with borrowers compared with men, resulting in lower defaults (Beck et al., 2013;Chakrabarty & Bass, 2014;Hartarska et al., 2014). ...
... A complementary effect arises when the mechanisms operate synergistically to reduce loan losses. For example, women are reported to undertake monitoring and resource provision roles
(Jonsdottir et al., 2015)
including strengthening networks with stakeholders, including borrowing members, and may switch efforts to the resource provision role when credit unions are subject to quarterly external financial monitoring. Strengthened links with borrowing members may lead to further reductions in loan losses. ...
The Effect of Bundling Trade Association Monitoring and Female Board Representation on Loan Losses in Community Credit Unions
Loan book management is important to community credit union survival, particularly in deprived localities. Consistent with agency theory, prior studies of credit unions report an association between individual monitoring mechanisms, trade association monitoring and female board representation respectively, and reduced loan losses. This study provides a more nuanced understanding by investigating the moderating influence of these monitoring mechanisms on the relationship between loan losses and deprivation and by considering the effect of bundle combinations of different levels of the two monitoring mechanisms on loan losses. The results reveal that credit unions subject to trade association monitoring have the lowest loan losses. However, in the absence of trade association monitoring, female board representation has a moderating effect on loan losses as deprivation increases. Finally, trade association monitoring and female board representation have a substitutive, rather than a complementary effect on loan losses.
... The literature on board member identity emphasises the importance of identification, namely with whom the director primarily identifies. Who they most identify, associate or empathise with, will influence the way they behave and make decisions within the boardroom (Hillman, Nicholson and Shropshire, 2008;
Jonsdottir et al., 2015;
Veltrop et al., 2021). Assuming the board's prime role is to protect the interests of the organisation and its stakeholders and to drive corporate governance, accountability and strategic direction (Madhani, 2017), then logic would dictate that those who associate with the board, as an entity in its own right, are the candidates most likely to have greatest impact. ...
Governance, board membership identity and socialised induction: A narrative on enabling an effective boardroom experience
A cursory look at the literature in the area of corporate governance identifies a number of core themes currently offering insights into boards and their changing role in organisational governance. Increasing discussion on diversity, gender, changing governance frames and the progressive conceptualisation of board membership as a profession in its own right, are all clear to be seen.
Given that boards and their role in governance transcend many sectors from industry, finance, and retail to the more emotionally laden service industries such as regulation of health and social care, how can organisations learn to grapple with the changing face of the boardroom and with wider societal expectations of their boards?
The suggestion in this thought paper is that by understanding the organisation’s governance frame and organisationally enabling the concept of board membership identity through a strategically aligned view of induction as a process of socialisation, a better board dynamic can evolve.
... Not only are time served and social relations among individuals significant for how women directors contribute to boards, but also how directors' construct their professional role identities. An interesting study of directors in Iceland shows that gender differences in their role identities as monitors or resource providers are more pronounced in mature male-dominated boards than in newly composed gender-balanced boards
(Jonsdottir et al. 2015)
. The idea that gendered social relations among directors on a board affects the nature of women's contributions is corroborated in a survey of directors in Israel: women directors were more concerned than men about whether they were adequately skilled and felt the need to constantly prove themselves (Talmud and Izraeli 1999). ...
The gender composition of corporate boards: A review and research agenda
LEADERSHIP QUART
Anja Kirsch
In recent years, the composition of boards and, particularly, the inclusion of women on boards has attracted significant scholarly interest and public debate. In this article, I comprehensively review the academic literature on board gender composition. Using the systematic review method, I ask whether women directors really are different from men on boards, what factors shape board gender composition, how board gender composition affects organizational outcomes, and finally, why board gender quotas and other forms of regulation are introduced and what outcomes can be expected. Based on my findings, I develop a conceptual framework that clarifies the causal processes underlying both women's access to boards and the effects of women's presence on boards. Finally, I offer a research agenda designed to enrich our understanding of board gender composition.
Women directors, board attendance, and corporate financial performance
Women’s Presence on Corporate Boards: Addressing Director Selection, Participation, and Gender Bias
Gender diversity of corporate boards is gaining attention as a global issue, but women’s presence on boards remains low despite increased numbers of qualified women. Most research compares gender diversity of boards and firm performance or corporate social responsibility compliance and reporting, ethics compliance, or other decisions impacting firm risk and success. Despite positive outcomes associated with gender diverse boards, few women directors are appointed, and progress is slow. Quotas and incentives have been considered and implemented in several countries to develop board gender diversity, but without enforced quotas, minimal change is seen. When women are appointed, they are often not present in sufficient number to impact board gender diversity. A direct focus on gender bias in director selection and board member participation is needed to provide a deeper understanding of women’s presence on boards.
Áhrif kynjakvóta á stjórnarbrag að mati stjórnarmanna
Audur Arna Arnardottir
| https://www.researchgate.net/publication/282349080_Director_identity_in_pre_and_post-crisis_Iceland_effects_of_board_life_stage_and_gender |
Study: Poziotinib Reduces Tumor Growth, Metastasis in HER2 Mutant Metastatic Breast Cancer
Findings suggest that the HER2 L755S mutation plays a role in the aggressiveness of lobular breast cancer observed in the clinic.
Study: Poziotinib Reduces Tumor Growth, Metastasis in HER2 Mutant Metastatic Breast Cancer
Findings suggest that the HER2 L755S mutation plays a role in the aggressiveness of lobular breast cancer observed in the clinic.
New research has found that the drug poziotinib, which is already approved for other cancer types, reduced tumor growth and multi-organ metastasis in laboratory tests and animal models assessing human epidermal growth factor receptor 2 (HER2)-mutant driven metastatic breast cancer.
Neratinib is frequently used for patients with HER2 mutations, but these responses are variable and often not durable. To further understand this variation, researchers investigated whether different HER2 mutations drove therapy responses, which led to the identification of a mutation that conferred therapeutic resistance and promoted metastatic behavior.
These findings, published in Cancer Research,in addition to the findings about poziotinib, support future clinical trials assessing the value of poziotinib to treat HER2-mutant driven breast cancer, according to the study authors.
“In this study we focused on 2 types of breast cancer—ductal breast cancer and lobular breast cancer—which is understudied when compared to ductal breast cancer,” said leading author Shyam M. Kavuri, PhD, assistant professor at Baylor’s Lester and Sue Smith Breast Cencer and the Department of Medicine, in a press release. “More than 20% of patients with these types of breast cancer develop a metastatic or invasive form of the disease, for which there is no current treatment.”
The investigators examined studies that sequenced the genes of human lobular and ductal breast cancers, specifically analyzing mutations in the HER2 gene. They found that the HER2 L755S mutation was more common among patients with metastatic lobular breast cancer than in patients with ductal breast cancer. Patients with these alterations also had significantly reduced overall survival (OS) compared to those carrying the natural or non-mutated form of HER2, suggesting that recurrent L755 alterations are associated with the more aggressive form of lobular breast cancer, according to the study.
The researchers did not detect any difference in OS among patients with ductal breast cancer and HER2 mutations. Kavuri said this suggests a significant difference between the lobular and the ductal forms of cancer and could have important clinical implications.
To further examine how this HER2 mutation influenced cancer behavior, the researchers conducted laboratory experiments in which the HER2 L755S gene was introduced into cells. Then they treated the modified cells with drugs approved to treat the human cancer.
“We found that having the HER2 L755S mutation conferred the cells resistance to treatments, including neratinib—the cells continued to grow,” said first author Rashi Kalra, MD, in the press release. “When human tumor cells carrying this mutation were grown in animal models, they developed metastasis more often than cells not carrying this mutation.”
These findings therefore suggest that the HER2 L755S mutation plays a role in the aggressiveness of lobular breast cancer observed in the clinic.
The team also searched for drugs that could better treat cancer carrying the HER2 L755S mutation. Of the drugs they tested, Kavuri said poziotinib was able to completely inhibit both tumor growth and metastasis in experimental models.
“We are excited by our findings,” said co-author Bora Lim, MD, in the press release. “Poziotinib offers the possibility of a more effective treatment option for HER2 mutant metastatic breast cancer. We are actively working on the development of a phase 2 clinical trial to determine the value of this drug in the treatment of patients with this devastating condition.”
Hepatitis D virus (HDV) can cause acute or chronic infection and only affects those with a positive hepatitis B surface antigen (HBsAg). 1HDV is a significant contributor to hepatitis B virus (HBV)-associated liver disease and has been estimated to cause 1 in 6 cases of cirrhosis and 1 in 5 cases of hepatocellular carcinoma in individuals with HBV. 2The global prevalence of HDV among individuals who are HBsAg positive has been estimated to be approximately 4.5% and varies based on geographical region, with the highest prevalence in Mongolia (36.9%). 2
Prevention
Transmission occurs through exposure to infected blood or bodily fluids. 3Individuals at risk of acquiring HDV include those with chronic HBV, household contacts and sexual partners of individuals with HDV, men who have sex with men, and individuals who inject drugs.
There is currently no vaccine for HDV; however, HBV vaccination does provide protection and is the only method of prevention. 3,4Vaccination does not prevent HDV infection in patients already infected with HBV.
Existing Treatment
Currently, there is no FDA-approved regimen for the treatment of HDV. For more than 30 years, off-label use of pegylated interferon-α (PEG-IFN-α) for a minimum of 48 weeks has been the mainstay of treatment for chronic HDV in individuals with elevated HDV RNA and active liver disease. 5However, treatment with PEG-IFN-α has been associated with limited sustained clinical response and high virologic relapses. 6,7PEG-IFN-α therapy also carries risks of significant toxicities, such as musculoskeletal pain, skin toxicity, fatigue, neutropenia, gastrointestinal symptoms, and flu-like symptoms, which often lead to discontinuation of therapy. Because chronic HDV infection is considered serious and life-threatening with limited treatment options, there is a dire need for more effective and safer therapies.
Hepatitis
Bulevirtide
Bulevirtide (Hepcludex; Gilead Sciences, Inc) is a first-in-class investigational entry inhibitor for the treatment of chronic HBV/HDV. 8It is a daily subcutaneous injection. Common adverse effects include headache, eosinophilia, dizziness, nausea, increased total bile salts, pruritus, arthralgia, fatigue, influenza-like illness, and injection site reactions.
In phase 2 trials, bulevirtide (BLV) was studied in combination with tenofovir disoproxil fumarate (TDF) in MYR202 (NCT03546621) and in combination with PEG-IFN-α in MYR203 (NCT02888106) and MYR204 (NCT03852433). 9-13
Combination therapy with BLV (2, 5, or 10 mg) and TDF for 24 weeks resulted in virologic response (VR), defined as a 2-log decline or undetectable HDV RNA by week 24, in 54%, 50%, and 77% of subjects, respectively, compared withonly 4% with TDF monotherapy. 9-11Relapse occurred in 87%, 94%, and87% of responders on BLV 2, 5, and10 mg, respectively.
In the MYR203 and MYR204 trials, VR was highest in patients treated with BLV and PEG-IFN-α.9,11,13 VR at week 72 was achieved in 53.3% of patients assigned to BLV 2 mg with PEG-IFN-α and 26.7% of patients on BLV 5 mg with PEG-IFN-α, all of whom were treated for 48 weeks in the MYR203 trial. A decline of more than 1 log HBsAg was observed in 47% of the BLV 2-mg group and 13% of the BLV 5-mg group.
VR in the MYR204 trial was achieved in 88% and 92% of patients taking BLV 2 and 10 mg, respectively, with PEG-IFN-α compared with 72% of patients taking BLV 10-mg monotherapy at week 24. 13Combined response of VR and alanine aminotransferase normalization at week 24 was achieved in 50% of theBLV 10-mg monotherapy arm, which was higherthan the combination arms. Final results have not yet been published.
Despite VR, the above studies suggest durable response is only achieved in patients who lose HBsAg. 9-13MYR301 (NCT03852719),a phase 3 study investigating BLV monotherapy at 2 or 10 mg, is currently underway. 13At the 24-week interim analysis, combined response was numerically higher in the 2-mg group (37%) than the 10-mg group (28%). 13
Based on results from MYR202 and MYR203, BLV was conditionally approved by the European Medicines Agency in 2020 for the treatment of chronic HDV with compensated liver disease. 14BLV was not as well received by the FDA and was not approved due to concerns with manufacturing and delivery of the medication, which is similar to other recent rejections turned approvals. The manufacturer released a statement regarding their plans to continue working toward approval with the FDA. 14
Conclusion
Although there is low prevalence of HDV in the United States, it is considered to be the most severe type of viral hepatitis. Existing treatment options are poorly tolerated, necessitating the development of novel agents.
BLV has promising safety and efficacy data from phase 2 and 3 trials, and additional data from ongoing studies will be helpful in determining its optimal use. Although news of BLV’s rejection by the FDA is a barrier to treatment of this severe infection, recent successes with other medications on the same trajectory suggest a potential positive outcome for BLV inthe future.
References
2. Stockdale AJ, Kreuels B, Henrion MYR, et al. The global prevalence of hepatitis D virus infection: systematic review and meta-analysis. J Hepatol. 2020;73(3):523-532. doi:10.1016/j.jhep.2020.04.008
3. Hepatitis D. World Health Organization. June 24, 2022. Accessed January 26, 2023. https://www.who.int/news-room/fact-sheets/detail/hepatitis-d
4. Hepatitis D questions and answers for health professionals. CDC. Reviewed March 9, 2020. Accessed January 26, 2023. https://www.cdc.gov/hepatitis/hdv/hdvfaq.htm#section2
5. Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases.9th Edition. Elsevier; 2019.
6. Wedemeyer H, Yurdaydin C, Hardtke S, et al. Peginterferon alfa-2a plus tenofovir disoproxil fumarate for hepatitis D (HIDIT-II): a randomised, placebo controlled, phase 2 trial. Lancet Infect Dis. 2019;19(3):275-286. doi:10.1016/S1473-3099(18)30663-7
7. Heidrich B, Yurdaydin C, Kabaçam G, et al. Late HDV RNA relapse after peginterferon alpha-based therapy of chronic hepatitis delta. Hepatology. 2014;60(1):87-97. doi:10.1002/hep.27102
8. HEPCLUDEX 2 mg powder for solution for injection. Electronic Medicines Compendium. Updated September 7, 2022. Accessed January 27, 2023. https://www.medicines.org.uk/emc/product/13482/smpc#gref
9. Lampertico P, Roulot D, Wedemeyer H. Bulevirtide with or without pegIFNα for patients with compensated chronic hepatitis delta: from clinical trials to real-world studies. J Hepatol.2022;77(5):1422-1430. doi:10.1016/j.jhep.2022.06.010
10. Wedemeyer H, Schöneweis K, Bogomolov P, et al. Safety and efficacy of bulevirtide in combination with tenofovir disoproxil fumarate in patients with hepatitis B virus and hepatitis D virus coinfection (MYR202): a multicentre, randomised, parallel-group, open-label, phase 2 trial. Lancet Infect Dis. 2023;23(1):117-129. doi:10.1016/S1473-3099(22)00318-8
11. Wedemeyer H, Schöneweis K, Bogomolov PO, et al. 48 weeks of high dose (10 mg) bulevirtide as monotherapy or with peginterferon alfa-2a in patients with chronic HBV/HDV coinfection. J Hepatol. 2020;73:S19-S57. doi:10.1016/S0168-8278(20)30651-6
12. Asselah A, Arama SS, Bogomolov P, et al. Safety and efficacy of bulevirtide monotherapy and in combination with peginterferon alfa-2a in patients with chronic hepatitis delta: 24 weeks interim data of MYR204 phase 2b study. J Hepatol. 2021;75:S291.
13. Wedemeyer H, Aleman S, Andreone P, et al. Bulevirtide monotherapy at low and high doses in patients with chronic hepatitis delta: 24-week interim data of phase 2 MYR301 study. J Hepatol. 2021;75:S294.
14. Gilead receives complete response letter from U.S. FDA for bulevirtide for the treatment of adults with hepatitis Delta virus. News release. Gilead Sciences, Inc. October 27, 2022. Accessed January 26, 2023. https://www.gilead.com/news-and-press/company-statements/gilead-receives-complete-response-letter-from-us-fda-for-bulevirtide-for-the-treatment-of-adults-with-hepatitis-delta-virus
About the Authors
Jenna Januszka, PharmD, BCPS, AAHIVP,is a PGY2 HIV/infectious diseases resident at the University of Illinois Chicago.
Cara Slaton, PharmD, BCIDP,is an infectious diseases clinical pharmacist at Orlando Health Orlando Regional Medical Center in Florida.
| https://www.pharmacytimes.com/view/study-poziotinib-reduces-tumor-growth-metastasis-in-her2-mutant-metastatic-breast-cancer |
Father's age at conception influences offspring's mutation rate [Archive] - Eupedia Forum
I saw this on my feed today..." Father's Age Influences Rate of Evolution http://www.sciencedaily.com/releases/2014/06/140612142307.htm The study is about chimpanzees, but there's some good information as to implications for humans as well. Sorry, the title should read: Father's age influences mutation rate
Father's age at conception influences offspring's mutation rate
I saw this on my feed today..."Father's Age Influences Rate of Evolution http://www.sciencedaily.com/releases/2014/06/140612142307.htm The study is about chimpanzees, but there's some good information as to implications for humans as well. Sorry, the title should read: Father's age influences mutation rate
That's right, the older the sperm the more mutations it has. There was a study blaming rising age of modern fathers and mothers for skyrocketing cases of Down syndrome in kids.
This caught my eye too... "Paternal age is an established risk factor in a number of disorders including schizophrenia and autism." It amazes me how many cases of autism we have nowadays, and I don't think better diagnostic procedures explains it all. Reminds me of an old proverb I grew up with too...old fathers, feeble children.
if this is true then it seems the best strategy for a woman would be to marry an older guy with a good income, play the ignorant conservative devoted wife and have kids with a young lover. Husbands beware... :) she might have genetical reasons for cheating.
if this is true then it seems the best strategy for a woman would be to marry an older guy with a good income, play the ignorant conservative devoted wife and have kids with a young lover. Husbands beware... :) she might have genetical reasons for cheating. If the kid is strong and healthy "damn, surely it is not mine!", lol.
One way out for older father is to get a young mother. I had a friend about 19 but his father was 80 while is mother was maybe 40. He seemed all right. We were in high school together. His father had four wives and this guy's mother was the fourth wife. I think most of the R1b mutations could have been that they had multiple wives and were making babies well into old age.:wink:
A very old story, gentlemen, and not limited to one country...Joseph and the Pharaoh's wife! http://www.womeninthebible.net/Master_of_the_Joseph_Legend_Flemish_c1500.jpg However, maybe we should keep in mind that often in the past, it was not the woman's choice...in this case, the old goat deserved everything he undoubtedly got! http://upload.wikimedia.org/wikipedia/commons/9/92/V.V.Pukirev_-_The_Arranged_Marriage.jpg
I did a study on paternal and maternal age and their correlation with autism. Increasing parental age is one of the factors implicated in the elevated rates of autism we are finding.
This explains a lot my great uncle born when his father was in his forties did need some adaptions, a horse that was a different size from his friends and he could only drive a Jag because of his difficuty in seeing out off it. He didn't even live to 90 only reaching 88 and height wise he only reached 6ft 5inches.
More scientific proof linking paternal age with increased mutations. Of course, not all would be deleterious, but my understanding is that most of them would be... Determinants of Mutation Rate Variation in the Human Germline: http://www.annualreviews.org/eprint/P39WXRWSQN7baFj2fb78/full/10.1146/annurev-genom-031714-125740 In terms of replication errors...from the paper: After puberty, sperm are continuously produced through the asymmetric division of self-renewing spermatogonial stem cells every 16 days (61). Five additional cell divisions (corresponding to four replication events) are required to obtain mature sperm. As a consequence, if puberty occurs at 13 years (116), approximately 38 + 23×(30 − 13) = 429 stem cell divisions have occurred if conception takes place at a paternal age of 30 years, and approximately 659 have occurred if conception takes place at a paternal age of 40 years. If mutations are due largely to replication errors, we expect most to be introduced in the paternal germline, at a rate that depends on paternal age. A greater contribution of paternal mutations was first noted in studies of human Mendelian disease (29, 55). This observation was lent strong support by molecular evolution studies of autosomes and X and Y chromosomes that reported lower divergence on the X than on the Y and autosomes (97, 104). Ovum are also produced throughout life, however, again according to the paper: In that regard, it is plausible that sequencing more families may yet reveal a maternal age effect on the number of maternal de novo mutations (46). This effect is expected to be subtle compared with the paternal one, however. This seems to be one of those cases where, perhaps because the linkage between paternal age and "weakness" of offspring was unknown in some cultures, or because power and wealth was more important, societal practices actually worked (and works) against the fitness of the group as a whole.
How bizarre...scientific research re-affirming a long established link between paternal age and defects in the offspring seems to have offended someone. I would suggest taking it up with all the scientists, instead of shooting the messenger! :)
Yet another new paper on this topic: New insights on human de novo mutation rate and parental age. W. S. W. Wong, B. Solomon, D. Bodian, D. Thach, R. Iyer, J. Vockley, J. Niederhuber. Germline mutations have a major role to play in evolution. Much attention has been given to studying the pattern and rate of human mutations using biochemical or phylogenetic methods based on closely related species. Massively parallel sequencing technologies have given scientists the opportunity to study directly measured de novo mutations (DNMs) at an unprecedented scale. Here we report the largest study (to our knowledge) of de novo point mutations in humans, in which we used whole genome deep sequencing (~60x) data from 605 family trios (father, mother and newborn). These trios represent the first group of approximately 2,700 trios who have undergone whole-genome sequencing (WGS) through our pediatric-based WGS research studies. The fathers ages range from 17 to 63 years and the mothers ages range from 17 to 43 years. We identified over 23000 DNMs (~40 per newborn) in the autosomal chromosomes using a customized pipeline and infer that the mutation rate per basepair is around 1.2x10-8 per generation, well within the reported range in previous studies. We were also able to confirm that the total number of DNMs in the newborn was directly proportional to the paternal age (P less than 2x10-16). Maternal age is shown to have a small but significant positive effect on the number of DNMs passed onto the offspring, (P =0.003) , even after accounting for the paternal age. This contradicts the prior dogma that maternal age only has an effect on chromosomal abnormalities related to nondisjunction events. Furthermore, 5% (22 total) of newborns in the analyzed group were conceived with assisted reproductive technologies (ARTs), and these infants have on average 5 more DNMs (Bias corrected and accelerated bootstrap 95% Confidence Interval, 1.24 to 8.00) than those conceived naturally, after controlling for both parents ages. Both parents ages remain significant as independently correlated with DNMs even after the families that used ARTs were removed from the analysis. Our study enhances current knowledge related to the human germline mutational rates.
| https://www.eupedia.com/forum/archive/index.php/t-30158.html?s=9b76c9afe651ce16c8944afea3386406 |
Electronics | Free Full-Text | Joint Vital Signs and Position Estimation of Multiple Persons Using SIMO Radar
Respiration rate monitoring using ultra-wideband (UWB) radar is preferred because it provides contactless measurement without restricting the person’s privacy. This study considers a novel non-contact-based solution using a single-input multiple-output (SIMO) UWB impulse radar. In the proposed system, the collected radar data are converted to several narrow-band signals using the generalized Goertzel algorithm (GGA), which are used as the input of the designed phased arrays for position estimation. In this context, we introduce the incoherent signal subspace methods (ISSM) for the direction of arrivals (DOAs) and distance evaluation. Meanwhile, a beam focusing approach is used to determine each individual and estimate their breathing rate automatically based on a linearly constrained minimum variance (LCMV) beamformer. The experimental results prove that the proposed algorithm can achieve high estimation accuracy in a variety of test environments, with an error of 2%, 5%, and 2% for DOA, distance, and respiration rate, respectively.
Joint Vital Signs and Position Estimation of Multiple Persons Using SIMO Radar
2
Laboratory for Energetic, Mechanics and Electromagnetism, Paris-Nanterre University, 92000 Ville-d’Avray, France
3
Laboratoire Traitement du Signal, École Militaire Polytechnique, Bordj El-Bahri 16111, Algeria
*
Author to whom correspondence should be addressed.
Electronics 2021 , 10 (22), 2805; https://doi.org/10.3390/electronics10222805
Received: 14 September 2021 / Revised: 10 November 2021 / Accepted: 15 November 2021 / Published: 16 November 2021
(This article belongs to the Special Issue Modern Techniques in Radar Systems )
Abstract
Respiration rate monitoring using ultra-wideband (UWB) radar is preferred because it provides contactless measurement without restricting the person’s privacy. This study considers a novel non-contact-based solution using a single-input multiple-output (SIMO) UWB impulse radar. In the proposed system, the collected radar data are converted to several narrow-band signals using the generalized Goertzel algorithm (GGA), which are used as the input of the designed phased arrays for position estimation. In this context, we introduce the incoherent signal subspace methods (ISSM) for the direction of arrivals (DOAs) and distance evaluation. Meanwhile, a beam focusing approach is used to determine each individual and estimate their breathing rate automatically based on a linearly constrained minimum variance (LCMV) beamformer. The experimental results prove that the proposed algorithm can achieve high estimation accuracy in a variety of test environments, with an error of 2%, 5%, and 2% for DOA, distance, and respiration rate, respectively.
Keywords:
impulse-response ultra-wideband (IR-UWB) radar
;
single-input multiple-output (SIMO)
;
generalized Goertzel algorithm (GGA)
;
direction of arrival (DOA)
;
respiration rate
1. Introduction
Non-contact vital sign (VS) detection, such as respiration rate, built upon a radio frequency (RF)-based system has attracted a great deal of interest in recent years. It is used in a growing field of applications, such as healthcare and clinical assistance, sleep and baby monitoring, survivor rescue and research operations, through the wall human detection, and human activity classification [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Recently, the impulse response ultra wide-band (IR-UWB) radar has gained more attention thanks to its high-range resolution, good penetration capability, and low power consumption [ 10 , 11 ].
The use of RF signals for VS waveform extraction lies in the detection of the chest motion associated with the VS activities of a human subject. Specifically, it is based on the emission and reception of electromagnetic (EM) waves. Notably, the phase variation on the received signal is exploited for this purpose [ 12 ]. To do so, several radar types have been investigated, including unmodulated continuous wave (CW) [ 13 ], frequency-modulated continuous-wave (FMCW) [ 14 ], step frequency continuous-wave (SFCW) [ 15 ], and IR-UWB [ 4 ]. Meanwhile, many signal processing techniques have been proposed, covering clutter rejection, human localization, and VS estimation [ 16 , 17 , 18 , 19 , 20 , 21 ]. Despite the great advances in the field, most research has focused on a single target for VS measurement. To better deal with complex and critical scenarios, such as people buried under debris, multiple-person VS motioning plays an important role in addressing these scenarios [ 5 , 8 ].
To date, two approaches have been mainly used to achieve the VS measurement of multiple persons. The first solution requires the range information associated with the human targets to separate their VS signals. In this context, a single-input single-output (SISO) radar is used for this purpose, namely FMCW, SFCW, or IR-UWB platforms [
22
]. Nevertheless, it is still difficult to obtain reliable separation when the persons are located at the same distance from the radar. The second one separates the VS signals based on the incident angle information. To this end, spatially distributed antennas have been exploited in designing the radar system, such as single-input multiple-output (SIMO) [
8
] and multiple-input multiple-output (MIMO) radars [
6
]. In particular, digital beamforming (DBF) plays an important role in beam scanning and beam focusing tasks thanks to its low-complexity structure, good control flexibility, and high accuracy [
8
].
In this work, a SIMO IR-UWB radar prototype is presented. The proposed system is based on a single IR-UWB radar in which eight spatially distributed antennas are connected to its receiving channel through a UWB RF switch. To deal with the array signal processing-based model, we propose a proper pre-processing step to obtain a multi-variant narrow-band signal via the generalized Goertzel algorithm (GGA) [ 23 ]. Further, we consider an incoherent signal subspace method (ISSM) for direction of arrival (DOA) estimation [ 24 ]. In particular, we use the incoherent multiple signal classification (IMUSIC) to estimate the incident angle of each person [ 25 , 26 ]. Then, we perform beam focusing at each estimated angle for VS separation using a linearly constrained minimum variance (LCMV) beamformer [ 27 ]. Finally, the respiration rate is estimated for each person by analyzing the spectrum of the separated signals.
In summary, the main contributions of this work are as follows:
The proposed SIMO IR-UWB radar system allows us to simultaneously measure the VSs of spaced persons at the same distance from the radar. It offers a low-cost and good solution for the non-contact Vs measurement of multiple persons in sleep and baby monitoring scenarios;
The chest motions of multiple targets are accurately separated with the combination of the IMUSIC and LMCV algorithms. The respiration rate estimation is significantly enhanced by forming individual narrow beam focusing on the chest regions associated with each person;
The experimental results are presented to investigate the performance of the proposed system, showing that our proposed method outperforms the state of the art.
The remainder of this paper is organized as follows. Section 1 presents the mathematical model of the IR-UWB SIMO radar and the problem setup. In Section 2 , we tackle the estimation procedure of position and respiration rate for each person. Experimental results and numerical analyses are described in Section 3 . Section 4 concludes this work.
2. Mathematical Model
UWB impulse radar has been widely used for VS detection thanks to its high-range resolution. In this context, it transmits very short pulses, usually in the order of picoseconds, to the human subject. As the electromagnetic wave returns from the chest’s body, the VS motions, which introduce a small displacement (typically in the order of millimeters) on the chest, will produce a phase variation in the received signal [ 12 ].
2.1. Received Signal for SISO Radar
Consider a finite number of persons
L
with incident angles
θ = [ θ 0 1 , θ 0 2 , . . . , θ 0 L ]
over a limited region, where the received signal, from
L
persons, can be simplified as:
r ( t , τ ) = ∑ l = 1 L α l p ( τ − τ l ( t ) ) , l = 1 , 2 , . . . , L .
(1)
where
t
and
τ
denote the slow and fast time indexes, respectively.
p ( τ )
represents the transmitted pulse.
α l
and
τ l ( t )
are the attenuations and the time of arrival (TOA) associated with the
l t h
person, respectively. These letters depend on the radar cross-section (RCS) of the human subject and its distance from the radar
d 0 l
. Assuming that the human chest remains stationary during the coherent processing interval (CPI), usually in the order of milliseconds, the TOA in Equation (
1
) is expressed as:
τ l ( t ) = 2 d 0 l + d l ( t ) c
(2)
where
d l ( t )
depicts the chest displacement of the
l t h
person, which can be expressed as [
4
]:
d l ( t ) = d r l cos ( 2 π f r l t )
(3)
where
d r l
and
f r l
represent the maximum displacement of the chest and the respiration frequency associated with the
l t h
person, respectively.
2.2. Received Signal for SIMO Radar
In our scheme, we consider a uniform linear array (ULA) composed of
M
antenna receivers. Depending on the incident angle of each person, the received signal at the
m t h
antenna can be expressed as:
r m ( t , τ ) = ∑ l = 1 L α l p ( τ − τ m l ( t ) ) + w m ( t , τ ) , m = 1 , 2 , . . . , M .
(4)
where
w m ( t , τ )
represents the measurement noise. Using the first antenna as a reference,
τ m l ( t )
in Equation (
4
) can be derived as:
τ m l ( t ) = 2 d 0 l + d r l ( t ) c + ( m − 1 ) d c sin ( θ 0 l )
(5)
where
d
depicts the inter-distance of the antenna array.
Figure 1
illustrates the receiving signal model of the SIMO radar.
Figure 1. Signal receiving model of array antenna.
3. Position and VS Estimation
In this section, we first establish an appropriate SIMO radar based on a single UWB impulse transceiver P440 for VS and position estimation. Then, we develop a method to transom the collected UWB data into multiple narrow-band signals. Next, we explain how to estimate the respiration rate of each person based on their estimated incident angles.
3.1. SIMO Radar System Structure
Figure 2
illustrates the basic modules of the SIMO radar system adopted in this work. Specifically, the impulse UWB transceiver P440 is used to transmit and receive data. In particular, it transmits a Gaussian impulse RF signal with a carrier frequency of
4.3
GHz and a bandwidth of
2.2
GHz. It acts as a short-range coherent radar using the monostatic radar module (MRM). On the other hand, a broadband RF switch HMC321A (covering a band from DC to 8 GHz) is used to select one specific antenna receiver at each scan to build an array receiver. Specially, we use a Raspberry Pi 4 to control and automate this process. Finally, the collated data are transferred to the PC via a WiFi connection for signal processing.
Figure 2. Overview of the SIMO radar-based respiratory measurement system for multiple persons.
3.2. Algorithm Scheme
The joint estimation approach exploits the spatial and spectrum, in the fast time domain, information of the received signals for estimating the human positions and separating their VS waveforms. Moreover, the temporal information, in the slow time domain, is used for respiration rate estimation. Figure 3 illustrates the process of the proposed method.
Figure 3. Block diagram of the proposed method.
3.2.1. Pre-Processing
In this section, we introduce a pre-processing step to transform the IR-UWB signals to multiple narrow-band signals. Specifically, we use the GGA to evaluate the Fourier transform (FT) at specific frequency indexes. Then, a complex band pass filter is applied to remove the clutter response and negative frequencies and enhance the VS waveform [ 4 ].
Applying the FT to Equation (
4
), in the fast time domain, reads:
R m ( t , ω ) = ∑ l = 1 L α l P ( ω ) e − j ω τ m l ( t ) + C m ( ω ) + W m ( t , ω )
(6)
where
P ( ω )
,
C m ( ω )
, and
W m ( t , ω )
represent the FT of the transmitted pulse, the clutter response, and the measurement noise, receptively. Inserting Equation (
5
) into Equation (
6
) results in:
R m ( t , ω ) = ∑ l = 1 L α l P ( ω ) e j β 0 l ( ω ) e j β ( ω ) ( m − 1 ) sin ( θ 0 l ) e j β r l ( ω ) sin ( 2 π f r l t ) + C m ( ω ) + W m ( t , ω )
(7)
where
β ( ω ) = − ω d c
,
β 0 l ( ω ) = − 2 ω d 0 l c
, and
β r l ( ω ) = − 2 ω d r l c
. Furthermore,
e j β r l ( ω ) sin ( 2 π f r l t )
in Equation (
7
) can be expressed, using the Bessel functions, as:
e j β r l ( ω ) sin ( 2 π f r l t ) = ∑ n = − ∞ ∞ J n ( β r l ( ω ) ) e j 2 π n f r l t
(8)
where
J n
depicts the first kind of Bessel function of order
n
. By further taking into consideration that
d r l
is small, in the order of millimeters, and regarding the range of
ω
, in the order of GHz, the quantity
β r l ( ω )
is close to zero. Hence, Equation (
8
) can be simplified, retaining only the Bessel functions from up to the second order, as:
e j β r l ( ω ) sin ( 2 π f r l t ) = J 0 ( β r l ( ω ) ) + J 1 ( β r l ( ω ) ) ( e j 2 π f r l t + e − j 2 π f r l t )
(9)
Inserting Equation (
9
) into Equation (
7
) reads:
R m ( t , ω ) = ∑ l = 1 L α l J 1 ( β r l ( ω ) ) P ( ω ) e j β 0 l ( ω ) e j β ( ω ) ( m − 1 ) sin ( θ 0 l ) ( e j 2 π f r l t + e − j 2 π f r l t ) + C m ′ ( ω ) + W m ( t , ω )
(10)
in which:
C m ′ ( ω ) = ∑ l = 1 L α l J 0 ( β r l ( ω ) ) P ( ω ) e j β 0 l ( ω ) e j β ( ω ) ( m − 1 ) s i n ( θ 0 l )
(11)
At this point, we apply the CBPF [
28
], presented in our previous work [
4
], to remove
C m ′ ( ω )
and enhance the VS waveform. The result of such a filter can be expressed as:
X m ( t , ω ) = ∑ l = 1 L e j β ( ω ) ( m − 1 ) s i n ( θ 0 l ) S l ( t , ω ) + N m ( t , ω )
(12)
where
S l ( t , ω ) = α l J 1 ( β r l ( ω ) ) P ( ω ) e j β 0 l ( ω ) e j 2 π f r l t
, which represents the source signal associated with the
l t h
person, and
N m ( t , ω )
depicts the filtered noise of
W m ( t , ω )
. Notice that, for each
ω
, we obtain an array signal processing-based model, which can be written in matrix form as:
X ( t , ω ) = A ( θ , ω ) S ( t , ω ) + N ( t , ω )
(13)
in which:
X ( t , ω ) = [ X 1 ( t , ω ) , X 2 ( t , ω ) , . . . , X m ( t , ω ) , . . . , X M ( t , ω ) ] T , N ( t , ω ) = [ N 1 ( t , ω ) , N 2 ( t , ω ) , . . . , N m ( t , ω ) , . . . , N M ( t , ω ) ] T , S ( t , ω ) = [ S 1 ( t , ω ) , S 2 ( t , ω ) , . . . , S 2 ( t , ω ) , . . . , S l ( t , ω ) ) ] T , A ( θ , ω ) = [ a ( θ 0 1 , ω ) , a ( θ 0 2 , ω ) , . . . , a ( θ 0 l , ω ) , . . . , a ( θ 0 L , ω ) ] ,
where
a ( θ 0 l , ω ) = [ 1 , e j β ( ω ) s i n ( θ 0 l ) , . . . , e j β ( ω ) ( m − 1 ) s i n ( θ 0 l ) , . . . , e j β ( ω ) ( M − 1 ) s i n ( θ 0 l ) ] T
. In view of this, the model presented in Equation (
13
) is established for several frequency indexes
Ω = [ ω 1 , ω 2 , . . . , ω k , . . . , ω K ]
, which are chosen from the IR-UWB radar frequency band. To do so, we use the GGA instead of FFT because we require a few spectral components. In such cases, the algorithm is significantly faster.
3.2.2. DOA Estimation
Initially, we perform the IMUSIC method on the received signal after the pre-processing step to estimate the DOA of each person with a high angular resolution. It is common to assume that the number of sources is known, or previously estimated by using MDL or AIC methods [
29
,
30
]. Firstly, the ideal covariance matrix is estimated using the sample covariance matrix for each frequency bin:
R ^ ( ω k ) = 1 N ∑ t = 0 N − 1 X ( t , ω k ) X H ( t , ω k )
(14)
where
( . ) H
represents the conjugate transpose. Then, the noise covariance matrix can be estimated, based on the eigenvalue decomposition of
R ^ ( ω k )
, as:
R ^ n ( ω k ) = Q n ( ω k ) Q n H ( ω k )
(15)
where
Q n ( ω )
is the estimated noise subspace obtained using the SVD on
R ^ ( ω k )
for each frequency bin. Secondly, the estimated
θ ^ 0 l
of the
l t h
person can be obtained by evaluating the peaks of the following spatial spectrum function [
25
]:
P I M U S I C ( θ ) = ∑ k = 1 K 1 a H ( θ , ω k ) R ^ n ( ω k ) a ( θ , ω k )
(16)
3.2.3. Distance Estimation
In order to estimate the distance of each person accurately, we use the well-known LCMV beamformer, which is widely used in acoustic array processing [
31
]. First, a weighted vector is designed according to certain criteria. In particular, the LCMV beamformer intends to make the desired direction
θ ^ 0 l
gain associated with the
l t h
person constant while minimizing the total output power with certain constraint conditions:
min w k w k H R ^ ( ω k ) w k s . t w k H C = f
(17)
in which:
f = [ 0 , 0 , . . . , 0 , 1 , 0 , . . . , 0 ] T C = [ a ( θ ^ 0 1 , ω ) , a ( θ ^ 0 2 , ω ) , . . . , a ( θ ^ 0 l − 1 , ω ) , a ( θ ^ 0 l , ω ) , a ( θ ^ 0 l + 1 , ω ) , . . . , a ( θ ^ 0 L , ω ) ]
(18)
Based on the work in [
8
], the weight vector is expressed as:
w k = R ^ − 1 ( ω k ) C C H R ^ − 1 ( ω k ) C f
(19)
Thus, the final output signal associated with the
l t h
person can be expressed as:
S ^ l ( t , ω k ) = w k H X ( t , ω k )
(20)
Using Equation (
12
), Equation (
20
) can be rewritten as:
S ^ l ( t , ω k ) = S l ( t , ω k ) + e l ( t , ω k ) S ^ l ( t , ω k ) = e − j 2 ω k d 0 l c s l ( t ) + e l ( t , ω k )
(21)
where
s l ( t ) = A l e j 2 π f r l t
,
A l = α l J 1 ( β r l ( ω k ) ) P ( ω k )
, and
e l ( t , ω k )
represents the estimation error. The matrix form of Equation (
21
) can be expressed as:
S ^ l ( t ) = a ( d 0 l ) s l ( t ) + e l ( t )
(22)
in which:
S ^ l ( t ) = [ S ^ l ( t , ω 1 ) , S ^ l ( t , ω 2 ) , . . . , S ^ l ( t , ω k ) , . . . , S ^ l ( t , ω K ) ] T , e l ( t ) = [ e l ( t , ω 1 ) , e l ( t , ω 2 ) , . . . , e l ( t , ω k ) , . . . , e l ( t , ω K ) ] T , a ( d 0 l ) = [ e − j 2 ω 1 d 0 l c , e − j 2 ω 2 d 0 l c , . . . , e − j 2 ω k d 0 l c , . . . , e − j 2 ω K d 0 l c ] T .
Notice that Equation (23) represents an array signal processing based-model. Thus, the subspace methods can be applied to estimate
d 0 l
. In our work, we use the MUSIC method in which the number of sources is fixed to one [
32
]. This procedure is repeated for each
l
. To this end, the VS signal of the
l t h
person can be extracted by applying a simple beam focusing technique as follows:
s ^ l ( t ) = a H ( d ^ 0 l ) S ^ l ( t )
(23)
3.2.4. Respiration Rate Estimation
In this section, we focus on the estimation of respiration rate from the extracted VS waveform
s ^ l ( t )
. Based on Equation (
23
),
s ^ l ( t )
can be expressed as:
s ^ l ( t ) ≈ A l e j 2 π f r l t
(24)
Applying the FT to Equation (
24
) leads to:
S ^ l ( f ) ≈ A l δ ( f − f r l )
(25)
where
δ
represents the Dirac function. Thus,
f r l
can be easily estimated by finding the peak of
S ^ l ( f )
, which is calculated using FFT.
4. Experimental Results
In this section, we describe the experiments that were carried out to assess the performance of the proposed method. Three human subjects participated in these experiments, in which an accelerometer was attached to their chest as a ground truth device for breathing rate estimation. Several scenarios were considered to ensure the accuracy of the obtained results. A record of 30 min was achieved for different scenarios; each record was divided into several realizations of 180 s (22.5 s for each channel). The errors were calculated as follows:
Error θ = 1 N r L ∑ l = 1 L ∑ n r = 1 N r | θ 0 l − θ ^ 0 l [ n r ] | | θ 0 l | × 100 % Error d = 1 N r L ∑ l = 1 L ∑ n r = 1 N r | d 0 l − d ^ 0 l [ n r ] | | d 0 l | × 100 % Error f r = 1 N r L ∑ l = 1 L ∑ n r = 1 N r | f r l − f ^ r l [ n r ] | | f r l | × 100 %
(26)
where
N r
represents the number of realizations that equal 10 in our experiment. The exact values of
θ 0 l
and
d 0 l
were set manually during the experiment.
Figure 4
depicts an example of such scenarios.
Figure 4. Human subject experiment setup: The persons are exposed to the radar at different positions, in which the accelerometer is attached to the chest in order to serve as a reference signal. ( a ) For one person. ( b ) For multiple persons.
Once the radar data were successfully recorded, they were transferred to the PC via a WiFi connection for signal processing. Figure 5 depicts the collected data of the first realization associated with each channel after the pre-processing step.
Figure 5. Collected radar data after the pre-processing step: ( a ) for one person, ( b ) for multiple persons.
4.1. Position and Respiration Rate Estimation of One Person
The first experiment concerned a position and breathing rate estimation scenario for one person. Several assays were performed. The person was exposed directly in front of the radar at different positions with a normal breathing rate. In this context, the incidence angles were set to − 45 ° , 0 ° , and 45 ° , the nominal distance to 1 m from the radar, and the exact value of the breathing rate was obtained by the accelerometer attached to the person’s chest. Based on the IMUSIC procedure, the angles were estimated with an error of 2 % . As an example, Figure 6 shows the estimated angles for the first realization.
Figure 6. Estimated DOA for one person associated with the first realization. ( a ) For θ 0 1 = − 45 ° . ( b ) For θ 0 1 = 0 ° . ( c ) For θ 0 1 = 45 ° .
After applying the LMCV beamformer, the distance was calculated using the MUSIC algorithm with an error of 5%. Figure 7 depicts an example result of such a process.
Figure 7. Estimated distance of one person at 1 m. ( a ) For θ 0 1 = − 45 ° . ( b ) For θ 0 1 = 0 ° . ( c ) For θ 0 1 = 45 ° .
Using the beam focusing technique, the respiration rate was estimated with an error of 1.73 %. Figure 8 shows the result of such a scheme for the first realization.
Figure 8. Extracted respiration signal and its FFT spectrum for one person located at d 0 1 = 1 m. ( a ) For θ 0 1 = − 45 ° . ( b ) For θ 0 1 = 0 ° . ( c ) For θ 0 1 = 45 ° .
4.2. Position and Respiration Rate Estimation of Multiple Persons
In this section, we evaluate the separation procedure. Two sets of experiments were conducted. Firstly, two human subjects were asked to stand at different positions. Specifically, the angles were set to θ 0 1 = 0 ∘ ; θ 0 2 = 45 ∘ , and the nominal distance to d 0 1 = d 0 2 = 1 m for both of them. Secondly, we increased the number of persons to three, in which the angles were set to θ 0 1 = − 30 ∘ ; θ 0 2 = 0 ∘ ; θ 0 3 = 45 ∘ , and the nominal distances to d 0 1 = 1 m; d 0 2 = 2.5 m; d 0 3 = 1.5 m. Figure 9 depicts the estimated angles using the IMUSIC algorithm for both experiments.
Figure 9. Estimated DOA for multiple persons associated with the first realization. ( a ) For two persons. ( b ) For three persons.
Applying the LCMV allowed us to separate the VS signals. First, we estimated the distance of each person using the MUSIC algorithm [ 32 ]. The results are shown in Figure 10 . Then, the respiration rate could be estimated with high accuracy and approximately 2.63 % error, as depicted in Figure 11 and Figure 12 .
Figure 10. Estimated distance of multiple persons. ( a ) For two persons at the same distance from the radar. ( b ) For three persons at different distances from the radar.
Figure 11. Extracted respiration signal of two persons. ( a ) FFT spectrum for θ 0 1 = 0 ∘ ; d 0 1 = 1 m. ( b ) FFT spectrum for θ 0 2 = 45 ∘ ; d 0 2 = 1 m.
Figure 12. Extracted respiration signal of three persons. ( a ) FFT spectrum for θ 0 1 = − 30 ∘ ; d 0 1 = 1 m. ( b ) FFT spectrum for θ 0 2 = 0 ∘ ; d 0 2 = 2.25 m. ( c ) FFT spectrum for θ 0 3 = 45 ∘ ; d 0 3 = 1.5 m.
As already mentioned, we used an accelerometer device to measure the respiration rate, which served as a reference signal for the comparison with our method. This allowed us to quantify the performance of the proposed system for the non-contact VS monitoring of multiple persons. Up to now, we have used the error presented in Equation ( 26 ) as a criterion, which is good for DOA and distance evaluation, since we manually set up the true values for both of them. However, this is not the case for the respiration rate, in which the true value is extracted from the accelerometer device.
In order to assess the comparability between our method and the accelerometer device-based method, we used Altman and Bland (B&A) plot analysis, which is an effective method to describe the agreement between measurements. The B&A graph plots the difference in two paired measurements against the mean of the two measurements [
33
].
Figure 13
depicts the result of such a plot, with a confidence interval limit of −20% (from −10% to 10%), which is an acceptable error for clinical applications. The differences between measurements of the same substance are not significant. This can be represented by the mean difference, which is 0.43% for one person and 0.41% for multiple persons.
Figure 13. B&A plot analysis expressed as percentages of the values. Shaded areas present confidence interval limits for mean and agreement limits: ( a ) for one person, ( b ) for multiple persons.
4.3. Discussions
To further verify the discrimination performance of the proposed scheme, a human subject was asked to stand at several distances from the radar. Two scenarios were considered in our laboratory. In the first scenario, the person was exposed directly in front of the SIMO radar. At each assay, the distance was changed with a step size of
0.5
m. In the second scenario, the person stood behind a wall, and the same assays were conducted with a step size of
0.25
m. The wall was made up of reinforced concrete with a 20 cm width. As can be seen from
Figure 14
, our system is capable of monitoring human subjects up to 3 m without obstacles and
0.5
m with an obstacle. Note that the maximum distance can be changed depending on the power of the transmitted signal, the material nature, and the size of the obstacle.
Figure 14. Error analysis with respect to the distance: ( a ) without obstacle, ( b ) with obstacle.
Furthermore, our system was compared with the state-of-the-art research based on spatially distributed array approaches in terms of angle resolution, maximum distance, and respiration rate error. As shown in Table 1 , the proposed system has the minimum respiration rate error. It also has the minimum angle resolution; this is due to its eight receiving antennas.
Table 1. Comparison with the state-of-the-art research.
5. Conclusions
In this work, we aimed to devise a non-contact-based solution for multiple-person monitoring that can ensure adequate measurement and preserves the person’s privacy. To this end, by combining an IR-UWB radar sensor and subspace methods, this study proposes a SIMO scheme that can identify each individual with its corresponding respiration rate. To interpret the collected UWB radar data using the subspace methods, we propose a pre-processing step, based on GGA, that converts the UWB data to multiple narrow-band signals that contain the spectrum and spatiotemporal features of each person. An ISSM is established for the proposed phased array system for DOA and distance estimation. Meanwhile, a separation procedure is introduced, based on LCMV, for individual identification and respiration rate estimation. The experimental results prove that the system can automatically find the direction and the distance of multiple human subjects and effectively detect their respiratory rates.
Author Contributions
Conceptualization, I.K., H.A. and M.N.E.K.; methodology, I.K., H.A. and M.N.E.K.; software, I.K. and H.A; validation, I.K., H.A. and A.M. (Ammar Mesloub); formal analysis, A.M. (Ammar Mesloub); investigation, A.M. (Abdelmadjid Maali); writing—original draft preparation, I.K.; writing—review and editing, I.K. and M.N.E.K.; visualization, I.K.; supervision, M.S.A. and A.M. (Abdelmadjid Maali). All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Conflicts of Interest
The authors declare that they have no conflict of interest.
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Figure 1. Signal receiving model of array antenna.
Figure 2. Overview of the SIMO radar-based respiratory measurement system for multiple persons.
Figure 3. Block diagram of the proposed method.
Figure 4. Human subject experiment setup: The persons are exposed to the radar at different positions, in which the accelerometer is attached to the chest in order to serve as a reference signal. ( a ) For one person. ( b ) For multiple persons.
Figure 5. Collected radar data after the pre-processing step: ( a ) for one person, ( b ) for multiple persons.
Figure 6. Estimated DOA for one person associated with the first realization. ( a ) For θ 0 1 = − 45 ° . ( b ) For θ 0 1 = 0 ° . ( c ) For θ 0 1 = 45 ° .
Figure 7. Estimated distance of one person at 1 m. ( a ) For θ 0 1 = − 45 ° . ( b ) For θ 0 1 = 0 ° . ( c ) For θ 0 1 = 45 ° .
Figure 8. Extracted respiration signal and its FFT spectrum for one person located at d 0 1 = 1 m. ( a ) For θ 0 1 = − 45 ° . ( b ) For θ 0 1 = 0 ° . ( c ) For θ 0 1 = 45 ° .
Figure 9. Estimated DOA for multiple persons associated with the first realization. ( a ) For two persons. ( b ) For three persons.
Figure 10. Estimated distance of multiple persons. ( a ) For two persons at the same distance from the radar. ( b ) For three persons at different distances from the radar.
Figure 11. Extracted respiration signal of two persons. ( a ) FFT spectrum for θ 0 1 = 0 ∘ ; d 0 1 = 1 m. ( b ) FFT spectrum for θ 0 2 = 45 ∘ ; d 0 2 = 1 m.
Figure 12. Extracted respiration signal of three persons. ( a ) FFT spectrum for θ 0 1 = − 30 ∘ ; d 0 1 = 1 m. ( b ) FFT spectrum for θ 0 2 = 0 ∘ ; d 0 2 = 2.25 m. ( c ) FFT spectrum for θ 0 3 = 45 ∘ ; d 0 3 = 1.5 m.
Figure 13. B&A plot analysis expressed as percentages of the values. Shaded areas present confidence interval limits for mean and agreement limits: ( a ) for one person, ( b ) for multiple persons.
Figure 14. Error analysis with respect to the distance: ( a ) without obstacle, ( b ) with obstacle.
Table 1. Comparison with the state-of-the-art research.
Research Paper Radar Type Number of Subjects Distance (m) Angle Resolution Respiration Rate Error [ 8 ] CW 3 3 15 ∘ None [ 9 ] CW 3 None 60 ∘ 8% [ 34 ] FMCW 2 1 60 ∘ None This paper UWB 3 3 15 ∘ 2%
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Kakouche, I.; Abadlia, H.; El Korso, M.N.; Mesloub, A.; Maali, A.; Azzaz, M.S. Joint Vital Signs and Position Estimation of Multiple Persons Using SIMO Radar. Electronics 2021, 10, 2805.
https://doi.org/10.3390/electronics10222805
AMA Style
Kakouche I, Abadlia H, El Korso MN, Mesloub A, Maali A, Azzaz MS. Joint Vital Signs and Position Estimation of Multiple Persons Using SIMO Radar. Electronics. 2021; 10(22):2805.
https://doi.org/10.3390/electronics10222805
Chicago/Turabian Style
Kakouche, Ibrahim, Hamza Abadlia, Mohammed Nabil El Korso, Ammar Mesloub, Abdelmadjid Maali, and Mohamed Salah Azzaz. 2021. "Joint Vital Signs and Position Estimation of Multiple Persons Using SIMO Radar" Electronics10, no. 22: 2805.
https://doi.org/10.3390/electronics10222805
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Malignant pleural mesothelioma: predictors and staging - Richards - Annals of Translational Medicine
Malignant pleural mesothelioma: predictors and staging
Review Article on Mesothelioma
Malignant pleural mesothelioma: predictors and staging
William G. Richards
Brigham and Women’s Hospital,
Harvard Medical School
,
Boston, MA 02115
,
USA
Correspondence to:
William G Richards, PhD. Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. Email:
wrichards@bwh.harvard.edu
.
Abstract:Malignant pleural mesothelioma remains a rapidly fatal cancer with few effective therapies. Unusual anatomic features complicate determination of stage and prognosis for individual patients. Validation of staging criteria has been difficult given the rarity of the disease and the fact that only a minority of patients undergo surgical resection with pathological examination of their tumors. Thus, additional heuristic factors and algorithms have been taken into account by clinicians to estimate prognosis and inform discussion of appropriate management strategies or clinical research protocols with patients.
Keywords:Mesothelioma; prognosis; staging
Submitted Mar 29, 2017. Accepted for publication May 30, 2017.
doi: 10.21037/atm.2017.06.26
Tumor staging refers to malignancy-specific algorithms that categorically classify individual patients’ tumors according to their state of progression through the typical natural history of the disease. Stage classification reflects anatomical properties of the malignancy observed at a point in time, including the size of the primary tumor, its direct invasion through specific tissue planes into adjacent structures or organs, and metastatic dissemination via the lymphatic or systemic circulation to form satellite lesions. If feasible, criteria for combining these observations to establish stage are organized in a tumor-node-metastasis (TNM) framework.
Staging serves the purposes of estimating prognosis, assessing risks and benefits of specific therapies, and selecting or stratifying homogeneous cohorts of patients to study in clinical trials. A half-century ago, Feinstein (1) recognized that anatomical staging alone may be insufficient to fully classify certain tumors for these purposes, as it neglects orthogonal and potentially informative dimensions such as tumor growth over time (indolent to aggressive) and the presence and severity of clinical symptoms. The ensuing decades have seen the development and periodic revision of international consensus staging systems which for most solid tumors [including malignant pleural mesothelioma (MPM)] remain based exclusively on anatomical criteria. However, there has been increasing recognition of the utility and importance of demographic, historical, clinical, molecular, immune and other factors, particularly for malignancies such as MPM for which the prognostic and predictive accuracy of anatomical staging are limited. Therefore, this review considers separately the topics of MPM staging and prognostic/predictive factors, models and biomarkers in relation to current and emerging therapeutic approaches to MPM.
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A number of independent staging systems for MPM have been proposed that differ by format and the significance attributed to specific classification criteria [for review, see reference (2)]. Each of the proposed staging systems was derived based on analyzing series of surgically resected cases of MPM. Disappointingly, none stratifies patient outcome accurately enough to provide useful prognosis for individual patients, to guide therapeutic choices, or to select homogeneous cohorts for clinical trials. Efforts to improve MPM staging have been impeded by the rarity of the disease, the complexity of its assessment and the general ineffectiveness of available therapy.
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Pathological staging classifies cases based on gross and microscopic analyses of pathological specimens from surgical resection. TNM criteria for MPM first appeared in the 4th edition Cancer Staging Manuals published by the International Union Against Cancer (UICC) (3) and The American Joint Committee on Cancer (AJCC) (4). The International Mesothelioma Interest Group (IMIG) proposed modifications to classification and stage grouping criteria (5) that were adopted by the AJCC and UICC and have since remained the international standard for MPM staging.
According to AJCC/UICC criteria, T classification is determined based on the extent of tumor invasion within the pleurae and into adjacent thoracic structures. T1 tumors are those that remain confined to unilateral pleural surfaces. The T2 classification includes tumors that have extended to involve interlobar fissures, lung parenchyma or diaphragm muscle. T3 tumors involve endothoracic fascia or mediastinal adipose tissue, extend into but not through the pericardium, or invade chest wall soft tissue at a single focus. T4 includes tumors with diffuse or multifocal chest wall soft tissue involvement, invasion of brachial plexus, bony components of chest wall or spine, mediastinal organs, contralateral pleura, or extension through diaphragm or pericardium. Unlike TNM staging of most solid tumors, criteria for T classification of MPM do not include consideration of tumor size, due to the impracticality of measuring tumors with irregular and highly variable morphology.
N classification of MPM follows the lung cancer map (6), which assumes that tumors invade pulmonary lymphatics that drain predictably and progressively through intraparenchymal and ipsilateral hilar lymph nodes (classified N1) to ipsilateral and midline mediastinal nodes (classified N2), and finally to contralateral and extrathoracic stations (classified N3). The lung map does not account for some nuances of MPM nodal invasion, however. For example, although MPM that is invasive from visceral pleura into pulmonary parenchyma may follow this metastatic pattern, direct lymphatic drainage from the diaphragmatic pleura to the mediastinal nodal chain has also been demonstrated (7) probably accounting for N2 nodal disease observed without evident N1 involvement in approximately 40% of patients (8-10). Although some studies have demonstrated worse prognosis for N2 than N1 (10,11), current TNM grouping criteria do not distinguish N1 from N2 involvement, each determining at minimum stage III. Indeed, the distinction may be rendered moot with the increasing application of lung-sparing surgery, where intrapulmonary nodal sampling is not generally undertaken. Nevertheless, evidence-based proposals have been made to refine N classification considering combined N1 and N2 involvement versus N1-only or N2-only disease (12), the number of involved nodes (8) or nodal stations (10), or the specific mediastinal stations involved (11).
M classification of MPM is binary. M1 indicates documented blood-borne metastasis. Distant metastases to brain, bone, kidney and adrenal glands have been documented (13), but are only rarely diagnosed (14), likely due to the comparatively rapid and fatal progression of local T4 disease involving vital intrathoracic organs.
The International Association for the Study of Lung Cancer (IASLC) staging committee is tasked with recommending data-driven adjustment of TNM classification and staging criteria for MPM in future AJCC/UICC editions. The committee’s approach has been to assemble an international database of MPM cases to support evidence-based recommendations. An initial phase of the analysis focused on pooling existing retrospective databases representing series of patients managed surgically at participating institutions, and essentially confirmed in a large international cohort the practical inadequacy of current staging criteria for MPM (15). The second phase of the IASLC Mesothelioma Staging Project is based on a database of prospective cases, and has resulted in published recommendations for adjustments to criteria for the upcoming 8 thedition (16).
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Clinical staging of MPM typically involves radiographic assessment of TNM classification criteria using chest computed tomography (CT), magnetic resonance imaging (MRI), and/or fluorodeoxyglucose positron emission tomography (FDG-PET) (17).
Imaging studies effectively identify areas of apparent extrathoracic tumor, indicating M1 disease and excluding consideration of primary surgical resection. However, among patients with radiographically localized MPM, clinical staging of MPM lacks accuracy to predict either patient outcome or pathological T or N status (18). In particular, significant understaging by clinical (relative to pathological) assessment has been documented (15,19). Overstaging has also been observed, but less commonly.
Chest CT
Based on considerations of availability and cost (20), CT is the most commonly used imaging modality to initially determine potential resectability by ruling out contralateral or distant metastasis, diffuse involvement of chest wall or direct tumor extension into the abdomen. Published guidelines for clinical workup of MPM patients recommend only CT beyond history, physical, and chest X-ray (21). However, CT is insensitive to detect focal tumor invasion of chest wall, pericardium, diaphragm, mediastinum or intralobar fissures as required for accurate T classification (22,23). Clinical determination of N status based on CT is similarly inaccurate with apparent lymphadenopathy being essentially uncorrelated with pathologically-proven nodal metastasis (24,25). Nodal enlargement is neither sensitive nor specific as an indicator of metastatic involvement, and nodal stations such as hilar and internal thoracic are difficult to distinguish from adjacent primary tumor on CT (24,26). Inter-observer variability with respect to staging parameters is also problematic. In a recent multi-institutional study (27), institutional radiologists understaged cases using CT relative to pathological findings, and two experienced reference radiologists who performed central review differed substantially on CT-based clinical staging.
FDG-PET
FDG-PET is an effective modality for identifying patients who may have metastasis to lymph nodes or extrathoracic sites (28-31). In particular, integrated PET-CT has been found to provide modest improvement to staging accuracy relative to CT, particularly for detection of T4 (32). PET-CT also detects mediastinal lymph node involvement with 75% specificity (but only 50% sensitivity) (33). PET-CT may be more accurate and less variable compared to CT for predicting AJCC/UICC pathological stage following induction chemotherapy (34). A consensus statement from the Austrian Mesothelioma Interest Group recommends that both CT and PET-CT have value for MPM staging (35).
Interestingly, the maximal standard uptake value (SUVmax) of the primary tumor correlates with the likelihood of nodal metastasis (30), but not with T classification (33). Given that SUVmax was found to be independently prognostic in a multivariate analysis accounting for TNM stage (36), the utility of FDG-PET may be more evident in prognosis, whereas accuracy, availability and cost considerations may limit its utility for staging per se.
It should be noted that if patients have previously undergone talc pleurodesis, interpreting FDG-PET results is difficult, because areas of PET-avid granulomatous talc reaction may be mistaken as evidence of tumor (37-39) or attributed undue prognostic significance (40).
MRI
MRI has been found more accurate than CT for distinguishing MPM from chest wall muscle and benign pleural disease (41), and to evaluate diaphragmatic invasion (42). Recently published early experience with sequential co-registered PET-MRI for local staging of MPM has been encouraging (43), although availability and cost may inhibit the routine use of these technologies for clinical MPM staging.
Surgical staging
Surgical staging has been used by some groups to detect metastatic disease that would preclude surgical resection and may be missed by imaging. Some authors have argued for surgical staging as a gold standard pre-operative assessment (44). Zielinski and colleagues used aggressive surgical staging to demonstrate that among 18 patients with clinical stage I or II MPM based on CT, 8 had involved mediastinal nodes, 8 had abdominal dissemination, and one had chest-wall invasion (45).
Cervical mediastinoscopy is a critical component of pre-surgical staging of non-small cell lung cancer. However, it has limited sensitivity for N2 classification of MPM because multiple relevant nodal stations are not accessible by the procedure. Although some reports find mediastinoscopy more accurate than CT for determining mediastinal lymph node involvement (25), others report sensitivity as low as 36% (46). Routine mediastinoscopy continues to be recommended for patients with epithelioid tumors (8,24), in accordance with the poor prognosis of patients with epithelioid histology tumors and nodal metastasis to superior N2 or N3 stations (11). Despite the well-documented prognostic value of pathological lymph node status, the mediastinoscopy result unfortunately does not accurately predict patient outcome after surgery (9).
Additional minimally invasive surgical assessment may be helpful for preoperative identification of advanced disease. For example, one study reported that in 20% of cases, disease extension beyond the ipsilateral hemithorax that had not been detected by CT, MRI, or PET was discovered using a combination of mediastinoscopy, contralateral thoracoscopy and laparoscopy (47). Varying combinations of esophageal ultrasound (EUS), endobronchial ultrasound (EBUS) (10,45,48), mediastinoscopy or transcervical extended mediastinal lymphadenectomy, and laparoscopy with abdominal lavage (45,46) have also been recommended.
In summary, the accuracy and reproducibility of TNM staging for MPM are impeded by lack of a quantitative measure reflecting tumor size, the number and complexity of T classification criteria, the vital nature (and thus pathologic inaccessibility) of many relevant margins and the increasing tendency to employ lung-sparing surgical procedures that leave many margins and lymph nodes unassessed. These facts led the IASLC staging committee to propose the concept of a “best” stage (bTNM) that combines available staging data obtained from multiple assessments (clinical, surgical, pathological) to mitigate incomplete data and improve TNM performance (15). Efforts are underway to further refine criteria (49-51) and to validate 3-dimensional quantitative estimates of tumor size to potentially augment T classification (27,52) in future editions of the staging system.
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Multiple clinical prognostic indicators may provide additional risk discrimination independent of anatomical stage. In general, such factors have been employed empirically by clinicians to augment stage in support of clinical decision making and patient counseling. Several multivariable models that combine and weight multiple factors have been proposed, and in some cases independently validated.
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The World Health Organization (53) distinguishes three major histological subtypes of MPM: epithelioid, sarcomatoid and biphasic (comprising both epithelioid and sarcomatoid elements). The distinction between epithelioid and non-epithelioid (sarcomatoid or biphasic) histology is the single most consistently reported prognostic factor, regardless of stage or treatment. Patients with epithelioid tumors have the more favorable outlook in terms of clinical course, tumor growth rate, resectability, severity of symptoms, responsiveness to chemotherapy, time to progression/recurrence and overall survival. Among 5,038 MPM cases in the SEER database with reported subtype, 65% were epithelioid, 13% were biphasic and 22% were sarcomatoid (54). Because regional heterogeneity of biphasic tumors results in low sensitivity of pleural biopsy to detect non-epithelioid disease (55), SEER data may overestimate the proportion of epithelioid tumors. Only 23% of patients underwent any cancer directed surgery and fewer still would have had definitive surgical resection and pathological determination of histology (54). There is mounting evidence based on comprehensive molecular profiling that MPM may self-sort into four subgroups roughly corresponding to the spectrum of histology and reflecting expression of biomarkers related to epithelial-mesenchymal transition (56).
The widely divergent clinical behavior and biology of epithelioid and non-epithelioid MPM have led some authors to advocate that staging and other prognostic criteria may need either to be specified separately or to otherwise account for histology. For example, analysis of prognosis in relation to TNM staging criteria considering epithelioid (11) and biphasic (57) histology separately reveals that among epithelioid tumors, patient survival is significantly related to both T- and N-status, whereas among biphasic tumors, OS is more strongly driven by T-status. Nodal metastasis is rarely if ever observed among sarcomatoid tumors.
Patient factors
Multiple demographic, historical, and clinical factors apart from histology have been reported to have prognostic relevance for patients with MPM. Factors portending poor prognosis include poor performance status (58-61), advanced age, male sex (15,54,58,59,62-64), preoperative anemia (65,66), high white blood cell count (58,66), high platelet count (66), weight loss (59,61,66), chest pain (59,66), low serum albumin (61,67) and high neutrophil/lymphocyte ratio (68,69).
Functional imaging
High metabolic activity associated with the primary tumor at diagnosis has been correlated to shorter OS. Benard and colleagues (70) found that SUVmax cut at the median value of 4 was associated with OS among 17 patients with MPM, although high SUVmax patients also had predominantly non-epithelioid tumors, confounding interpretation. Flores and colleagues (30,36,71) have reported that SUVmax and histologic subtype were independently prognostic, although subsequent work supports an association of very high SUVmax (>10) with pleomorphic epithelioid and non-epithelioid histology (72). Among patients who have undergone surgical resection, higher tumor SUVmax observed at the time of tumor recurrence has been associated with shorter subsequent OS (73).
Diffusion-weighted MRI can quantitatively predict biphasic histology (74). Higher apparent diffusion coefficient values are associated with epithelioid histology, while lower values are indicative of non-epithelioid tumor. In particular, diffusion-weighted MRI may be helpful to guide biopsy in areas of suspected sarcomatoid differentiation.
Type of treatment
Several large studies report on the association of specific therapeutic interventions with prognosis. Application of cancer-directed surgery, but not radiation therapy, is associated with good prognosis among 14,228 cases in the SEER dataset (54), as is curative- ( vs.palliative-) intent surgery among surgical patients constituting the IASLC dataset (15). Nakas (64) identified neoadjuvant or adjuvant chemotherapy as factors independently associated with favorable prognosis among 252 surgically treated (extrapleural pneumonectomy or extended PD) patients, as did Bovolato and colleagues (19) in a retrospective analysis of 1,227 surgical and non-surgical cases from six institutions. When interpreting such studies, it is important to acknowledge the potential influence of selection bias (i.e., that patients who undergo surgery, chemotherapy or radiation therapy, by virtue of being fit enough to do so, may have better prognosis than those that do not, independent of any anti-tumor effect of the therapy) and guarantee time bias (i.e., that patients who die soon after diagnosis, before therapy can be delivered, will always be counted in the “No Treatment” group, regardless of treatment efficacy).
Tumor size
Similar to many solid tumors, the size of an MPM tumor is prognostic, but is challenging to measure. The prognostic value of tumor volume, estimated from 3-dimensional reconstruction of CT scans (27,65,75) or measured directly as fluid displacement by pleurectomy specimens (76), has been established. Prognosis attributed to “glycolytic volume”, a hybrid metric that weights radiographic volume by FDG-PET SUV (40), likely derives in significant part from tumor volume itself, because SUV alone was not found to be independently prognostic. As an anatomical attribute of the tumor, tumor size technically should constitute an element of staging. Efforts are underway to determine the feasibility of incorporating tumor volume into future editions of staging systems (27,52), but meanwhile, tumor size measurements remain useful to augment staging based on current criteria when estimating prognosis.
Molecular classification
The advent and clinical validation of high-throughput platforms for molecular analysis has provided the potential for assessment of immune (77) and molecular (78) biomarkers relevant to response prediction and prognosis. These assays often can utilize specimens obtained using percutaneous or endoscopic fine-needle biopsies (79,80). Such minimally-invasive procedures, while applicable to a broader proportion of patients with MPM, yield specimens that usually are inadequate for pathologic prognostic assays that require intact tissue architecture, such as determination of histological subtype or evaluating prognostic immunohistochemical markers such as merlin and survivin (81) or CD9 (82). Some tumor-related mutations and expression levels of specific genes are associated with known prognostic factors such as histology and sex (82,83). In addition, though, molecular analysis may have sensitivity to detect prognostic features of the tumor that are orthogonal to established factors. For example, tumors that are classified histologically as epithelioid cluster into several subgroups that are associated with distinctly different patient prognosis, based on expression levels of genes related to epithelial-mesenchymal transition (56).
Prognostic models
A number of distinct prognostic classification systems have been proposed, reflecting the variety of patient populations observed, treatment strategies applied and statistical modeling approaches taken. For example, two long-standing prognostic MPM classifiers based on, and therefore specific to, patients enrolled on clinical trials of chemotherapy were derived by the EORTC (58) and the CALGB (59). Both systems were subsequently validated in similar (i.e., enrolled on chemotherapy clinical trials) patient cohorts (84,85). Performance status, a strong driver of both classifiers, is less relevant for patients undergoing surgery-based therapy, for which marginal functional status would be a disqualifier.
For patients undergoing surgical therapy, the IASLC Staging Committee derived a prognostic classifier based on analysis of a large international database. The model identified sex, age, histology, “best” TNM stage, and palliative vs curative intent surgery as independently prognostic (15). Further analysis of the same dataset identified additional prognostic factors including weight loss, chest pain, low hemoglobin, high platelet and white blood cell counts that were found to independently contribute to poor prognosis when added to the baseline model (66). Opitz and colleagues (86) proposed a prognostic score that is specific to patients undergoing neoadjuvant platinum-based chemotherapy followed by surgery, as objective response to neoadjuvant chemotherapy constitutes a component of the score.
Several proposed prognostic models target specific histological subgroups. A prognostic nomogram that considers weight loss and glycolytic volume (PET SUV integrated with tumor volume) is proposed for prognosis of patients with non-sarcomatous tumors undergoing chemotherapy (40). Gill and colleagues found CT-derived tumor volume and preoperative anemia to be independently prognostic among surgically-treated patients with epithelioid tumors (65).
Among prognostic models derived in unselected cohorts, some include application of specific therapies as factors and as such are potentially subject to aforementioned interpretive biases (19), whereas others focus exclusively on patient factors (61).
Predictive models
Bille and colleagues (60) found that for patients with unresectable MPM, epithelioid histology, good performance status and elevated lymphocyte count at diagnosis were associated with clinical benefit from 1 stline chemotherapy.
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MPM presents significant challenges to meaningful classification by anatomical staging systems such as TNM. Determining and validating reliable indicators of disease course, efficacy of particular therapeutic options, and expected overall survival has been hampered by the relative rarity and anatomical complexity of the disease. Historical, demographic, clinical, and pathological factors can improve prognostic assessment of patients in cases where staging information is equivocal or unavailable. However, prognostic algorithms involving these parameters tend to be developed and validated in the context of specific management strategies, and accordingly exhibit substantial variability. To date, no consensus approach has emerged to effectively classify, prognosticate and rank management options within unselected populations of patients with MPM.
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Cite this article as: Richards WG. Malignant pleural mesothelioma: predictors and staging. Ann Transl Med 2017;5(11):243. doi: 10.21037/atm.2017.06.26
| https://atm.amegroups.com/article/view/15266/15362 |
Editorial Summary - Scientific American
Scientific American is the essential guide to the most awe-inspiring advances in science and technology, explaining how they change our understanding of the world and shape our lives.
The Sciences
Editorial Summary
UNDERGROUND RAILROAD—A company has been organized in London to tunnel from the Post Office to the marble arch entrance on Hyde Park. Mr. Hawkshaw, the engineer of the proposed line, states that it shall be constructed without any interruption of the street traffic between the hours of six in tho morning and ten at night. Any diggings made during the night will be covered in, and the paving replaced before six in the morning. The trains are to be drawn by wire ropes j from fixed engines at each end, so that the air of the tunnel will not be poisoned by the smoke and vapors of locomotives; and, as there can be no collisions, trains will start every two minutes. In the opinion of competent engineers, the substitution of locomotives for ropes was a mistake, whether regarded from the scientific or the economic point of view. The proposed new tunnel road will have nine stations, and the estimated cost is seven million dollars. Improved means of communication in cities is one of the greatest necessities of the day. We want, if possible, to get rid of the surface roads-
THB STBAMBE PBEBIEE.—The salvation of the French steamer Pereire from utter destruction upon the occasion of the accident in the recent attempted voyage from Havre to
I New York, seems little less than a miracle. On January 20th she encountered a tremendous hurricane, and at about two oclock on the following afternoon, an immense wave formed of about seven hundred tuns of water, fell like an avalanche on the deck. Twenty-four out of the thirty-six furnaces were extinguished, four persons were killed, and twenty-one seriously injured. Some of the fatal accidents took place on deck. One young lady was killed while reading in the saloon —the water struck her on the back of the neck, and broke the spinal column. That the steamer was saved and brought
back to port after shipping this immense wave, speaks vol-
I umes for the staunchness of her construction.
GOOD TESTIMONY.—W. Haddon Marriott, of Baltimore, writes us as follows: When I reached home this evening I was agreeably surprised to find awaiting me my letters patent, which upon examination I find to be in every particular satisfactory, and therefore, I must tender you my sincere thanks for the promptness, uprightness, and thorough ability which you have shown in executing the trust confided to you. I shall not only recommend you to such of my friends as need your invaluable advice and assistance, but shall deem it a prixilege to be able to point them to honest, upright men, so rare now-a-days, who will not betray their confidence. To show my confidence in you, I am about to place in your hands another, I think, far more valuable case, trusting to your justly given and undisputed ability.
PAINTING ZINC.—A difficulty is often experienced in causing oil colors to adhere to sheet zinc. Boettger recommends the employment of a mordant, so to speak, of the following composition : One part of chloride of copper, 1 of nitrate of copper, and 1 of sal-ammoniac, are to be dissolved in 64 parts of water, to which solution is to be added 1 part of commercial hydrochloric acid. The sheets of zinc are to be brushed over with this liquid, which gives them a deep black color; in the course of from 12 to 24 hours they become dry, and to their now dirty gray surface a coat of any oil color will firmly adhere. Some sheetB of zinc prepared in this way, and afterwards painted, have been found to entirely withstand all the atmospheric changes of winter and summer.
COPPEE SMOKE.—The smoke from the copper-smelting works of Swansea, Wales, has long been a nuisance to the neighborhood, and the frequent occasion of litigation. Mr. Vivian, one of the principal owners, has at length devised a plan for condensing the sulphureous vapors, thereby converting them into oil of vitriol. This discovery will restore to agriculture thousands of acres of land which the noxious vapors have rendered sterile, and will relive the inhabitants of the murky cloud which has nearly smothered them. The oil of vitriol thus manufactured will be useful, in the preparation of the compounds necessary to redeem the land from the unfruitful state into which it has fallen.
Two lads of this city, aged respectively 8 and 10 yeare, who recently mounted the cow-catcher of the locomotive Leonard W. Jerome, intending to take a short ride along the Eleventh avenue, supposing the engine would stop after moving a short distance, were carried to Peekskill, forty miles away. They were in a position where the engineer could not see them,and upon their arrival at Peekskill, one of them fell off upon the ground senseless, and the other was too weak to walk. After being cared for, the boys were returned to this city. We venture to say they will hereafter give the cowcatcher a wide berth.
TEEMPEBB VELOCIPEDE.—In another column we publish the illustration and description of the above velocipede. The inventor says he is 69 years old and that he can ride his machine an hour or two with a good walking motion, reading the SCIENTIFIC AMEEICAN, with comfort, and turn inside a circle four feet diameter, steering with one foot only. The machine can be used as a one-wheeled velocipede; that is, with the rider over the driving Wheel and the hind wheels used only as steadiers.
THE contrast between the mildness of the winter in the United States and elsewhere, and the violence of the storms at sea, is attracting attention. IB there any connection between these phenomena ? If any other than the universal law of J compensation throughout all the operations of nature, what is it?
This article was originally published with the title "Editorial Summary" in Scientific American 20, 10, 155 (March 1869)
doi:10.1038/scientificamerican03061869-155a
| https://www.scientificamerican.com/article/editorial-summary-1869-03-06/?error=cookies_not_supported&code=e5a2050f-bed0-4c1f-9fc3-042e85f1f586 |
Institut für Zeitgeschichte: Former Fellows 2014
Former Fellows 2014
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Sari J. Siegel
(USA), PhD student, University of Southern California, "Medicine Behind Barbed Wire: Jewish Prisoner-Physicians in Nazi Labor, Concentration, and Extermination Camps in the Greater German Reich, 1938-1945" (July – November 2014, München und Berlin).
Sari J. Siegel about her project:
My research examines an important yet widely overlooked group in Holocaust history—Jewish inmates who utilized their medical knowledge in Nazi camps. Focusing on the labor, concentration, and extermination camp systems in the Greater German Reich between 1938 and 1945, I draw particular attention to the dynamic natures of camp conditions and the prisoner-physicians’ strategies to save their own lives as they attempted to treat fellow inmates and uphold their Hippocratic promise to “do no harm.” My work combines survivor testimonies and legal documents with contemporary government and organizational records for insight into how contextual variables and individual traits shaped the actions of these doctors in the camps. Since the prisoner-physicians’ medical activities placed them within survivor and memoirist Primo Levi’s “gray zone,” analysis of their behavioral shifts allows me to illuminate a new aspect of this morally ambiguous realm.
During my fellowship at the IfZ – Zentrum für Holocaust-Studien, I will work with, among other sources, the Institut für Zeitgeschichte’s database of all German post-war judicial proceedings regarding Nazi crimes, as prisoner-physicians’ witness statements provide information not only on Nazi medical crimes but also on their own experiences as inmate doctors in the camps.
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Yurii Radchenko
(Ukraine), Lector, Kharkiv Collegium, “Ukrainian Hilfspolizei, Self-Government, and the Holocaust in Ukraine: The Case of the Military Administration Zone” (August – November 2014).
Yurii Radchenko about his project:
My project focuses on the activity of the Ukrainian Hilfspolizei and self-government in the military administration zone (Kharkiv, Chernihiv, Sumy, Stalino, Voroshylovhrad oblasts) with regard to the murder of Jews and the plundering of Jewish property. It also investigates the motivations of those who joined the Ukrainian police and self-government in the military administration zone. Ukrainian auxiliary forces took part in the extermination of Jews in many regions of Ukraine. But what was the level of their participation in the persecution, plundering, and murder of Jews in eastern Ukraine? What was the subordination between the bodies of the self government (mis’ka uprava, rayonna uprava, sil’s’kyi starosta) and the local Ukrainian police? Did policemen take part in mass shootings, or did they play an auxiliary role? Who were the members of the Ukrainian police in the Kharkiv, Chernihiv, Sumy, Stalino, and Voroshylovhrad oblasts? What about their background and collective social portrait? What image of the Ukrainian policeman and members of self-government did the official Nazi propaganda try to create (especially in the local newspapers)? I study how strong was the influence and the degree of infiltration into the Ukrainian police of OUN and NTS-NP in the mostly Russian-speaking regional centers of eastern Ukraine, how deeply did integral nationalistic ideology penetrate the Weltanschauung of Ukrainian policemen and members of self-government in the military administration zone and what were the motivations that led Ukrainian policemen to take part in anti-Jewish actions.
<here is a image 14e11152db312f84-a1db206ff3efb0b8>
Froukje Demant
(Netherlands), PhD student, Deutschlandinstitut der Universität Amsterdam, „The Daily Relations of Jews and Non-Jews in the German-Dutch Border Region, 1925-1955“ (August – November 2014).
Froukje Demant about her project:
My research examines the everyday relations and interpersonal interactions of Jews and non-Jews in the German-Dutch border region (specifically the Westmünsterland, Grafschaft Bentheim and Twente) between 1925 and 1955. By focussing on the micro level of everyday relations between neighbours, classmates, acquaintances and friends, this research analyses the social mechanisms that preceded the physical extinction of the Jews, and the ways in which Jews and non-Jews shaped and negotiated ways to live together after the Holocaust. In the years under Nazi rule, both Jews and non-Jews experienced a shift in, and later a breakdown of, their normality, but their experiences differ dramatically in terms of extent and intensity. Still, after the war they had to find ways to live together again and rebuild some sort of new normality. During my four-months stay as a Fellow at the IfZ-Zentrum für Holocaust-Studien, I will focus on the Jewish/non-Jewish relations in the immediate post war years. First, I will study the changes and reversals in the power relations between Jews and non-Jews , and how the returned Jews perceived these changes. Second, I will compare the situation of Jews who decided to return and Jews who did not return. Through this comparison, I will explore in the motivations behind the decision to return or not return, and the communication of Jews who did not return with their former, non-Jewish friends and acquaintances.
EHRI Fellows 2014
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Katarzyna Person
(Poland) holds a PhD in History from Royal Holloway, University of London. She has held has held postdoctoral fellowships from Yad Vashem’s International Institute for Holocaust Research, the Center for Jewish History in New York, and La Fondation pour la Mémoire de la Shoah.
She is currently an assistant professor at the Jewish Historical Institute in Warsaw and the coordinator of the Underground Archive of the Warsaw Ghetto publication project. She has written a number of articles on the Holocaust and its aftermath in occupied Europe, and has edited four volumes of documents from the underground archive of the Warsaw Ghetto. Her book, Assimilated Jews in the Warsaw Ghetto 1940–1943, was published in 2014 by Syracuse University Press. As a Humboldt postdoctoral fellow in the IfZ she is currently finishing a book project dealing with Jews from Poland in the displaced persons camps in Germany. B.A., Geschichte, Yale University M.A., Komparative Geschichte Ostmittel- und Südosteuropas, Central European University (Budapest, Ungarn).
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Aleksandra Loewenau
(United Kingdom), postdoctoral research assistant “Rebuilding Lives of Jewish Survivors of Medical Experiments at Auschwitz: A Comparative Study”.
Loewenau’s project is a continuation of her doctoral research, which produced a monograph that present correlations between three groups of Polish victims of Nazi medical experiments with a particular emphasis on trauma and consequent changing behavior patterns during and after the war.
<here is a image e7dbf8c52e85dbbd-8860a46a38aedb2f>
Matt Lawson
(United Kingdom), “Film Music of German Holocaust cinema”.
Lawson’s research focuses on the music used in German depictions of the Holocaust on screen. His research has been disseminated at conferences across the UK, and also at international events in Italy, Poland, Germany, Australia and the Netherlands.
<here is a image afddf1a011a582ae-ec968f33487f280c>
Devra Katz
(Israel), “Emotions in Stutthof: An Analysis of the Social Function of Emotions in a Prisoner Society”.
Katz investigated the function of emotions among prisoners in the Stutthof concentration camp. Her research explores various examples of emotions through prisoners’ experiences in friendships, relationships, intimacy, survival, bonding, and shame by dissecting survivor testimonies in both German and Yiddish. She examined the subjective and collective social role of emotions that have largely been overlooked in traditional circles of historiography.
| https://www.ifz-muenchen.de/en/center-for-holocaust-studies/fellowships/ehemalige-fellows-2014?cHash=77e8cd751c91a137936e0c821f2074b7&no_cache=1&print=1&type=98 |
(PDF) Subjective method for tracheal tube cuff inflation: performance of anesthesiology residents and staff anesthesiologists. Prospective observational study
PDF | Background and objectives Poor monitoring of tracheal tube cuff pressure may result in patient complications. The objective method of using a... | Find, read and cite all the research you need on ResearchGate
Subjective method for tracheal tube cuff inflation: performance of anesthesiology residents and staff anesthesiologists. Prospective observational study
February 2020
Brazilian Journal of Anesthesiology (English Edition) 70(1)
DOI: 10.1016/j.bjane.2020.02.001
Andrea Tavares Ferrreira
Abstract and Figures
Background and objectives
Poor monitoring of tracheal tube cuff pressure may result in patient complications. The objective method of using a manometer is recommended to keep safe cuff pressure values (20‒30 cm H2O). However, as manometers are not readily available, anesthesiologists use subjective methods. We aimed to assess appropriateness of a subjective method for attaining cuff pressure and the expertise level of manometer handling among anesthesiology staff and residents in a university teaching hospital.
Methods
Prospective observational study, recruiting participants that performed tracheal intubation and the subjective method for tube cuff inflation. Patients with difficult airway, larynx and trachea anatomic abnormality and emergency procedures were not included. Up to 60 minutes after tracheal intubation, an investigator registered the cuff pressure using an aneroid manometer (AMBU®) connected to the tube pilot balloon.
Results
Forty-seven anesthesiologists were included in the study – 24 residents and 23 staff. Mean (SD) and medians (IQR) measured in cmH2O were, respectively, 52.5 (27.1) and 50 (30‒70). We registered 83% of measurements outside the recommended pressure range, with no difference between specialists and residents. The level of expertise with the objective method was also similar in both groups. Pressure adjustments were performed in 76.6% of cases.
Conclusion
The subjective method for inflating the tracheal tube cuff resulted in a high rate of inadequate cuff pressures, with no difference in performance between anesthesiology specialists and residents.
Percentage of participants, according to recommended (20---30 cm H2O) cuff pressure measured (n = 47). …
Profile of the professionals studied and the cuff pressure for all groups. …
Comparison between staff and residents as to knowledge of recommended range for tracheal cuff pressure and use of objective method employing manometers (n = 47). …
Figures - available via license: CC BY-NC-ND
Content may be subject to copyright.
Duarte
NMC,
et
al.
Subjective
method
for
tracheal
tube
cuff
inflation:
perfor-
mance
of
anesthesiology
residents
and
staff
anesthesiologists.
Prospective
observational
study .
Braz
J
Anesthesiol.
2020.
https://doi.org/10.1016/j.bjane.2020.02.001
ARTICLE IN PRESS
+Model
BJANE-74322;
No.
of
Pages
6
Braz
J
Anesthesiol.
2020; xxx(xx) :xxx- - -xxx
SCIENTIFIC
ARTICLE
Subjective
method
for
tracheal
tube
cuff
inflation:
performance
of
anesthesiology
residents
and
staff
anesthesiologists.
Prospective
observational
study 夽
Nádia
Maria
da
Conceic ¸ão
Duarte a , ∗ ,
Ana
Maria
Menezes
Caetano a ,
Gustavo
de
Oliveira
Arouca b ,
Andrea
T avares
Ferrreir a b ,
José
Luiz
de
Figueiredo a
a Universidade
Federal
de
Pernambuco,
Hospital
das
Clínicas,
Departamento
de
Cirurgia,
Recife,
PE,
Brazil
b Universidade
Federal
de
Pernambuco,
Faculdade
de
Medicina,
Recife,
PE,
Brazil
Received
5
August
2019;
accepted
27
September
2019
KEYWORDS
T racheal
intubation;
T racheal
tube;
Cuff
pressure;
Manometer;
Anesthesiologist
Abstract
Background
and
objectives:
Poor
monitoring
of
tracheal
tube
cuff
pressure
may
result
in
patient
complications.
The
objective
method
of
using
a
manometer
is
recommended
to
keep
safe
cuff
pressure
values
(20- - -30
cm
H 2 O).
However ,
as
manometers
are
not
readily
available,
anesthesi-
ologists
use
subjective
methods.
We
aimed
to
assess
appropriateness
of
a
subjective
method
for
attaining
cuff
pressure
and
the
expertise
level
of
manometer
handling
among
anesthesiology
staff
and
residents
in
a
university
teaching
hospital.
Methods:
Prospective
observational
study ,
recruiting
participants
that
performed
tracheal
intubation
and
the
subjective
method
for
tube
cuff
inflation.
Patients
with
difficult
airway ,
larynx
and
trachea
anatomic
abnormality
and
emergency
procedures
were
not
included.
Up
to
60
minutes
after
tracheal
intubation,
an
investigator
registered
the
cuff
pressure
using
an
aneroid
manometer
(AMBU ® )
connected
to
the
tube
pilot
balloon.
Results:
Forty-seven
anesthesiologists
were
included
in
the
study
---
24
residents
and
23
staff.
Mean
(SD)
and
medians
(IQR)
measured
in
cmH 2 O
were,
respectively ,
52.5
(27.1)
and
50
(30- - -70).
We
registered
83%
of
measurements
outside
the
recommended
pressure
range,
with
no
differ-
ence
between
specialists
and
residents.
The
level
of
expertise
with
the
objective
method
was
also
similar
in
both
groups.
Pressure
adjustments
were
performed
in
76.6%
of
cases.
夽 Institution:
Centro
de
Ciências
da
Saúde
---
Universidade
Federal
de
Pernambuco.
Presentation
Certificate
for
Ethical
Appreciation:
CAAE:
44486515.7.0000.5208.
Date
of
the
protocol
approval
of
IRB:
09/04/2015.
∗ Corresponding
author .
E-mail:
nadiaduarte2011@gmail.com
(N.M.C.
Duarte).
https://doi.org/10.1016/j.bjane.2020.02.001
0104-0014/©
2020
Sociedade
Brasileira
de
Anestesiologia.
Published
by
Elsevier
Editora
Ltda.
This
is
an
open
access
article
under
the
CC
BY -NC-ND
license
( http://creativecommons.org/licenses/by-nc-nd/4.0/ ).
Please
cite
this
article
in
press
as:
Duarte
NMC,
et
al.
Subjective
method
for
tracheal
tube
cuff
inflation:
perfor-
mance
of
anesthesiology
residents
+Model
BJANE-74322;
No.
2
Duarte
Conclusion:
The
subjective
method
for
inflating
the
tracheal
tube
cuff
resulted
in
a
high
rate
of
inadequate
cuff
pressures,
with
no
and
20
and
30
cm
H 2 O. 3
Non-compliance
to
the
recommended
pressure
may
lead
to
complications.
Cuff
inflation
pressures
below
20
cm
risk
of
gas
leakage
compromising
lung
venti-
lation,
in
addition
to
facilitating
aspiration
of
secretions
and
oropharyngeal
and
gastric
contents. 4 Inflation
pressures
30
cm
H 2 O
may
overcome
the
local
capil-
lary
pressure,
reducing
blood
flow
to
the
mucosa
of
the
anterolateral
wall
of
the
Pressures
cm
H 2 O
can
cause
vascular
occlusion
and
tracheal
ischemia. 5
As
consequence,
to
prevent
tracheal
pressure
must
be
kept
at
the
minimum
value
possi-
ble
to
ensure
adequate
tracheal
mucosa
blood
flow ,
but
must
be
high
secure
safe
sealing
of
the
space
between
the
tube
and
trachea
walls. 6- - -10
Distinct
strategies,
using
subjective
and
objective
meth-
ods,
have
to
attain
adequate
control
of
the
cuff
pressure
and
reduce
the
risks
of
However ,
evidence
adds
up
against
using
subjective
meth-
and
also
signals
toward
a
non-correlation
between
measured
cuff
pressure
and
age,
sex,
height
and
weight
of
patients.
Additionally ,
pressures
this
article
in
press
as:
Duarte
NMC,
et
al.
Subjective
method
for
tracheal
tube
cuff
inflation:
perfor-
mance
of
anesthesiology
residents
and
staff
anesthesiologists.
Prospective
observational
study .
Braz
J
Anesthesiol.
2020.
https://doi.org/10.1016/j.bjane.2020.02.001
ARTICLE IN PRESS
+Model
BJANE-74322;
No.
of
Pages
6
Subjective
method
for
tracheal
tube
cuff
inflation:
performance
of
anesthesiology
3
manometers
to
perform
the
objective
method
for
setting
such
pressures.
The
assumption
was
that
tracheal
tube
cuff
inflation
using
the
subjective
method
would
result
in
a
high
prevalence
of
cuff
pressures
above
or
below
the
recom-
mended
limits,
and
that
the
knowledge
Parwani
V,
Hoffman
RJ,
Russell
A,
et
al.
Practicing
paramedics
cannot
generate
or
estimate
safe
endotracheal
tube
cuff
pressure
using
standard
techniques.
Prehosp
Emerg
Care.
2007;11:307- - -11.
... Cuff pressures are out of the recommended range 60%-80% of the time in the clinical setting. [6][7][8][9][10][11][12][13]
[14]
This statistic is particularly concerning in the pediatric population as airway complications related to cuff pressures can lead to serious patient safety concerns. 2,15,16 Cuff overinflation is directly correlated to airway complications such as sore Introduction: Endotracheal tube (ETT) cuff pressures are frequently out of the recommended range of 20-30 cm H 2 O. ...
... These methods are used 98% of the time in the clinical setting but are subjective and not consistently accurate. 7,13,
14,
[24][25][26] Also, the inflation method used is at the provider's discretion resulting in a wide variety of methods used in the clinical setting. With objective measurements not being used, estimation techniques being unreliable, and the wide range of methods practitioners use in the clinical setting, cuff pressures continue to be inaccurate. ...
Endotracheal Tube Cuff Pressures in the Operating Room of a Pediatric Hospital: A Quality Improvement Initiative
Article
Full-text available
Dec 2022
Kelly M Moon
Sherry Donaworth
Molly S Hagele
Joseph D. Tobias
Unlabelled:
Endotracheal tube (ETT) cuff pressures are frequently out of the recommended range of 20-30 cm H2O. This can lead to multiple iatrogenic complications ranging from cough, sore throat, and tracheal edema to more serious medical issues such as tracheal stenosis, aspiration, nerve injuries, and tracheal rupture. Additionally, current methods to inflate ETT cuffs vary between anesthesia providers and are not consistent in the recommended range. The objective of this quality improvement project was to increase the percentage of cuff pressures between 20 and 30 cm H2O.
Methods:
Four plan-do-study-act (PDSA) cycles were completed in the operating rooms at Nationwide Children's Hospital over 9 months to assess ways to improve the accuracy of obtaining recommended ETT cuff pressures. Control charts were used to evaluate the primary outcome measure.
Results:
Preimplementation, ETT cuff pressures were out of the recommended range 76% of the time. Cuff pressures were out of the recommended range 64% of the time with the addition of the air method, 84% of the time in the tidal volume ratio cycle, and 50% of the time using the removal of air technique. The removal of air method was the most effective in achieving cuff pressures within the recommended pressure range (P < 0.001).
Conclusions:
Using quality improvement methodology, the percentage of ETT cuff pressures falling within the recommended pressure range increased using the removal of air technique. This approach is a simple and practical method that can be easily implemented in the clinical setting and would provide additional safety in the anesthetic management of pediatric patients.
... This could be explained considering the high self-confidence of the senior anesthetists that might be a barrier toward learning despite the value of the experience for safe anesthetists' clinical practice. The absence of manometer usage to measure the cuff inflation pressures could be another reason [21,
22]
. ...
Endotracheal tube cuff inflation pressure varieties and response to education among anesthetists
Article
Full-text available
Dec 2022
Abdelrhman Alshawadfy
Wesam F Alyeddin
Mohamed A. Elsadany
Background
This study aimed to evaluate endotracheal tube (ETT) cuff inflation pressure (CIP) applied by anesthetists as well as the effect of an interview and feedback on their CIP accuracy.
Methods
This single-blind, controlled trial involved two series of CIP measurements in intubated patients before and after an interview and feedback of the participating anesthetists who were asked to inflate the cuffs for all intubated patients as per their clinical judgment. The cuff pressures were measured using a manometer and accordingly adjusted to 25 cm H2O by the researchers. For each anesthetist, 3 measurements were recorded, and the mean pressure values were calculated for each setting. The anesthetists were initially blinded, then they were informed about the pressure values and the adjustments. The primary outcome was the anesthetists’ accuracy regarding ETT inflation following the feedback. The secondary outcomes were pressure values in senior and junior anesthetists as well as in scheduled and emergency operations.
Results
The study enrolled 28 anesthetists; six registrars or senior registrars and 22 residents. Interview and feedback significantly lowered the mean pressure applied by the anesthetists. The cuff inflation pressure decreased from 33.8 ± 1.95 to 30.8 ± 3.24 and from 32.9 ± 2.38 to 29.9 ± 3.44 for emergency and scheduled surgeries, respectively. Furthermore, the frequency of safe CIP increased significantly for both emergency and scheduled surgeries. However, the senior staff showed no significant increase in safety CIP.
Conclusion
Anesthetists improved their accuracy of CIP after educational feedback. ETT cuff pressures should be routinely measured in intubated patients under general anesthesia.
Anterior servikal omurga cerrahisi sonrası farklı endotrakeal tüp kaf basınçlarının disfajı üzerine etkileri
Article
Full-text available
Jun 2022
Sedef Gülçin Ural
İbrahim Tör
of two different endotracheal cuff pressures on postoperative dysphagia, sore throat, dysphonia, and hospital stay in anterior cervical spine surgery.
Materials and Methods: Seventy patients scheduled for surgery were randomly divided into two groups. After intubation, the endotracheal cuff pressure was inflated to 20 cmH2O and 25 cmH2O in Group I (n=35) and Group II (n=35), respectively. The degree of dysphagia was assessed with the Bazaz dysphagia score. The sore throat was evaluated via Visual Analog Scale. Total pain score regarding the operation site was evaluated using VAS. Hoarseness was evaluated based on the presence of any changes to the voice asharsh or strained. Dysphagia, dysphonia, and sore throat were assessed on the post-surgical 1st and 24th hours.
Results: No differences in demographic data were present between the groups. Dysphagia and sore throat at the post-surgical 1st and 24th hours were significantly lesser in Group I than in Group II. The frequency of dysphonia was significantly less in Group I than compared to Group II only at the post-surgical 1st hour. No differences in VAS scores at the post-surgical 1st and 24th hours were present between the groups.
Conclusion: In this study, it was shown that the risk of developing dysphagia after surgery was significantly reduced with 20 cmH2O endotracheal cuff pressure compared to 25 cmH2O. Also, lower cuff pressure was associated with a milder sore throat, less hoarseness at 1 hour postoperatively, and a shorter hospital stay.
Study On Device System to Reduce Tracheal Mucosal Injury in Intubation Patients
Article
Apr 2022
Dai Won Suh
Seung Bong Lee
Sung-Min Kim
The purpose of this study was to develop an automatic bronchial aspiration system to minimize tracheal mucosal damage in ventilator patients. Operation performances of the system's suction pressure, bronchial intubation depth, suction cycle, and tube cuff pressure were tested. To check clinical results, subjects underwent endoscopy after applying the previous manual method for 24 hours. After that, they underwent endoscopy after applying the proposed suction system for 24 hours. For quantitative evaluation of test results, tracheal mucosal injury was divided into five grades: Grade 0 = normal, Grade 1 = erythema or edema, Grade 2 = erosion, Grade 3 = hemorrhage, and Grade 4 = ulcer or necrosis. In the performance test, an error of up to 12 mmHg occurred within the normal operation error range for suction pressure control. The insertion depth control had a maximum error of 7.0 mm within the normal operation error range. On the other hand, there was no error in the time control or the tube cuff pressure control. In the clinical trial, after using the proposed system for five subjects to find changes in tracheal mucosal injury by endoscopy, reduced injury or no change in injury was found. The system proposed in this study is confirmed to be able to remove sputum while minimizing tracheal mucosal injury that can occur when using previous manual suction device.
Continuous versus intermittent endotracheal cuff pressure control for the prevention of ventilator-associated respiratory infections in Vietnam: Study protocol for a randomised controlled trial
Article
Apr 2018
TRIALS
Vu Quoc Dat
Ronald B Geskus
Marcel Wolbers
Behzad Nadjm
Background:
Ventilator-associated respiratory infection (VARI) comprises ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT). Although their diagnostic criteria vary, together these are the most common hospital-acquired infections in intensive care units (ICUs) worldwide, responsible for a large proportion of antibiotic use within ICUs. Evidence-based strategies for the prevention of VARI in resource-limited settings are lacking. Preventing the leakage of oropharyngeal secretions into the lung using continuous endotracheal cuff pressure control is a promising strategy. The aim of this study is to investigate the efficacy of automated, continuous endotracheal cuff pressure control in preventing the development of VARI and reducing antibiotic use in ICUs in Vietnam.
Methods/design:
This is an open-label randomised controlled multicentre trial. We will enrol 600 adult patients intubated for ≤ 24 h at the time of enrolment. Eligible patients will be stratified according to admission diagnosis (180 tetanus, 420 non-tetanus) and site and will be randomised in a 1:1 ratio to receive either (1) automated, continuous control of endotracheal cuff pressure or (2) intermittent measurement and control of endotracheal cuff pressure using a manual cuff pressure meter. The primary outcome is the occurrence of VARI, defined as either VAP or VAT during the ICU admission up to a maximum of 90 days after randomisation. Patients in both groups who are at risk for VARI will receive a standardised battery of investigations if their treating physician feels a new infection has occurred, the results of which will be used by an endpoint review committee, blinded to the allocated arm and independent of patient care, to determine the primary outcome. All enrolled patients will be followed for mortality and endotracheal tube cuff-related complications at 28 days and 90 days after randomisation. Other secondary outcomes include antibiotic use; days ventilated, in ICU and in hospital; inpatient mortality; costs of antibiotics in ICU; duration of ICU stay; and duration of hospital stay.
Discussion:
This study will provide high-quality evidence concerning the use of continuous endotracheal cuff pressure control as a method to reduce VARI, antibiotic use and hospitalisation costs and to shorten stay.
Trial registration:
ClinicalTrials.gov, NCT02966392 . Registered on November 9, 2016. Protocol version: 2.0; issue date March 3, 2017.
Comparison of endotracheal tube cuff pressure changes using air versus nitrous oxide in anesthetic gases during laparoscopic abdominal surgeries
Article
Full-text available
Feb 2018
Insuflação de balonete de tubo traqueal por método subjetivo: desempenho de médicos residentes e esp...
February 2020 · Revista Brasileira de Anestesiologia
Nádia Maria Da Conceição Duarte
Ana Maria Menezes Caetano
Gustavo de Oliveira Arouca
[...]
Jose Luiz Figueiredo
Background and objectives: Poor monitoring of tracheal tube cuff pressure may result in patient complications. The objective method of using a manometer is recommended to keep safe cuff pressure values (20‒30 cm H2O). However, as manometers are not readily available, anesthesiologists use subjective methods. We aimed to assess appropriateness of a subjective method for attaining cuff pressure and ... [Show full abstract] the expertise level of manometer handling among anesthesiology staff and residents in a university teaching hospital.
Methods: Prospective observational study, recruiting participants that performed tracheal intubation and the subjective method for tube cuff inflation. Patients with difficult airway, larynx and trachea anatomic abnormality and emergency procedures were not included. Up to 60 minutes after tracheal intubation, an investigator registered the cuff pressure using an aneroid manometer (AMBU®) connected to the tube pilot balloon.
Results: Forty-seven anesthesiologists were included in the study – 24 residents and 23 staff. Mean (SD) and medians (IQR) measured in cmH2O were, respectively, 52.5 (27.1) and 50 (30‒70). We registered 83% of measurements outside the recommended pressure range, with no difference between specialists and residents. The level of expertise with the objective method was also similar in both groups. Pressure adjustments were performed in 76.6% of cases.
Conclusion: The subjective method for inflating the tracheal tube cuff resulted in a high rate of inadequate cuff pressures, with no difference in performance between anesthesiology specialists and residents.
Article
Full-text available
Case Series of Inflation Pressures of the Endotracheal Tube Cuffs among Intubated Patients at an Acc...
January 2016 · Hong Kong Journal of Emergency Medicine
Patrick Siu Chung Leung
Chung Ho Yin Andrews
Chan Wai Kun
Tsui Sik Hon
Despite the frequent use of endotracheal tubes in daily practice of emergency medicine, not much emphasis has been put on the measurement of cuff pressure. We attempted to conduct a case series study of prospectively recruited patients to illustrate the risk of inappropriate cuff inflation without manometry. It was found that the pilot balloon palpation was an inaccurate method to estimate cuff ... [Show full abstract] under- or over-inflation, with large discrepancies when compared with an objective measure. Such discrepancies might be independent of doctors' and nurses' working experience in airway management. Use of an aneroid manometer remains an economical and cost-effective way to obtain an instantaneous yet reasonably reliable result and should become a routine in emergency departments.
Full-text available
Measurement of endotracheal tube cuff pressure: Instrumental versus conventional method
Khan Mueenullah
Rashid Khokar
Sadia Qureshi
[...]
Motasim Shiraz
Objective:
To evaluate the conventional practice of endotracheal tube (ETT) cuff inflation and pressure measurement as compared to the instrumental method.
Study design:
Prospective observational study.
Place and duration of study:
Department of Anaesthesia, King Saud University Hospital, Riyadh, Saudi Arabia (June 2014-July 2014).
Methods:
A total of 100 adult patients were observed ... [Show full abstract] according to the syringe size used Group-1 (10 ml) and Group-2 (20 ml) for ETT cuff inflation in general anesthesia. Patients with anticipated difficult intubation, risk for aspiration, known anatomical laryngotracheal abnormalities, and emergency cases were excluded. Trachea was intubated with size 8 or 8.5 mm and 7.0 or 7.5 mm ETT in male and female patients respectively. The ETT cuff was inflated with air by one of the anesthesia technician. Cuff pressures were measured using aneroid manometer. ETT cuff pressure of 20-30 cm of water was considered as standard.
Results:
In 69% of the patients, the cuff pressure measurements were above the standard. Age (P = 0.806), weight (P = 0.527), height (P = 0.850), and gender (P = 1.00) were comparable in both groups. The mean cuff pressure in Group-1 and Group-2 was 32.52 ± 6.39 and 38.90 ± 6.60 cm of water (P = 0.001). The cuff inflation with 20 ml syringe resulted in higher cuff pressure as compared to 10cc syringe 37.73 ± 4.23 versus 40.74 ± 5.01 (86% vs. 52%, P = 0.013).
Conclusion:
The conventional method for ETT cuff inflation and pressure measuring is unreliable. As a routine instrumental cuff pressure, monitoring is suggested.
Article
Benchmarking the Applicability of Four Methods of Endotracheal Tube Cuff Inflation for Optimal Seali...
March 2017 · Journal of perianesthesia nursing: official journal of the American Society of PeriAnesthesia Nurses / American Society of PeriAnesthesia Nurses
Georgia Tsaousi
Chryssa Pourzitaki
Dimitra Chlorou
[...]
Dimitrios Vasilakos
Purpose
To assess the comparable applicability of four methods of endotracheal tube cuff (ETTc) inflation on the basis of optimal level of intracuff pressure and presence of intubation-related complications.
Design
Double-blind, randomized trial.
Methods
A total of 139 adult surgical patients scheduled to undergo nitrous oxide–free general anesthesia were assigned into one of four groups ... [Show full abstract] according to the method used for ETTc inflation. The cuff pressure and air volume applied in each method, and laryngotracheal complications were recorded.
Findings
The highest and lowest ETTc pressure and air volume values were recorded in palpation and minimum leak technique group, respectively. Laryngotracheal complaints were maximized in palpation and minimized in minimal occlusive volume and minimum leak techniques.
Conclusions
The air-return back into the syringe method emerges as an attractive and simple-to-perform alternative regarding effective ETTc sealing and low incidence of intubation-related morbidity when a cuff manometer is not readily available.
Study Registration
ACTRN12615000699561.
| https://www.researchgate.net/publication/339121323_Subjective_method_for_tracheal_tube_cuff_inflation_performance_of_anesthesiology_residents_and_staff_anesthesiologists_Prospective_observational_study |
American Writer Tells Story of Cambodian ‘Women on the Rise’
Anne Elizabeth Moore, a feminist writer and artist, spent about four months living and working with young Cambodian women in a dormitory in Phnom Penh.
Cambodia
American Writer Tells Story of Cambodian ‘Women on the Rise’
The Cambodian Grrrl and New Girl Law: Drafting a Future for Cambodia
WASHINGTON DC —
Editor’s note: In the face of modernization and democratization, there is a rise of young Cambodian women across all sectors in Cambodia. A renowned American artist and writer, Anne Elizabeth Moore, wrote two books about Cambodian women:The Cambodian Grrrl andNew Girl Law: Drafting a Future for Cambodia . Moore, a feminist writer and artist, spent about four months living and working with young Cambodian women in a dormitory in Phnom Penh. She recently spoke to VOA Khmer in Washington via phone.
What brought you to Cambodia and how did your two-book projects about Cambodian girls come about?
I became interested in Cambodia after […] you know, I grew up in the United States, of course, and I began self-publishing myself when I was 11 years old. It was sort of a natural response of growing up in very over-mediated environment where TV, even breakfast cereal, toys, and games and everything, was trying to sell me something. And my response to that was to basically create a media entity that was a young girl’s respond to this over-commercialized, constant messaging about how I should be and what I should look like.
And I had been doing that since the 1980s, until 2007. And I had been running a magazine in the last days of 2007. And we decided to close the magazine down, and I was very frustrated. It was a magazine called Punk Planet. I was very frustrated, because it was a lot of people who had been doing self-publishing for a long time. And the United States is supposed to be this great place for democracy to happen. And the fact that we couldn’t, all of a sudden, put this magazine out anymore because government regulations had changed enough so that we no longer were able to put it out at the scale that we had been doing for, at that point, 12 years.
And I just felt that democracy had failed me, and so I began looking at other places around the world where democracy wasn’t accepted as one thing, and of course, in Cambodia, that was, the No. 1 thing at the time, in 2007, the No. 1 question was: What does democracy mean in a place where there isn’t always freedom of the press, where it’s not assumed that you are going to be able to get accurate information from, you know, TV or print media? So I was at first drawn to Cambodia as a site of interest, but then once I found out about a dormitory for young women to go to college for the first time, I started communicating with them and some administrators there, and they invited me to come and stay with them and do a self-publishing project.
Your book started with the curiosity about Chbap Srei, a kind of Cambodian handbook for young women. How did you learn about Chbap Srei?
Yes, well I was lucky to be living in a dormitory with 32 young women who had just moved to Phnom Penh for the first time. And in most cases, there may be two or three young women that were from Battambang or Siem Reap or Phnom Penh. But really for the most part, the majority of the 32 young women who I was living with were from the provinces, and they all had known about Chbap Srei. They all had copies of it on their desks. And they all were really, really well aware that this document existed, which sort of outlined a set of social rules for girls. And they told me about it. But then of course, as I started to travel throughout the country and met with other expats who were working especially in social services, it was something that expats working in Cambodia and expats working in Cambodia had known about for a while and their view was different from mine. They were a little bit more alarmed about what the content was.
How would you describe your book in general?
Well, I think Cambodian Grrlcame out, and it was very well received. It won a number of awards, and people were very excited about it. I still get weekly emails from readers who just fell in love with the book and the young women that I was working with. But also I think to some degree, they fell in love with the idea that you could go someplace and you could offer a very small skill to a group of people that would find it so useful and interesting.
In many ways, that is flattering, but in many ways it is also a big problem especially right now when we have a very particular kind of imperialism, where white people are sort of taking credit for a lot of things that are happening out there around the world, especially in developing nations. So the point of New Girl Lawthen was to actually say that: Yes, I did this and I was working with these young Cambodian women. But what I brought to them was secondary to what they did with it. The story of New Girl Lawin particular is an attempt to explain how little I really did as a white woman from America coming to Cambodia with 32 young women in Cambodia who actually knew their culture, what they needed out of a demand for gender equity in media far better than I would. So that was the purpose of putting that book out.
In New Girl Law, there are new 20 drafted laws about Chbap Srei, indicating changes in young Cambodian women’s attitudes. How would you describe these changes? How do you see the position of these young women in today’s Cambodian society?
Do you think of the changes of women’s attitudes as “resistance” to the norms and traditions that many old Cambodian people have been strongly held, as opposed to their role in protecting their culture?
Well, for one thing, Sreinith, I would ask you that question. Do those rules seem workable to you? If not, what do you want them to be? And the reason that I would put it that way is that the women that I was working with—and I just had dinner with them in February, and it was the first time I really was able to have a reunion, and caught up after seven years, and really talk about the way some of this stuff emerged in our lives—they were very, and are today, invested in maintaining traditional roles for women on one hand but also in developing further opportunities for their own economic security and eradicating many of domestic violence issues, and just opening up more opportunities for them.
So they felt like these 20 rules that they drafted under the New Girl Lawdid both of those things. But I think for a young Cambodian woman, especially ones working in media, such as yourself, would have a much better idea than I would whether or not that is true. And it’s hard to negotiate both of those things at the same time.
But also for the young Cambodian women that I was working with in 2007, their No. 1 rule was to be patient. It was absolutely: be patient and stay strong and be feminine and all of these amazing ways that they wanted to start to push Cambodian culture were all rooted in the understanding of what a traditional Cambodian feminine role looked like.
There are very few books written about Cambodian women. There are three academic books looking at sex trafficking, migration of young Cambodian women from rural areas to the cities for factory work, and history of Cambodian women in politics. How do you think your book is different from them?
Yes, I did a literary overview as I was researching, of course, the project and the books themselves, which came several years after the original project. Yes, I was shocked when there weren’t very many, especially when there is such a keen interest in sex work in Cambodia and in the garment trade in the United States.
I was just so lucky to live with these young Cambodian women, who are open and excited to have come to the city from all over the provinces. I do feel that I was given a very unique opportunity to get to know young women on new turf but also on their own terms. And I feel like my work in Cambodia is very much rooted in my experiences there, you know, as a white person for sure, and as an American young woman from the cultural underground of Chicago, definitely. But also as someone who was beholden to a group of 32 young women, from the second I stepped out of the plane, to respect their culture and try to understand what they wanted and needed from their future. And I think that sociologists and other, you know, activists and other ways of approaching culture, just produce different kinds of work. But as an immersion journalist, and as an investigative reporter, my number one job is to listen. And I feel like that’s what those two books are about, in particular was just me really trying to listen and trying to relay their stories and needs and desires in a language that people back home in the US would understand.
Could you tell us what would you want the world to learn about these young Cambodian women through your book?
In 2007 when I wrote this book, if I had known that eventually it would be possible for a young woman from Cambodia working in the media to call me up and want to have a conversation about it, I probably would not have written it. I would have just waited, right. Because the reason that my book exists, The Cambodian Grrland the New Girl Lawis to try to argue that that future should take place. And I have no idea whether or not it was helpful or instructive in that. But I know that the young women that I was working with, some of whom do work in the media and some of whom work in other areas, have all become strong owners of their own voices. And my hope is that those would be heard and respected in their own rights.
Do you have a plan for this book to be translated into Khmer so that it can reach the larger Cambodian audience?
I would very much like to. We have been talking about various translations in various Asian languages for several years, but we haven’t actually found a way to do that yet. I know that for a while, there was a young woman who was translating Cambodian Grrlin Mandarin on her own. And so there might be bootleg copies at least in Mandarin available somewhere. But we haven’t found the way to have it translated yet into Khmer. So anyone who is interested in doing that should get in touch with me then, we can totally make that happen.
Do you have anything to say to the girls whom you worked with and Cambodian girls and women who may listen to you right now?
I just love them. You know, young Cambodian women are just in a unique place. I think the relationship between young Cambodian women and women in the United States is pretty unique. Our two nations have this terrible, war-torn history as well as this continued economic disadvantage that the US just takes the garment production that is 70 percent what your factories are producing. And it is just so disgusting, and that is so the foundation on which all American and Cambodian relationships are set, and that is just really hard to get around that. But to then spend time with young Cambodian women over the years, and I’ve also gone back to teach in colleges and done other projects with young women around the country, and I literally love young Cambodian women like with all of my heart because they tend to be the kindest and sweetest and funniest people that I have ever worked with. So if they ever need anything or if you need anything, Sreinith, then just let me know.
I am honored to talk to you. I literally feel that I have been waiting for seven years to speak to a young Cambodian woman journalist, so thank you so much.
The exciting part is that we are now at a place where young Cambodian women are reading this book, and they are emailing me and calling me about it. I literally don’t care about the awards when that kind of stuff happens, and that is so much more exciting to me.
| https://www.voacambodia.com/a/american-writer-tells-story-of-cambodian-women-on-the-rise/2590466.html |
(PDF) Prevalence and Predictive Factors of Low-bone Mineral Density in Patients with Addison Disease on Long-term Corticosteroid Replacement Therapy
PDF | Addison disease (AD) is associated with high risk of decreased bone mineral density (BMD) and osteoporosis. Causes are complex, including lifelong... | Find, read and cite all the research you need on ResearchGate
February 2023
DOI: 10.5772/intechopen.109814
License CC BY 3.0
In book: Updates on Corticosteroids [Working Title]
Authors:
Dhouha Ben Salah
Dhouha Ben Salah
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References (43)
Figures (1)
Abstract and Figures
Addison disease (AD) is associated with high risk of decreased bone mineral density (BMD) and osteoporosis. Causes are complex, including lifelong glucocorticoid replacement therapy. The aim of our study was to assess the influence of glucorticoid replacement therapy on BMD among patients with AD and determine predictive factors of low BMD. A descriptive and analytical cross-sectional study was conducted at the department of endocrinology-diabetology at HediChaker Hospital, including 50 patients with AD for at least 5 years. Serum levels of bone turnover markers were measured and BMD was determined. The mean age of patients was 49.5 ± 13.9 years. Received average daily dose of hydrocortisone (HC) was 27.4 ± 6.7 mg. Mean cumulative HC dose was 374.636 ± 283.821 mg. Mean T-score at lumbar spine and femoral neck was –0.61 ± 1.06 (range,–4.2–1.1) and –1.18 ± 1.33 (range,–2.9–1.3), respectively. Low BMD was observed in 48% of patients. No fracture was observed. Patients who developed osteoporosis were significantly older than those with normal BMD (p = 0.018). Menopause was a significant predictor of incident osteoporosis (p = 0.006). Furthermore, osteoporosis was significantly more prevalent among females (p = 0.046). Daily and cumulative HC dose were higher in patients with osteoporosis than those with normal osteodensitometry. Glucocorticoid replacement therapy in AD may induce bone loss. Thus, glucocorticoid therapy must be adjusted to the lowest tolerable dose.
summarizes the results of several studies that have analyzed BMD in patients with AD. Some studies have also investigated the risk of osteoporotic fractures in AD patients.
…
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Chapter
Prevalence
and
Predictive
Factors
of
Low-bone
Mineral
Density
in
Patients
with
Addison
Disease
on
Long-term
Corticosteroid
Replacement
Therapy
Dhouha
Ben
Salah
and
Khouloud
Boujelben
Abstract
Addison
disease
(AD)
is
associated
with
high
risk
of
decreased
bone
mineral
density
(BMD)
and
osteoporosis.
Causes
are
complex,
including
lifelong
glucocorti-
coid
replacement
therapy.
The
aim
of
our
study
was
to
assess
the
influence
of
glucorticoid
replacement
therapy
on
BMD
among
patients
with
AD
and
determine
predictive
factors
of
low
BMD.
A
descriptive
and
analytical
cross-sectional
study
was
conducted
at
the
department
of
endocrinology-diabetology
at
HediChaker
Hospital,
including
50
patients
with
AD
for
at
least
5
years.
Serum
levels
of
bone
turnover
markers
were
measured
and
BMD
was
determined.
The
mean
age
of
patients
was
49.5 13.9 years. Received average daily dose of hydrocortisone (HC) was
27.4 6.7 mg. Mean cumulative HC dose was 374.636 283.821 mg. Mean T-score at
lumbar
spine
and
femoral
neck
was – 0.61 1.06 (range, – 4.2 – 1.1) and – 1.18 1.33
(range, –
2.9 – 1.3), respectively. Low BMD was observed in 48% of patients. No frac-
ture
was
observed.
Patients
who
developed
osteoporosis
were
significantly
older
than
those
with
normal
BMD
(p
=
0.018).
Menopause
was
a
significant
predictor
of
inci-
dent
osteoporosis
(p
=
0.006).
Furthermore,
osteoporosis
was
significantly
more
prevalent
among
females
(p
=
0.046).
Daily
and
cumulative
HC
dose
were
higher
in
patients
with
osteoporosis
than
those
with
normal
osteodensitometry.
Glucocorticoid
replacement
therapy
in
AD
may
induce
bone
loss.
Thus,
glucocorticoid
therapy
must
be
adjusted
to
the
lowest
tolerable
dose.
Keywords: Addison disease, glucocorticoid replacement therapy, bone mineral
density
1.
Introduction
Patients
with
AD
lack
sufficient
endogenous
secretion
of
glucocorticoids
[1].
The
treatment
of
AD
usually
involves
lifelong
glucocorticoid
replacement
therapy,
most
usually
oral
hydrocortisone
(HC).
Nevertheless,
glucocorticoid
replacement
therapy
1
usually
produces
cortisol
levels
higher
than
the
normal
physiological
endogenous
secretion
[2].
In
spite
of
the
fact
that
prolonged
substitution
with
glucocorticoids
carries
a
sig-
nificant
risk
of
bone
loss
by
a
proapoptotic
action
on
osteoblasts,
promoting
osteo-
clastic
activity
[3],
and
decreasing
intestinal
calcium
absorption
[4],
BMD
assessment
is
not
indicated
in
regular
follow-up
of
patients
with
PAI.
To
date,
few
researches
have
focused
on
skeletal
health
in
patients
with
AD.
The
majority
of
studies
included
relatively
small
series
of
patients
and
reported
variable
results
between
BMD,
gluco-
corticoid
dose,
duration
disease
(duration
therapy),
glucocorticoid
regimens,
and
cumulative
dose
[5 – 9]. Several studies reported normal BMD [8], while others showed
reduced
density
in
all
or
some
bone
sites
[6].
Thus,
the
aim
of
our
study
was
to
assess
the
impact
of
glucocorticoid
replacement
therapy
on
bone
density
in
patients
with
AD
and
determine
predictive
factors
of
low
BMD
in
this
population.
2.
Materials
and
methods
2.1
Study
design,
area,
and
period
A
cross-sectional
study
was
carried
out
at
the
department
of
Endocrinology-
Diabetology
of
Hedi
Chaker
Academic
Hospital
-Sfax – Tunisia, from March 2020 to
July
2021.
In
addition,
the
study
comprised
retrospective
collection
of
clinical
data
from
patients ’ medical records.
Inclusion
criteria
were
patients
with
AD
and
disease
duration
of
at
least
5
years.
Patients
under
the
age
of
18
years,
presenting
conditions
that
may
affect
bone
homeostasis
(hypogonadism
except
physiological
menopause,
primary
hyperparathy-
roidism,
hyperthyroidism,
rheumatoid
arthritis,
chronic
renal
failure,
hepatocellular
dysfunction,
hemochromatosis,
chronic
pancreatitis,
gastrointestinal
diseases
that
cause
malabsorption
syndrome
and
prolonged
immobilization),
taking
drugs
that
may
interfere
with
bone
metabolism
(heparin,
vitamin
K
antagonist,
thiazide
diuretics,
calcitonin,
bisphosphonates,
anticonvulsant
drugs
and
hormone
therapy
for
meno-
pause)
were
excluded.
Patients
meeting
the
inclusion
criteria
were
recruited.
All
patients
gave
their
writ-
ten
informed
consent
before
being
assessed.
A
total
of
80
patients
with
AD
were
contacted,
37.5%
of
the
patients
did
not
respond
or
declined
to
be
assessed.
Lastly,
50
patients
with
AD
were
recruited
in
the
present
study.
The
data
of
patients
including
age,
gender,
age
at
diagnosis,
disease
duration,
physical
activity,
Body
Mass
Index
(BMI),
and
menopausal
status
for
female
patients
were
assessed.
2.2
Glucocorticoid
treatment
All
patients
were
treated
with
HC.
The
average
daily
HC
doses
were
assessed
(mg
and
mg/kg)
and
were
adjusted
for
body
surface
area
(mg/m
2
).
As
well,
cumulative
glucocorticoid
dose,
defined
as
the
cumulative
amount
of
glucocorticoid
intake
since
the
time
of
diagnosis
to
the
date
of
BMD
measurement,
was
estimated
by
summing
partial
cumulative
doses
for
each
time
period
during
which
the
dose
remained
constant.
2
Updates
on
Corticosteroids
To
determine
partial
cumulative
dose,
we
have
used
the
following
formula:
daily
hydrocortisone
dose
in
milligrams
or
in
milligrams = kg ðÞ x time period
:
2.3
Biochemical
markers
of
bone
turnover
Serum
samples
of
patients
were
collected
to
measure
calcium,
phosphorus,
alkaline
phosphatase
(ALP),
vitamin
D,
and
parathyroid
hormone
(PTH)).
An
ALP
level
above
150
IU/l
was
considered
as
high.
PTH
(normal
range,
15 – 65 pg./ml) and vitamin D (normal range, 30 – 100 ng/ml)
were
measured
by
electrochemiluminescence
immunoassay
(ECLIA).
2.4
BMD
BMD
was
evaluated
using
dual-energy
X-ray
absorptiometry
(DEXA),
at
the
lum-
bar
spine
(L1 – L4) (trabecular bone) and femoral neck (cortical bone) sites, based on a
standard
protocol.
The
results
were
expressed
as
BMD
in
g/cm
2
,
T-
and
Z-
scores
expressed
as
standard
deviation
(SD),
in
both
lumbar
and
femoral
sites.
Referring
to
the
World
Health
Organization
(WHO)
classification,
osteoporosis
is
defined
as
a
T-score ≤ 2.5 SD and osteopenia as a T-score between 2.5
and 1 SD [10].
2.5
Statistical
analysis
Statistical
analysis
of
data
was
done
by
using
the “ Statistical Package for Social
Sciences ” (SPSS) version 25.
Thus,
we
performed
a
univariate
analysis
based
on
the
comparison
of
means
on
paired
series
using
the
Student
test
and
the
non-parametric
Mann – Whitney –
Wilcoxon
test
for
unpaired
series.
Several
regression
analyses
were
achieved
to
recognize
factors
impacting
BMD
in
patients
with
AD.
Current
BMD
was
correlated
with
cumulative
and
average
daily
glucocorticoid
doses,
as
well
as
with
clinical
and
laboratory
data.
A
point
estimate
of
Odds
ratio
(OR)
with
a
95%
confidence
interval
was
deter-
mined
to
evaluate
the
strength
of
relationship.
Statistical
significance
was
accepted
if
p-value <
0.05.
3.
Results
3.1
Clinical
descriptive
data
Median
age
of
patients
was
49.5 13.9 years old with extremes ranging from 18 to
78
years.
There
were
40
females
and
10
males.
The
majority
of
patients
(70%)
were
aged
between
40
and
50
years
old.
Ten
percent
of
patients
were
smokers.
Two
thirds
(66%)
of
patients
were
not
physically
active.
Approximately
42.5%
of
females
were
postmenopausal.
All
patients
took
neither
calcium
oral
supplementation
nor
estrogen
replacement
therapy.
Average
age
at
diagnosis
of
AD
was
35.5 14.6 years (range, 0 – 70 years).
3
Prevalence
and
Predictive
Factors
of
Low-bone
Mineral
Density
in
Patients
with
Addison …
DOI:
http:/
/dx.doi.org/
10.
5
7
72/intechopen.
1 09814
Average
AD
duration
was
13.9 8.7 years (range, 5 – 35 years).
Patients ’ average weight was 72.5 kg (range, 62 – 107 kg), and average BMI was
estimated
at
28.1
kg/m
2
(range,
21.2 – 45.8 kg/m
2
).
Overweight
was
noted
in
48%
of
patients
and
obesity
in
26%.
3.2
Glucocorticoid
treatment
Average
daily
HC
dose
at
the
time
of
AD
diagnosis
was
25.7 9.1 mg
(range,
15 – 50 mg) corresponding to 0.47 0.21 mg/kg (range, 8 – 1.08 mg/kg)
and
an
average
daily
dose
adjusted
for
body
surface
area
of
16.29 7.54 mg/m
2
(range,
15.6 – 37.94 mg/m
2
).
HC
was
prescribed
twice
a
day
for
67%
of
patients
with
an
initial
daily
dose
greater
than
30
mg
in
44%
of
patients.
During
follow-up,
the
average
daily
HC
dose
was
27.4 6.7 mg (range, 15 –
42.1
mg)
corresponding
to
0.388 0.128 mg/kg (range, 0.175 – 0.711 mg/kg) and a
mean
dose
per
body
surface
area
of
14.836 4.658 mg/m
2
(7.486 – 31.460 mg/m
2
)
( Figure 1 ).
Thirty-nine
(78%)
patients
received
a
mean
daily
HC
dose
greater
than
11
mg/m
2
.
Cumulative
HC
dose
was
374.636 283.821 mg (range, 60 – 1184, 94 mg)
corresponding
to
5.924 4.648 mg/kg (range, 0.875 – 17.238 mg/kg).
3.3
Bone
turnover
markers
Mean
serum
calcium
and
phosphorus
levels
were
2.29 0.13 mmol/l
(range,
1.9 – 2.55 mmol/l) and 1.10 0.18 mmol/l (range, 0.8 – 1.66 mmol/l),
respectively.
Figure
1.
Average
daily
HC
dose
during
follow
up
of
patients
with
AD.
4
Updates
on
Corticosteroids
Hypocalcemia
was
observed
in
18%
of
patients
after
a
mean
AD
duration
of
11.9 7.1 years (range, 4 – 26 years) and a mean cumulative HC dose of
317.7 211.7 mg (range, 75 – 702 mg).
In
fact,
hypocalcemia
had
no
significant
correlation
with
none
of
glucocorticoid
replacement
duration
(p
=
0.397)
or
glucocorticoid
dose
(p
=
0.680).
Mean
ALP
was
77.2 28.5 IU/l (range, 15 – 190 IU/l). Patients presenting
an
increased
ALP
level
(18%)
received
higher
cumulative
HC
intake
but
without
statistical
significance
(413.4 348 mg versus 365.5 271 mg, p = 0.7).
Mean
vitamin
D
level
was
22.28 14.14 ng/ml (range, 5.6 – 78.6 ng/ml).
Hypovitaminosis
D
was
observed
in
66%
of
patients.
All
patients
with
hypocalcemia
had
hypovitaminosis
D.
Mean
PTH
level
was
51.79 23.84 pg./ml (range, 16.36 – 139 pg./ml). An elevated
PTH
level
was
observed
in
20%
of
patients
who
presented
with
all
vitamin
D
deficiency.
Finally,
biochemical
parameters
of
bone
turnover
in
patients
with
AD
showed
no
significant
correlation
with
none
of
AD
duration
or
glucocorticoid
dose.
3.4
BMD
in
patients
with
AD
The
average
BMD
at
lumbar
spine
and
femoral
neck
was
0.928 0.174 g/cm
2
(range,
0.596 – 1287 g/cm
2
)a
n
d0
.
9
4
5 0.145 g/cm
2
,(
r
a
n
g
e
,0
.
6
8
7 – 1.265 g/cm
2
),
respectively.
The
data
on
BMD
at
both
lumbar
spine
and
femoral
neck
are
shown
in Table 1
.
The
T-scores
at
lumbar
spine
were
lower
than
at
femoral
neck.
Similarly,
lumbar
spine
Z-scores
were
lower
than
at
femoral
site.
Twenty-four
(48%)
patients
had
reduced
BMD
(less
than
2
standard
deviations
[SD]
of
the
mean
value
of
an
age-matched
reference
population).
Among
these
patients,
12
had
osteoporosis,
corresponding
to
24%
of
all
patients
including
in
our
study.
Also,
osteopenia
was
observed
in
24%
of
patients.
But,
none
had
a
history
of
spontaneous
or
traumatic
fracture.
3.5
Predictive
factors
for
low
BMD
in
patients
with
AD
Patients
with
low
BMD
were
significantly
older
than
those
with
normal
BMD
(53.6 11.8 years versus 45.17 15.04 years, p = 0.04).
As
well,
BMD
was
significantly
more
frequent
in
postmenopausal
women
(risk
ratio
=
3.7,
p
=
0.049)
(p
=
0.049).
No
significant
BMD
variation
was
observed
according
to
BMI
(p
=
0.71)
or
AD
duration
(p
=
0.79).
PTH
level
was
higher
in
patients
with
decreased
BMD
but
without
a
statistically
significant
association
(56 21.8 pg./ml versus 48.1 25.4 pg./ml, p = 0.1).
Scores
(SD)
Mean SD Minimum – Maximum
T-score
lumbar
spine
(L1 – L4) -1.18 1.33 4.2-1.1
T-score
femoral
neck 0.61 1.06 2.9-1.3
Z-score
lumbar
spine
(L1 – L4) 0.92 1.18 3.5-1.3
Z-score
femoral
neck 0.28 0.79 1.8-1.3
Abbreviation:
SD,
standard
deviation.
Table
1.
Results
of
bone
densitometry
in
lumbar
spine
and
femoral
neck.
5
Prevalence
and
Predictive
Factors
of
Low-bone
Mineral
Density
in
Patients
with
Addison …
DOI:
http:/
/dx.doi.org/
10.
5
7
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1 09814
Also,
vitamin
D
level
was
lower
in
patients
presenting
low
BMD
compared
to
those
with
normal
BMD
but
still
without
statistically
significant
correlation
(19 10.2 ng/
ml
versus
25.2 16.6 ng/ml, p = 0.2).
As
for
glucocorticoid
therapy
dose,
although
it
was
higher
in
patients
with
reduced
BMD,
no
correlation
was
observed
between
cumulative
HC
dose
and
low
BMD.
Table
2 shows daily and cumulative glucocorticoid dose variation between
patients
with
normal
BMD
and
those
with
low
bone
mass.
3.6
Predictive
factors
for
osteoporosis
in
patients
with
AD
Patients
who
developed
osteoporosis
were
significantly
older
than
those
with
normal
BMD
(p
=
0.018).
The
menopause
was
also
a
significant
predictor
of
incident
osteoporosis
(p
=
0.006).
Furthermore,
osteoporosis
was
significantly
more
prevalent
Glucocorticoid
dose
Normal
BMD
(n
=
30)
Low
BMD
(n
=
20)
p-value
Daily
dose
(mg)
25.6 6.3 26.0 7.3 0.969
Daily
dose
(mg/kg)
0.4 0.1 0.4 0.1 0.336
Daily
dose
per
body
surface
(mg/m
2
)
15.0 4.8 14.7 4.6 0.892
Cumulative
dose
(mg)
338.9 236.8 408.9 324 0.774
Cumulative
dose
(mg/kg)
5.0 3.9 6.8 5.2 0.322
Abbreviation:
BMD,
bone
mineral
density.
Table
2.
Correlation
between
glucocorticoid
dose
and
BMD.
Clinical/Laboratory
data
No
osteoporosis
(n
=
30)
Osteoporosis
(n
=
12)
p-value
Age
(year)
46.7 13.6 58.4 11.4 0.018
Gender
Male
10
(20%)
0
(0%)
0.046
Female
28
(56%)
12
(24%)
Menopause
8
(21%)
9
(75%)
0.006
BMI
(kg/m
2
)
Normal
BMI
[5 – 25] 23 (54.8%) 7 (16.7%) 0.514
Overweight
[25 – 30] 7 (16.7%) 1 (2.4%)
Obesity
( > 30) 2 (4.8%) 2 (4.8%)
Disease
duration
13.2 8.0 16.4 10.9 0.412
Parathyroid
hormone
(pg/ml)
50.6 23.9 55.8 24.3 0.375
Vitamin
D
(ng/ml)
23.7 14.9 17.3 9.9 0.175
Calcemia
(mmol/I)
2.3 0.1 2.3 0.1 0.510
Phosphoremia
(mmol/l)
1.1 0.2 1.2 0.2 0.122
Alcaline
phosphatase
(IU/I)
72.3 20.3 92.9 43.2 0.275
Abbreviation:
BMI,
body
mass
index.
Table
3.
Relationships
between
osteoporosis
and
patients ’ clinical/laboratory data.
6
Updates
on
Corticosteroids
among
females
(p
=
0.046).
No
significant
association
was
found
between
osteoporo-
sis
and
AD
duration
as
shown
in Table 3
.
Then,
we
studied
the
effect
of
glucocorticoid
replacement
therapy
on
BMD
and
the
occurrence
of
osteoporosis
in
patients
with
AD.
Daily
and
cumulative
HC
doses
were
higher
in
patients
with
osteoporosis
than
those
with
normal
osteodensitometry
(26.5 8.3 mg/day versus 25.6 6.3 mg/day;
462.2 373.2 mg versus 344.6 245.5 mg), but none of these factors had a significant
impact
on
the
occurrence
of
osteoporosis
as
shown
in Table 4
.
4.
Discussion
4.1
Glucocorticoid
effects
on
calcium-phosphorus
metabolism
and
bone
health
Glucocorticoid
therapy
is
the
primary
cause
of
secondary
osteoporosis.
This
complication
is
essentially
dependent
on
the
dose
and
duration
of
glucocorti-
coid
treatment
[12].
According
to
the
medical
literature,
bone
loss
occurs
in
two
stages:
an
early
stage
characterized
by
a
sharp
decline
in
BMD
of
between
6
and
12%
over
the
first
year
of
treatment,
followed
by
a
long-term
phase
where
BMD
slowly
declines
at
a
rate
of
roughly
3%
per
year
[12,
13].
Thus,
early
in
the
course
of
treatment,
osteoporotic
fractures
are
significantly
more
common
as
a
result
of
high-dose
synthetic
corticosteroid
therapy
[14,
15].
The
bone
effe
cts
of
glucoco
rticoid
are
com
plex,
resulting
from
di
rect
effects
on
b
one
tissue
and
ind
irect
reper
cussions
on
ca
lcium
homeo
stasis
and
sex
st
eroid
produc
tion.
Glucocorticoids
exert
a
proapoptotic
effect
on
osteoblasts
and
osteocytes
[16].
Type
I
collagen,
a
vital
component
of
bone,
cannot
be
synthesized.
The
main
impact
of
glucocorticoids
on
bone
cell
function
is
the
reduction
of
osteoformation
activity
by
osteoblasts,
resulting
in
a
low
osteocalcin
level
[16].
Glucocorticoids
also
promote
bone
resorption
through
other
various
mechanisms,
such
as
raising
RANKL
(Receptor
Activator
of
Nuclear
Factor κ B Ligand) synthesis
and
reducing
in
osteoprotegerin
level,
an
osteoclastogenesis
inhibitor.
In
addition,
glucocorticoids
affect
phosphocalcic
metabolism
by
decreasing
intes-
tinal
calcium
absorption
by
inhibiting
its
transport
and
increasing
renal
calcium
excretion
[4,
17].
This
leads
to
hypocalcemia
and
consequently
secondary
hyperpara-
thyroidism
[11,
18].
Finally,
glucocorticoids
influence
gonadal
hormone
production
by
inducing
hypogonadism
and
may
in
some
situations
also
reduce
adrenal
androgens
production
[16].
Glucocorticoid
dose
No
osteoporosis
(n
=
30)
Osteoporosis
(n
=
12)
p-value
Daily
dose
(mg)
25.6 6.3 26.5 8.3 0.954
Daily
dose
(mg/kg)
0.4 0.1 0.4 0.2 0.146
Daily
dose
per
body
surface
(mg/m
2
)
14.7 4.6 15.3 5.0 0.683
Cumulative
dose
(mg)
344.6 245.5 462.2 373.2 0.487
Cumulative
dose
(mg/kg)
5.5 4.3 7.0 5.6 0.407
Table
4.
Correlation
between
glucocorticoid
dose
and
BMD.
7
Prevalence
and
Predictive
Factors
of
Low-bone
Mineral
Density
in
Patients
with
Addison …
DOI:
http:/
/dx.doi.org/
10.
5
7
72/intechopen.
1 09814
In
fact,
sex
steroids
promote
osteoblast
proliferation
and
maturation,
while
they
inhibit
osteoclastic
activity
conversely,
which
results
in
an
optimal
concentration
of
calcium
at
sites
of
bone
mineralization.
Estrogens
also
act
directly
on
bone
tissue
where
their
main
effect
is
to
inhibit
osteoclastic
activity
[19].
As
prescribed
at
supraphysiological
levels,
glucocorticoid
replacement
therapy
in
AD
could
have
similar
effects
on
phosphocalcic
metabolism
and
the
same
induced
bone
side
repercussions
[20,
21].
4.2
Bone
turnover
markers
in
patients
with
AD
In
our
study,
18%
of
the
patients
had
hypocalcemia
after
a
mean
disease
duration
of
11.9 7.1 years, without statistically significant association with HC dose or disease
duration.
Our
findings
are
in
agreement
with
those
of
Suliman
et
al.
[22]
reporting
low
levels
of
ionized
calcium
in
patients
with
AD
compared
to
controls
(p < 0.001) but without
a
significant
association
with
HC
dose.
Indeed,
hypocalcemia
is
uncommon
in
isolated
AD.
The
majority
of
reported
cases
of
hypocalcemia
were
part
of
an
autoimmune
polyendocrinopathy
(AIP)
associating
AD
with
celiac
disease
or
hypoparathyroidism
[23,
24].
In
our
study,
the
vitamin
D
deficiency
observed
in
66%
of
patients
could
partly
explain
this
hypocalcemia.
Some
data
in
medical
literature
suggested
an
association
between
vitamin
D
defi-
ciency
and
AD.
Ramagopalan
et
al.
[25]
observed
a
significantly
high
prevalence
of
autoimmune
diseases
including
AD
among
13,260
patients
hospitalized
for
hypovitaminosis
D
in
a
British
center.
It
was
proposed
that
vitamin
D
deficiency
may
disrupt
the
immune
response
and
induce
inflammatory
responses
that
would
trigger
the
development
of
autoimmune
diseases.
In
addition,
it
has
recently
been
demonstrated
that
skin
hyperpigmentation
reduces
the
skin ’ s capacity to generate vitamin D3 when ultraviolet B radiation is
present
[26].
The
high
melanin
content
of
their
skin
may
account
for
hypovitaminosis
D,
which
often
observed
in
patients
with
AD.
4.3
BMD
in
patients
with
AD
Several
researches
have
been
interested
in
assessing
BMD
in
AD.
In
our
series,
low
BMD
was
observed
in
almost
half
of
the
patients
(48%)
of
whom
24%
had
femoral
and/or
vertebral
osteoporosis.
The
mean
lumbar
spine
and
femoral
neck
Z-scores
were
low
( 0.92 1.18
and 0.28 DS, respectively) but remained within the normal range (between 2
and
+
2).
Despite
the
fact
that
their
findings
are
conflicting,
the
majority
of
studies
revealed
that
patients
with
AD
experience
a
more
frequent
decline
in
BMD
than
the
general
population
[27 –
30].
Zelissen
et
al.
[6]
were
the
first
to
find
in
1994
the
bone
loss
in
91
patients
with
AD,
with
an
estimated
prevalence
of
32%
in
women
and
7%
in
men.
According
to
Leelarathna
et
al.
[28],
more
than
50%
of
AD
patients
included
in
their
study
(n
=
292)
had
osteopenia,
and
one
patient
out
of
5
developed
osteoporosis.
Bone
demineralization
was
predominant
in
the
lumbar
spine,
in
agreement
with
our
results.
8
Updates
on
Corticosteroids
Other
studies
did
not
observe
a
significant
decrease
in
BMD
in
patients
with
AD
[8,
31].
Camozzi
et
al.
[32]
analyzed
BMD
in
87
patients
with
AD
compared
to
81
healthy
controls,
and
no
higher
risk
of
reduced
BMD
was
found
in
AD
patients
in
comparison
with
controls.
Table
5 summarizes the results of several studies that have analyzed BMD in
patients
with
AD.
Some
studies
have
also
investigated
the
risk
of
osteoporotic
fractures
in
AD
patients.
Study,
reference
number
Year
Country
Population
Study
design
Results
Zellissen
[6]
1994
Netherlands
91
AD
Cross-sectional
Decreased
BMD
in
32%
of
women
and
7%
of
men.
Florkowski
[33]
1994
New
Zealand
14
AD
Observational
Women
with
AD
showed
a
higher
risk
of
low
BMD
in
comparison
with
males.
Braatvedt
[30]
1999
New
Zealand
29
AD
Observational
A
significant
decrease
in
BMD
in
males
Heureux
[27]
2000
France
24
AD
Prospective
More
than
half
of
patients
(58%)
had
osteoporosis.
Jódar
[31]
2003
Spain
25
AD
Cross-sectional
No
significant
reduction
of
BMD
in
patients
with
AD.
Arlt
[24]
2006
United
Kingdom
23
AD
23
CI
Cross-sectional
BMD
in
patients
with
AD
is
generally
normal
and
does
not
require
long-term
monitoring.
Levås
[29]
2009
Norway
United
Kingdom
New
Zealand
292
AD
Cross-sectional
Z-score
was
significantly
reduced
at
both
femoral
neck
( 0.28 SD
in
Norway
and 0.21 SD in New
Zealand)
and
lumbar
spine
( 0.17 SD in Norway and 0.57
SD
in
New
Zealand).
Leelarathna
[28]
2010
United
Kingdom
48
AD
Retrospective
More
than
half
of
patients
with
AD
had
osteopenia
and
1
in
5
patients
had
osteoporosis.
Chandy
[34]
2016
India
41
AD
Cross-sectional
Osteoporosis
was
observed
in
43%
of
patients
with
AD
versus
25%
in
control
patients.
Camozzi
[32]
2018
Italy
87
AD
Cross-sectional
No
significant
difference
in
BMD
was
observed
between
patients
with
AD
and
healthy
controls.
Our
study
2021
Tunisia
50
AD
Cross-sectional
Low
BMD
was
observed
in
48%
of
patients,
24%
of
whom
had
osteoporosis.
Abbreviation:
AD,
Addison
Disease;
CI,
Corticotropic
Insufficiency;
BMD,
Bone
Mineral
Density.
Table
5.
Synopsis
of
main
clinical
studies
analyzing
BMD
in
patients
with
AD.
9
Prevalence
and
Predictive
Factors
of
Low-bone
Mineral
Density
in
Patients
with
Addison …
DOI:
http:/
/dx.doi.org/
10.
5
7
72/intechopen.
1 09814
A
Swedish
study
examined
the
risk
of
hip
fracture
in
patients
with
AD
who
showed
a
higher
risk
compared
to
healthy
controls
(6.9
vs.
2.7%
in
controls;
p
< 0.001) [35].
Similarly,
Camozzi
et
al.
[32]
showed
that
31.1%
of
patients
with
AD
had
at
least
one
vertebral
fracture
related
to
osteoporosis,
compared
with
only
12.8%
of
control
subjects
(odds
ratio
=
3.09).
4.4
Predictive
factors
of
low
BMD
in
patients
with
AD
*Disease
duration
Lee
et
al.
[36]
have
demonstrated
that
bone
loss
occurs
early
in
AD,
even
before
diagnosis,
since
glucocorticoids
promote
osteoblastic
precursor
d
ifferentiation,
and
therefore,
hypocorticism
might
result
in
osteoblastic
immaturity
and
reduced
bone
mass.
Studies
investigating
the
correlation
between
the
age
of
AD
and
bone
status
are
heterogeneous,
and
their
results
are
contradictory.
However,
the
majority
of
findings
have
not
reported
a
correlation
between
disease
duration
and
BMD
in
patients
with
AD
[6,
8,
28,
31,
34].
*Age
Bone
demineralization
in
the
general
population
begins
progressively
from
the
age
of
25
years
and
increases
linearly
with
age.
In
fact,
aging
lea
ds
to
an
osteoform
ation
decr
ease
by
a
reductio
n
of
osteoblast
activit
y
as
well
as
an
acc
eleration
of
bone
resor
ption
due
to
a
state
of
hype
rparathy
-
roidism
sec
ondary
to
the
hypo
vitami
nosis
D
frequen
tly
observed
in
t
he
elderly
sub
ject.
This
bone
loss
increases
rapidly
after
menopause
in
women
and
remains
constant
in
men
[37,
38].
In
AD
patients,
the
curve
of
bone
mass
evolution
according
to
age
is
similar
to
that
of
the
general
population.
Thus,
Jodar
et
al.
[31]
observed
that
no
BMD
variation
according
to
age
was
found.
Similarly,
Valero
et
al.
[39]
in
their
cross-sectional
study
of
30
AD
patients
with
an
average
age
of
52.2
years
reported
the
same
result.
In
our
study,
patients
with
low
BMD
were
older
than
those
with
normal
BMD
but
without
significant
differences.
*Menopause
Various
studies
studying
BMD
in
AD
patients
reported
a
more
frequent
bone
loss
(osteopenia
and/or
osteoporosis)
in
menopausal
women
[5,
32,
33,
39].
In
a
comparative
study
reported
by
Camozzi
et
al.
[32],
none
of
the
menopausal
women
in
the
control
group
experienced
an
osteoporotic
fracture,
while
menopausal
AD
women
had
a
fracture
rate
of
53%.
This
finding
suggests
a
major
impact
of
glucocorticoid
replacement
therapy
in
the
occurrence
of
atraumatic
fractures
in
menopausal
AD
women.
*Glucocorticoid
dose
Most
of
studies
concur
that
optimal
glucocorticoid
replacement
therapy
requires
a
daily
dose
of
15
to
20
mg
equivalent
to
10 – 12 mg/m
2
[1,
40].
A
recent
Endocrine
Society
Clinical
Practice
Guideline
recommended
a
daily
HC
dose
of
15 – 25 mg for patients with AD [2]. But most of AD patients seemed to be on
supraphysiological
glucocorticoid
doses,
resulting
in
catabolic
repercussions
on
bone
health.
In
our
study,
78%
of
patients
received
a
daily
HC
dose
greater
than
11
mg/m
2
.
Higher
mean
cumulative
HC
doses,
particularly
in
patients
with
osteoporosis,
were
observed
in
patients
with
low
BMD.
10
Updates
on
Corticosteroids
Several
studies
have
examined
the
impact
of
HC
dose
on
bone
health
in
patients
with
AD
[5,
6,
30,
41].
In
a
study
involving
91
patients
with
AD,
Zelissen
et
al.
[6]
observed
that
mean
BMD
was
negatively
correlated
with
current
glucocorticoid
dose
but
only
in
men
(p
=
0.032).
Patients
treated
with
a
daily
HC
dose
of
less
than
13.6
mg/m
2
had
normal
BMD
instead
of
those
receiving
more
than
16.4
mg/m
2
.
In
another
prospective
study,
Schulz
et
al.
[5]
reported
that
HC
dose
reduction
from
30.8 8.5 mg/d to 21.4 7.2 mg/d induced a significant
improvement
in
lumbar
spine
and
femoral
Z-scores
in
90
AD
patients
(from
0.93 1.2 to
0.65 1.5 (p < 0.05) and from
0.40 1.0 to 0.28 1.0
(p < 0.05), respectively) [5].
In
contrast,
Koetz
et
al.
observed
that
lower
glucocorticoid
dose
did
not
improve
BMD
in
81
AD
patients
[8]
.
These
same
findings
were
also
reported
by
Jodar
et
al.
[31],
Florkowski
et
al.
[33],
Valero
et
al.
[39],
and
Chandy
et
al.
studies
[34].
Finally,
the
vast
majority
of
medical
researches
concur
that
high
cumulative
glu-
cocorticoid
dose
is
associated
with
an
increased
prevalence
of
bone
demineralization
in
AD
patients.
Table
6 summarizes several studies assessing glucocorticoid dose ’ s impact on BMD
in
patients
with
AD.
Study,
reference
number
Year
Country
Population
Study
design
HC
dose
Impact
of
glucocorticoid
dose
on
BMD
Zellissen
[6]
1994
Netherlands
91
AD
Cross-
sectional
29.2 7.0 mg/day Significant
correlation
between
daily
HC
dose
and
low
BMD
(p
=
0.032)
in
men.
Valero
[39]
1994
Spain
25
AD
Cross-
sectional
30
mg/day
No
correlation
was
found
Florkowski
[33]
1994
New-
Zealand
14
AD
Cross-
sectional
27.6 6.1 mg/day No correlation
was
found
Braatvedt
[30]
1999
New
Zealand
29
AD
Observational
24
+
2.4
mg/day
CD:2.28
+
0.64
g/kg
Negative
correlation
between
daily
and
cumulative
glucocorticoid
dose
and
BMD
Jódar
[31]
2003
Spain
25
AD
Cross-
sectional
21.9 13.3 mg/day No correlation
was
found
Koetz
[8]
2012
Germany
122
AD
Cross-
sectional
21.9 4.9 mg/day No correlation
was
found
Chandy
[34]
2016
India
41
AD
Cross-
sectional
13.0 3.0 mg/m
2
No
correlation
between
daily
glucocorticoid
dose
and
low
BMD.
11
Prevalence
and
Predictive
Factors
of
Low-bone
Mineral
Density
in
Patients
with
Addison …
DOI:
http:/
/dx.doi.org/
10.
5
7
72/intechopen.
1 09814
5.
Conclusions
Glucocorticoid
replacement
therapy
in
AD
may
induce
bone
loss.
Identification
of
predictive
factors
of
low
BMD
in
patients
with
AD
is
useful
in
the
management
of
long-term
glucocorticoid
therapy ’ s bone impact.
Thus,
glucocorticoid
therapy
must
be
adjusted
to
the
lowest-tolerable
dose
and
regular
measurement
of
bone
mineral
density
may
be
useful
to
identify
patients
at
risk
for
the
development
of
osteoporosis.
Finally,
further
studies
are
needed
to
better
analyze
these
factors
and
control
BMD
during
the
course
of
AD.
Acknowledgements
We
appreciate
the
cooperation
of
all
patients
who
participated
in
this
study,
especially
during
the
COVID-19
pandemic.
Author
contributions
Khouloud
Boujelben: Conceptualization (equal); data curation (equal); formal
analysis
(equal);
investigation
(equal);
methodology
(equal);
project
administration
(equal);
validation
(equal);
writing – original draft (equal); writing – review and
Study,
reference
number
Year
Country
Population
Study
design
HC
dose
Impact
of
glucocorticoid
dose
on
BMD
Schulz
[5]
2016
Germany
90
AD
Prospective
30.8 8.5 mg/day A decrease in
daily
glucocorticoid
dose
from
30.8
mg
to
21.4
mg
induced
a
significant
improvement
in
BMD
at
both
lumbar
spine
and
femoral
neck
sites.
Camozzi
[32]
2018
Italy
87
AD
Cross-
sectional
35
mg/day
Our
study
2021
Tunisia
50
AD
Cross-
sectional
27.4 6.7 mg/day
CD:374.636 283.821 mg
5924 4648 mg/kg
Significant
correlation
between
daily
and
cumulative
dose
and
low
BMD
Abbreviation:
Hc,
hydrocortisone;
BMD,
home
mineral
density;
AD,
Addison
disease;
CD:
cumulative
dose.
Table
6.
Synopsis
of
main
clinical
studies
assessing
the
impact
of
glucocorticoid
dose
on
BMD
in
patients
with
AD.
12
Updates
on
Corticosteroids
editing
(equal). Dhouha Ben Salah: Data curation (equal); formal analysis (equal);
methodology
(equal);
validation
(equal);
writing – original draft (equal).
Conflict
of
interest
No
author
has
any
conflict
of
interest.
Author
details
Dhouha
Ben
Salah*
and
Khouloud
Boujelben
Department
of
Endocrinology
Diabetology,
Hedi
Chaker
Hospital,
Sfax
University,
Tunisia
*Address
all
correspondence
to:
bs.dhoha@gmail.com
©
2023
The
Author(s).
Licensee
IntechOpen.
This
chapter
is
distributed
under
the
terms
of
the
Creative
Commons
Attribution
License
(htt p://creativecommons.org/licenses/by/3.0),
which
permits
unrestricted
use,
distribution,
and
reproduction
in
any
medium,
provi
ded
the
original
work
is
properly
cited.
13
Prevalence
and
Predictive
Factors
of
Low-bone
Mineral
Density
in
Patients
with
Addison …
DOI:
http:/
/dx.doi.org/
10.
5
7
72/intechopen.
1 09814
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Jul 2021
Shan-Shan Li Shi-Hao He Peng-Yu Xie Dai-Feng Li
Osteoporosis (OP) is a chronic bone disease characterized by aberrant microstructure and macrostructure of bone, leading to reduced bone mass and increased risk of fragile fractures. Anti-resorptive drugs, especially, bisphosphonates, are currently the treatment of choice in most developing countries. However, they do have limitations and adverse effects, which, to some extent, helped the development of anabolic drugs such as teriparatide and romosozumab. In patients with high or very high risk for fracture, sequential or combined therapies may be considered with the initial drugs being anabolic agents. Great endeavors have been made to find next generation drugs with maximal efficacy and minimal toxicity, and improved understanding of the role of different signaling pathways and their crosstalk in the pathogenesis of OP may help achieve this goal. Our review focused on recent progress with regards to the drug development by modification of Wnt pathway, while other pathways/molecules were also discussed briefly. In addition, new observations made in recent years in bone biology were summarized and discussed for the treatment of OP.
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Therapy options for adrenal insufficiency and recommendations for the management of adrenal crisis Article Full-text available
Mar 2021 ENDOCRINE
Hanna Franziska Nowotny Faisal Ahmed Sophie Bensing Nicole Reisch
Adrenal insufficiency (AI) is a life-threatening condition requiring life-long glucocorticoid (GC) substitution therapy, as well as stress adaptation to prevent adrenal crises. The number of individuals with primary and secondary adrenal insufficiency in Europe is estimated to be 20–50/100.000. A growing number of AI cases are due to side effects of GC treatment used in different treatment strategies for cancer and to immunotherapy in cancer treatment. The benefit of hormone replacement therapy is evident but long-term adverse effects may arise due to the non-physiological GC doses and treatment regimens used. Given multiple GC replacement formulations available comprising short-acting, intermediate, long-acting and novel modified-release hydrocortisone as well as subcutaneous formulations, this review offers a concise summary on the latest therapeutic improvements for treatment of AI and prevention of adrenal crises. As availability of various glucocorticoid formulations and access to expert centers across Europe varies widely, European Reference Networks on rare endocrine conditions aim at harmonizing treatment and ensure access to specialized patient care for individual case-by-case treatment decisions. To improve the availability across Europe to cost effective oral and parenteral formulations of hydrocortisone will save lives.
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Re-thinking the bone remodeling cycle mechanism and the origin of bone loss
Article Full-text available
Sep 2020 BONE
Jean-Marie Delaissé Thomas Levin Andersen Helene Bjoerg Kristensen
Kent Søe
Proper bone remodeling necessarily requires that osteoblasts reconstruct the bone that osteoclasts have resorbed. However, the cellular events connecting resorption to reconstruction have remained poorly known. The consequence is a fragmentary understanding of the remodeling cycle where only the resorption and formation steps are taken into account. New tools have recently made possible to elucidate how resorption shifts to formation, thereby allowing to comprehend the remodeling cycle as a whole. This new knowledge is reviewed herein. It shows how teams of osteoclasts and osteoblast lineage cells are progressively established and how they are subjected therein to reciprocal interactions. Contrary to the common view, osteoclasts and osteoprogenitors are intermingled on the eroded surfaces. The analysis of the resorption and cell population dynamics shows that osteoprogenitor cell expansion and resorption proceed as an integrated mechanism; that a threshold cell density of osteoprogenitors on the eroded surface is mandatory for onset of bone formation; that the cell initiating osteoprogenitor cell expansion is the osteoclast; and that the osteoclast therefore triggers putative osteoprogenitor reservoirs positioned at proximity of the eroded bone surface (bone lining cells, canopy cells, pericytes). The interplay between magnitude of resorption and rate of cell expansion governs how soon bone reconstruction is initiated and may determine uncoupling and permanent bone loss if a threshold cell density is not reached. The clinical perspectives opened by these findings are discussed.
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Vertebral fractures assessed with dual-energy X-ray absorptiometry in patients with Addison’s disease on glucocorticoid and mineralocorticoid replacement therapy Article Full-text available
Feb 2018 ENDOCRINE
Valentina Camozzi Corrado Betterle
Anna Chiara Frigo Giovanni Luisetto
Purpose:
to assess bone damage and metabolic abnormalities in patients with Addison's disease given replacement doses of glucocorticoids and mineralocorticoids.
Methods:
A total of 87 patients and 81 age-matched and sex-matched healthy controls were studied. The following parameters were measured: urinary cortisol, serum calcium, phosphorus, creatinine, 24-h urinary calcium excretion, bone alkaline phosphatase, parathyroid hormone, serum CrossLaps, 25 hydroxyvitamin D, and 1,25 dihydroxyvitamin D. Clear vertebral images were obtained with dual-energy X-ray absorptiometry in 61 Addison's disease patients and 47 controls and assessed using Genant's classification.
Results:
Nineteen Addison's disease patients (31.1%) had at least one morphometric vertebral fracture, as opposed to six controls (12.8%, odds ratio 3.09, 95% confidence interval 1.12-8.52). There were no significant differences in bone mineral density parameters at any site between patients and controls. In Addison's disease patients, there was a positive correlation between urinary cortisol and urinary calcium excretion. Patients with fractures had a longer history of disease than those without fractures. Patients taking fludrocortisone had a higher bone mineral density than untreated patients at all sites except the lumbar spine.
Conclusions:
Addison's disease patients have more fragile bones irrespective of any decrease in bone mineral density. Supra-physiological doses of glucocorticoids and longer-standing disease (with a consequently higher glucocorticoid intake) might be the main causes behind patients' increased bone fragility. Associated mineralocorticoid treatment seems to have a protective effect on bone mineral density.
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Ostéodensitométrie : intérêts dans la prise en charge de la fragilité osseuse
Article
Dec 2020
Eric Lespessailles
Résumé
La mesure de la densité minérale osseuse surfacique est un marqueur intermédiaire de résistance osseuse et fait partie des prédicteurs les plus forts du risque de fracture. L’Organisation mondiale de la santé définit l’ostéoporose par un T-score inférieur ou égal à −2,5 dans le rachis ou dans l’extrémité supérieure du fémur. Au début de la prise en charge, pour la prévention, pour le diagnostic de l’ostéoporose, pour l’évaluation et la prédiction du risque de fracture mais aussi pour le suivi des traitements de l’ostéoporose, la mesure de la densité minérale osseuse surfacique est indispensable. L’acquisition, l’analyse et l’interprétation de cet examen requièrent une assurance de qualité incluant un contrôle qualité des appareils, la formation des opérateurs et une expertise du médecin pour l’interprétation des résultats.
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Towards the tailoring of glucocorticoid replacement in adrenal insufficiency: the Italian Society of Endocrinology Expert Opinion Article
Nov 2019 J ENDOCRINOL INVEST
Andrea M Isidori Giorgio Arnaldi
Marco Boscaro Md Andrea Lenzi
Context
Glucocorticoid (GC) replacement therapy in patients with adrenal insufficiency (AI) is life saving. After over 50 years of conventional GC treatment, novel formulations are now entering routine clinical practice.
Methods
Given the spectrum of medications currently available and new insights into the understanding of AI, the authors reviewed relevant medical literature with emphasis on original studies, prospective observational data and randomized controlled trials performed in the past 35 years. The Expert Opinion of a panel of selected endocrinologists was sought to answer specific clinical questions. The objective was to provide an evidence-supported guide, for the use of GC in various settings from university hospitals to outpatient clinics, that offers specific advice tailored to the individual patient.
Results
The Panel reviewed available GC replacement therapies, comprising short-acting, intermediate and long-acting oral formulations, subcutaneous formulations and the novel modified-release hydrocortisone. Advantages and disadvantages of these formulations were reviewed.
Conclusions
In the Panel’s opinion, achieving the optimal GC timing and dosing is needed to improve the outcome of AI. No-single formulation offers the best option for every patients. Recent data suggest that more emphasis should be given to the timing of intake. Tailoring of GS should be attempted in all patients—by experts—on a case-by-case basis. The Panel identified specific subgroups of AI patients that could be help by this process. Long-term studies are needed to confirm the short-term benefits associated with the modified-release GCs. The impact of GC tailoring has yet to be proven in terms of hospitalization rate, morbidity and mortality.
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Glucocorticoids and Bone: Consequences of Endogenous and Exogenous Excess and Replacement Therapy Article
Jun 2018
Rowan Samual Hardy Hong Zhou
Markus J Seibel Mark S Cooper
Osteoporosis associated with long-term glucocorticoid therapy remains a common and serious bone disease. In addition, in recent years it has become clear that more subtle states of endogenous glucocorticoid excess may have a major impact on bone health. Adverse effects can be seen with mild systemic glucocorticoid excess but there is also evidence of tissue-specific regulation of glucocorticoid action within bone as a mechanism of disease. This review article will examine a) the role of endogenous glucocorticoids in normal bone physiology, b) the skeletal effects of endogenous glucocorticoid excess in the context of endocrine conditions such as Cushing’s disease/syndrome and autonomous cortisol secretion (subclinical Cushing’s syndrome), and c) the actions of therapeutic (exogenous) glucocorticoids on bone. We will review the extent to which the effect of glucocorticoids on bone is influenced by variations in tissue metabolising enzymes and glucocorticoid receptor expression and sensitivity. We will consider how the effects of therapeutic glucocorticoids on bone are complicated by the effects of the underlying inflammatory disease being treated. We will also examine the impact that glucocorticoid replacement regimens have on bone in the context of primary and secondary adrenal insufficiency. We conclude that even subtle excess of endogenous or moderate doses of therapeutic glucocorticoids are detrimental to bone. However in patients with inflammatory disorders there is a complex interplay between glucocorticoid treatment and underlying inflammation, with the underlying condition frequently representing the major component underpinning bone damage.
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Effects on bone health of glucocorticoid replacement therapy in primary and secondary adrenal insufficiency: A review Article
Mar 2018
Giuseppe Bentivegna G Osella Anna Pia M. Terzolo
This review focuses on the effects of glucocorticoid replacement therapy on bone health in patients with primary and secondary adrenal insufficiency. The negative impact of glucocorticoids on bone is related to a number of factors, namely dose and type of steroid used, duration of therapy, and cumulative dose. Although “substitutive” in nature, GRT often produce cortisol levels that may be over the true physiological range; therefore, patients may be chronically exposed to a slight cortisol excess potentially affecting bone health and increasing the risk of fractures. Glucocorticoids are the first cause of secondary osteoporosis. They act on bone impairing not only bone mineral density (BMD) but also bone quality, so BMD obtained by DXA measurements does not fully reflect the negative effects on the skeleton. We explore scientific literature on this focus. A lot of papers are related to small series of patients studied several years ago; most of these studies evaluated BMD effects and results are often conflicting, with few data about fractures. The recent guidelines suggest, for the replacement therapy of adrenal insufficiency, the use of daily doses of glucocorticoid lower than previously used and new glucocorticoid formulations become available, potentially safer, with lower deleterious effects on bone health.
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Use of high-dose intermittent systemic glucocorticoids and the risk of fracture in patients with chronic obstructive pulmonary disease Article
Feb 2018 BONE
Olorunfemi A Oshagbemi Andrea Burden Kimberly N. Shudofsky Frank de Vries
View
Vitamin D and the Skin: An Update for Dermatologists
Article
Oct 2017
Elio Kechichian Khaled Ezzedine
Vitamin D plays a key role in skeletal and cardiovascular disorders, cancers, central nervous system diseases, reproductive diseases, infections, and autoimmune and dermatological disorders. The two main sources of vitamin D are sun exposure and oral intake, including vitamin D supplementation and dietary intake. Multiple factors are linked to vitamin D status, such as Fitzpatrick skin type, sex, body mass index, physical activity, alcohol intake, and vitamin D receptor polymorphisms. Patients with photosensitive disorders tend to avoid sun exposure, and this practice, along with photoprotection, can put this category of patients at risk for vitamin D deficiency. Maintaining a vitamin D serum concentration within normal levels is warranted in atopic dermatitis, psoriasis, vitiligo, polymorphous light eruption, mycosis fungoides, alopecia areata, systemic lupus erythematosus, and melanoma patients. The potential determinants of vitamin D status, as well as the benefits and risks of vitamin D (with a special focus on the skin), will be discussed in this article.
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Discover more about: Addison Disease
Article
Effect of Glucocorticoid Replacement Therapy on Bone Mineral Density in Patients with Addison Diseas...
February 1994
· Annals of Internal Medicine
Peter M. J. Zelissen
To study the influence of glucocorticoid replacement therapy on bone mineral density. Cross-sectional. University hospital in the Netherlands. 91 patients with Addison disease who had been receiving glucocorticoid replacement therapy for a mean of 10.6 years (range, 0.5 to 36.5 years). Bone mineral density of the lumbar spine and both femoral necks using a dual-energy x-ray absorptiometer and
... [Show full abstract]
basal serum concentrations of adrenocorticotropin, gonadal hormones, and adrenal androgens. Decreased bone mineral density (less than 2 standard deviations [SD] of the mean value of an age-matched reference population) was found in 10 of 31 men (32%; 95% Cl, 17% to 51%) and in 4 of 60 women (7%; Cl, 2% to 16%). No statistically significant differences were found between men and women with regard to age, duration of glucocorticoid substitution, or glucocorticoid dose, either in absolute quantities or when expressed per kilogram of body weight. However, in men with decreased bone mineral density, the daily hydrocortisone dose per kilogram of body weight (0.43 +/- 0.08 mg/kg; mean +/- SD) was significantly (P = 0.032) higher than in men with normal bone mineral density (0.35 +/- 0.10 mg/kg). After correction for possible confounding variables, a significant linear correlation was found between hydrocortisone dose per kilogram of body weight and bone mineral density of the lumbar spine in the men (regression coefficient, -0.86; Cl, -1.60 to -0.13; P = 0.029) but not in the women. Long-term treatment with standard replacement doses of glucocorticoids may induce bone loss in men with Addison disease. Adjustment of glucocorticoid therapy to the lowest acceptable dose is mandatory in Addison disease, and regular measurement of bone mineral density may be helpful in identifying men at risk for the development of osteoporosis.
Read more
Article Full-text available
Impact of hydrocortisone replacement on bone mineral density and bone turnover markers in patients w...
July 2022
· Endocrine Regulations
Meriem Yazidi C. Danguir Dhouha Maamer [...] Melika Chihaoui
Objective. The study was aimed to assess the effect of hydrocortisone (HC) replacement therapy on bone mineral density (BMD) and bone turnover markers in patients with primary adrenal insufficiency (PAI).
Methods. A cross-sectional study was conducted in 37 PAI patients treated with HC. BMD and selected bone turnover markers (β-crosslaps and osteocalcin) were measured. A stepwise binary logistic ... [Show full abstract]
regression model was applied to determine the independent variables associated with low BMD.
Results. Osteoporosis was noted in 14.3% and osteopenia in 34.3% of cases. These patients were older (p=0.01) and received higher daily HC dose compared to patients with normal BMD (p=0.01). BMD values in the lumbar spine and the femoral neck were negatively correlated with daily HC dose (r=–0.36, p=0.03 and r=–0.34, p=0.05, respectively). Plasma osteocalcin was negatively correlated with disease duration (r=–0.38, p=0.02) and cumulative HC dose (r=–0.43, p<0.01). In multivariate analysis, a daily HC dose ≥12 mg/m2/day was independently associated with a higher risk of osteopenia/osteoporosis [OR (95% CI), 9.0 (1.1–74.6); p=0.04].
Conclusions. Impaired bone mineralization in patients with PAI is correlated with HC dose. A daily HC dose ≥12 mg/m ² /day was associated with an increased risk of osteopenia and osteoporosis in these patients.
View full-text
Preprint Full-text available
Long-Term Outcomes of Conventional And Novel Steroid Replacement Therapy On Bone Health In Primary A...
December 2021
Valentina Guarnotta Claudia Di Stefano Carla Giordano
Purpose: To compare dual-release hydrocortisone (DR-HC) and conventional glucocorticoids (GCs) on bone metabolism in patients with primary adrenal insufficiency (PAI).
Methods: Thirty-five patients with PAI maintained conventional GCs (group A), while other 35 were switched to DR-HC (group B). At baseline and after 18, 36 and 60 months of conventional GCs and DR-HC treatment, the clinical and ... [Show full abstract]
bone metabolic parameters were evaluated.
Results: After 60 months of follow-up, patients in group A had a significant increase in Body Mass Index (BMI) (p=0.004) and Waist Circumference (WC) (p=0.026) and a significant decrease in osteocalcin (p=0.002), bone alkaline phosphatase (p=0.029), lumbar spine bone mass density (BMD) T and Z scores (p<0.001 and p=0.001, respectively) than baseline. By contrast, patients in group B had a significant decrease in WC (p=0.047) and increase in bone alkaline phosphatase (p=0.019), lumbar spine BMD T score (p=0.032), femoral neck BMD T and Z scores (p=0.023 and p=0.036, respectively) than baseline.
Conclusions: Long-term conventional steroid replacement therapy is associated with a decrease in BMD, notably at lumbar spine, and an increase in vertebral fractures rate. By contrast, DR-HC treatment is associated with improvement of BMD.
View full-text
Article Full-text available
Long-term outcomes of conventional and novel steroid replacement therapy on bone health in primary a...
August 2022
· Scientific Reports
Valentina Guarnotta Claudia Di Stefano Carla Giordano
Steroids affect bone health causing osteoporosis and fractures. The study aims to compare dual-release hydrocortisone (DR-HC) and conventional steroids on bone metabolism in patients with primary adrenal insufficiency (PAI). Thirty-five patients with PAI on conventional steroids (group A) and 35 patients switched to DR-HC (group B), consecutively referred at our hospital, were evaluated at
... [Show full abstract]
baseline and after 18, 36 and 60 months of treatment. After 60 months of follow-up, patients in group A had a significant increase in body mass index (p = 0.004) and waist circumference (WC) (p = 0.026) and a significant decrease in osteocalcin (p = 0.002), bone alkaline phosphatase (p = 0.029), lumbar spine bone mass density (BMD) T and Z scores (p < 0.001 and p = 0.001, respectively) and vertebral fractures rate (p = 0.021) than baseline. By contrast, patients in group B had a significant decrease in WC (p = 0.047) and increase in bone alkaline phosphatase (p = 0.019), lumbar spine BMD T score (p = 0.032), femoral neck BMD T and Z scores (p = 0.023 and p = 0.036, respectively) than baseline. Long-term conventional steroid replacement therapy is associated with a decrease in BMD, notably at lumbar spine, and increase in vertebral fractures rate. By contrast, DR-HC treatment is associated with improvement of BMD.
View full-text
Article
Effects on bone health of glucocorticoid replacement therapy in primary and secondary adrenal insuff...
March 2018
Giuseppe Bentivegna G Osella Anna Pia M. Terzolo
This review focuses on the effects of glucocorticoid replacement therapy on bone health in patients with primary and secondary adrenal insufficiency. The negative impact of glucocorticoids on bone is related to a number of factors, namely dose and type of steroid used, duration of therapy, and cumulative dose. Although “substitutive” in nature, GRT often produce cortisol levels that may be over
... [Show full abstract]
the true physiological range; therefore, patients may be chronically exposed to a slight cortisol excess potentially affecting bone health and increasing the risk of fractures. Glucocorticoids are the first cause of secondary osteoporosis. They act on bone impairing not only bone mineral density (BMD) but also bone quality, so BMD obtained by DXA measurements does not fully reflect the negative effects on the skeleton. We explore scientific literature on this focus. A lot of papers are related to small series of patients studied several years ago; most of these studies evaluated BMD effects and results are often conflicting, with few data about fractures. The recent guidelines suggest, for the replacement therapy of adrenal insufficiency, the use of daily doses of glucocorticoid lower than previously used and new glucocorticoid formulations become available, potentially safer, with lower deleterious effects on bone health.
Read more
Last Updated: 06 Mar 2023
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