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Global: Bolton World Catalog > Formicidae > Myrmicinae > Strumigenys > Strumigenys szalayi
See all Strumigenys szalayi in All Antweb
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Species: Strumigenys szalayi
Name Status:
Taxonomic Hierarchy:
Subfamily: Myrmicinae Genus: Strumigenys
Taxonomic History (provided by Barry Bolton, 2013)
Strumigenys szalayi Emery, 1897c PDF: 578, pl. 14, figs. 10, 11 (w.q.) NEW GUINEA. AntCat AntWiki
Taxonomic history
Senior synonym of Strumigenys australis: Brown, 1971c: 75.
See also: Bolton, 2000: 906.
Distribution:
Islands of Luzon, Mindanao, Mindoro, Negros
Taxon Page Author History
Specimen Data Summary
Found most commonly in these habitats: 1 times found in low canopy, looks like secondary forest; breadfruit, pandanus, strand veg, etc., 2 times found in swamp forest, 1 times found in 1° rainforest, 1 times found in moist forest
Collected most commonly using these methods or in the following microhabitats: 1 times davis-sifting; incidental aspirated, 1 times Hand-Collected from 1 square meter of sifted leaf litter, 1 times Winkler
Elevations: collected from 50 - 840 meters, 413 meters average
7 Specimens Imaged | View All 14 Specimens for this species
CASENT0178415
CASENT0178462
CASENT0178463
CASENT0199965
CASENT0900758
CASTYPE06891-01
CASTYPE06891-02
Enlarge Map
TOOLS:
View:
- Browse Specimens for this species (14 examples)
- View Strumigenys szalayi in Google Earth
Comparison Tool:
- Compare images of the Specimens within this species
Catalog:
- See Hymenoptera Name Server
Download:
Specimen Data:
- KML
- Tab-delimited
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Methodology article
High-utility conserved avian microsatellite markers enable parentage and population studies across a wide range of species
Deborah A Dawson1*, Alexander D Ball1,4, Lewis G Spurgin1,2, David Martín-Gálvez1,5, Ian R K Stewart3, Gavin J Horsburgh1, Jonathan Potter1, Mercedes Molina-Morales1,6, Anthony W J Bicknell1,7, Stephanie A J Preston1, Robert Ekblom1,8, Jon Slate1 and Terry Burke1
Author Affiliations
1 Department of Animal and Plant Sciences, University of Sheffield, Sheffield, S10 2TN, UK
2 School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, UK
3 Department of Biology, University of Delaware, Newark, DE, 19716, USA
4 Current address: Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK
5 Current address: Estación Experimental de Zonas Áridas (CSIC), Almería, E-04120, Spain
6 Current address: Departamento de Zoología, Universidad de Granada, Granada, E-18071, Spain
7 Current address: Plymouth University, Marine Biology and Ecology Research Centre, Davy Building, Drake Circus, Plymouth, PL4 8AA, UK
8 Current address: Department of Ecology and Genetics, Uppsala University, Norbyv. 18D, Uppsala, SE-75236, Sweden
For all author emails, please log on.
BMC Genomics 2013, 14:176 doi:10.1186/1471-2164-14-176
The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2164/14/176
Received:16 October 2012
Accepted:19 February 2013
Published:15 March 2013
© 2013 Dawson et al.; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
Microsatellites are widely used for many genetic studies. In contrast to single nucleotide polymorphism (SNP) and genotyping-by-sequencing methods, they are readily typed in samples of low DNA quality/concentration (e.g. museum/non-invasive samples), and enable the quick, cheap identification of species, hybrids, clones and ploidy. Microsatellites also have the highest cross-species utility of all types of markers used for genotyping, but, despite this, when isolated from a single species, only a relatively small proportion will be of utility. Marker development of any type requires skill and time. The availability of sufficient “off-the-shelf” markers that are suitable for genotyping a wide range of species would not only save resources but also uniquely enable new comparisons of diversity among taxa at the same set of loci. No other marker types are capable of enabling this. We therefore developed a set of avian microsatellite markers with enhanced cross-species utility.
Results
We selected highly-conserved sequences with a high number of repeat units in both of two genetically distant species. Twenty-four primer sets were designed from homologous sequences that possessed at least eight repeat units in both the zebra finch (Taeniopygia guttata) and chicken (Gallus gallus). Each primer sequence was a complete match to zebra finch and, after accounting for degenerate bases, at least 86% similar to chicken. We assessed primer-set utility by genotyping individuals belonging to eight passerine and four non-passerine species. The majority of the new Conserved Avian Microsatellite (CAM) markers amplified in all 12 species tested (on average, 94% in passerines and 95% in non-passerines). This new marker set is of especially high utility in passerines, with a mean 68% of loci polymorphic per species, compared with 42% in non-passerine species.
Conclusions
When combined with previously described conserved loci, this new set of conserved markers will not only reduce the necessity and expense of microsatellite isolation for a wide range of genetic studies, including avian parentage and population analyses, but will also now enable comparisons of genetic diversity among different species (and populations) at the same set of loci, with no or reduced bias. Finally, the approach used here can be applied to other taxa in which appropriate genome sequences are available.
Background
Microsatellite loci are suitable for a wide range of applications and have remained the most commonly used marker for studies of population structure and paternity since the early 1990s [1-3]. The use of microsatellites is likely to continue to be used for many years to come. They are comparatively cheap to genotype and provide more population genetic information per marker than biallelic markers such as single nucleotide polymorphisms (SNPs; [4]). A single set of microsatellite markers can be used to genotype several related species, but SNP markers lack cross-species utility, and are therefore only suitable for population and paternity studies where the project involves just a single species. Microsatellites can be successfully used for genotyping samples of low DNA concentration or low-quality samples (such as museum and non-invasive samples, e.g. feather, hair and faecal samples), in contrast to, for example, SNPs and genotyping-by-sequencing methods. A relatively large amount of DNA (typically 250 ng per individual) is usually required for SNP-typing versus >1 ng for microsatellite-based genotyping. Microsatellites have a wide range of other applications, and for some of these they have been found to be more suitable than SNPs, e.g. in genetic stock identification ([5], cf. [6]). They are the most convenient marker to establish if an individual (plant, for example) is a clone of its parent. They enable investigation of ploidy in a species, which for many species remains unknown. Plants and insects can be haploid, diploid or tetraploid, etc. and in some cases, one sex may be haploid and the other diploid (e.g. some wasp species). Finally, microsatellites enable the rapid identification of cryptic species (e.g. [7]) and have been used successfully to identify species hybrids (e.g. [8,9]).
Unfortunately, like most markers, the isolation, development and validation of microsatellite markers can take time to complete and therefore prove costly. Due to their low abundance in birds compared to other taxa [10,11], enrichment protocols are routinely employed to isolate avian microsatellite loci. The enrichment and cloning of microsatellite sequences is a skilled task, and is, therefore, often out-sourced, to be performed at specialist research facilities or by commercial laboratories. The use of 454-pyrosequencing can increase the number of loci isolated (e.g. [12]) but this also has to be performed at a specialist facility and can therefore increase costs [13]. Several weeks are then usually required for the in-house stages of primer testing and validating markers.
Moreover, the development and selection of microsatellite markers using a single population from an individual species often results in ascertainment bias [14]. Thus, even when markers amplify in multiple species, they are often most polymorphic in the same population and/or species from which they have been isolated (e.g. [15-19]), preventing meaningful cross-species comparisons. Ideally, any marker type would be applicable to several species to enable cross-species comparisons and allow investigation of karyotype and genome evolution. The cross-species utility of microsatellites is higher than other types of markers. However, when microsatellites are developed in the traditional way, from a cloned single species, their utility is normally limited to closely-related taxa.
Since the early demonstrations of cross-species microsatellite amplification in birds (e.g. [20], attempts have been made to identify a useful number of primer sets of high utility in a wide range of avian species. A small number of such primer sets of high cross-species utility have been identified (e.g. [21]; see also the BIRDMARKER webpage http://www.shef.ac.uk/nbaf-s/databases/birdmarker webcite, [22]). Unfortunately, loci that are polymorphic are often rendered useless for genetic studies due to deviation from Hardy–Weinberg equilibrium and high null allele frequencies [23]. However, Durrant et al. [24], demonstrated, by testing the 34 TG conserved microsatellite markers developed by Dawson et al. [21], that it is possible to identify at least 20 validated polymorphic loci in species of Passeridae or Fringillidae (classification based on Sibley & Monroe [25]), with the term “validated” indicating that each locus, when assessed in a single population of unrelated individuals, adhered to Hardy–Weinberg equilibrium and had an estimated null allele frequency lower than 10%. Between 12–40 of such validated markers are normally sufficient for parentage and population studies (e.g. [26-28]), although some analyses, such as heterozygosity–fitness correlations, may require larger numbers of loci [29,30]. A large number of zebra finch (Taeniopygia guttata) expressed sequence tag (EST) microsatellite loci have been identified as useful in the blue tit (Cyanistes caeruleus) and, due to the relatively large genetic distance between zebra finch and blue tit, these are expected to be of utility in multiple species of Paridae [31]. However, although sufficient conserved markers probably exist for paternity and population studies of most species of Paridae, Passeridae and Fringillidae, additional loci are required to combine with existing conserved markers and enable genetic studies and cross-species comparisons in the large majority of bird species (including over 5,000 passerines and 4,000 non-passerines, [25].
To identify highly conserved microsatellite loci in the avian genome, the ideal scenario would be to compare homologous sequences in the two most genetically distant avian species. The two most genetically distant bird groups are the ratites and non-ratites [32]. However, there are relatively few species of ratites (n = 57, [25], none of which have as yet had their genomes sequenced (as of 10th February 2013). In order to attempt to identify such highly-conserved microsatellite loci in the avian genome, Dawson et al. [21] previously compared homologous sequences in two very distantly related species, the zebra finch and chicken (Gallus gallus). The primer sequences of these loci were a complete match to both zebra finch and chicken and the marker names were therefore given the prefix “TG” representing the first letters of the binomial names of these two species Taeniopygia guttata and Gallus gallus. The zebra finch and chicken are both non-ratites but belong to two distantly related groups of birds and have the highest recorded genetic distance for any two bird species based on DNA: DNA melting temperature (Δ Tm) hybridisation distances (28.0, [33]. Both of these species have now had their whole genomes sequenced and assembled (see http://www.ensembl.org webcite).
Dawson et al. [21] identified loci that amplified in all non-ratite bird species, a high proportion of which were polymorphic in most species tested. This earlier study utilised microsatellites mined from zebra finch EST sequences with very strong similarity to their chicken homologue, but where the repeat region in zebra finch was not necessarily present in its chicken homologue. The longest uninterrupted string of dinucleotide repeat units in the sequenced zebra finch and chicken alleles was low for most loci (zebra finch: n = 3–15, mean 8 repeats; chicken: n = 0–13, mean 6 repeats). For the markers developed in this way, the proportion of loci polymorphic in a species was inversely related to the genetic distance from the “source” species – the “source species” being regarded as zebra finch, the species that contained the most uninterrupted microsatellite repeat units. Passerine species were regarded as those with a genetic distance of 12.8 or less from zebra finch based on DNA: DNA melting temperature (Δ Tm) hybridisation distances [25]. On average, 47% of those TG loci amplifying were polymorphic in passerines and 22% in non-passerines (zebra finch and chicken data excluded; [21]. The variability of a locus is related to the number of repeats it possesses [34]. The decrease in polymorphism with increasing genetic distance may have been due to a correlated reduction in the number of repeat units in the target species compared to the source species. In this new study, we have attempted to identify markers that are polymorphic in a larger range of species.
We followed the approach of Dawson et al. [21] by identifying highly similar homologous sequences in two distantly related species (zebra finch and chicken). However, here we (1) selected homologous sequences in which both species contained repeat motifs, (2) attempted to align sequences that contained more repeat units than in the earlier study (≥ 8, in both species) and (3) we searched the whole genome for conserved microsatellite loci (i.e. not just for microsatellites in EST sequences, as performed by Dawson et al. [21]). Microsatellites with more repeat units generally have higher mutation rates [35,36] and are therefore expected to be more variable. The use of the whole genome was expected to increase the number of useful loci identified due to the huge increase in the number of microsatellite sequences that were now available. It is unclear if the source origin of the sequence (i.e. anonymous genomic sequence versus EST) would be expected to have any influence on locus variability. There is evidence that there is no difference between the variability of microsatellite markers developed from non-EST and EST sequences but other studies suggest non-EST markers may be more variable than those from ESTs (cf. [37-39]). We developed a set of conserved markers for 24 loci using the stated criteria and assessed their utility across a wide range of avian species. Additionally, we compared the utility of the new marker set to that of the previously-developed conserved marker set [21].
Methods
Identification of microsatellite loci in the zebra finch and chicken genome
In order to identify microsatellite sequences we searched the contigs and supercontigs of the unassembled zebra finch genome (now assembled and published by [40]) and the assembled chicken genome version 2.1 [41], using a version of the SPUTNIK software modified by Cornell University (http://wheat.pw.usda.gov/ITMI/EST-SSR/LaRota/ webcite, [42]. We identified sequences containing any dinucleotide repeat regions (CA, GA, AT, GC or their complements) which had more than ten repeats and which were at least 90% pure (i.e. >18 bp long; Table 1). We extracted 200 bp of sequence flanking either side of the repeat region, or all of the available sequence if it was less than 200 bp.
Table 1. Identification of avian microsatellite sequences of high cross-species utility*
Identification of highly-conserved microsatellite loci
The length of the sequence compared against another affects the strength of the E-value obtained. The zebra finch sequences extracted and used for the BLAST sequence comparison to chicken were 421–487bp long (Table 2). We attempted to create a zebra finch–chicken consensus primer set for all zebra finch microsatellite sequences that exhibited an NCBI BLAST E-value of E-59 or better (lower) when compared to their chicken microsatellite homologue (Table 2). BLAST E-value scores were obtained using standalone blastN (version 2.2.8 of Blast for 32-bit Windows; [43]).
Table 2. Sequence origins, homology and primer sequences of 24 Conserved Avian Microsatellite ( CAM ) loci
Additional file 1. Genotypes observed for 12 species at 24 CAM loci.
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Additional file 2. Full sequence data for 24 conserved avian microsatellite (CAM) loci.
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Additional file 3. Primer melting temperatures in zebra finch and chicken for 24 conserved avian microsatellite (CAM) markers.
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Additional file 4. Allelic richness versus genetic distance for each CAM marker.
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Additional file 5. Typical numbers of loci polymorphic among those amplifying for a selection of passerine and non-passerine species from a selection of different studies.
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Additional file 6. Homology of CAM loci to expressed sequence tags (ESTs), genes, other microsatellites and BACs.
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Creation of a consensus hybrid sequence and primer design
Consensus zebra finch–chicken sequences were created by aligning homologous sequences using MEGA3 software [44] and replacing mismatching bases and gaps with the code “n” to represent an unknown base. We used the zebra finch–chicken consensus microsatellite sequences to design primer sets using PRIMER3 software [45]. The primer sequences were designed from the consensus zebra finch–chicken hybrid sequence including “n” at those base pair locations where the zebra finch and chicken bases did not match. When necessary, we altered the “General Primer Picking Conditions” and set the “Max #N’s” parameter (maximum number of unknown bases (N) allowable in any primer) to “1” or “2” so that degenerate bases (if needed) could be included in the primer sequence. Primers were selected to have a melting temperature between 57–63°C and the maximum allowable difference in the melting temperature between the forward and reverse primer was set as 1.0°C. However, it should be noted that the melting temperature assigned to an unknown “n” base by PRIMER3 is an average of all four bases and not the melting temperature of any actual base. The real melting temperature of primer sequences including degenerate bases will be different to that requested in the PRIMER3 selection criteria and also stated in the PRIMER3 output. The actual melting temperature will therefore be 0.88/2.18°C higher than that stated if the actual base at the location of the degenerate base was a G/C and 0.55/2.41°C lower if an A/T. We manually selected the primer-binding sites to be positioned in regions where the sequences were highly similar between zebra finch and chicken and attempted to include as few degenerate bases as possible, but most primers (encompassing 18 pairs) required the inclusion of degenerate bases. These degenerate bases were placed at the sites where a base mismatch occurred between the zebra finch and chicken sequence in an attempt to make the primer sequences amplify in multiple species. We used a maximum of two degenerate bases per primer and a maximum of three per primer pair (Table 2). With two degenerate bases per primer the difference in true melting temperatures versus those calculated by PRIMER3 ranges from a maximum of -4.82°C (n × 2 versus T × 2) to +4.36°C (n × 2 versus G × 2). The (multiple) different combinations of alternative primer sequences due to the inclusion of degenerate primer bases were not checked for adherence to PRIMER3 primer design criteria prior to ordering the primer sets due to the complexity of performing this task. The forward primer of each primer set was labelled with either a HEX or 6-FAM fluorescent dye (Table 2). The loci were named with the prefix CAM representing “Conserved Avian Microsatellite”.
Genome locations
All of the sequences were assigned chromosome locations in the zebra finch and chicken genomes by performing a BLAT search against each genome, using the masked genome and the distant homologies settings implemented on the ENSEMBL webpage (http://www.ensembl.org/Multi/blastview webcite; methods as in [46,47]; Table 3, Figure 1). The genome assemblies used were the Taeniopygia_guttata-3.2.4 (v 1.1), released 14 July 2008 [40] and the chicken genome assembly version 2.1 [41]. The locations of the loci were displayed using MAPCHART software [48].
Figure 1. Chromosome locations of the CAM loci in the chicken and zebra finch genomes. Gga, chicken (Gallus gallus) chromosome. Tgu, zebra finch (Taeniopygia guttata) chromosome. The exact chromosomal locations of the loci (in base pairs) are provided in Table 2. Those loci underlined are less than 5Mb apart and may display linkage disequilibrium.
Table 3. Repeat motif, chromosome locations and locus variability of 24 Conserved Avian Microsatellite ( CAM ) loci
Cross-species amplification and polymorphism
The 24 primer sets developed were used to genotype a minimum of four individuals from each of eight species of Passeriformes and one species each of Ciconiiformes (Charadriiformes), Strigiformes, Coraciiformes and Galliformes (including zebra finch and chicken; classification following Sibley & Monroe [25]). The species tested covered a wide range of genetic distances from the zebra finch (species identities and sample sizes are provided in Table 4).
Table 4. Details of the 12 species tested and a summary of utility of the Conserved Avian Microsatellite (CAM) markers*
All individuals had been sampled in the wild with the exception of the zebra finch and chicken individuals (Table 4). The latter were sampled from captive populations maintained at the University of Sheffield and the United States Department of Agriculture (Agriculture Research Service, East Lansing, USA), respectively. For each species, all individuals genotyped were unrelated as known, except for the chicken and European rollers. All four chicken were siblings and three of the European rollers were siblings. The chicken individuals genotyped were four siblings from the East Lansing mapping population, which consists of fifty-two BC1 animals derived from a backcross between a partially inbred jungle fowl line and a highly inbred white leghorn line [49]. These individuals, therefore, will display a maximum of four alleles per locus, but often fewer. Additionally, a higher proportion of the chicken siblings might be expected to be heterozygous than in a wild population because the mother and father of the chicken pedigree originated from different breeds. Polymorphism in chickens at the TG and CAM loci was omitted from analyses for three reasons: (1) the chicken individuals tested belonged to a backcrossed mapping pedigree; (2) all the other species tested were comparable, being all at a genetic distance of 28 from chicken (genetic distance: DNA: DNA melting temperature (Δ Tm) hybridisation distance, [33]) and, finally, (3) the primer sets had been engineered more specifically to amplify in chicken than in the other species tested. The European rollers genotyped initially included four nestlings sampled from two nests (including three siblings from one nest). When the loci that failed to amplify were rechecked, unrelated European roller individuals were used. All individuals genotyped were sampled from a single population, except the Leach’s storm-petrels, for which the six individuals were sampled from four populations, and Berthelot’s pipits, for which each of the four individuals sampled was from a different population.
Approximately 20–50 μl of blood was collected from each individual and stored in 1.5 ml of absolute ethanol in rubber-sealed screw-topped microfuge tubes. Genomic DNA was extracted using an ammonium acetate precipitation method [50] or a salt extraction method [51]. Each DNA extraction was tested for amplification and sex-typed using the Z-002[52] or (for the Berthelot’s pipit and the European roller) P2/P8[53] sex-typing markers.
Each primer set was tested in isolation (single-plexed) in all species. Primer sets (using the zebra finch version of the primer sequence) were checked for their potential to form hairpins and to identify any PCR incompatibilities due to primer sequence similarity using AUTODIMER software [54], http://www.cstl.nist.gov/strbase/software.htm webcite) using a ‘conservative minimum threshold score’ of seven.
Single-plex PCR reactions were performed in 2-μl volumes using QIAGEN Multiplex PCR Master Mix (QIAGEN Inc.) for all species except the European roller and its reruns. Each 2-μl PCR contained approximately 10 ng of lyophilised genomic DNA, 0.2 μM of each primer and 1 μl QIAGEN Multiplex PCR Master Mix [55]. For all species, PCR amplification was performed in the same laboratory in Sheffield using a DNA Engine Tetrad 2 thermal cycler (model PTC, MJ Research, Bio-Rad, Hemel Hempstead, Herts, UK). PCR amplification was performed using an annealing temperature of 56°C or a touchdown PCR program (Table 4). Slightly different PCR protocols were used for some species, since they were performed by different researchers at different times and using different DNA Taq polymerases (Table 4). However, these differences are not expected to have any measurable effect. The European roller amplifications were performed in a 10-μl PCR reaction that contained approximately 20 ng of genomic DNA, 0.5 μM of each primer, 0.2 mM of each dNTP, 2.0 mM MgCl2 and 0.25 units of Taq DNA polymerase (Bioline) in the manufacturer’s buffer (final concentrations: 16 mM (NH4)2SO4, 67 mM Tris–HCl (pH 8.8 at 25°C), 0.01% Tween-20). Products were diluted 1 in 500 prior to separation on an ABI 3730 48-well capillary DNA Analyser and allele sizes were assigned using GENEMAPPER v3.7 software (Applied Biosystems, California, USA). The same DNA Analyser at Sheffield was used for separating the amplified products for all species. Alleles were scored separately for each species, using species-specific allele bin sets, in different sessions by different researchers but in the same laboratory and using the same methods (details in Table 4).
Previous work has identified that it is worth retesting any markers that fail to amplify at the first PCR attempt [21]. All markers that failed to amplify were therefore rechecked by performing a repeat PCR and the majority amplified at the second PCR attempt. When the 24 markers were initially tested, a maximum of six markers (25%) failed to amplify in a single species; however, the majority amplified at the second PCR attempt (Table 4 and Additional file 1).
For four species, Berthelot’s pipit, rifleman, Leach’s storm petrel and European roller, a proportion of the CAM and TG loci [21] were assessed in a larger sample of unrelated individuals (n = 17–30) from a single population in order to check for Hardy–Weinberg equilibrium and estimate null allele frequencies (calculated using GENEPOPv4.0.10, [56] and CERVUSv3.0.3, [57]). The characteristics of the CAM and TG marker sets were then compared for these four species, in terms of the number of loci deviating from Hardy–Weinberg equilibrium and the proportion possessing high null allele frequency estimates.
All statistical analyses were carried out in R version 2.14.1 [58]. Differences in the proportions of polymorphic loci across passerines and non-passerines, and between CAM and TG loci, were tested using chi-squared (χ2) tests. Linear regression was used to test for whether the percentage of polymorphic loci per species was related to the genetic distance from zebra finch.
Results and discussion
Identification of microsatellite sequences in the zebra finch and chicken genomes
There were similar total numbers of dinucleotide microsatellite sequences of eight or more repeats in the zebra finch and chicken genomes (6,458 versus 6,581, respectively; Table 1). Hits to the “unknown” chromosome were not included, since duplicate sequences have been observed on both the named chromosomes and the ‘unknown’ chromosome and these occurrences are probably artefacts of the assembly process (DAD pers. obs.). It should also be noted that a male was sequenced to obtain the zebra finch genome, whereas a female was used for the chicken, so that only the chicken genome includes sequence derived from the W chromosome. However, due to the small size of the W chromosome (representing only 0.02% of the assembled chicken genome), its inclusion is not expected to influence significantly the total number of microsatellites detected.
Only one chicken and no zebra finch microsatellites were found that contained a GC/CG motif, suggesting that these motif types are rare and/or shorter than eight units in length in the avian genome. Although the total numbers of microsatellite loci were similar between the zebra finch and chicken, the zebra finch possessed a higher proportion of AT/TA repeats, and fewer CA/GT and GA/CT motifs, than chicken (Table 1; heterogeneity test, χ2 = 381.6, d.f. = 2, p < 0.0001). These differences were unexpected and the reasons for them are currently unknown.
Identification of highly conserved microsatellite loci
Forty-two homologous microsatellite loci were identified in both the zebra finch and chicken, with each pair having a BLAST E-value better than E-59. None of these newly identified conserved sequences matched any of the conserved EST-based microsatellite loci for which primer sets had already been developed by Dawson et al. [21]. The conserved loci possessed the following dinucleotide motifs: CA/GT motif (n = 22), AT/TA (n = 16) and GA/CT (n = 4). The distribution of motif types in the conserved loci did not differ from expectation based on their frequencies in the zebra finch (heterogeneity test, χ2 = 5.42, d.f. = 2, p = 0.07) or chicken genome (heterogeneity test, χ2 = 2.95, d.f. = 2, p = 0.23; Table 1). All 42 zebra finch sequences were aligned with their chicken homologues in an attempt to create a consensus hybrid sequence.
Creation of a consensus hybrid sequence and primer design
Consensus primer sets were created for 24 of the 42 unique loci identified (57%) using the primer design criteria outlined above (Tables 1 & 2; full sequences of the loci are provided in Additional file 2). In contrast to Dawson et al. [21], we were not able to create primer sets that were always 100% homologous to chicken but all matched 100% to zebra finch, and were at least 86% similar to their homologous chicken sequences (by including 1–2 degenerate bases in 25 primers). Only a single degenerate base in just one primer was required in the earlier EST study, which then matched 100% to both species (34 primer sets; [21]). Many more degenerate bases were used in the CAM marker set than in the earlier TG marker set (CAM: 28 degenerate bases spread over 18 of the 24 markers; TG: one degenerate base in one of the 34 markers; this study versus Dawson et al. [21]). Only six CAM consensus sequences contained regions of microsatellite-flanking sequence that were identical in zebra finch and chicken for a sufficient length from which to design primers without using any degenerate bases (CAM-06, CAM-13, CAM-17, CAM-18, CAM-20 and CAM-24; Table 2). The remaining 18 primer sets contained between 1–2 degenerate bases per primer sequence (a maximum of 3 degenerate bases per primer pair) and, of these, only six were 100% matches to both zebra finch and chicken, when accounting for the degenerate bases used. We attempted to design the most consensus primers we could. The primer sequences of the remaining 12 degenerate primer sets were a 100% match to zebra finch and a match to chicken of between 86–96%.
As expected, all 24 loci possessed dinucleotide motifs in chicken and zebra finch, with the majority being the CA/GT motif (n = 16), although some had AT/TA (n = 4) and GA/CT (n = 4) motifs. The same motif type was present in both chicken and its zebra finch homologue at all 24 loci (Table 3). Most loci possessed several different dinucleotide repeat regions and some also possessed additional mononucleotide repeat regions in the sequence (Table 3). When the longest string of uninterrupted dinucleotide repeats at each orthologous locus was compared between chicken and zebra finch there was a significant difference in the number of repeat units (paired t-test, t = 2.18, d.f. = 23, P = 0.04; 15 loci had fewer repeats in chicken, six had more and three the same number of repeat units; Table 3). The 24 selected loci possessed a minimum of eight uninterrupted dinucleotide repeat units (in both species) and a maximum of 27 in zebra finch and 20 in chicken (Table 3).
No hairpins were detected in any primer sequences when analysed using only the pure zebra finch version of each primer (assessed using AUTODIMER software). Three pairs of primer sequences displayed some degree of similarity and should be avoided as potential multiplex combinations to prevent the risk of forming primer dimers (CAM-02R–CAM-15R, CAM-03R–CAM-20F and CAM-05R–CAM-06R). However, the check for primer similarity (using AUTODIMER software) is of limited utility when checking primers containing degenerate bases because the degenerate bases are regarded as unknown bases and some unidentified primer pairs may turn out to be incompatible. We therefore recommend typing the loci both singly and in multiplex PCR reactions to confirm that the genotypes match before routinely using any multiplex set, especially when the primer sequences contain degenerate bases. When up to three degenerate bases are used, as in this study, the maximum number of forward and reverse sequence combinations per primer set is eight and the resulting variation in annealing temperatures between the forward and reverse primers might potentially cause PCR amplification problems. We recommend designing primer sets for standard microsatellite loci using PRIMER3 with a maximum difference between the forward and reverse primer melting temperature of 0.5°C. However, a difference of up to 2°C has been found to be acceptable for the amplification of many primer sets (e.g. [59]). Unreliable PCR amplification of these loci is most likely in the non-passerine species, as they are more genetically distant from zebra finch and are therefore more likely to exhibit base mismatches in the primer binding regions. Incomplete PCR amplification can be identified by testing a range of annealing temperatures, performing repeat PCRs and/or the typing of a pedigree (if available), and, if detected, can be improved by PCR optimisation methods.
Homology to expressed and coding sequence
Highly conserved microsatellites have been successfully isolated from ESTs [21]. The majority of the 24 CAM sequences (17/24) were found to be homologous to avian ESTs, avian (or mammalian) mRNA sequences or known genes (identified by sequence similarity searches of the GenBank nr, EST (“EST_others”) nucleotide databases and the zebra finch and chicken genomes; Table 2). Some of the microsatellite sequences were located within exons, which may explain why these sequences are conserved among many species.
Genome locations and linkage
All 24 loci could be assigned a location in both the zebra finch and chicken genome based on sequence similarity. Twenty-three loci were assigned to an autosomal location and one locus (CAM-11) was assigned to the Z chromosome in both species (Figure 1). Two pairs and one triplet of loci were assigned locations less than 5 Mb apart in both the chicken and zebra finch genomes; there is therefore an increased possibility of these loci being in linkage disequilibrium because recombination rates between them will be relatively low: CAM-02–CAM-03 on Gga7/Tgu7, CAM-05–CAM-06–CAM-07 on Gga1/Tgu1A and CAM-13–CAM-23 on Gga6/Tgu6 (Figure 1). Several CAM loci were typed in a pedigree of over 300 house sparrows (JS et al. unpublished data). This analysis confirmed, as expected, that loci CAM-05, CAM-06 and CAM-07 were all linked. Additionally, loci CAM-01 and CAM-12 were also linked in the house sparrow linkage map (JS et al. unpublished data; both loci located on chromosome 2 in zebra finch (27 Mb apart) and chicken (5 Mb apart), Figure 1). Loci CAM-02 and CAM-13 were not typed in the house sparrow pedigree so could not be checked for linkage to the other locus located on the same chromosome (CAM-03 and CAM-23 respectively).
Cross-species amplification
All loci amplified in both zebra finch and chicken (Tables 3 & 4, Figure 2). The ranges of allele sizes obtained by genotyping zebra finches and chickens were close to those expected based on the respective genome sequences, with the exception of locus CAM-09 in chicken. The maximum difference between the expected allele size and the allele size range observed for each species was 11 bp (except CAM-09 in chicken; Table 3); since the source genome sequence was isolated from an individual belonging to a different population to the individuals genotyped, small allele size differences (such as 1–20 bp) are expected. Locus CAM-09 was 101 bp smaller in size in chicken than expected, however, this marker remains of potential utility in other species. We suspect that a deletion may have occurred in the chicken (breed/population) genotyped, or that a different locus is being amplified, possibly due to poor similarity of the CAM-09 primer sequences to chicken (three degenerate bases were used (one in the forward primer and two in the reverse) but, despite this, three bases in the forward primer and two in the reverse still did not match chicken 100%; Table 2). It was surprising that, despite up to three chicken–primer base mismatches per primer sequence (in addition to the presence of up to two degenerate bases), and the differences in primer annealing temperatures in different species caused by this (Additional file 3), all the primer sets amplified in chicken. Amplification may have been assisted by the use of a touchdown PCR program and the use of the QIAGEN Multiplex PCR Master Mix, which enhances the likelihood of successful PCR amplification from primers with differing annealing temperatures. For the majority of loci (including CAM-09), the sizes of the alleles observed in the ten other species tested were very similar to those expected and observed in zebra finches (and/or chickens, except CAM-09) (Additional file 1). It is expected that for each species a few loci will not possess high sequence similarity and, because the identity of those not possessing sequence similarity is different in each species, this does not present a problem. We compared sequences to the recently released collared flycatcher (Ficedula albicollis) and budgerigar (Melopsittacus undulates) genome sequences (http://www.ensembl.org/index.html webcite; Dawson et al. unpublished data). A homologue was identified in each case and all contained a microsatellite repeat (including CAM-09; CAM-24 cannot be checked because it cannot be identified in the available assemblies). This suggests the correct target locus was being amplified in the majority of species–marker tests.
Figure 2. Percentage of CAM loci amplified (white squares) and polymorphic (black circles), alongside genetic distance from the zebra finch (grey triangles) for 12 species. % Polymorphic, proportion of loci polymorphic of those amplifying for each set of loci. Four individuals were genotyped for each species at 24 loci. Genetic distance, DNA:DNA Δ Tm hybridisation distance [33].
The degree of sequence similarity between distantly related species affects the range of species that will amplify [60]. Those markers designed from sequences with high similarity between distantly related species (i.e. those with an E-value of E-80 or better between zebra finch and chicken) have been found to amplify in virtually all birds [21]. Dawson et al. [21] used a different BLAST program (WU-BLAST) when assessing loci for potential cross-species utility. However, the BLAST E-values obtained via WU-BLAST and NCBI BLAST (as used for this study) for the same sequence are normally very similar (DAD unpublished data). During this study we utilised sequences with a lower similarity between zebra finch and chicken (those displaying a BLAST E-value better than E-59). This weaker cut-off was necessary to enable the identification of homologous sequences that possessed eight repeats in both zebra finch and chicken but the trade-off was that in most cases the poorer similarity made it impossible to design primers that were a complete match to both zebra finch and chicken. The reduced primer similarity to chicken was expected to lower the utility of these markers in species distant to zebra finch but it was hoped that, for those species close to zebra finch (passerines), a high number of polymorphic loci would be identified. On average, 94% of loci amplified in each of the seven passerine species tested (range 83–96%) and 95% amplified in each of three non-passerine species (range 92–96%; zebra finch and chicken data excluded, Table 4, Figure 2). The number of loci that amplified within each species was not related to their genetic distance from the zebra finch (Figure 2).
Cross-species polymorphism
Of the CAM loci that amplified, 56–83% (mean 68%) were polymorphic in each passerine compared to 32–56% (mean 42%) in each non-passerine, and this difference was significant (zebra finch and chicken data excluded; χ2 = 6.42, d.f. = 1, P = 0.01; Table 4). Additionally, more of the amplifying CAM loci were polymorphic than the amplifying TG loci ([21]; zebra finch and chicken data excluded; χ2 = 7.81, d.f. = 1, P = 0.005). Of the TG loci that amplified, 24–76% (mean 47%) were polymorphic in a passerine species and 18–26% (mean 22%) in a non-passerine species [21]. When assessed in a minimum of four individuals per species, the species with the highest proportion of polymorphic CAM loci was, as expected, the zebra finch (92%), followed by the chaffinch (Fringilla coelebs; 83%), while the lowest proportion in a passerine was 56% in the great tit (Parus major; Table 4, Figure 2).
When all 24 CAM markers were considered as a whole, the proportion of loci polymorphic per species was negatively correlated with genetic distance from the zebra finch (Figure 2), as was also previously found for the TG loci [21], despite the fact that the CAM loci displayed a repeat region of at least eight repeat units in chicken (chicken excluded; CAM loci: F = 27.55, d.f. = 1, 9, R2 = 0.73, P = 0.0005; TG loci: F = 15.30, d.f. = 1, 17, R2 = 0.44, P = 0.001; Figure 3A). Additionally, the mean number of alleles per polymorphic locus decreased with increasing genetic distance from the zebra finch (chicken excluded; F = 22.99, d.f. = 1, 9, R2 = 0.68, P < 0.001; Figure 4A). These regressions remained significant after controlling for differences between passerines and non-passerines, and when a phylogenetic correction was used (data not shown), indicating that the effect of genetic distance on polymorphism was a linear, rather than group effect. Approximately 20% more of the loci that amplified were polymorphic per species than was achieved previously by studies attempting to create conserved avian microsatellite loci. Each marker displayed a varying degree of cross-species utility (Figure 5, Additional file 4), possibly due to the differing degree of primer sequence similarity to chicken (Table 4, Additional file 3). In order to investigate this, we selected two subsets of six CAM markers: (Set 1) those that were a 100% match to chicken (and zebra finch) and possessed no degenerate bases (CAM-06, CAM-13, CAM-17, CAM-18, CAM-20 and CAM-24) and (Set 2) those which displayed poor similarity to chicken (but a 100% match to zebra finch; CAM-03, CAM-04, CAM-10, CAM-15, CAM-21 and CAM-23) and analysed these two groups separately. For Set 1 (the highly conserved markers), there was no relationship between the percentage of species polymorphic and genetic distance from zebra finch (linear regression: R2 = 0.11, d.f. = 10, P = 0.15, zebra finch and chicken excluded; Figure 3B). This appears to be a result of more markers in this set being polymorphic in those species distant to zebra finch (Figure 3B). However, in Set 2 (the more weakly conserved markers), the percentage polymorphism declined significantly with genetic distance from zebra finch (linear regression: R2 = 0.75, d.f. = 10, P = 0.0002, zebra finch and chicken excluded; Figure 3C). Set 2 also displayed a decrease in the mean number of alleles with increasing genetic distance from zebra finch (R2 = 0.8, d.f. = 10, P = 0.0002; Figure 4C), whereas in Set 1 there was no such fall (R2 = 0.07, d.f. = 10, P = 0.42; Figure 4B). In order to identify why markers with poor primer sequence similarity to chicken displayed a fall in variability as genetic distance increased, we checked both sets of loci for sequence similarity with the collared flycatcher and budgerigar genome sequences. These species are both useful for this investigation because their genetic distance from chicken is the same as the other species used in this study (genetic distances (Δ Tm): collared flycatcher–chicken = 28 and budgerigar–chicken = 28; collared flycatcher–zebra finch = 11.7 and budgerigar–zebra finch = 23.1; [33]). We checked how many bases in each primer sequence mismatched with their zebra finch and chicken homologue and how the repeat regions varied between the species. This revealed that for both Set 1 and Set 2, only two and one primer sets completely matched flycatcher respectively, but the number of bases mismatching in each primer set was quite low in both groups (a maximum of three mismatches per primer set, except for CAM-06 and CAM-21). In the more distant budgerigar, when the weakly-conserved markers of Set 2 were analysed, there were more mismatches per primer set than observed in the flycatcher: four markers had over three bases mismatching per primer set, one marker had one mismatch and for only one marker did both the forward and reverse primer sequences completely match budgerigar. Whereas, in the strongly-conserved marker Set 1, for the five homologous loci that could be identified (i.e. except CAM-24) all primer sets were a complete match to budgerigar. It was surprising that the primer sequences of the markers in Set 1 displayed higher similarity to budgerigar than flycatcher. All loci in both sets contained at least five uninterrupted repeats both species, except CAM-03 in budgerigar (CAM-24 could not be checked). There was no relationship between the mean number of repeats possessed and the number of bases mismatching in the primer sequences (mean number of repeats in Set 1 versus Set 2, flycatcher: 11 versus 11, budgerigar: 6 versus 7). This suggests that primer sequence similarity is the main factor affecting the identification of a polymorphic locus in this set of 24 CAM markers. Based on the number of repeats observed in budgerigar, other CAM loci would be expected to be polymorphic in non-passerines but the primers appear to be amplifying only one of the alleles (19 loci had more than 5 repeats in budgerigar and a maximum of 11 repeats observed; CAM-24 could not be checked). Perhaps, in distantly related species, mismatches between the target sequence and primer sequence result in amplification failure of some alleles due to large differences in the melting temperatures between the forward and reverse primer and between these and the PCR annealing temperature used. These base mismatches and mismatched melting and annealing temperatures may lead to only a single allele (with highest similarity to the primers) being amplified during the PCR. It is unclear why the primer set does not simply fail to amplify a product but perhaps the use of QIAGEN Multiplex PCR Master Mix reaction buffer enables amplification even when a primer set has poor similarity to the target. Alternatively, perhaps those displaying poor similarity to chicken are amplifying a different (invariant) locus in many of those species distant to zebra finch although this seems unlikely based on the agreement between the observed and expected allele size for each locus. The six well-conserved markers in Set 1 for which the proportion of polymorphic loci did not decrease with genetic distance (i.e. CAM-06, CAM-13, CAM-17, CAM-18, CAM-20 and CAM-24) are expected to be of highest utility in species most distant to zebra finch.
Figure 3. Percentage of CAM (black) and TG (grey) microsatellite markers polymorphic in relation to genetic distance from zebra finch. A: All 24 CAM markers included (CAM = this study; TG = Dawson et al. [21]); B: Six CAM markers with 100% primer sequence similarity to chicken (and zebra finch); C: Six CAM markers with poor primer sequence similarity to chicken (but 100% identical to zebra finch). Percentage markers polymorphic, proportion of loci polymorphic of those amplifying for each set of loci (CAM and TG sets). Genetic distance, DNA:DNA Δ Tm hybridisation distance [33]. Four individuals were genotyped at 24 loci for each of the 11 species (including zebra finch Taeniopygia guttata but excluding chicken Gallus gallus; see text).
Figure 4. Allelic richness (mean number of alleles per polymorphic locus) of the CAM markers in relation to genetic distance from zebra finch.* A: All 24 CAM markers included; B: Six CAM markers with 100% primer sequence similarity to chicken (and zebra finch); C: Six CAM markers with poor primer sequence similarity to chicken (but 100% identical to zebra finch). Genetic distance, genetic distance of the genotyped species from zebra finch (Taeniopygia guttata) DNA:DNA ΔTm hybridisation distance [33]. *Four individuals were genotyped at 24 loci for each of 11 species (including zebra finch Taeniopygia guttata but excluding chicken Gallus gallus; see text).
Figure 5. Number of species (A) amplified and (B) polymorphic at each individual CAM locus. Black bars represent passerines and grey bars non-passerines. Each locus was tested in 12 species (including zebra finch Taeniopygia guttata and chicken Gallus gallus), which included 8 passerine species, and 4 non-passerine species. Classification of species as passerine or non-passerine was following Sibley & Monroe [25]. The data presented is based on the genotyping of 4 individuals per species. For details of which species failed to amplify see Additional file 1.
We deduce that there are several important factors for ensuring polymorphism across the widest range of species (and for avoiding null alleles) when designing conserved markers: (1) the most distantly related species possible should be selected for designing the primers; (2) the similarity of the homologous regions should be high (displaying a BLAST E-value of E-80 or better); (3) a minimum of 8 uninterrupted repeats should be present in each species’ sequence used in the alignment; (4) the primer sequence must match both/all species 100%; (5) the use of degenerate bases should ideally be avoided or else minimized (to no more than one degenerate base per primer set); (6) the forward and reverse primer melting temperatures should ideally be within 0.5°C of each other (maximum 2°C); and (7) when degenerate bases are used it is important to confirm that all the alternative states of the forward and reverse primers are compatible and ensure that the melting temperature of all alternative states are within 0.5°C of each other.
The CAM loci were of utility in non-passerine birds. The nearest avian order, in terms of genetic distance, to Passeriformes is the order Ciconiiformes (also known as Charadriiformes, shorebirds and allies, [33]). We tested one ciconiiform, the Leach’s storm-petrel, in which 23 (96%) loci amplified and 13 (56%) of those amplifying were found to be polymorphic (Table 4, Additional file 1, Figure 2). In the two species very distant from both zebra finch and chicken, the barn owl and European roller, most of the markers amplified (92–96%) and 32–39% of those amplifying were polymorphic; Table 4, Additional file 1, Figure 2). When tested in chicken, 38% of the loci (n = 9) were polymorphic (Tables 4, Additional file 1).
Typical proportions of loci polymorphic among those amplifying in other studies
The levels of variability in each species when typed with the CAM loci might be affected by factors other than genetic distance, for example, genetic bottlenecks, founder effects, or long-term inbreeding, though we are unaware that these factors have affected any of the species/populations we typed. Additional polymorphic loci have been genotyped in the same three non-passerine species that we tested and this work did not suggest that any of the three species had exceptionally low variability (barn owl, [61]; Leach’s storm-petrel, [62]; European roller, [63]).
We found the proportions of CAM loci polymorphic among those amplifying to vary between 38–92% per species when all 24 loci were considered (Table 4; i.e. including those markers with good zebra finch–chicken primer sequence similarity and those loci in which it was poor). These figures are typical of those found in other studies. The proportion of loci polymorphic of those amplifying appears to vary widely among species (Additional file 5).
It is currently unclear if non-passerines are generally less variable than passerines. Further species need to be tested and more work performed to resolve this. If, however, the majority of non-passerine species do display lower variation than passerines then possible causes could be: (1) smaller effective population sizes in non-passerines, (2) higher microsatellite mutation rates in passerines compared to non-passerines or (3) different life histories between passerine and non-passerines. (1) Using a database for North American birds (Partners in Flight Landbird Population Estimates Database, http://rmbo.org/pif_db/laped/default.aspx webcite, [64]), we found that passerines generally exhibited much larger population sizes than non-passerines (mean ± s.e. individuals per population = 15,524,224 ± 1,950,522 for passerines and 2,789,765 ± 835,772 for non-passerines; independent samples t-test, t = 5.83, d.f. = 383, P < 0.0001). The higher mean population size of passerines may lead to them retaining more genetic variability than non-passerines. (2) Microsatellite mutation rates vary among species [34]. Microsatellites may mutate more rapidly in passerines than non-passerines and, as a result, passerines are more variable. (3) The typically longer generation time of non-passerines [65] is expected to result in a lower evolutionary rate [66]. In contrast, non-passerines generally display lower levels of extra-pair paternity (EPP) than passerines [67]. A high rate of EPP will increase the variance in male reproductive success and reduce the effective population size (Ne), and hence the level of genetic variability. However, the difference in male variance and the consequent effect on Ne will be relatively small.
Individual marker performance
Nineteen loci were polymorphic in a minimum of 50% of the eight passerine species tested (when all loci were assessed in a minimum of 4 individuals/species; Figure 5, Additional file 1). The best performing loci in passerines were CAM-13 and CAM-19, which were polymorphic in all eight passerine species tested (including zebra finch, Figure 5, Additional file 1). Seven further loci were polymorphic in seven of the eight passerine species tested (CAM-01, CAM-02, CAM-05, CAM-10, CAM-15, CAM-17 and CAM-20, Figure 5, Additional file 1). The poorest performing locus, CAM-22, failed to amplify in five passerine species (however, all non-passerines amplified; Figure 5).
Locus homology to bird EST/genic sequences
Seventeen of the 24 markers developed were homologous to a bird EST sequence and/or gene (all markers except CAM-02, CAM-03, CAM-04, CAM-09, CAM-12, CAM-22 and CAM-24; Table 2, Additional file 6). Homology to bird EST/genic sequences, which are expected to be most conserved, did not reduce the number of species found to be polymorphic. In fact, the opposite was true: markers homologous to EST/genic bird sequences were more polymorphic across bird species (χ2 = 11.77, d.f. = 1, P = 0.006). This is in accordance with evidence from previous studies, which have failed to show that microsatellite markers developed from non-EST sequences are more variable than those from ESTs [37,38].
Null alleles
For four species: Berthelot’s pipit, rifleman, Leach’s storm petrel and European roller, some of the polymorphic CAM and TG loci (n = 5–12) were additionally typed in 17–30 individuals from a single population and assessed for deviation from Hardy–Weinberg equilibrium and null allele frequencies estimated (Additional file 7). When the data from these four species was combined, there was no overall difference in the proportion of loci displaying high estimated null allele frequencies between the CAM and TG loci (χ2 =0. 0.001, d.f. = 1, P = 0.98; Additional file 7).
Additional file 7. Estimated null allele frequencies at CAM loci for six species.
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It is likely that null alleles will be more common in more distant species, especially when using primer sets that are less conserved (between chicken and zebra finch). If this happens, the amplified product could be sequenced and species-specific primer sets designed.
Chromosome locations and sex linkage
All individuals genotyped with the CAM loci were of known sex based on plumage characteristics or PCR sex-typing. The individuals genotyped included both males and females for each species. Males (ZZ) of all species amplified at all loci, indicating that no CAM loci were purely W-linked in any species.
All the predicted genome locations of these loci were autosomal except for locus CAM-11, which was predicted to be Z-linked (Figure 1). Genotypic evidence supported the suggested Z-linked status of this locus in every species in which it was polymorphic: zebra finch, house sparrow, Berthelot’s pipit, chaffinch, Eurasian bullfinch, rifleman, European roller and Leach’s storm-petrel (Additional file 1). All females were hemizygous whereas at least some males were heterozygous, 5–28 males and 3–22 females per species (regarding Leach’s storm-petrel, see below). In Leach’s storm-petrels, CAM-11 amplified both W and Z-linked alleles and could be used to sex-type individuals. Females were hemizygous, displaying one allele of size 113 bp (n = 22 females) and males were heterozygous or homozygous with observed allele sizes of 134, 136, 138 and 145 bp (n = 26 males). This suggests that the 113-bp allele is located on the W chromosome and the 134–145-bp alleles are located on the Z chromosome. The absence of an amplified Z-allele in females suggests that the 113-bp W allele is amplified in preference to the Z alleles that must also be present. This is expected to happen, for example, if the primers are a better match to the W locus than the Z locus. Upon re-examination, very weak Z alleles (peak heights of 97–288 relative fluorescence units (RFU)) were seen in some female chromatographs, supporting this hypothesis. These weakly-amplified female Z alleles were only observed when the peak height of the W allele was well over 2000 RFU (most over 6000 RFU) and they often failed to amplify at all when the sample was rerun. Locus CAM-11 may prove suitable for sex-typing other related species of Charadriiformes, such as petrels, albatrosses and shearwaters and this is under investigation.
Future directions for identifying conserved microsatellite markers
Since this study began, four additional avian genomes have been sequenced and assembled: the turkey (Meleagris gallopavo), mallard duck (Anser platyrhynchos), collared flycatcher (Ficedula albicollis) and budgerigar (Melopsittacus undulates; as of 10th February 2013; http://www.ensembl.org/ webcite). As the costs of sequencing whole genomes continue to fall, many more bird genomes will be sequenced in the near future, so providing an increasingly rich resource for developing conserved markers. For example, following the release of the turkey and mallard genome sequence, it is now possible to identify microsatellite markers that are conserved between the chicken, turkey and mallard, and design conserved primer sets that should then amplify in a wide range of galliform and anseriform species. There are approximately 250 living species of Galliformes, which are separated from their nearest order, the Craciformes (chachalacas, curassows, guans and megapodes), by a genetic distance (Δ Tm) of 21.6 [33]. Since the genetic distance between chicken and turkey is less than the difference between chicken and zebra finch (11.1 versus 28.0), it should be possible to create a much larger number of conserved markers for the Galliformes. However, because chicken and turkey are separated by a relatively small genetic distance (11.1), these sets would probably not be particularly highly conserved and would, therefore, be useful for only a subset of galliform species and few non–Galliformes. A comparison of zebra finch and turkey would not be expected to yield many additional new conserved microsatellite sequences, since the majority should have been identified in the zebra finch–chicken comparisons already performed (this study and Dawson et al. [21]). The approach used here can also be applied to the mallard genome sequence to identify highly conserved sequences and create markers (i.e. zebra finch–mallard markers) suitable for the majority of Anseriformes and Galliformes (via chicken–mallard, turkey–mallard and chicken–turkey–mallard markers).
Birds belong within the reptilian clade. Only two non-avian reptile genomes have been sequenced and assembled: the anole lizard (Anolis carolinensis) and Chinese softshell turtle (Pelodiscus sinensis) (http://www.ensembl.org/ webcite; as of 10th February 2013). The anole lizard is more closely related to birds than the turtle (http://www.ensembl.org/info/about/species_tree.pdf webcite). Only one CAM locus had an identifiable lizard homologue, which included a microsatellite containing at least eight repeat units and which matched to both sides flanking the repeat region (CAM-20), but even for this locus it is probably not possible to create a consensus bird–lizard primer set due to low sequence similarity.
This study and that of Dawson et al. [21] indicate that few (if any) conserved microsatellite markers will be usefully polymorphic across all bird species (passerines and non-passerines). There are 23 orders of extant birds that are separated by a genetic distance (DNA: DNA melting temperature (Δ Tm) hybridisation distance) of more than 20 [33], classification based on Sibley & Monroe [25]). This study and that of Dawson et al. [21] indicate that when the required (genome and/or EST) sequence data from each avian order becomes available, a conserved set of over 50 markers can be created that will be of high utility for all the species within that order. It is likely that future avian genome sequencing projects will include species originating from different bird orders and so facilitate the creation of conserved microsatellite marker sets suitable for genotyping and comparing multiple species.
Conclusions
We have successfully developed primer sets for 24 polymorphic microsatellite loci that are of high utility in passerine birds, with some utility in non-passerine species. The microsatellite markers described here are particularly useful for genotyping species closely related to the zebra finch, such as those belonging to the Passeridae and Fringillidae families, which encompass 1,383 species [25]). When these markers are combined with 34 conserved markers developed previously [21], the requirement to isolate microsatellite loci will be alleviated for most genetic studies of passerine birds. These conserved loci are suitable for many applications, including studies of population structure, parentage and relatedness; they can also contribute towards linkage mapping and the identification of gene order rearrangements among many species. The less polymorphic loci will be useful, where required, for distinguishing between species and identifying hybrid birds (such as occur naturally in warblers, flycatchers, petrels, ducks, owls and other raptors). These loci also have potential for studying the population genetics of extinct or highly endangered species in which it is difficult to develop microsatellite libraries due to the lack of sufficient (high-quality) DNA. Conserved markers can potentially be used to genotype samples from museum collections or from other non-invasive sources (such as mouth swabs or feathers). The loci will, in particular, enable the comparison of populations and species at the same loci, and so allow genetic variability to be compared directly, without ascertainment bias.
Abbreviations
BLAST: Basic Local Alignment Search Tool; bp: base pair; CAM: Conserved Avian Microsatellite; EST: Expressed sequence tag; He: Expected heterozygosity; Ho: Observed heterozygosity; HWE: Hardy–Weinberg equilibrium; ng: nanogram; PCR: Polymerase chain reaction; RFU: Relative fluorescence unit; Ta: Annealing temperature; TG: Taeniopygia guttataGallus gallus conserved microsatellite markers; Tm: Melting temperature
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
DAD coordinated the project, designed and completed the analyses and wrote the manuscript. RE and JS performed the data mining to identify numbers and frequencies of different microsatellites in the zebra finch and chicken genomes. JS identified and extracted suitable zebra finch genomic sequences and their chicken homologues from which to design the primers. ADB designed the primer sets. ADB, LGS, GJH, JP, DM-G, MM-M, AWJB, and SAJP tested primer sets in various species. LGS, IRKS and TB assisted with the analyses. ADB, LGS, DM-G, IRKS, JS and TB contributed to writing the manuscript. All authors read and approved the final manuscript.
Acknowledgements
We thank those who collected or supplied tissue samples, or extracted DNA (identified in Table 4). We are grateful to Rob Freckleton who kindly assisted with analyses. This work was funded by the UK Natural Environment Research Council and the UK Biotechnology and Biological Sciences Research Council.
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Research article
A before and after study of the impact of academic detailing on the use of diagnostic imaging for shoulder complaints in general practice
Norm A Broadhurst1, Christopher A Barton2*, Debra Rowett3, Lisa Yelland2, David K Martin1, Angela Gialamas2 and Justin J Beilby2
Author Affiliations
1 Department of Orthopaedics, Finders University, Bedford Park, South Australia, Australia
2 Discipline of General Practice, School of Population Health and Clinical Practice, University of Adelaide. Adelaide, South Australia. Australia
3 DATIS, Repatriation Hospital, Daw Park, South Australia. Australia
For all author emails, please log on.
BMC Family Practice 2007, 8:12 doi:10.1186/1471-2296-8-12
The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2296/8/12
Received:3 May 2006
Accepted:27 March 2007
Published:27 March 2007
© 2007 Broadhurst et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
The aim of this study was to assess the impact that Academic Detailing (AD) had on General Practitioners' use of diagnostic imaging for shoulder complaints in general practice and their knowledge and confidence to manage shoulder pain.
Methods
One-to-one Academic Detailing (AD) for management of shoulder pain was delivered to 87 General Practitioners (GPs) in metropolitan Adelaide, South Australia, together with locally developed clinical guidelines and a video/DVD on how to examine the shoulder. Three months after the initial AD a further small group or an individual follow up session was offered. A 10-item questionnaire to assess knowledge about the shoulders was administered before, immediately after, and 3 months after AD, together with questions to assess confidence to manage shoulder complaints. The number of requests for plain film (X-ray) and ultrasound (US) imaging of the shoulder was obtained for the intervention group as well as a random comparison group of 90 GP's from the same two Divisions. The change in the rate of requests was assessed using a log Poisson GEE with adjustment for clustering at the practice level. A linear mixed effects model was used to analyse changes in knowledge.
Results
In an average week 54% of GPs reported seeing fewer than 6 patients with shoulder problems. Mean (SD) GP knowledge score before, immediately after and 3-months after AD, was 6.2/10 (1.5); 8.6/10 (0.96) and; 7.2/10 (1.5) respectively (p < 0.0001). Three months after AD, GPs reported feeling able to take a more meaningful history, more confident managing shoulder pain, and felt their management of shoulder pain had improved. Requests for ultrasound imaging were approximately 43.8% higher in the period 2 years before detailing compared to six months after detailing (p < 0.0001), but an upward trend toward baseline was observed in the period 6 months to 1 year after AD. There was no statistically significant change in the rate of requests from before to after AD for plain-radiographs (p = 0.11). No significant changes in the rate of requests over time were observed in the control groups.
Conclusion
These results provide evidence that AD together with education materials and guidelines can improve GPs' knowledge and confidence to manage shoulder problems and reduce the use of imaging, at least in the short term.
Background
Shoulder pain is third following back and neck pain as a musculoskeletal reason for presenting to general practice in Australia. Approximately 10% of the adult population are expected to visit a General Practitioner (GP) for shoulder pain at least once in a lifetime [1,2].
Despite the finding that 50% of acute shoulder pain resolves in 8–10 weeks many patients present with the anticipation of having some kind of imaging [3,4]. There are a range of diagnostic imaging tests that can be used in the evaluation of shoulder pain including plain radiographs, arthrography, computed tomography, ultrasound, and magnetic resonance imaging [5]. The history and physical examination are keys to most shoulder pain diagnoses, particularly when used in combination. Often no imaging is required, or plain radiographs are the sole imaging study needed [5].
Over recent years the Diagnostic Imaging Section of the Australian Government Department of Health and Ageing identified a marked increase in the use of ultrasound imaging for problems relating to the shoulder. The increase in the number of ultrasounds performed for shoulder complaints have been at considerable cost to the Commonwealth Health Insurance Commission (HIC). In the year to April 2002, the cost increased by 110% to $12.9 million. The number of x-ray and ultrasound services performed in 2001–02 when compared with the previous year also increased by 110% to 152,073 investigations. GPs in Australia are unable to order magnetic resonance imaging (MRI) and so these costs are not considered here.
A project devised in three parts was initiated by the Musculoskeletal Ultrasound Project Team of the Australian Government Department of Health and Ageing and operated through the auspices of the Musculoskeletal Foundation of Australia. Stage I was to determine what was written by GPs on imaging request forms and then to compare this with the radiologist's report. This study found that about one third (34%) of requests for ultrasound imaging of the shoulder contained no tangible information to assist the radiological examination [6]. When a clinical diagnosis was provided by a GP, the degree of accuracy with the ultrasound findings was only 22%.
The results from Stage II [7] showed most imaging is ordered at the first visit of the patient presenting with shoulder pain, with the majority of patients having imaging ordered within five weeks of the first GP visit. Age (45–65 years), pain on activity, and shoulder pain present for ≥ 5 weeks increased the likelihood for a person to have imaging. Imaging (results similar in both Stage I and Stage II) revealed some pathology in 75% of patients.
The preliminary work completed in Stage I and Stage II provided good evidence that guidelines for imaging of shoulder complaints need to be established, and that GPs might benefit from education about management of shoulder problems. Stage III of the study presented here, sought to improve the assessment and management of shoulder complaints through the use of Academic Detailing to GPs, and to improve the knowledge and confidence of GPs to manage shoulder pain.
Methods
Ethics approval was granted from the University of Adelaide Human Research Ethics Committee on 19 November 2003.
A 'before and after' study design was implemented involving two metropolitan divisions of General Practice (The Adelaide Central and Eastern (ACE) Division and the Western Division of General Practice (WDGP) who assisted the study team to recruit General Practitioners from the membership lists of these Divisions. GPs were eligible to participate if they were members in one of these Divisions and were working ≥ 0.5 full time equivalent (FTE). All GPs in the two Divisions who met the selection criteria were invited to participate.
GPs interested in participating in the study faxed a signed agreement to the Drug and Therapeutic Information Service (DATIS) at the Repatriation General Hospital, South Australia who made appointments with the GPs for Academic Detailing.
Details of academic detailing
Two Specialists provided the Academic Detailing to GPs (NB and DM), at the GPs practice between December 2004 and March 2005.
Arrangements for Academic Detailing were coordinated through the DATIS Director (DR) and her staff, who are recognised experts in the field of Academic Detailing. The Detailers (NB and DM) provided one to one guidance to GPs on how to correctly assess the shoulder, and after having corrected the technique the GP was provided with education materials that included a DVD and guidelines (see Additional file 1). These were left with the GPs to be used during future patient assessments. The Detailing session lasted from 45 to 60 minutes.
Additional File 1. A guideline for shoulder imaging developed in consensus by 6 orthopaedic surgeons. Guidelines developed for the study for use by GPs to manage shoulder pain.
Format: DOC Size: 893KB Download file
This file can be viewed with: Microsoft Word Viewer
At the initial AD visit each GP received:
• The reason for and the objectives of the study
• An evidence-based outline for shoulder imaging
• A video/DVD on the anatomy and examination of the shoulder. The Detailer used the video as a guide during an active demonstration on how to examine the shoulder.
• A reference information sheet to aid the management of patients with shoulder pain (see Additional file 1).
Three months after the initial AD a follow up session was offered either in small groups or on a one-to-one basis.
Questionnaires
Demographic information about the GP and the practice they work in was collected by questionnaire. GPs then completed a ten-item questionnaire to determine knowledge about identifying and managing shoulder problems (see Additional file 2). The knowledge questionnaire was repeated immediately after the detailing, and again at the follow up visit when GPs also completed a 27-item questionnaire regarding confidence to manage shoulder problems and satisfaction with the AD model.
Additional File 2. Assessment of knowledge about musculoskeletal problems of the shoulder. The questionnaire used in the study to assess GP knowledge about management of shoulder pain.
Format: DOC Size: 35KB Download file
This file can be viewed with: Microsoft Word Viewer
Questions asked referred to:
• The project generally;
• Assessment of study materials
• Assessment of the AD presentation
• Use of treatment modalities as a consequence of the Detailing.
Imaging request data
The number of requests for plain film (Medicare Benefits Schedule Item number 57703) and US imaging (Medicare Benefits Schedule item number #55808) of the shoulder was provided by the HIC for all GPs on a month-by-month basis for the period January 2001 to March 2005.
Imaging requests were also obtained for a comparison group of 90 randomly selected GPs from the Adelaide Central and Eastern Division of General Practice (60 GPs), and the Western Division of General Practice (30 GPs) membership list.
Statistical analysis
Data was initially entered into a Microsoft Access database and then transferred to SPSS version 12.0 for data cleaning purposes and preliminary data analysis. Frequency and range checks were carried out to ensure quality of data entry. Further statistical analysis was undertaken using SAS version 9.1 (Cary, NC, USA).
Demographic data and data collected from the confidence to manage shoulder problems questionnaire were analysed descriptively using frequencies. GP knowledge scores were analysed using a linear mixed effects model to investigate whether there was a change in knowledge across the three different testing times. Practice was included as a random effect and the model allowed for heterogeneity of variances across the testing times.
A log Poisson GEE was fitted to the HIC data of monthly imaging requests to investigate whether there was a change in the rate of requests made over four time periods of interest (period 1 = two year period before academic detailing, period 2 = month of Detailing, period 3 = six month period after Detailing, and period 4 = six month period after time period 3) and whether this change was different in the AD and control groups. Adjustment for clustering was made at the practice level. In order to define the four time periods of interest for a control GP, an 'Academic Detailing' month had to be assigned. This assignment was made randomly and ensured that within each division, an approximately equal percentage of GPs in the control and AD groups were assigned to each month in which AD was carried out. Results were adjusted for month since the data exhibited seasonal variation.
A p-value ≤ 0.05 was required for statistical significance.
Results
Of the 369 ACE Division GPs 59 (16%) agreed to participate and out of 247 GPs in the WDGP 33 (13%) participated. Five GPs who initially responded to the invitation to participate either withdrew consent or were unable to complete the study leaving a total of 87 for the final analysis. Approximately half of GPs reported seeing fewer than 6 patients with shoulder problems a week. Further demographic details of the GPs can be found in Table 1.
Table 1. Demographic details of participating General Practitioners1.
Figure 1 shows the time-adjusted rate of requests for plain x-ray and ultrasound made by GPs in the two years before the study (Time period 1), during the month of AD (Time period 2), in the six months immediately after AD (Time period 3), and in the next six-month period (Time period 4). There was no evidence to suggest a change in the rate of requests over the different time periods for plain x-ray in the intervention group compared to the control group (P = 0.11). Figure 1 also shows the time-adjusted rate of requests for ultrasound made by intervention and control group GPs. There is strong evidence to suggest that changes in the rate of requests over time periods were different for the AD and control groups (p = 0.02). The rate ratio describes the ratio of the rate of an event in one group to the rate in another group. In this context, we can use the rate ratio to compare the rate of requests between the AD and control groups, or during different time periods within the same group. Post hoc testing indicates that the estimated rate ratio comparing time 1 to time 3 for the AD group is 1.438 (p < 0.0001). This means that requests were approximately 43.8% more frequent during time 1 compared to time 3 in the academic detailing group, after adjusting for everything else in the model.
Figure 1. Adjusted rates of requests by time for plain shoulder x-ray (MBS Item 57703) and ultrasound (MBS Item 55808). Time Period 1 represents the two-year period before academic detailing; 2) represents the month of academic detailing; 3) represents the six-month period after academic detailing; 4) represents the six-month period after time 3. † – Time Period 3 compared with Time Period 1 in the Academic Detailing group (p < 0.01). †† – Time Period 4 compared to Time Period 3 in the Academic Detailing group (p = 0.036).
However, the estimated rate ratio comparing time 3 to time 4 is 0.80413 (p = 0.036). This means that requests were approximately 19.6% less frequent during time 3 compared to time 4 in the academic detailing group, after adjusting for everything else in the model. This indicates that in the period 6 months to 1 year after the academic detailing, the number of requests for ultrasound trended significantly upward toward baseline, but still tended to be less frequent than prior to the academic detailing, although this did not reach statistical significance (time 1 vs time 4, p = 0.13) (Table 2).
Table 2. Post Hoc testing of adjusted imaging rates for ultrasound (MBS item 55808).
There were no other statistically significant differences in the rate of requests, either comparing time periods within treatment groups or comparing AD and control at each time period (Table 2).
The mean (St Dev) GP knowledge before detailing was 6.2/10 (1.5). Immediately after the detailing, this rose to 8.6/10 (0.96). Three months after the detailing, knowledge remained higher compared to pre-test knowledge (7.2/10 (1.5). There was very strong evidence of a change in knowledge amongst the 87 GPs over the three testing times (p < 0.0001) and post hoc analyses revealed significant differences in mean scores between each pair of testing times (p < 0.0001 in each case). Knowledge was greatest immediately after academic detailing, and remained significantly higher than baseline 3 months after academic detailing.
There was no evidence to suggest that any of the demographic variables had an effect on the average test score, except for the total number of patients per week (p = 0.0496). However, the post hoc analysis did not reveal a clear relationship between the total number of patients per week and average knowledge score and this result is considered an artefact.
Three months after academic detailing most GPs reported feeling able to take a more meaningful history, felt more confident managing shoulder pain, and felt that their management of shoulder pain had improved (Table 3).
Table 3. GPs confidence to manage musculoskeletal problems three months after participating in academic detailing
Discussion
The major goal of this study was to reduce the number of referrals for shoulder imaging, and this was achieved in the first six months after academic detailing for ultrasound imaging of the shoulder, but not for x-ray imaging. However, over the next six month period this could not be sustained and the frequency of requests for ultrasound imaging returned toward pre-academic detailing levels. While these GPs had increased knowledge and were more confident in managing shoulder pain, this was in contrast to the trend toward baseline in the number of imaging requests seen 12 months after detailing.
An assessment as to why GP's gravitated to their pre-AD level of practice in respect to managing shoulder pain is needed. Failure to maintain the reduced use of ultrasound could be due to limited exposure to patients with shoulder pain; time restraints in general practice that might lead to regression after the initial encouragement; or the threat of patient dissatisfaction or even legal challenge, therefore unnecessary imaging is ordered in the absence of a confident assessment. The later point may reflect declining confidence in assessment with time, as indicated by the decay in knowledge, and increasing use of ultrasound six months to one year after the initial academic detailing.
While previous studies on musculoskeletal management have shown deficiencies in the management of patients with pain in general practice, this study has established potential cost savings in the short term, from reduced use of ultrasound imaging. A more detailed and concentrated educational program might be necessary to sustain changes observed in imaging use for management of shoulder problems.
Guidelines for managing some musculoskeletal problems are well known and have a proven cost benefit [8-12]. The cost savings per item number from this study based on a 40% decrease in 6 months translates to a saving of ~$7000 per doctor per year. The big question would be whether a detailed educational program on shoulder management would be cost effective and enduring?
Limitations of the study
The primary limitation of this study is the low participation rate (16% in ACE Division and 13% in the WDGP). Those GPs that did participate were self-selected and so it is possible that they had a special interest in musculoskeletal problems. An inspection of the number of imaging requests made per month indicate that GPs who volunteered for academic detailing requested more imaging than control group GPs who did not volunteer to participate in academic detailing. However, there was a large range in the number of patients that GPs reported as presenting with shoulder complaints in an average week. Hence, it is likely that some of the GPs in this study had a special interest in musculoskeletal problems, but clearly not all did. A second limitation is that we did not evaluate whether our intervention actually made the use of imaging more appropriate according to the guideline. A final limitation relates to repeated testing of knowledge. Since the same questions were asked at each testing time, there may have been a learning effect.
Conclusion
Academic Detailing has proven to be a means of containing shoulder imaging use in the short term. Further research is required to determine if the increase in knowledge and confidence for managing shoulder problems translates into better clinical management as well as reducing cost in the long term, while not compromising health outcomes and quality of life.
Competing interests
The author(s) declare that they have no competing interests.
Authors' contributions
NB was involved in conception and design, gaining funding, he developed study materials including guidelines and Academic Detailing materials, performed Academic Detailing, oversaw day-to day management of the project, provided insight to data analysis, and helped draft the manuscript. CB provided day-to-day management of project, sought ethics approvals, recruited GP participants, entered and analysed data, provided insight to data analysis, and helped draft the manuscript. DR was involved in conception and design, provided advice on the Academic Detailing program, co-ordinated delivery of Detailing, and provided insight to data analysis. LY performed advanced statistical analyses and interpretation and helped draft the manuscript. DM helped develop Academic Detailing materials and performed Academic Detailing. AG was involved in conception and design, gaining ethics approval and recruiting GPs prior to going on maternity leave. JB was involved in conception and design, gaining funding and provided insight to data analysis. All authors read and approved the final manuscript.
Acknowledgements
Funded by the Diagnostic Imaging Reform Implementation Package, Diagnostic Imaging Section, the Australian Department of Health and Ageing.
We would like to thank Donna Logan from the Drug and Therapeutics Information Service for her assistance with organisation of the Academic Detailing sessions. Don Allan and Janette Bridger from the Adelaide Central and Eastern Division of General Practice assisted with recruiting and liaising with GPs in this Division. We also thank Catherine Trott and Arie Bansemer, from the Western Division of General Practice for assistance liaising with GPs in the Western Division of General Practice.
References
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BMJ 2005, 331:1124-1128. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
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Br J Gen Pract 1996, 46:309-316. PubMed Abstract | PubMed Central Full Text
3. van der Heijden GJ: Shoulder disorders: a state of the art review.
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4. van der Windt DA, Koes BW, Boeke AJ, Deville W, De Jong BA, Bouter LM: Shoulder disorders in general practice: the prognostic indicators of outcome.
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Aust Fam Physician 2004, 33(8):668-669. PubMed Abstract | Publisher Full Text
7. Broadhurst NA, Gialamas A, McElroy HJ, Beilby JJ: How do Australian GP’s manage shoulder dysfunction?
Aust Fam Physician 2004, 33 (10):861-2, 864. PubMed Abstract | Publisher Full Text
8. Hoffman JR, Wolfson AB, Todd K, Mower WR: Selective cervical spine radiography in blunt trauma: methodology of the national Emergency X-radiography Utilizatio Study (NEXUS).
Ann Emerg Med 1998, 32(4):461-469. PubMed Abstract | Publisher Full Text
9. Spitzer WO, Skovron ML, Salmi LR, Cassidy JD, Duranceau J, Suissa S, Zeiss E: Scientific monograph of the Quebec Task Force on Whiplash-Associated Disorders: redefining "whiplash" and its management.
Spine 1995, 20(8 Suppl):1S-73S. PubMed Abstract
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12. Stiell IG, Wells GA, Vandemheen KL, Clement CM, Lesiuk H, De Maio VJ, Laupacis A, Schull M, McKnight RD, Verbeek R, Brison R, Cass D, Dreyer J, Eisenhauer MA, Greenberg GH, MacPhail I, Morrison L, Reardon M, Worthington J: The Canadian C-Spine Rule for radiography in alert and stable trauma patients.
JAMA 2001, 286(15):1841-1848. PubMed Abstract | Publisher Full Text
Pre-publication history
The pre-publication history for this paper can be accessed here:
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Pre-publication history
Repeated Aspergillus isolation in respiratory samples from non-immunocompromised patients not selected based on clinical diagnoses: colonisation or infection?
Jose Barberan*, Bernardino Alcazar, Eduardo Malmierca, Francisco Garcia de la Llana, Jordi Dorca, Daniel del Castillo, Victoria Villena, Melissa Hernandez-Febles, Francisco-Javier Garcia-Perez, Juan-Jose Granizo, Maria-Jose Gimenez, Lorenzo Aguilar and on behalf of the ASP Investigator Group
BMC Infectious Diseases 2012, 12:295 doi:10.1186/1471-2334-12-295
Pre-publication versions of this article and reviewers' reports
Original Submission - Version 1 Manuscript 21 Mar 2012
Reviewer's Report Jesus Guinea 21 Apr 2012
Reviewer's Report Ritesh Agarwal 23 May 2012
Resubmission - Version 2 Manuscript Author's comment 06 Sep 2012
Reviewer's Report Ritesh Agarwal 23 Sep 2012
Editor's comment Editor's comment 06 Nov 2012
Editorial acceptance 07 Nov 2012
Published 12 Nov 2012
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Research article
Immunohistochemical analysis based Ep-ICD subcellular localization index (ESLI) is a novel marker for metastatic papillary thyroid microcarcinoma
Tada Kunavisarut1,6, Ipshita Kak1, Christina MacMillan2, Ranju Ralhan1,2,3,5,7* and Paul G Walfish1,2,3,4,5,7
Author affiliations
1 Alex and Simona Shnaider Laboratory in Molecular Oncology, Department of Pathology & Laboratory Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 60 Murray Street, Suite L6-304, Toronto, ON, M5T 3L9, Canada
2 Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, 600 University Avenue, Room 6-423, Toronto, ON, M5G 1X5, Canada
3 Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology-Head and Neck Surgery, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada
4 Department of Medicine, Endocrine Division of Mount Sinai Hospital and University of Toronto Medical School, Toronto, ON, M5G 1X5, Canada
5 Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, ON, M5G 2N2, Canada
6 Department of Medicine, Division of Endocrinology and Metabolism, Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand
7 Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology-Head and Neck Surgery Program, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, 600 University Avenue, Room 413, Toronto, ON, M5G 1X5, Canada
For all author emails, please log on.
Citation and License
BMC Cancer 2012, 12:523 doi:10.1186/1471-2407-12-523
Published: 15 November 2012
Abstract
Background
Thyroid cancer is among the fastest growing malignancies; almost fifty-percent of these rapidly increasing incidence tumors are less than or equal to 1cm in size, termed papillary thyroid microcarcinoma (PTMC). The management of PTMC remains a controversy due to differing natural history of these patients. Epithelial cell adhesion molecule (EpCAM) is comprised of an extracellular domain (EpEx), a single transmembrane domain and an intracellular domain (Ep-ICD). Our group reported nuclear Ep-ICD correlated with poor prognosis in thyroid cancer (Ralhan et al., BMC Cancer 2010,10:331). Here in, we hypothesized nuclear and cytoplasmic accumulation of Ep-ICD and loss of membranous EpEx may aid in distinguishing metastatic from non-metastatic PTMC, which is an important current clinical challenge. To test our hypothesis, Ep-ICD and EpEx expression levels were analyzed in PTMC and the staining was correlated with metastatic potential of these carcinomas.
Methods
Thirty-six PTMC patients (tumor size 0.5 - 1cm; metastatic 8 cases and non-metastatic 28 cases) who underwent total thyroidectomy were selected. The metastatic group consisted of patients who developed lymph node or distant metastasis at diagnosis or during follow up. The patients’ tissues were stained for Ep-ICD and EpEx using domain specific antibodies by immunohistochemistry and evaluated.
Results
PTMC patients with metastasis had higher scores for nuclear and cytoplasmic Ep-ICD immunostaining than the patients without metastasis (1.96 ± 0.86 vs. 1.22 ± 0.45; p = 0.007 and 5.37 ± 0.33 vs. 4.72 ± 1.07; p = 0.016, respectively). Concomitantly, the former had lower scores for membrane EpEx than the non-metastatic group (4.64 ± 1.08 vs. 5.64 ± 1.51; p = 0.026). An index of aggressiveness, Ep-ICD subcellular localization index (ESLI), was defined as sum of the IHC scores for accumulation of nuclear and cytoplasmic Ep-ICD and loss of membranous EpEx; ESLI = [Ep − ICDnuc + Ep − ICDcyt + loss of membranous EpEx]. Notably, ESLI correlated significantly with lymph node metastasis in PTMC (p = 0.008).
Conclusion
Nuclear and cytoplasmic Ep-ICD expression and loss of membranous EpEx were found to correlate positively with metastasis in PTMC patients. In addition, ESLI had the potential to identify metastatic behavior in PTMC which could serve as a valuable tool for solving a current dilemma in clinical practice.
Keywords:
ESLI; EpCAM; Ep-ICD; EpEx; Papillary thyroid Microcarcinoma; Aggressiveness; Metastatic
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Research article
Can a "good death" be made better?: A preliminary evaluation of a patient-centred quality improvement strategy for severely ill in-patients
Jeff Powis1, Edward Etchells1*, Douglas K Martin2, Susan K MacRae2 and Peter A Singer2
Author Affiliations
1 Department of Medicine, University of Toronto, Sunnybrook and Women's College and Health Sciences Centre, 2075 Bayview Avenue, Room C410, Toronto, ON, Canada, M4N 3M5
2 University of Toronto Joint Centre for Bioethics, 88 College Street, Toronto, ON, Canada, M5G 1L4
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BMC Palliative Care 2004, 3:2 doi:10.1186/1472-684X-3-2
The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1472-684X/3/2
Received:26 January 2004
Accepted:23 May 2004
Published:23 May 2004
© 2004 Powis et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
Abstract
Background
Prior studies attempting to improve end-of-life care have focused on specific outcomes deemed important to healthcare providers, with disappointing results. Improvement may be best achieved by identifying concerns important to individual patients, communicating the patients' concerns to the treating medical team, and repeating the process frequently until all concerns are addressed. Our objective was to conduct a preliminary evaluation of this innovative patient-centred quality improvement strategy.
Methods
Initial interviews elicited participants' ideas for improvement, which were then fed back to health care providers by the study investigator. A rapid-cycle change model ensured frequent reassessment and continued feedback. The study involved 36 seriously ill, hospitalized patients on teaching general medical inpatient units of a tertiary care hospital. The main outcome measure was participants' ratings of satisfaction within different domains of care on follow-up interviews.
Results
The proportion of participants who rated various aspects of their care as "excellent" or "very good" on initial interview was 72% for overall care, 64% for symptom control, 66% for level of support, and 75% for discussions about life sustaining treatments. Patients and families identified many actionable steps for improvement such as; better control of pain and shortness of breath, better access to physicians and medical information, more help with activities of daily living, improving the patient's environment, and shorter waits for nursing care, diagnosis, and treatment. Following feedback to the clinical team, participants reported improvement in overall care (32%), symptom control (44%), and support (40%). Only a minority had further discussions about life sustaining treatments.
Conclusion
A patient-centred approach using rapid-cycle change was feasible and shows promise for improving the quality of end-of-life care. It should be evaluated on a larger sample in a controlled trial.
Keywords:
Patient-centred; end-of-life care; quality improvement
Background
Implicit in the question, "What is a good death?" is the question of how to make deaths better. Prior studies of quality improvement in end-of-life care have focused on specific outcomes deemed to be important from the providers' perspective, such as reducing time to first dose of analgesic, educating patients about pain control, or increasing the completion rate of advance directives [1-6]. The largest of these studies, the SUPPORT trial, was unable to demonstrate a significant change in outcome measures dealing primarily with life-sustaining treatment decisions. The focus of the study dealt with physicians' concerns related to end-of-life care. These concerns formed the basis for discussions between study nurses and patients, while patients' concerns were not specifically addressed. In a SUPPORT substudy focused on pain control, a pain intervention was designed, but very few patients received measurable changes in their pain management, and the study was negative [3].
Improvement in end-of-life care may arguably be best grounded in the perspective of individual patients and their families by focusing on issues considered important to them [7-12]. Almost two decades ago Julia Neuberger, former Chief Executive of the King's Fund, met with seriously ill patients in a Boston hospital to identify their concerns and personally fed back these concerns to the medical team and hospital administration (Neuberger J, Personal communication). This strategy involving rapid feedback of individual patients' preferences through direct discussions with the treating medical team has never been formally studied within end-of-life care.
We set out to test the feasibility and potential impact of such a strategy, so we chose a rapid-cycle improvement design involving frequent reassessment and feedback [13]. Our objective was to determine whether this type of patient-centred improvement strategy, with more direct and intense feedback of patient's preferences, might be associated with better patient satisfaction with end of life care. If the results of this preliminary evaluation were encouraging then a larger controlled study would be warranted.
Methods
Participants and setting
This prospective study was conducted in January, February, and April 2002 on the general medical inpatient teaching units at Toronto's University Health Network (UHN), Western Site. A Palliative care consult service was involved in patient care if requested by the treating medical team and continued to provide usual care during the study period. Eligible participants were required to have an estimated prognosis of less then one year, and needed to be aware of their diagnosis and estimated prognosis. The potential participant's prognosis was estimated by the treating medical team. If the participant was unable to respond appropriately to the interviewer (JP) on two separate occasions, a family member or close friend was interviewed instead.
Sampling and sample size
We approached 63 consecutive potentially eligible participants during the study period. Six did not meet eligibility criteria: one patient's prognosis on further testing was deemed to be greater than one year and five patients were incapable yet did not have family members or close friends to interview. Another 21 refused for the following reasons: too tired (5), too busy dealing with their illness (5), not yet ready to talk about their illness (5), and miscellaneous reasons (6). Therefore, our study sample comprised 36 participants.
Strategies for improvement
We used information from patients and families to stimulate change. First, we encouraged patients and families to reflect on their experience and needs [14,15]. Second, we identified specific aspects of care that the patients and families felt were high priority for improvement. Third, we relayed this information to the treating senior medical resident and nursing team leader. A medical resident (JP) who had recently worked on the unit relayed the information. No specific advice was given to caregivers on how to best address each participant's concern. For example, in one interview we determined that a patient's eyes were sore; we informed the treating team the patient's eyes were sore, not how to treat the sore eyes. Finally, follow-up interviews sought participants' views about changes in their care, as well as any new suggestions for feedback. Health care providers and participants were very receptive to the feedback process.
Data collection
One investigator (JP) interviewed all participants. We used a previously developed patient-centred taxonomy of care as a framework for interviews [7]. The interview guide included questions regarding the participants' satisfaction with overall care, symptom control, support from the healthcare team and discussions about life sustaining treatments. Each domain was addressed by both open-ended questions as well as asking the participant to rate their satisfaction on a scale from "excellent" to "poor", or on follow-up interviews "better", "same", or "worse". Follow-up interviews were conducted approximately every four days and were continued until the patient was discharged, declined further interview, or died. An interpreter was used with non-English speaking participants. All interviews were audiotaped and transcribed. Initial interviews took approximately 30–60 minutes; follow-up interviews approximately 15–30 minutes; and feedback to caregivers took approximately 15–30 minutes.
Analysis of data
We listed the concerns identified by the patients and families at initial interview, then grouped these concerns by theme, using content analysis [16]. We summarized the number of patients rating their care as improved, unchanged, or worse after each cycle of interviews and feedback. The main measure of improvement was patient or family ratings of care.
Research ethics
This study was approved by the UHN Committee for Research on Human Subjects. All participants provided written informed consent.
Results
The baseline demographics of the 36 participants are shown in Table 1.
Table 1. Characteristics of participants
Two participants withdrew because they were too tired to continue with the questioning. Of the remaining 34, 13 patients died in hospital, 20 patients were discharged, and one was alive in hospital at the end of the study period. After the initial interview 6 patients were discharged and 3 died, leaving 25 participants who underwent the first follow-up interview. Eleven patients were discharged and 4 died after the first follow-up interview, leaving 10 participants for the second follow-up interview (See Figure 1).
Figure 1. Patient follow-up during study period
Initial interview
The average number of days from admission to initial interview was 10. Patients were interviewed alone 33% (12 of 36) of the time, families were interviewed alone 58% (21 of 36) and patients and families were interviewed together 8% (3 of 36) of the time. Satisfaction with end-of-life care on the initial interview is shown in Figure 2. The proportion of participants who rated various aspects of their care as "excellent" or "very good" was 72% for overall care, 64% for symptom control, and 66% for level of support. The median response for all domains was "very good". 20 (57%) of the participants reported discussions with their treating team about what treatments they might want if they were to get sicker. Of these, 75% rated their satisfaction with these discussions as "excellent" or "very good". The median response was "very good". Of the 16 individuals who did not have discussions about life sustaining treatment issues at the time of initial interview only 2 requested further discussions as a point for feedback.
Figure 2. Participants' ratings of satisfaction with care at time of initial interview
The initial concerns or issues raised by the participants and relayed to the health care team are grouped according to theme as shown in Table 2.
Table 2. Participant priorities for improving care
First follow-up interview
The follow-up data for overall care, symptom control and support are shown in Figure 3. Following feedback to the clinical team, participants reported improvements in overall care (32%), symptom control (44%), and support (40%). One participant rated their initial satisfaction with symptom control as being excellent, yet at follow-up interview felt it was worse because of the new onset of painful oral ulcers.
Figure 3. Participants' evaluation of the change in care at time of follow-up interview one
Of the 25 participants who had at least one follow-up interview, only six reported subsequent discussions about life sustaining treatments. Five of the six rated their satisfaction with these discussions as the same, and one rated their satisfaction as better. Four of the six had identified the need for further discussions at the time of the initial interview.
Second follow-up interview
As shown in Figure 4, the responses from the second follow-up interview show less improvement but the trend continues for overall care with 30% of this small sample saying their care had improved, and only 10% saying it had worsened. There was no continued improvement for symptom control and support. Only three participants reported subsequent discussions about life sustaining treatment at second follow-up. Two of the three rated their satisfaction with discussions as the 'same', and one rated their satisfaction as better. Two of the three had identified the need for further discussions at the previous interviews.
Figure 4. Participants' evaluation of the change in care at time of follow-up interview two
Discussion
To our knowledge, this is the first evaluated attempt in a clinical setting to improve end-of-life care by combining rapid-cycle change and a patient-centred perspective. In our patient population we found plenty of room for improvement with 28% of patients and families reporting their satisfaction with overall care as only "good", "fair", or "poor." Patients and families identified actionable steps for improvement such as, better control of pain and shortness of breath, better access to physicians and medical information, more help with activities of daily living, improvement of the patient's environment and shorter waits for nursing care, diagnosis, and treatment. Our strategy was associated with improvements in ratings of overall care, symptom control, and support. We made little improvement in the area of discussions regarding life sustaining treatments as few patients asked for further discussions on life sustaining treatment issues and such discussions rarely occurred without feedback.
The reported improvement in multiple domains of end-of-life care in our study is in contrast to the disappointing results of previous trials to improve end-of-life care [3,4]. The largest of these studies, the SUPPORT trial failed to change physicians' behaviors or measurable outcomes [4]. One possible reason for the SUPPORT trials' lack of significant change was the untargeted focus on life-sustaining treatments or pain. By contrast, we focused on issues deemed important by individual patients, and found pent up concerns of dying patients and their families that had not been addressed by the standard provider-focused approach to end-of-life care. Few patients identified life sustaining treatment discussions as a priority, and for many of our patients, pain was not the primary symptom of concern. Our approach released patients' concerns into the care process allowing for individually important change to occur. We strived for frequent and complete feedback to our treating physicians. In the SUPPORT study, although complete feedback was the intent, only 34% of study physicians recalled receiving any feedback [3].
The rapid-cycle change model utilized in this study has had prior successes in end-of-life care. In 1997 the Institute for Healthcare Improvement and the Centre to Improve Care of the Dying used a rapid cycle change program to improve important processes of care, such as time from request to first dose of analgesia [1,2]. The flexibility of the rapid cycle change method may be well suited for the complexities of end of life care.
There are several limitations to this study. First, there is no concurrent control group so we do not know what participants' perceptions would have been in the absence of any intervention. In our attempt to initiate change we tested this innovative approach for feasibility and utility. It would have been premature to do a controlled trial, but now that we have defined a clear intervention it would be reasonable to proceed with such a study. Second, our data reflects the experiences of a small group of patients at a single hospital. However, despite the relatively small sample size, we were able to show that our innovative approach led to improvement. Third, the intervention and satisfaction assessments were performed by a single resident physician (JP) known to the healthcare staff. The positive effect of the intervention may reflect the popularity and enthusiasm of the interviewer. However, the interviewer (JP) used a standardized questionnaire to identify participant's concerns and acted simply as a conduit between participants and their caregivers. The changes in care were carried out by many different members of the healthcare team. We believe that the major impact was the feedback of patients' concerns, and the role of the individual interviewer was secondary. Finally, there were a relatively large number of potential participants (33.3%) who refused to participate. The number of refusals did not surprise us, as it is consistent with prior work with severely ill patients [1,2]. Many patients refused because they were too tired, too busy dealing with illness, or not read to talk about their illness. We suspect that these potential participants were not completely satisfied with their care, and would also have responded to a patient-centred quality improvement strategy
Our study tested the utility of an innovative initiative to induce change within end-of-life care. We found that our patient-centred approach using rapid cycle change was feasable and shows promise for improving the quality of end-of-life care. It should be evaluated on a larger sample in a controlled trial
Authors' contributions
JP interviewed all participants and communicated feedback to the treating medical teams. All investigators were involved in development of the quality improvement strategy, in data analysis and manuscript preparation.
Competing interests
None declared.
Acknowledgements
DKM is supported by an Ontario Ministry of Health and Long-Term Care Career Scientist award. PAS is supported by a Canadian Institutes of Health Research Distinguished Investigator award. This research project was support by The University Health Network and the University of Toronto Joint Centre for Bioethics. We would like to thank the staff on 8A, 8B and 3A Fell for their assistance in implementing participants' suggestions for improvement.
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Research article
Echinacea purpurea and osteopathic manipulative treatment in children with recurrent otitis media: a randomized controlled trial
Richard A Wahl1*, Michael B Aldous2, Katherine A Worden3 and Kathryn L Grant4
Author affiliations
1 Department of Pediatrics, University of Arizona, Tucson, Arizona, USA
2 Department of Pediatrics, Saltzer Medical Group, Nampa, Idaho, USA
3 Department of Osteopathic Manipulative Medicine, Midwestern University, Glendale, Arizona, USA
4 Department of Pharmacology, University of Arizona, Tucson, Arizona, USA
For all author emails, please log on.
Citation and License
BMC Complementary and Alternative Medicine 2008, 8:56 doi:10.1186/1472-6882-8-56
The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1472-6882/8/56
Received:2 May 2008
Accepted:2 October 2008
Published:2 October 2008
© 2008 Wahl et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
Recurrent otitis media is a common problem in young children. Echinacea and osteopathic manipulative treatment have been proposed as preventive measures, but have been inadequately studied. This study was designed to assess the efficacy of Echinacea purpurea and/or osteopathic manipulative treatment (OMT) for prevention of acute otitis media in otitis-prone children.
Methods
A randomized, placebo-controlled, two-by-two factorial trial with 6-month follow-up, conducted 1999 – 2002 in Tucson, Arizona. Patients were aged 12–60 months with recurrent otitis media, defined as three or more separate episodes of acute otitis media within six months, or at least four episodes in one year. Ninety children (44% white non-Hispanic, 39% Hispanic, 57% male) were enrolled, of which 84 had follow-up for at least 3 months. Children were randomly assigned to one of four protocol groups: double placebo, echinacea plus sham OMT, true OMT (including cranial manipulation) plus placebo echinacea, or true echinacea plus OMT. An alcohol extract of Echinacea purpurea roots and seeds (or placebo) was administered for 10 days at the first sign of each common cold. Five OMT visits (or sham treatments) were offered over 3 months.
Results
No interaction was found between echinacea and OMT. Echinacea was associated with a borderline increased risk of having at least one episode of acute otitis media during 6-month follow-up compared to placebo (65% versus 41%; relative risk, 1.59, 95% CI 1.04, 2.42). OMT did not significantly affect risk compared to sham (44% versus 61%; relative risk, 0.72, 95% CI 0.48, 1.10).
Conclusion
In otitis-prone young children, treating colds with this form of echinacea does not decrease the risk of acute otitis media, and may in fact increase risk. A regimen of up to five osteopathic manipulative treatments does not significantly decrease the risk of acute otitis media.
Trial registration
ClinicalTrials.gov Identifier: NCT00010465
Background
By age 3 years, most children (50–84%) experience at least one episode of acute otitis media (AOM). Recurrent otitis media is also common; 10% to 19% of children suffer 3 or more episodes during the first year alone [1]. In children with recurrent otitis media, conventional approaches to decreasing the risk of further episodes include prophylactic antibiotic therapy and surgical insertion of tympanostomy tubes to prevent accumulation of middle ear effusion. The effectiveness of these approaches is limited and controversial [2,3].
Complementary and alternative medicine (CAM) use in pediatric patients remains relatively common. One survey of parents at an urban pediatric emergency department reported an overall incidence of CAM use of 15%. Herbal remedies were used by 40% of those families that reported use of CAM modalities[4]. CAM approaches are often used for treatment of recurrent otitis media. A survey of pediatric clinic patients in Quebec revealed that ear, nose, and throat problems accounted for 24% of child visits to alternative medicine practitioners [5], and a survey of parents at a British pediatric otolaryngology clinic found that 29% reported CAM use, with echinacea and manipulative treatments frequently cited [6].
A recent report suggested a benefit of osteopathic manipulative treatment (OMT) in reducing episodes of AOM in otitis-prone children [7]. The osteopathic concept of recurrent otitis media postulates that predisposing structural dysfunction contributes to Eustachian tube dysfunction and is amenable to treatment with OMT, particularly in the cranial region [8-11].
Echinacea is an herb commonly used for treatment of upper respiratory tract infections. In vitro studies suggest a stimulatory effect of Echinacea purpurea preparations on various components of the immune system [12-14]. Several studies demonstrate improvement in the severity and duration of the common cold in adults treated with echinacea products [15]. Others, including the most rigorous study in children, show no benefit [16,17]. Because most episodes of AOM follow upper respiratory tract infections, it is plausible that treatment of such infections with echinacea might decrease the risk of subsequent AOM.
We conducted a randomized, double-blind, placebo controlled trial between 1999 – 2002 to assess the efficacy of echinacea treatment (at the time of upper respiratory infections) and OMT for the prevention of AOM in children with recurrent otitis media.
Methods
Definitions
No generally accepted diagnostic definition for AOM existed at the time of our study[18]. We defined AOM as an acute illness with at least one symptom (fever, rhinorrhea, cough, otalgia, irritability, lethargy, anorexia, vomiting, or diarrhea) and at least two otoscopic findings of middle-ear inflammation (injection, opacity, fullness, or impaired mobility) or purulent otorrhea. This definition is consistent with the later 2004 American Academy of Pediatrics guidelines on otitis media[19]. Recurrent otitis media was defined as at least 3 separate episodes of AOM within a 6-month period, or 4 episodes in one year. In order for episodes to be considered separate, the protocol required otoscopic documentation of resolution of one episode, or at least two weeks without symptoms following completion of antibiotic therapy, prior to onset of the subsequent episode.
Subjects
Children aged 12–60 months with recurrent otitis media (as documented in their medical records) were recruited from the Arizona Health Sciences Center Pediatric Clinic and from private pediatric offices in Tucson, Arizona. Children were excluded for unwillingness to participate, congenital malformations of the ears, nose, or throat (e.g., cleft palate), known or suspected allergy to echinacea, immune deficiency including HIV infection, or tuberculosis. Children taking prophylactic antibiotics or who had tympanostomy tubes in place were excluded from enrollment. The Arizona Health Sciences Center Pediatric Clinic serves an urban population, of which approximately 75% are covered by Medicaid.
Randomization
Randomization was done in blocks of eight using a random number table by a clinical pharmacist (KLG) having no contact with participants. Children were randomly assigned to one of four groups in a two-by-two factorial design. The first group received placebo extract orally and sham manipulation. The second group received Echinacea purpurea extract and sham manipulation. The third group received placebo extract and true OMT. The last group received Echinacea purpurea extract and true OMT. Sequentially numbered, indistinguishable bottles of echinacea or placebo were provided in advance. After informed consent was obtained, the parent was given the next bottle in sequence, and the pharmacist was telephoned to determine which of two osteopathic physicians was assigned (also determined randomly). The osteopathic physician independently contacted the pharmacist to learn whether a child was to receive sham or true osteopathic manipulative treatment. Children, families, and pediatricians were blinded to the group assignment of each subject.
Interventions
Children assigned to echinacea treatment received a 1:1 weight-to-volume 50% ethanol liquid extract of the fresh roots and dried mature seeds of Echinacea purpurea manufactured by Eclectic Institute, Inc. (Sandy, Oregon). All echinacea came from the same lot number, with an analysis by the manufacturer confirming 50% root and seed extract of Echinacea purpurea. A similar, identically labeled placebo prepared by Eclectic Institute contained 50% ethanol, 45% filtered water, food coloring and thickeners. Parents were instructed to give 0.5 ml orally 3 times daily for 3 days at the onset of cold symptoms, followed by 0.25 ml orally 3 times daily for 7 more days.
All children were scheduled for osteopathic sessions as soon as possible after entry, then 2, 4, 8, and 12 weeks later. At each visit, children assigned to OMT received diagnostic examinations and concurrent treatments as deemed necessary by the treating physician. Treatment modalities were limited to cranial osteopathy, balanced membranous/ligamentous tension, and/or myofascial release (applied directly or indirectly). These treatments consist of gentle manipulations of the cranium, pelvis, diaphragm, and other structures. No high velocity or thrusting maneuvers were performed. At the discretion of the osteopathic physician, an osteopathic percussion hammer could also be used for treatment, which allowed gentle vibration in tissues at variable frequencies. Children assigned to sham manipulation received an osteopathic examination only (palpation of the cranial bones and muscles and other structures) without treatment maneuvers.
The osteopathic physicians were well-respected members of the Tucson osteopathic community with practices restricted to manipulative treatment. All were members of the American Academy of Osteopathy and the Cranial Academy.
In addition to the study interventions, all parents received educational materials regarding otitis risk factors. If after enrollment a child received prophylactic antibiotics, otolaryngology referral, or tympanostomy tubes (usually for further recurrences of AOM), this information was recorded, but the child was allowed to remain in the study. Such decisions were made on clinical grounds by the treating clinician and were not influenced by the child's participation in the study.
Follow-up
After enrollment, children were prospectively followed for 6 months, with monthly telephone contact, and availability for evaluation 5 days per week by study pediatricians (MBA and RAW) if AOM was suspected. Children diagnosed with ear infection during weekends were asked to see one of the study physicians early the following week to confirm the diagnosis. In addition, children received otoscopic and physical examinations at entry, at 3 months, and at 6 months by study pediatricians, who were blinded to the treatment assignment of subjects.
Data collection
At enrollment, a questionnaire was used to collect information about the child's previous episodes of AOM, past medical history, cigarette smoke exposure, previous use of study alternative interventions, family history of allergy, and recurrent otitis media. The results of otoscopic and physical examinations were recorded at entry, 3, and 6 months, and at the time of any evaluation for possible AOM. At monthly telephone contacts, parents were asked if the child had any suspected or diagnosed ear problems during the previous month, and whether any side effects of the interventions were suspected. Parents were also asked at the 3- and 6-month visits whether they believed their child was receiving placebo for each study intervention.
Main outcome measures
The primary study outcome was the occurrence of a first episode of AOM during the study period as defined above. The final analysis was performed using only episodes of AOM that were sufficiently well documented in the medical record to meet the definition as described in the paper. A secondary outcome was the number of episodes of AOM. For this secondary outcome measure, all physician-diagnosed episodes of AOM were included, without respect to the case definition for AOM.
Analysis
Children were analyzed in the groups into which they were randomized. An initial analysis was done to determine if there was any important interaction between the effects of echinacea and OMT on the occurrence of AOM. Since none was found, the two interventions were considered independently. For each intervention, the cumulative incidence of AOM during follow-up was compared between treatment and placebo groups using chi-square analysis and the relative risk (RR) with 95% confidence interval (CI). P was considered significant at P < 0.05. The time to first episode of AOM was compared between groups using Kaplan-Meier analysis and the log rank test. Kaplan-Meier curves were truncated at 200 days of follow-up. Cox regression was used to estimate the relative risk of AOM during follow-up with adjustment for confounding effects of other factors. The median number of episodes of AOM during follow-up was compared using the Mann-Whitney nonparametric test. Analyses were performed using SPSS for Windows (Version 11.5.0, SPSS Inc., Chicago, IL) and EpiInfo (Version 5.01b, CDC and USD, Inc., Stone Mountain, GA).
Sample size
We assumed the risk of having at least one episode of AOM during 6 months of observation among children with recurrent otitis media to be 60%. With no effect modification between echinacea and osteopathic treatment, a final sample of 100 children (50 subjects per group for each analysis), was needed to provide 80% power to detect a 50% reduction in the risk of AOM associated with the treatment being analyzed (alpha = 0.05). This magnitude of risk reduction is comparable to that observed with antibiotic prophylaxis [20].
The study was conducted with the approval of the University of Arizona Human Subjects Committee, and informed consent was obtained from a parent or guardian of each subject.
Results
Ninety children were enrolled in the study, 74 from the university-based clinic and 16 from private practice sites. Subjects had a median age of 1.5 years. The majority was male (57%) and white non-Hispanic (44%) or Hispanic (39%). Despite randomization, there were notable differences among treatment groups in the frequency of potentially confounding factors, especially gender, presence of siblings in the home, frequency of AOM prior to study entry, and daycare attendance (Table 1).
Table 1. Subject characteristics according to assigned treatment group
Six subjects (7%) withdrew or were lost to follow-up within 3 months of enrollment (1–2 in each group). Only 19% of subjects attended all 5 scheduled osteopathic visits, but 64% had 3 or more treatment visits (see CONSORT diagram [21]: Additional file 1). The percentage of subjects that came for follow-up examinations was 69% at 3 months and 62% at 6 months. Medical record information on the occurrence of AOM during at least 3 months of follow-up was available for 84 subjects (93%). The length of follow-up ranged from 2 to 278 days (median 183).
Additional file 1. CONSORT Wahl et al. CONSORT (Consolidated Standards of Reporting Trials) patient flow diagram.
Format: PDF Size: KB Download file
This file can be viewed with: Adobe Acrobat Reader
Of 84 children followed for 3 months or more, 44 (52%) had one or more episodes of AOM as defined above. The cumulative incidence of AOM varied from 39% to 80% among the treatment groups (P = 0.04) (Figure 1). The highest rate of AOM was among children receiving echinacea alone.
Figure 1. Cumulative incidence of AOM according to assigned treatment group. The P value is for at least one group being significantly different from the others.
The pattern of variation in incidence rates among the treatment groups did not suggest any plausible effect modification between echinacea treatment and OMT on the risk of AOM (Figure 1). In addition, a likelihood ratio test for interaction between the two treatments using Cox regression was not significant (P = 0.40). Therefore, the independent effects of echinacea and OMT were assessed separately.
The use of echinacea was associated with an increased risk of AOM of borderline statistical significance. Sixty-five percent of children assigned to echinacea experienced AOM compared to 41% of children taking placebo (RR 1.59, 95% CI 1.04, 2.42). The Kaplan-Meier analysis using all 90 subjects yielded nearly identical results (Figure 2).
Figure 2. Kaplan-Meier estimates of the probability of AOM according to treatment with echinacea or placebo.
OMT was not significantly associated with the risk of AOM. Forty-four percent of children receiving OMT experienced AOM compared to 61% of children undergoing sham treatment (RR 0.72, 95% CI 0.48, 1.10). Restriction of the analysis to 56 children who had 3 or more osteopathic treatment visits did not change the findings (RR 0.70, 95% CI 0.41, 1.19). Results of Kaplan-Meier analysis using all 90 children were similar (Figure 3).
Figure 3. Kaplan-Meier estimates of the probability of AOM according to treatment with osteopathic manipulative treatment (OMT) or sham.
We estimated the effects of echinacea and OMT on the risk of AOM after adjustment for confounding factors using Cox regression in all 90 subjects (Table 2). The adjusted relative risk of AOM for echinacea treatment was 1.73 (95% CI 0.94, 3.18). The adjusted relative risk for OMT was 0.84 (95% CI 0.44, 1.61). Four variables (younger age, male gender, Hispanic ethnicity, and presence of one or more siblings at home) were independently associated with the risk of AOM and were included in the regression model.
Table 2. Cox regression estimates of the effect of echinacea and osteopathic manipulative treatment on the risk of AOM after adjustment for other factors
There was no significant difference in the median number of episodes of AOM during the study period between treatment and placebo groups for either echinacea or OMT. Comparisons were made using the Mann-Whitney nonparametric test.
One subject withdrew from the study following an adverse effect (vomiting after taking the echinacea placebo). One additional subject reported adverse effects (vomiting and non-urticarial rash two days after starting echinacea for a viral upper respiratory illness) but did not withdraw. Neither adverse effect was considered to have been caused by the study medication. As reported in monthly telephone interviews and at the 3- and 6-month visits, there was no statistically significant difference in reporting of any side effects between placebo and treatment groups for either echinacea or OMT.
Parents were unable to distinguish whether their child was receiving echinacea treatment or placebo. However, when asked about OMT after 3 months, parents of children assigned to OMT were significantly more likely to believe their child was receiving actual OMT than parents of children assigned to sham (Figure 4). Even so, only 20% of parents of children assigned to sham treatments believed their child to be receiving placebo. Interestingly, the ability to distinguish OMT from sham treatment disappeared entirely by 6 months.
Figure 4. Parents' beliefs about osteopathic treatment assignment after 3 months in study (n = 54).
Discussion
We found that preventive treatment with osteopathic manipulation did not result in a statistically significant decrease in the risk of AOM in otitis-prone children. Treatment with an alcohol extract of Echinacea purpurea root and seeds at times of upper respiratory infection was associated with a modestly increased risk of AOM. This effect was of borderline statistical significance and may have been due to chance.
As noted, the randomization process resulted in an unequal distribution of certain otitis risk factors among treatment groups. The group receiving echinacea alone appeared to be at higher risk based on several factors, and this chance occurrence may have been responsible for the higher rate of otitis in the echinacea group. We adjusted for known confounding factors, resulting in modest changes in relative risk estimates, but the possibility of incomplete adjustment, or unmeasured confounding by other factors cannot be excluded.
This is the first randomized, placebo-controlled trial of Echinacea purpurea for the prevention of AOM. We chose to treat children at the time of upper respiratory tract infections, rather than using a prolonged preventive regimen, based on the finding that echinacea appeared to be more effective in treatment than prevention of URI in adults [22]. Two subsequent randomized trials did not confirm this pattern in children. Taylor and colleagues found the pressed juice of E. purpurea aerial plant to be of no benefit to children in treatment of the common cold [16]. Cohen reported a significant reduction in colds and other respiratory outcomes following preventive use of a product containing liquid extracts of E. purpurea aerial plant, E. angustifolia root, propolis, and vitamin C [23]. The latter study also showed a decreased risk of acute otitis media with the echinacea product, but was not designed to measure this outcome in a rigorous way. Recent studies have confirmed our premise that AOM in children is a frequent complication of viral upper respiratory tract infection [24,25].
Research on the therapeutic use of echinacea is complicated by the fact that there are three species of echinacea in common use, and preparations are made from various combinations of leaves, flowers, roots, and seeds of the plant. Furthermore, various methods of preparation are used, including alcohol or glycerin extraction, desiccation, and juicing. These issues are discussed elsewhere with respect to the present study [26]. Our results cannot be generalized to other forms of echinacea.
One previous study evaluated OMT for prevention of AOM in otitis-prone children [7]. The authors reported a statistically significant decreased frequency of AOM episodes and fewer surgical episodes among treated children. That protocol called for 9 osteopathic treatment visits, compared with 5 in the present study. As noted by the authors, that study did not have a placebo control, and the control group had a very high dropout rate, a combination of factors with a significant potential to introduce bias.
The main limitations of this study were small sample size and incomplete compliance with osteopathic treatments and follow-up visits. Our final analysis involved 84 subjects, yielding 73% power to detect a 50% risk reduction under our initial assumptions. The borderline increased risk associated with echinacea treatment make a protective effect of this form and dosage schedule of echinacea very unlikely, despite the sample size.
Because we were able to identify episodes of AOM through medical record review, the incomplete compliance with follow-up pediatrician visits had limited impact on our findings. However, it is possible that the lack of a statistically significant benefit found for OMT was the result of inadequate compliance with OMT visits. An analysis restricted to subjects attending 3 or more treatment visits did not suggest a greater protective effect of OMT, but the sample size was small. On the other hand, research personnel exerted considerable effort at getting subjects to these visits, with limited success, perhaps because the children were not ill at those times. An analysis of the reasons for limited participation by families with OMT may be useful for future OMT research.
An ancillary purpose of this study was to determine if a suitable sham for osteopathic manipulation could be devised. A previous study of sham chiropractic treatment in children did not evaluate how parents perceived the sham treatment[27]. We hoped to be able to show that parents would be unable to distinguish examination alone from examination and concurrent treatment. In fact, about 20% of parents of sham recipients (versus 4% in the true treatment group) correctly thought that the child was receiving sham manipulation. However, the large majority of parents of sham recipients could not tell that the "sham manipulation" was placebo. Some osteopathic physicians believe any "hands-on" contact has potential therapeutic benefit. To the extent this is true, our "sham" treatment could mask an actual benefit of OMT.
Conclusion
Treatment of upper respiratory infections in otitis-prone children with an alcohol extract of the roots and seeds of Echinacea purpurea does not decrease the risk of AOM, and may in fact increase risk. In the same population of children, a preventive regimen of from one to five osteopathic manipulative treatments over three months did not significantly decrease their risk of acute otitis media.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
Each author of this research paper has directly participated in planning, execution, or analysis of the study. RAW and MBA performed the clinical examinations on all study subjects. KAW coordinated the osteopathic assessments and treatments. KLG (now deceased) provided the subject randomization and assured that the other authors remained blinded to treatment arm protocols. MBA performed all statistical analyses. RAW, MBA, and KAW read and approved the final manuscript.
Acknowledgements
This research was supported by the National Center for Complementary and Alternative Medicine, N.I.H. This is an individual project under Ghishan F, Weil A (Co-PI's). Pediatric Center for Complementary/Alternative Medicine (NIH P50 HL61212-01), 1998 – 2002.
The authors wish to acknowledge the assistance of Theresa Cisler, D.O., Ilene Spector, D.O., and the Clara Vista Pediatric Group in Tucson, Arizona. Viola Frymann, D.O., Philip Greenman, D.O., and Francis Brinker, N.D. provided valuable advice.
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Clinical Pediatrics 2001, 40:265-269. PubMed Abstract | Publisher Full Text
27. Sawyer CE, Evans RL, Boline PD, Branson R, Spicer A: A feasibility study of chiropractic spinal manipulation versus sham spinal manipulation for chronic otitis media with effusion in children.
J Manipulative Physiol Ther 1999, 22(5):292-298. PubMed Abstract | Publisher Full Text
Pre-publication history
The pre-publication history for this paper can be accessed here:
http://www.biomedcentral.com/1472-6882/8/56/prepub
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Category: Organizations > Sciences > Biotechnology
VAS - Verdi Ambiente e Società Onlus - Italia
Italian enviromentalist organization fighting against GMO and biotech agriculture.
Ratings/Review of this resource:
Contact Person: Guido Pollice
E-Mail: vas@vasonline.it
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Rate This Video
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Wetlands of Nebraska, Part 2 (14:18)
Wetlands of Nebraska, Part 2 (14:18)
Learn about Nebraska's wetlands and the important values they provide. Explore the diversity of these habitats and the wildlife variety in them and of how the wetlands play roles in the lives of Nebraskans. A production of Nebraska Game & Parks and Nebraska Educational Telecommunications...with funding from Nebraska Game & Parks, U.S. Environmental Protection Agency and Ducks Unlimited.
Publishing Information
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Ogden FamilySearch Library/Staff & VolunteersEdit This Page
From FamilySearch Wiki
Revision as of 08:41, 19 September 2012 by WWS36 (Talk | contribs)
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
STAFF
Director: Emil Hanson
Associate Directors: Richard Jorgenson - Personnel, Richard W. Moyle - Instruction, Ron Jepperson - Computers, Joan Blanchard - Administrative, and Cornelius Dejong - Digitizing
Shift Supervisor and an Assistant Supervisor: Available on each shift, with shift members serving as cashiers, trainers, and mentors.
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AIR
From Forensics Wiki
Jump to: navigation, search
AIR
Maintainer: Steve Gibson
Modding Nanni Bassetti
OS: Cross-platform
Genre: Disk imaging
License: GPL
Website: air-imager.sourceforge.net
The Automated Image and Restore or AIR is a GUI front-end to dd and dc3dd designed for easily creating forensic bit images.
Features:
1. auto-detection of IDE and SCSI drives, CD-ROMs, and tape drives
2. choice of using either dd or dcfldd
3. image verification between source and copy via MD5 or SHA1/256/384/512
4. image compression/decompression via gzip/bzip2
5. image over a TCP/IP network via netcat/cryptcat
6. supports SCSI tape drives
7. wiping (zeroing) drives or partitions
8. splitting images into multiple segments
9. detailed logging with date/times and complete command-line used
External Links
Personal tools
Namespaces
Variants
Actions
Navigation:
About forensicswiki.org:
Toolbox
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About this Journal Submit a Manuscript Table of Contents
Discrete Dynamics in Nature and Society
Volume 2012 (2012), Article ID 189316, 18 pages
doi:10.1155/2012/189316
Research Article
A Signal Coordination Control Based on Traversing Empty between Mid-Block Street Crossing and Intersection
1College of Civil and Transportation Engineering, Hohai University, Nanjing 210098, China
2College of Harbour, Coastal and Offshore Engineering, Hohai University, Nanjing 210098, China
Received 29 June 2012; Revised 6 September 2012; Accepted 11 September 2012
Academic Editor: Wuhong Wang
Copyright © 2012 Changjiang Zheng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
To solve the problem in pedestrian Mid-Block street crossing, the method of signal coordination control between mid-block street crossing and intersection is researched in this paper. The paper proposes to use “distance-flow rate-time” graph as the tool for building coordination control system model which is for different situations of traffic control. Through alternating the linear optimization model, the system outputs the distribution of signal timing and system operational factors (delays in vehicles and mid-block street crossing). Finally, taking one section on the Taiping North Road in Nanjing as an example, the signal coordination control is carried out. And the results which are delays in the vehicles and mid-block street crossing are compared to those in the current distribution of signal timing.
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About this Journal Submit a Manuscript Table of Contents
International Journal of Distributed Sensor Networks
Volume 2012 (2012), Article ID 489794, 21 pages
doi:10.1155/2012/489794
Review Article
Enabling Cyber Physical Systems with Wireless Sensor Networking Technologies
1Department of Computer Science and Information Engineering, Tamkang University, New Taipei City 25137, Taiwan
2Department of Computer Science and Information Technology, University of the District of Columbia, Washington, DC 20008, USA
3Department of Computer Science and Information Engineering, National University of Tainan, Tainan 700, Taiwan
Received 17 February 2012; Accepted 18 March 2012
Academic Editor: Joel Rodrigues
Copyright © 2012 Chih-Yu Lin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
How to Cite this Article
Chih-Yu Lin, Sherali Zeadally, Tzung-Shi Chen, and Chih-Yung Chang, “Enabling Cyber Physical Systems with Wireless Sensor Networking Technologies,” International Journal of Distributed Sensor Networks, vol. 2012, Article ID 489794, 21 pages, 2012. doi:10.1155/2012/489794
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Bibliography: Nel mondo di Ciro il Grande (Part 3 of 3)
You are not logged in. If you create a free account and sign in, you will be able to customize what is displayed.
Title: Nel mondo di Ciro il Grande (Part 3 of 3)
Author: Poul Anderson
Year: 1961
Variant Title of: Brave to Be a King (by Poul Anderson ) [may list more publications, awards and reviews]
Type: SERIAL
Series: Time Patrol
Series Number: 2
Language: Italian
ISFDB Record Number: 1040227
User Rating: This title has fewer than 5 votes. VOTE
Current Tags: Merril05 (1)
Publications:
Copyright (c) 1995-2011 Al von Ruff.
ISFDB Engine - Version 4.00 (04/24/06)
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Activity Not Available
Estimated Cost
Analyzed over 2 years ago based on code collected over 2 years ago.
Project Cost Calculator
$ .00
420,856 lines
113 person-years
$ 6,193,388 *
*Using the Basic COCOMO Model
Estimate seems way too high?
Ohloh scans all files at any given code location to calculate the cost estimate.
Ohloh lets you exclude files and direc-tories from this calculation on the Code Locations page. You can get a more realistic estimate by excluding:
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About Cost Estimates
• Software cost estimation is tricky business even when all the variables are known -- knowlegdge which we certainly don't have.
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• For those familiar with the details, we are using coeffcients a=2.4 and b=1.05.
• Please note that COCOMO was created to model large institutional projects, which often don't compare well with distributed open-source projects.
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Copyright © 2013 Black Duck Software, Inc. and its contributors, Some Rights Reserved. Unless otherwise marked, this work is licensed under a Creative Commons Attribution 3.0 Unported License . Ohloh ® and the Ohloh logo are trademarks of Black Duck Software, Inc. in the United States and/or other jurisdictions. All other trademarks are the property of their respective holders.
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"Some Girl(s)" comedy clip features Adam Brody, Emily Watson (video)
PanARMENIAN.Net - Before it gets premiered at the 2013 SXSW Festival in early March, "Some Girl(s)" debuts its first sneak peek online via Deadline. The clip features a simple scene involving Adam Brody and Emily Watson, AceShowbiz said.
The two are seen revisiting a room, which is said to keep "lots of memories" for both Brody and Watson. The latter, however, doesn't seem to recall fond memories between them in the room. Instead, she accuses him of being "vampiric" and "cannibalistic" for telling their story in his book. When Brody tries to explain that the book is just fiction, she laughs instead.
Brody plays an author who writes a book called "The Calculus of Desire". On the eve of his wedding, the successful writer travels around the country to meet up with ex-lovers in an attempt to make amends for his wrongdoings. It seems that Watson is one of his ex-girlfriends.
"Some Girl(s)" will be screened on March 9 at SXSW. The film marks the first big screen feature from director Jennifer Getzinger since 2002's "The Guru". Rounding up the cast ensemble are Kristen Bell, Jennifer Morrison, Zoe Kazan, Mia Maestro, and Laura Perloe.
Partner news
Top stories
The jewels were to be loaned to celebrities who have arrived on the French Riviera town for its famous annual film festival.
The list of the finalists also includes Hungary, Azerbaijan, Georgia, Romania, Norway, Iceland, Finland and others.
Set in the gritty blue-collar neighborhood of God’s Pocket, story follows a man stuck with a debt he can't pay.
"Catching Fire" follows Katniss and fellow Hunger Games victor Peeta as they embark on a "Victor's Tour" throughout 12 districts of Panem.
Partner news
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This work is licensed under a Creative Commons Attribution-ShareAlike 3.0 United States License.
An XML version of this text is available for download, with the additional restriction that you offer Perseus any modifications you make. Perseus provides credit for all accepted changes, storing new additions in a versioning system.
load focus English (Alexander Thomson, 1889)
hide References (6 total)
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hideData/Identifiers
Citation URN: urn:cts:latinLit:phi1348.phi011.perseus-lat1:87
Document URN: urn:cts:latinLit:phi1348.phi011.perseus-lat1
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CMD sent two reporters to track ALEC in Oklahoma
Click here to help support our future investigations.
Shelley Moore Capito
From SourceWatch
Jump to: navigation, search
This is a profile of a U.S. Representative. (See the West Virginia portal for all incumbents, candidates and blogs.)
Things you can do:
Shelley Moore Capito currently serves the Second Congressional district of West Virginia
Shelley Moore Capito, a Republican, has represented the Second Congressional District of West Virginia in the U.S. House of Representatives since 2001. (map)
Contents
Record and controversies
General information about important bills and votes for can be found in Congresspedia's articles on legislation. You can add information you find on how Shelley Moore Capito voted by clicking the "[edit]" link to the right and typing it in. Remember to cite your sources!
Iraq War
Capito voted for the Authorization for Use of Military Force Against Iraq Resolution of 2002 that started the Iraq War.[1]
For more information see the chart of U.S. House of Representatives votes on the Iraq War.
Environmental record
For more information on environmental legislation, see the Energy and Environment Policy Portal
Oil
Shelley Moore Capito has voted in favor of big oil companies on 82% of important oil-related bills from 2005-2007, according to Oil Change International. These bills include Iraq war funding, climate change studies, clean energy, and emissions.[2] See below for oil money in politics.
ARMPAC money
Capito was the largest recipient of former House Majority Leader Tom DeLay's ARMPAC campaign contributions. DeLay is being prosecuted on charges of felony money laundering of campaign finances and conspiracy to launder money. As of December 2005, Capito had not offered to return any of the $48,500 she received.[1]
Immigration
On July 12, 2007, Rep. Capito sponsored an amendment to the housing bill, which House Republicans successfully added in a procedural tactic, that would make it more difficult for illegal immigrants to receive housing assistance. The measure was attached to the bill through a "motion to recommit," which passed 233-186. The procedure "essentially amended the bill by sending it back to committee, changing it, and instantaneously bringing it back to the floor. The underlying bill passed 383-83." The added provision would "require recipients of public housing assistance to provide proof of legal residency, such as a Social Security card or passport."
Main article: U.S. immigration legislation in the 110th Congress
Congressional page board resignation
Capito, along with Rep. Ginny Brown Waite (R-Fla.), resigned from the board governing the House page program on December 6, 2007, alleging the House clerk did not inform her properly about page infractions. Two pages were dismissed after being caught shoplifting, while two others were dismissed for sexual activity. Capito said there had been "numerous occurrences" in 2007 in which board members had not received timely information about incidents involving pages. She noted the "failed leadership of the clerk of the House and the continued lack of oversight" as prompting her resignation. Capito said she had no other alternative to show her serious concerns about the page program’s management problems.[3]
Main article: 2007 House Page Board Resignations
Bio
Capito was born November 26, 1953. A resident of Charleston, Capito is the daughter of Arch A. Moore, Jr., who twice served as that state's Governor (1969-1977; 1985-1989). She was educated at Duke University and at the University of Virginia and served two terms in the West Virginia House of Delegates.
When 2nd District Congressman Bob Wise decided to make what turned out to be a successful run for governor in 2000, Capito won the Republican nomination and subsequent general election. She was the first Republican to represent West Virginia in Congress since 1983, as well as the first woman elected to Congress from West Virginia in her own right. She was reelected in 2002 against Humphreys and in 2004 against former newscaster Erik Wells by surprisingly large margins, becoming the first West Virginia Republican to win reelection to Congress since her father, who represented the First District in the state's northern region from 1957 to 1969.
Her voting record has been moderate by Southern Republican standards. She is the only pro-choice member of West Virginia's House delegation, despite the fact that the West Virginia Republican Party is strongly pro-life. She also has strong ties to organized labor, a rarity among congressional Republicans.
2006 election
In 2006, the Democrats nominated Mike Callaghan to challenge Capito in her bid for reelection. (See U.S. congressional elections in 2006) Capito retained her seat.
Money in politics
This section contains links to – and feeds from – money in politics databases. <crpcontribdata>cid=N00009771&cycle=2006</crpcontribdata>
Links to more campaign contribution information for Shelley Moore Capito
from the Center for Responsive Politics' OpenSecrets.org site.
Fundraising profile: 2006 election cycle Career totals
Top contributors by organization/corporation: 2006 election cycle Career totals
Top contributors by industry: 2006 election cycle Career totals
Oil Money in Politics
Shelley Moore Capito has received $71,350 in oil contributions during the 110th congress. $22,250 of those dollars were from industry PACS. In total, Capito has accepted $280,595 from oil companies between 2000 and 2008, which makes her one of the top recipients of oil money.[4]
Committees and Affiliations
Committees
Committee assignments are not yet available for the 110th Congress.
Committee assignments in the 109th Congress (2005-2006)
Coalitions and Caucuses
More Background Data
Wikipedia also has an article on Shelley Moore Capito. This article may use content from the Wikipedia article under the terms of the GFDL.
Contact
DC Office:
1431 Longworth House Office Building
Washington, DC 20515
Phone: 202-225-2711
Fax: 202-225-7856
Web Email
Website
District Office- Charleston:
4815 MacCorkle Avenue, Southeast
Charleston, WV 25304
Phone: 304-925-5964
Fax: 304-926-8912
District Office- Martinsburg:
300 Foxcroft Avenue, Suite 102
Martinsburg, WV 25401
Phone: 304-264-8810
Fax: 304-264-8815
2008 Campaign Contact Information
Official Capito for Congress campaign website
Mailing Address:
P.O. Box 11519
Charleston, WV 25339
Physical Address:
164 Court Street
Charleston, WV 25301
Phone: 304-342-1094
Fax: 304-342-5020
capito@capitoforcongress.com
Articles and resources
References
1. Roll call vote, Authorization for Use of Military Force Against Iraq Resolution of 2002.
2. Vote Tracker, Oil Change International.
3. Susan Crabtree, "Two GOP lawmakers resign from page board," The Hill, December 6, 2007.
4. See "Follow the Oil Money," "Follow the Coal Money," and vote tracker from Oil Change International and Appalachian Voices.
External resources
Local blogs and discussion sites
Corresponding article on Wikipedia and Cause Caller. (If Cause Caller link does not work, pick from its list of senators and representatives.)
Current Office: U.S. House of Representatives
111th Congress
Leadership Position:
Committees Chaired:
Committees,
Ranking Member On:
Caucuses:
Committees:
110th Congress
Leadership Position:
None
Committees Chaired:
Committees,
Ranking Member On:
Caucuses:
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West Virginia House of Delegates,
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RSS vs. Atom
There have been some interesting questions and discussions on the Ask Phil forum. For example, Nathan Stocks said:
It often seems like once I hear about something new it suddenly appears everywhere. RSS is apparently one of these.
I read up on RSS today, and it's essentially an agreed-upon XML format to publish web content, especially blogs.
Then I run across a feature article about RSS vs. Atom on c|net (news.com).
Atom was developed by an IBM Software Engineer and is backed by Google and Six Apart (makers of moveable type), while just about all of the rest of the big players are currently backing RSS.
Anyway, the article is about a proposed merging of the two formats. ÊHas anyone out there had a lot of experience with Atom? ÊIs it better or worse than RSS, or just different? ÊWould merging the two formats be a good thing?
From Forums for Windley's Enterprise Computing Weblog - RSS vs Atom
Referenced Fri Mar 12 2004 09:59:19 GMT-0700
Ray Matthews, who runs the RSS in Government weblog and probably knows as much about the uses of RSS as anyone replied:
There were informative discussion sessions about Atom (http://www.atomenabled.org) at both the recent SDForum Web Services SIG meeting (see Brian Cantoni's notes at http://www.cantoni.org/2004/02/25/sdforum) and at RSS Winterfest (see http://www.socialtext.net/rss-winterfest/index.cgi?rss_and_atom). ÊMuch of the debate seems to center on which is better, RSS or Atom, and which will prevail?
RSS has taken off because of it's simplicity. The Atom backers, a group of critics largely put off by Dave Winer's perceived godfather influence, say that Atom is simpler even than RSS 2.0 and that it offers additional capabilities. ÊFor example, you can differentiate between content in an original posting and its replication thereafter through the blogosphere. ÊI think that many developers have been genuinely stoked. Ê
There has been a mixture of reactions amongst those developing aggregators. For the most part they've enthusiastically embraced it. ÊOf course they're going to jump in and support any new "standard"; they need to so to keep their market share. ÊMany, though, realize that Atom is still an unborn child that may or may not make it in the real world. ÊGoogle has gone so far as to support it exclusively with their free Blogger service, forcing the hand of aggregator developers who would have preferred to wait and see. ÊI think that was a premature decision. Ê
All the ruckus about burying the hatchet and merging RSS 2.0 and Atom into a backward compatible RSS/Atom may be a sideshow. ÊAre content syndicators rushing to embrace Atom? No. Most new business users of RSS are generating feeds using barebones RSS 0.91. ÊMany using syndication for higher-end needs and opting for RSS 1.0 or NewsML are similarly unimpressed with the hullabaloo. Ê
Two things are certain. It's a good idea to bring RSS and Atom under the umbrella of a standards organization such as the IETF, and the RSS spec will continue to evolve, hopefully keeping its simplicity and continuing to support extensionability. ÊAs for me, I'll continue to generate my content in every conceivable format (let the subscriber choose), and use parsers liberal enough to accommodate all.
From Forums for Windley's Enterprise Computing Weblog - RSS vs Atom
Referenced Fri Mar 12 2004 10:01:05 GMT-0700
The debate over RSS 2.0 vs. RSS 1.0 vs Atom generates a lot of smoke, but in reality, unless you build aggregator software, its not all that germane right now. ÊEventually, it will be because there will be a lot of other programs that read and generate RSS (which is the term I use generically). This will happen faster if there's a common format. I think there's reason for optimism that either the market or the proponents of the different versions will decide on a common format soon. Ê Dave Winer's offer is an excellent beginning.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
7307.0 - Wheat Stocks and Exports, Australia, Nov 2011 Quality Declaration
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 12/01/2012
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Wheat Grain Stored
Includes: Stocks of wheat grain stored by bulk grain handlers at month end for Australia and states and territories.
Wheat Grain Exported
Includes: Wheat grain exports during the month for Australia and states and territories.
Wheat Grain Committed
Includes: Wheat grain committed for export at the month end for Australia and states and territories.
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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Review
?Microarray analysis of gene expression in lupus
Mary K Crow1* and Jay Wohlgemuth2
Author Affiliations
1 Mary Kirkland Center for Lupus Research, Hospital for Special Surgery, New York, NY, USA
2 Expression Diagnostics, Inc, South San Francisco, CA, USA
For all author emails, please log on.
Arthritis Res Ther 2003, 5:279-287 doi:10.1186/ar1015
The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/5/6/279
Received:26 August 2003
Revisions received:22 September 2003
Accepted:1 October 2003
Published:13 October 2003
© 2003 BioMed Central Ltd
Abstract
Recent advances in the study of global patterns of gene expression with the use of microarray technology, coupled with data analysis using sophisticated statistical algorithms, have provided new insights into pathogenic mechanisms of disease. Complementary and reproducible data from multiple laboratories have documented the feasibility of analysis of heterogeneous populations of peripheral blood mononuclear cells from patients with rheumatic diseases through use of this powerful technology. Although some patterns of gene expression, including increased expression of immune system cell surface activation molecules, confirm previous data obtained with other techniques, some novel genes that are differentially expressed have been identified. Most interesting is the dominant pattern of interferon-induced gene expression detected among blood mononuclear cells from patients with systemic lupus erythematosus and juvenile dermatomyositis. These data are consistent with longstanding observations indicating increased circulating interferon-α in the blood of patients with active lupus, but draw attention to the dominance of the interferon pathway in the hierarchy of gene expression pathways implicated in systemic autoimmunity.
Keywords:
gene expression; interferon; microarray; statistical algorithms; systemic lupus erythematosus
Introduction: the dawning of the microarray era
The concept that the identification of genes that are differentially expressed in a disease state will elucidate disease mechanisms has driven the development of new technology. Earlier approaches, including Northern blotting, polymerase chain reaction (PCR), and RNase protection, have permitted analysis of small numbers of gene transcripts, but the value of characterizing a broad spectrum of gene products expressed in a cell population or in a disease state has stimulated the invention of more sophisticated tools. Subtractive hybridization and representational difference analysis, comparing gene expression in two cell populations, are time-intensive approaches used in the late 1990s to assist in gene discovery and to identify molecular pathways relevant to a disease. Microarray analysis, a system in which thousands of oligonucleotide sequences are spotted on a solid substrate, usually a glass slide, and RNA-derived material from a cell population is hybridized to the gene array, is an innovative technology that has already changed our understanding of the mechanisms that underlie disease [1].
The utility of microarray analysis of gene expression was demonstrated impressively in 2000 when Alizadeh and colleagues used this technique to study the malignant cell population of patients with diffuse large B cell leukemia [2]. Although individual patient samples were not readily differentiated on the basis of traditional cell surface phenotypic markers, microarray analysis discerned two discrete tumor groups: those with a gene expression profile similar to that of germinal center B cells from healthy individuals and those with a profile similar to that of activated mature B cells. Significantly, these two groups were characterized by markedly different clinical courses: B cell lymphomas of the germinal center type had a 5-year survival of 76%, whereas lymphomas of the activated B cell type were associated with a 16% 5-year survival. As striking as this study was, at that time confidence was not high that microarray analysis of gene expression could be successfully applied to heterogeneous populations of cells, cells that were not monoclonal.
Numerous investigations over the past several years have demonstrated that significant and useful microarray data can be derived from more complex cell samples, including cell populations from peripheral blood. Although such studies face challenges in data interpretation, several laboratories have used microarray analysis to study mononuclear cells from patients with autoimmune diseases. When studying mixed cell populations, gene expression profiling can successfully detect differential gene expression in specific cell types present in the samples under comparison. However, it can also measure and reflect the cellular composition of the sample. The contribution of variable enrichment of a cell population in a sample can be sorted out by combining cell sorting or histology with expression profiling experiments. Cell sorting can also be used as an initial step in sample preparation to enrich for specific cell types in a cell mixture to overcome sensitivity and specificity limitations of arrays.
The recent advances in the analysis of broad gene expression patterns have rapidly led to new insights into pathogenic mechanisms of rheumatic diseases and are supporting new initiatives in therapeutic drug development. Most striking are microarray data that have refocused attention on the interferon (IFN) pathway in systemic lupus erythematosus (SLE) [3-6].
Analysis of microarray data
A statistical analysis of appropriately normalized microarray data is as important as the cell preparation, initial hybridization, and data extraction in deriving valuable information from this technology. Arrays are useful because they allow large-scale screening for differential gene expression. However, the thousands of variables in the analyses represent a significant statistical problem. Theoretically, when using an array with 1000 genes and a standard t-test with a significance at the P < 0.05 level, one would expect to identify 50 genes that are 'differentially expressed' by chance alone. Corrections for multiple comparisons, such as the Bonferroni method, can be used to address this problem but tend to lose efficacy with very large numbers of comparisons, and some differentially expressed genes might not appear as significant [7,8]. Significance analysis of microarrays (SAM) is an approach that uses an estimate of the false detection rate to make an estimate of significance under conditions in which thousands of data points are being compared [9]. We have learned that no one statistical algorithm is sufficient to derive an accurate view of the genes significantly overexpressed or underexpressed in one population compared with another.
Although a comparative analysis of the current statistical approaches to microarray data is beyond the scope of this review, we will direct the reader to several of the most useful algorithms that we and others have used to derive a comprehensive data set that includes genes most significantly differentially expressed between cell populations (Table 1). When analyzing microarray data from two sets of patient-derived samples, we first use the SAM algorithm with parameters set to determine the genes significantly overexpressed or underexpressed in the patient group of interest compared with the control group [9]. The false detection rate is set at approximately 5% (indicating that in only 5 cases out of 100 will a gene be erroneously identified as significantly differentially expressed). Additional algorithms, including supervised harvesting classification and a method termed 'shrunken centroids', are then applied to the data set [10-16]. Genes that either are identified in several of the algorithms or are most highly ranked in one of the algorithms are then used in a hierarchical clustering approach to identify additional genes that are coexpressed with the most significantly differentially expressed genes.
Table 1. Statistical algorithms used in analysis of microarray data
Array data can be internally validated by, for example, carrying multiple probes for the same gene. When data from all such probes in a particular experiment are identified as correlating in an array experiment, the probability of the finding being real is increased. Further, when data from multiple genes that are known to be coexpressed in a cluster or cellular pathway are correlated, the result has greater significance than data from a single gene. Microarray analysis cannot be relied on to develop a definitive rank order of the most significant gene products associated with a particular disease or cell state. Rather, the technology is most useful in drawing attention to pathways, and sometimes individual genes, that are most relevant to the recent in vivo experience of the cell population being studied.
As revealing as microarray data can be, confirmation of the data using more accurate, quantitative, and less variable approaches, such as real-time PCR, and validation in a second patient population are essential for drawing meaningful conclusions [17].
Early microarray data from the use of SLE peripheral blood
In early 2003, Rus and colleagues reported data from a study of gene expression in peripheral blood mononuclear cells (PBMC) from 21 lupus patients and 12 controls [18]. The microarray assay used (Panorama Cytokine Gene Array membranes; Sigma Genosys, Inc) included 375 genes enriched in cytokines, chemokines, cell surface receptors, and other immune-system cell surface molecules, including adhesion molecules. Data analysis comprised several approaches: selection of genes with mean expression in the SLE group that was more than 2.5-fold that observed in the healthy control group; genes that were significantly different between groups with the use of the Mann–Whitney U-test at a significance level of P < 0.05; and SAM analysis with a false detection rate of 8%. Fifty genes were identified as differing by more than 2.5-fold, and 20 genes differed between groups on the basis of the Mann–Whitney U-test, of which 15 differed by more than 2.5-fold between groups. The importance of confirming microarray data with an additional technique was clearly illustrated in this report. The gene that showed the greatest fold difference between SLE and control groups by microarray, that encoding ciliary neurotrophic factor receptor α (CNTFR), could not be confirmed by reverse transcriptase PCR (RT–PCR). Increased expression of two other genes that were also studied by RT–PCR, CXCR2 and that encoding pre-B-cell colony-enhancing factor (PBEF), was confirmed, although the fold increase as assessed by RT–PCR was less than estimated by microarray. Of the genes significantly overexpressed, the products of some, including MMP3, TNFRSF1B (TNF receptor 2), IL1B, and FCGRIA, have been documented to be increased in SLE. Among other genes with increased expression were TNFSF10 (encoding TRAIL), TNFRSF10C and TNFRSF10D (TRAIL receptors 3 and 4), IL1RAP (interleukin-1 receptor accessory protein), TGFBR3 (transforming growth factor-β receptor type III), and CCR7 (a T cell chemokine receptor important for the recruitment of CD4 T cells to the periarteriolar lymphoid sheath). Although the Rus study did not provide an opportunity to detect the expression of genes that were not obviously directly related to immune system function, it drew attention to several genes that had not been studied previously in detail in SLE. Overall, the data presented in this study supported the value of the microarray approach for detecting genes differentially expressed among PBMC from lupus patients.
A second early report came from Maas and colleagues, who showed PBMC microarray data from a small number of patients with SLE (n = 9), rheumatoid arthritis (RA; n = 9), type I diabetes mellitus (n = 5) or multiple sclerosis (n = 4), along with nine control subjects before and after immunization with influenza vaccine [19]. The array used (Research Genetics GF-211 membrane) included more than 4000 genes, and the statistical analysis was based on Eisen's Cluster and Treeview software, as well as the Research Genetics Pathways 3.0 program used to locate differentially expressed genes in pathways related to the immune system [15]. As in the Rus study, microarray analysis of unfractionated PBMC provided data that seemed to be reproducible and statistically significant, and characterization of the cell composition of the PBMC indicated that a variable presence of mononuclear cell populations could not account for differential gene expression. However, the analysis was not able to distinguish a gene expression profile that was distinct for SLE as compared with RA or other autoimmune diseases. Ninety-five genes were identified that distinguished the samples from all four autoimmune diseases from healthy controls, including those encoding the cell surface receptors TGFBR2, CSF3R, and BMPR2, which were overexpressed in the autoimmune patients, and several genes implicated in apoptosis (TRADD, TRAF2, CASP6, CASP8), which were underexpressed. It is of interest that ADAR, an IFN-induced gene encoding the RNA-specific adenosine deaminase, was highly overexpressed in most patients with autoimmune disease. Increased RNA editing, dependent on the ADAR protein, has been identified in T cells in patients with SLE [20]. The patterns seen in the patients with autoimmune disease were distinct from those observed in samples from healthy subjects who had received influenza vaccination, suggesting that the pathways involved in the immunopathogenesis of autoimmune disease do not simply reflect an active immune response to an antigen. This study relied mainly on clustering algorithms to identify genes that were differentially expressed among the study groups and also eliminated from analysis genes whose expression levels did not vary by more than 3SD from their means, supporting our view that multiple approaches, including algorithms such as SAM, are useful in discerning gene expression relevant to disease-specific molecular pathways.
Interferon-induced gene expression in rheumatic diseases
A gene expression profile identified by microarray analysis and consistent with IFN-mediated gene transcription in a rheumatic disease was first reported by Tezak and colleagues in a study of muscle biopsy tissue from four patients with juvenile dermatomyositis (JDM) [21]. Data from biopsies were compared with gene expression data from two healthy control peripheral blood samples as well as previously obtained microarray data from muscle biopsy samples from patients with Duchenne muscular dystrophy by using Affymetrix HuFL GeneChips. Genes showing at least a twofold difference in comparisons of JDM samples with each of two control samples were used to develop a list of differentially expressed genes. Ninety-one genes showed more than twofold increased expression, and 87 genes showed more than twofold lower expression. It should be noted that in studies using small numbers of patient samples, although genes might be identified that are truly differentially expressed between the samples, the variable expression patterns might be unrelated to the disease state. In this study, fold differences between patient samples and controls were highly variable (ranging from 3.8-fold to 96.4-fold higher in patients than in controls), but the list of differentially expressed genes was striking for its enrichment in those that have been linked to IFN. MX1, MX2, G1P3, IRF7, and C1ORF29 were among the IFN-induced genes overexpressed in the JDM muscle samples. Increased expression of several genes, including G1P3 (encoding IFN-induced 6–16) and CDKN1A (p21 cyclin kinase inhibitor), were confirmed by real-time PCR, and G1P3 expression was also identified in JDM peripheral blood. It is of interest that there was no significant increase in mRNA for either IFN-α or IFN-γ, although IFN-γ protein was seen in JDM muscle by using immunohistochemistry. The authors interpreted their data as consistent with effects of both IFN-α/β and IFN-γ on gene expression. In addition to this set of IFN-induced genes, gene expression profiles indicating ischemia and myofiber degeneration and regeneration were detected.
Data supporting a pathogenic role for type I IFN (predominantly IFN-α) in SLE have been available for 25 years, with type II IFN (IFN-γ) also being implicated in murine models of lupus [22-31]. It has only been recently that microarray data from several laboratories have refocused attention on this important cytokine and its downstream targets. Studies from our laboratory and from others have used more extensive microarrays than those used in the two SLE studies described above to characterize the broad gene expression profile operative in the peripheral blood of patients with SLE [3-6]. Most striking is an 'IFN signature', a prominent overexpression of mRNAs encoded by genes regulated by IFNs and similar to that detected in JDM muscle.
Detection of an interferon signature in SLE by using microarray technology
Ambitious projects aimed at characterizing broad gene expression profiles in large numbers of SLE PBMC samples have come to fruition in 2003. Baechler and colleagues have reported microarray data from 48 SLE patients and 42 healthy controls with Affymetrix U95A GeneChips [4]. After eliminating genes that were highly sensitive to induction ex vivo, 4566 genes remained for analysis. An initial set of genes was selected on the basis of an unpaired Student's t-test (apparently without correction for multiple comparisons) and further selection based on a more than 1.5-fold difference in expression between lupus samples and controls, a difference of at least 100 units in the expression value, and P < 0.001 by t-test. SAM analysis was not used in this study. In the full data set, 161 genes fulfilled all of these criteria. Hierarchical clustering of these genes was then performed to identify gene expression patterns among the study samples. As in the JDM study, a striking increase in the expression of a group of genes previously reported to be induced by IFN was observed in about half of the SLE subjects. The authors identified 23 of the 161 differentially expressed genes as targets of IFN by determining gene expression of PBMC cultured for 6 hours either with IFN-α plus IFN-β or with IFN-γ. It should be noted that the patterns of gene expression induced in PBMC by type I and type II IFNs can vary with time after initial stimulation. The data from Baechler, then, provide only a partial assessment of IFN-regulated genes at a single point in time.
The pattern of expression of the IFN-regulated genes was complex (Table 2). Eleven of the IFN-regulated genes that were differentially expressed between SLE and control PBMC clustered together and were preferentially induced by a combination of IFN-α and IFN-β. However, two genes preferentially induced by IFN-γ (SERPING1 and FCGR1A) were also significantly increased in the SLE patients and clustered with the IFN-α/β-induced genes. Additional genes, preferentially induced by IFN-α/β but not clustering with the major IFN-induced group (CD69, RGS1, IL1RN, and AGRN), were also increased in the SLE group, and two genes repressed by IFN-α/β were significantly underexpressed in the SLE patients. Three genes significantly overexpressed in SLE were decreased in expression by both IFN-γ and IFN-α/β (EREG, THBS1, and ETS1). These are decreased somewhat more by IFN-γ than by IFN-α/β. Taken together, these SLE data, along with the very useful information about genes induced by type I and type II IFNs, support the type I IFNs as being particularly important in the gene expression pattern that distinguishes SLE PBMC from those of healthy controls. Confirmation of these data by a more quantitative technique will be essential to determine more precisely the relative expression of this gene set in patients with SLE, as well as those with other autoimmune diseases.
Table 2. Interferon-induced genes identified in large-scale microarray analyses of SLE PBMC
In addition to the IFN-regulated genes, the Baechler study documented an increased expression of genes encoding immune system activation antigens, including TNFR6 (encoding Fas), CD54 (ICAM-1), and CD69 in the SLE samples, along with FCGRIA (as observed in the Rus study) and FCGRIIA (Table 3) [4]. Other genes detected by Rus and colleagues were also identified (IL1B, IL1RB). Genes with decreased expression in the SLE samples included TCF3 (encoding transcription factor E2 α), important in B cell development; TCF7 (transcription factor 7 [T-cell specific, HMG box]), a polymorphism of which has been associated with type I diabetes; and LCK (lymphocyte-specific tyrosine kinase), which mediates T cell activation.
Table 3. Selected gene families overexpressed or underexpressed in SLE PBMC
A second extensive gene expression study by Bennett and colleagues also used Affymetrix U95AV2 microarrays to analyze PBMC from 30 pediatric lupus patients ranging in age from 6 to 18 years (mean age 13), 12 patients with juvenile chronic arthritis (JCA), and 9 healthy control children [5]. Of the 30 SLE patients, 18 were studied no more than 1 year after diagnosis, reflecting the gene expression profile at a point in time closer to the onset of symptoms than is usually possible to document in adult SLE patients. Data were analyzed with a correction for multiple comparisons. With this approach, 15 genes were found differentially expressed between SLE patients and healthy controls, and 14 of those 15 were identified as targets of IFN. Several of the most significantly differentially expressed genes were among those identified in the Baechler study (C1ORF29, MX1, LY6E, PLSCR1, and APOBEC3B) and others identified with less stringent statistical criteria were also found in the Baechler study (Table 2) or are closely related to genes identified by Baechler (OAS1, OAS2, MX2). In addition, Bennett identified IFI44 (encoding hepatitis C-associated microtubular aggregate protein), IFIT4 (termed CIG49 by those authors), CIG5 (viperin), and C1ORF29 as nearly universally expressed in their SLE subjects. The JCA samples did not demonstrate overexpression of IFN-induced genes.
Although neither the Baechler study nor the Bennett study confirmed the IFN-regulated gene expression signature by using more quantitative techniques, the similarity of results derived from the two studies is remarkable, strongly supporting the significance of the IFN pathway in SLE and also demonstrating the power of microarray technology, even when applied to heterogeneous populations of peripheral blood cells.
Additional observations by Bennett and colleagues included the significant overexpression of DEFA3, encoding the neutrophil-specific α 3 defensin that is predominantly expressed in precursors of mature polymorphonuclear cells [5]. Sorting of granular cells identified by flow cytometry confirmed a population of early granulocyte cells not present in mononuclear cell populations from controls. DEFA3 and another neutrophil gene FPRL1 (encoding formyl peptide receptor-like-1), along with several of the IFN-induced genes, were highly correlated with disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index.
Our laboratories have performed microarray analyis on PBMC samples from 22 SLE, 15 RA, 8 osteoarthritis, 2 JCA, and 9 control PBMC samples and have detected a gene expression signature virtually identical to that described by the other groups (Table 2) [3]. Importantly, our data were derived from a microarray (proprietary to Expression Diagnostics, Inc) distinct from that used by Baechler and Bennett and included more than 8000 gene sequences, most of which were identified from subtracted and normalized cDNA libraries isolated from resting and activated leukocytes. We have found that, in contrast to the RA, osteoarthritis, and JCA patients, and healthy controls, most adult SLE patients express the IFN gene signature (example data shown in Fig. 1). Moreover, we have confirmed the increased expression of several of those overexpressed genes by using real-time PCR analysis and in a second cohort of SLE patients [3]. Of great interest is the identity of the stimulus for the IFN-induced gene expression signature. It is noteworthy that none of the SLE or JDM studies identified significantly increased expression of type I or type II IFN mRNA, with the exception of a recent report by Han and colleagues [6] that detected IFN-ω, another type I IFN species, by using a distinct microarray system (Mergen ExpressChip DNA Microarray System Human HO4) in a study of 10 SLE patients and 8 healthy controls. The Han study also detected an increased expression of several of the genes identified in the other three studies (Table 2). In contrast to the Baechler and Bennett reports, which note that type I and II IFNs are undetectable in serum from most SLE patients, we have measured plasma IFN-α protein by ELISA and are currently analyzing those data in relation to the IFN target gene expression data, as well as measures of clinical disease activity. Importantly, our data provide direct support for IFN-α in the gene expression profile observed in SLE PBMC (KA Kirou, C Lee, S George, K Louca, M Peterson, MK Crow, unpublished observations). However, it should be noted that the IFN signature is complex, as described in detail for the Baechler study, and additional work will be required to determine the relative roles of type I and type II IFN in the gene expression profile observed in SLE peripheral blood. Analysis of the age of study patients, time from diagnosis, organ system involvement, and current therapy, along with gene expression data, will be essential for an understanding of the place of IFN family members in disease pathogenesis.
Figure 1. Exemplary gene sequences that cluster with PRKR and OAS3. Hierarchical clustering was performed on the total study population to determine genes that cluster with PRKR and OAS3. A visual demonstration of the expression of a selection from those genes, comprising a partial IFN signature, is shown. Data are shown from a subset of SLE samples tested (n = 14) and from rheumatoid arthritis (RA) (n = 11), juvenile chronic arthritis (JCA) (n = 2), and control samples (n = 8). Relative expression compared with an internal control ranged from approximately -0.5 (bright green) to 0.5 (bright red).
Beyond the impressive IFN gene signature, each of the studies identified additional genes that were differentially expressed in SLE and control samples. In view of the biological, patient, and assay variation encountered in gene profiling of SLE, a diagnostic gene signature might prove most useful clinically. An algorithm such as shrunken centroids can be used to develop a robust multigene classifier that can be tested in clinical studies as a measure of diagnosis or clinical outcome [11].
Microarray analysis of gene expression at sites of tissue damage
The next generation of reports describing global gene expression patterns based on microarray assays will probably derive from studies of tissue samples from sites of disease activity. Unpublished data presented at scientific meetings demonstrate the feasibility of microarray analysis of glomeruli from lupus nephritis kidneys and from skin lesions of lupus patients. As valuable as those data will be, we are encouraged that peripheral blood seems to provide a reasonable sampling of those gene pathways that are activated and relatively disease specific.
Conclusion
Since the dramatic illustration of the clinical utility of microarray technology in patients with malignant disease 3 years ago, efforts to study mixed mononuclear cell populations in patients with autoimmune diseases have been remarkably successful. Not only are microarray-derived data interpretable and significant, but they have drawn our attention back to a key cytokine pathway. Increased expression of IFN in patients with active SLE was first reported in 1979, but relatively few investigators have pursued the role of IFN in SLE [22]. An important exception is the group led by Ronnblom and Alm, who noted the induction of lupus autoantibodies and clinical lupus in patients receiving therapeutic IFN-α [26]. That group has gone on to characterize the IFN-producing cells as well as some of the properties of immune complexes that induce the production of IFN by plasmacytoid dendritic cells [32-37]. In addition, Bennett's collaborators, led by Banchereau, have presented functional data showing the induction of efficient stimulators of allogeneic T cell responses by IFN-α in SLE sera [28]. Now, the repeated appearance of IFN-induced genes among the most significantly overexpressed genes in data derived from multiple laboratories using distinct microarrays raises the profile of IFN as a pathogenic mediator of the myriad alterations to the immune system seen in SLE.
In view of the important effects of IFN on immune system function, including activities that could contribute to the development of systemic autoimmunity, this cytokine system might represent an excellent target for therapeutic modulation [38-44]. At the same time, both type I and type II IFNs are important, if not essential, for effective host defense against pathogenic microbes. The weight of data are consistent with the action of type I IFNs as primary mediators of the observed gene expression signature in SLE, with significant consequences for the development of clinical disease. However, additional potential mediators of the IFN gene signature, including CpG DNA or double-stranded RNA, are candidates that should be explored.
Competing interests
MKC is a scientific advisor to Expression Diagnostics, Inc, and JW is Vice-President, Research and Development, Expression Diagnostics, Inc. Research conducted by MKC was supported through a contract between Expression Diagnostics, Inc. and Hospital for Special Surgery.
Abbreviations
CNTFR = ciliary neurotrophic factor receptor; IFN = interferon; JCA = juvenile chronic arthritis; JDM = juvenile dermatomyositis; PBEF = pre-B-cell colony-enhancing factor; PBMC = peripheral blood mononuclear cells; PCR = polymerase chain reaction; RA = rheumatoid arthritis; SAM = significance analysis of microarrays; SLE = systemic lupus erythematosus.
Acknowledegments
We thank our collaborators at the Hospital for Special Surgery and Expression Diagnostics, Inc, particularly Dr Kyriakos Kirou and Ms Christina Lee and Ms Sandhya George, for their contributions to the work described in this review. MKC is supported by a Target Identification in Lupus Grant from the Alliance for Lupus Research, by a Novel Research Grant from the Lupus Research Institute, and by the Mary Kirkland Center for Lupus Research.
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37. Magnusson M, Magnusson S, Vallin H, Ronnblom L, Alm GV: Importance of CpG dinucleotides in activation of natural IFN-alpha-producing cells by a lupus-related oligodeoxynucleotide.
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38. Ronnblom L, Alm GV: A pivotal role for the natural interferon α-producing cells (plasmacytoid dendritic cells) in the pathogenesis of lupus.
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39. Aman MJ, Tretter T, Eisenbeis I, Bug G, Decker T, Aulitzky WE, Tilg H, Huber C, Peschel C: Interferon-alpha stimulates production of interleukin-10 in activated CD4+ T cells and monocytes.
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41. Kirou KA, Vakkalanka RK, Butler MJ, Crow MK: Induction of Fas ligand-mediated apoptosis by interferon-alpha.
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42. Radvanyi LG, Banerjee A, Weir M, Messner H: Low levels of interferon-alpha induce CD86 (B7.2) expression and accelerates dendritic cell maturation from human peripheral blood mononuclear cells.
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44. Crow MK: Interferon-alpha: a new target for therapy in SLE?
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Investigating Pragmatic Competence: The Case of Requests in Interchange Series
Bahareh Koosha, Hossein Vahid Dastjerdi
Abstract
This study aimed at investigating the use of request forms presented in Richard’s Interchange Series, Books I, II, and III, widely used in Iranian foreign language teaching Institutes. For this purpose, Alcon et al.’s (2005) taxonomy of peripheral modification devices used in requests was used to locate the instance of request forms in such texts. Results showed that the series fail to include materials which are needed for meaningful and, at the same time, face saving communication when resort to different kinds of requests is required. A large number of peripheral modification devices are not presented in the texts studied and those which have received some attention are different in terms of frequency of exposure. Also, there is no balance between the presentation of internal and external modifications in the different books studied. The findings of this study have implications for textbook writers, materials developers, language teachers and learners.
Full Text: PDF DOI: 10.5539/ass.v8n1p54
This work is licensed under a Creative Commons Attribution 3.0 License.
Asian Social Science ISSN 1911-2017 (Print) ISSN 1911-2025 (Online)
Copyright © Canadian Center of Science and Education
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Connexions
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You are here: Home » Content » Using Historical Documents
About: Using Historical Documents
Collection type: Course
Course by: AnaMaria Seglie. E-mail the author
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Name: Using Historical Documents
ID: col11316
Language: English (en)
Summary: This course provides useful ways and materials from which to discuss historical records, documentation, print culture, and rare materials for AP history teachers. Teachers and students could use these modules to discuss and learn about different forms of historical research and historiography.
Collection Subtype: Course
Subject: Humanities
Keywords: historiography, Jefferson Davis, Mexican-American documents, plagiarism, rare documents, translation
License: Creative Commons Attribution License CC-BY 3.0
Authors: AnaMaria Seglie (aseglie@gmail.com)
Copyright Holders: AnaMaria Seglie (aseglie@gmail.com)
Maintainers: AnaMaria Seglie (aseglie@gmail.com), Melissa Bailar (melba@rice.edu), Lorena Gauthereau-Bryson (lorena@rice.edu)
Latest version: 1.6 (history)
First publication date: May 10, 2011 10:20 am GMT-5
Last revision to collection: Aug 5, 2011 2:41 pm GMT-5
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Version History
Version: 1.6 Aug 5, 2011 2:41 pm GMT-5 by Lorena Gauthereau-Bryson
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added translations
Version: 1.5 Aug 3, 2011 1:59 pm GMT-5 by Lorena Gauthereau-Bryson
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Version: 1.4 Jul 18, 2011 11:19 am GMT-5 by AnaMaria Seglie
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Version: 1.3 Jul 11, 2011 1:13 pm GMT-5 by Lorena Gauthereau-Bryson
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added new module
Version: 1.2 Jun 22, 2011 11:36 am GMT-5 by AnaMaria Seglie
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Version: 1.1 Jun 2, 2011 1:52 pm GMT-5 by AnaMaria Seglie
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Category:Clarion County, PennsylvaniaEdit This Page
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Changes related to "Category:Greensville County, Virginia"
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Smolke:SU Meeting Schedule
From OpenWetWare
Revision as of 18:02, 9 December 2012 by Remus W (Talk | contribs)
Jump to: navigation, search
Home Contact Internal Protocols Lab Members Publications Research
Contents
General Group Meeting Schedule
Date Time Location Research Presentation
25-Sep 2:00 pm 300 Stephanie G
2-Oct 2:00 pm 300 Isis
9-Oct 2:00 pm 300 cancelled
16-Oct 2:00 pm 300 Brent
23-Oct 2:00 pm 300 Kate
30-Oct 2:00 pm 299 Yen-Hsiang
6-Nov 2:00 pm 300 Eric H
13-Nov 2:00 pm 300 Andy
20-Nov 2:00 pm 300 Leo
27-Nov 2:00 pm 300 Ryan
4-Dec 10:00 am 300 Jonathan K (PDI)
11-Dec 10:00 am 300 Peng Wang (PDI)
18-Dec 2:00 pm 300 Xiaofan
8-Jan 2:00 pm 300 Maureen
15-Jan 2:00 pm 299 Drew K
22-Jan 2:00 pm 300 Kathy
29-Jan 3:30 pm 300 Remus
5-Feb 2:05 pm 105 Jay
12-Feb 2:00 pm 299 Mike S
19-Feb 2:00 pm 300 Melina
26-Mar 2:00 pm 300 TBD
On deck: Stephanie G
How It Works
Group meeting will be held at the indicated time and room in Y2E2. Research presentations should be on the order of 45-60 minutes. A projector will be available in the room, but it is the responsibility of the presenter to bring the appropriate adapter and cord. The current plan is to skip group meeting food. Note, that the initial SOL ('state of the lab') address will be given by the PI to kick off the research year.
Suggested Times for Winter Quarter
Conflicts:
Stephanie - MW 8-9, M 12-1:30, TTh 4:15-5:30
Melina - MTuWTh 12-1:30, Th 4-6
Yen-Hsiang - TTh 9-10:30 & 4:00-5:30, MWF 11-12
Mike - T9-11am, W3-5:30pm
Suggested times:
Tu 2 pm
Th 10 am
Post Doc Interview Schedule
Peng Wang, Tues Dec 11
Time Location Who
9:30 am 269A Christina
10:00 am 300 research presentation
11:00 am red atrium Isis
11:30 am red atrium Jay
12:00 pm lunch Kate, Mike
1:00 pm red atrium Ryan
1:30 pm red atrium
2:00 pm red atrium Stephanie
2:30 pm red atrium
3:00 pm red atrium Yen-Hsiang
3:30 pm red atrium Melina, remus
4:00 pm red atrium Maureen
4:30 pm dinner Christina
Google Calendar
You can access this Google calendar with the account smolketc@aol.com (ask someone for the password) and sign up to receive a reminder for a meeting, edit details of that meeting if schedule changes, etc. You can also link it to your own google calendar, and you can link that to your calendar on your computer or iPhone etc. Ask me if you want to know how. -Leo
Personal tools
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Quotation added by staff
Why not add this quote to your bookmarks?
And Jesus said unto them, Because of your unbelief: for verily I say unto you, If ye have faith as a grain of mustard seed, ye shall say unto this mountain, Remove hence to yonder place; and it shall remove; and nothing shall be impossible unto you. Bible
Source: The Bible, Matthew 17:20. · This quote is about uncategorised · Search on Google Books to find all references and sources for this quotation.
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The Bible (sometimes The Holy Bible, The Book, Good Book, Word of God, The Word, or Scripture), from Greek, (ta) biblia, "(the) books", is the classical name for the Hebrew Bible of Judaism or the combination of the Old Testament and New Testament of Christianity ("The Bible" actually refers to at least two different Bibles). It is thus applied to sacred scriptures. Many Christian English speakers refer to the Christian Bible as "the good book" (Gospel means "good news"). For many people their Bible is the revealed word of God, or an authoritative record of the relationship between God, the world and humankind.
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Experience the blissfulness of the choiceless life. Let Existence determine what you will do. You never really had a choice anyway, did you? Oshana Dave
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Dave Oshana started sharing his practical, experiental approach to spirituality after being irrevocably transformed on 19 June 2000. Oshana credits his transformation to the Enlightenment Transmission - a universal force that helps to free individuals from spiritual limitation.
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A man's life is 20 years of having his mother ask him where he is going, 40 years of having his wife ask the same question and, at the end, perhaps having the mourners wondering too. Unknown, Source
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The most successful career must show a waste of strength that might have removed mountains, and the most unsuccessful is not that of the man who is taken unprepared, but of him who has prepared and is never taken. On a tragedy of that kind our national morality is duly silent. Forster, Edward M.
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Caye Caulker
From Wikitravel
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Caye Caulker [1] is a small island off the coast of Belize, 1.6 km (1 mi) west of the Barrier Reef. It's about 8.2 km (5 mi) in length with a population of 1,300 and counting.
[edit] Understand
Caye Caulker is popular with backpackers and budget travelers for its (relatively) cheap prices, laid-back vibe, and abundance of restaurants and bars. There aren't really any proper beaches to speak of, but plenty of docks are spread around the island where you can pull up a plastic chair and get your sun on, or hang out at one of the ocean front restaurants or walk down to "The Split" which is a popular swimming area and if you're feeling a bit thirsty, The Lazy Lizard Bar is just couple steps away from the water.
There are only 3 roads in town, all sandy. Front Street runs along the east coast, Back Street along the west coast, and Middle Street exactly where you'd expect it. The vast majority of places of interest to a visitor will be found along Front Street and the west coast.
The local cultural influences are Mestizo, Garifuna and Creole.
[edit] History
On early British maps the island's name is spelled "Cay Corker." Known historically for its plentiful supply of exposed fresh water at La Aguada, one theory holds that this island was a favourite stop for sailors to replenish and cork water bottles. The Spanish name of the island is Cayo Hicaco, which means "the island of the cocoplum." "Caye Caulker" could be an anglicised pronunciation of Cayo Hicaco. Another theory is that boats were caulked in the protected bay, La Ensenada, on the western side of the island leading to the "Caulker" name.
Recent history of Caye Caulker began when Mestizo refugees from the Mexican Caste Wars arrived. With few inhabitants, food could be grown with sustainable methods of agriculture. The coconut and the fishing industry became important economic staples of the island. Even today a few of the older women continue to process coconut oil for their own use and to sell, although generally the coconuts themselves are harvested and shipped to the mainland.
[edit] Get in
[edit] By air
Caye Caulker Airport (IATA: CUK) is located at the southern end of the island. Belize is served by both Maya Island Air [2], air viva and Tropic Air [3]. Flights leave hourly from Belize City to San Pedro, and will stop here if there is demand. These local planes leave from the international airport and the cost is approximately US$75 one-way and about $45 from the municipal airstrip, and takes about 10-15 min. These planes also leave from the Belize City Municipal Airport (IATA: TZA) and the cost is less.
If you're coming in from Mexico you can fly from Corozal, 20 min from the Mexican border at Chetumal. The flights stop in Ambergris and Caye Caulker if there's demand, and will save you the 4+ hour bus ride to Belize City.
[edit] By sea
Catch a Water Taxi in Belize City to Caye Caulker and they have frequent runs to the island everyday rain or shine. The ride takes about 45 min, and then continues on to San Pedro. On windy days the trip can be a little rough, but most times is smooth. Sit towards the back of the boat for a smoother ride.
• Caye Caulker Water Taxi Association [4] - $20Bz one-way, or $35Bz round-trip. (Check their website for departures). Caye Caulker Water Taxi is located at the foot of the Swing Bridge in Belize City.
• San Pedro Water Taxi [5] - $20Bz one-way and $35Bz round-trip. (Check their website for departures). Boats leave Belize City from the Brown Sugar Marketplace at 9am, 11am, 12pm, 1pm, 3pm, 4pm and 5:30pm to Caye Caulker and from San Pedro on the beach behind the town council every hour and a half starting at 7am.
If you are coming from Mexico you can get a boat directly from Chetumal to San Pedro and then to Caye Caulker, it runs everyday, leaving at 3PM and 3:30PM, US$35, 2.5 hr. While twice the cost, this route is a much better option than trekking down to Belize City and getting the boat there. Tickets can be bought at the Maritime Terminal or Muelle Fiscal itself or from a slow speaking large friendly dude at Chetumal ADO terminal.
[edit] Get around
There are only three main streets on Caye Caulker - Front Street, Middle Street and Back Street - none of which are paved. Front Street, the easternmost street, is the busiest and has almost everything for tourists on it. Everything is within walking distance, it takes approximately 20 min to slow-walk from the Front Pier to almost anywhere.
There are few cars on the island, so everyone gets around on golf carts, bicycles or on foot. With a golf cart, you can go around the entire island in 30 min.
There are many places on the island who rent bicycles.
For golf carts check with C&N Golf Cart Rentals and Caye Caulker Golf Cart Rentals.
Recommended: Hire golf cart driver Peter Rash to give you a tour of the island and ask to hear his stories of his Mayan family and Caye Caulker. The 45-minute ride is very interesting. Peter's taxi office also offers very reasonable bike rentals if you want to pedal yourself around.
[edit][add listing] See
• The Forest Reserve covers the northern 100 acres of the island. It's mostly dense mangrove forest. The local Audubon group sometimes organizes morning birdwatching tours.
• Caye Caulker Marine Reserve, also known as the local reef. The local reef is close enough that you can see the waves breaking on it from the island itself.
• Hol Chan Marine Reserve, (6.4 km (4 mi) south of San Pedro, Ambergris Caye), +501 226-2247, [6]. Has been protected for longer than the local reef, and so it usually has more mature marine life (i.e. bigger fish) as well as more people, though it's never terribly crowded. It's further away than the local reef. edit
• Shark and Ray Alley. Tour operators will toss food into the water in order to attract nurse sharks and southern sting rays. You can swim with them, and even touch them if you're quick. Nurse sharks can bite, contrary to myth, but they are also territorial so these sharks are very used to humans.
• The Blue Hole is circular in shape, over 300 m (984 ft) across and 124 m (407 ft) deep, with many fish, sharks, and corals. The Blue Hole is possibly the most famous dive site in Belize, even though it's nearly straight down. It's at least an hour boat ride away from Caye Caulker. The dive depth is normally described as 40 m (130 ft).
[edit][add listing] Do
Caye Caulker is a small, very laid-back Caribbean island. In fact, its motto is "Go Slow" and that is exactly what you should do. It is an ideal place to spend a few days while taking a break from travelling around the rest of Central America.
Chill out at The Lazy Lizard located at "the split," a little bar on its own near what can only be described as the island's only beach, however, do not expect Rio or Hawaii - there is no sand here. The "beach" is a sunken area of a picnic area surrounded by cement sea walls, damage from the hurricane and smartly kept as it was in 1961. On the walls you'll see the young and hip lazing about, catching a tan. When it gets too hot, you can jump into the water and climb back again, or make the short walk to the Lazy Lizard to refresh your drink.
[edit] Snorkelling and diving
Much of the activity on the island centers around snorkelling and diving (about a dozen operators offering trips) and scuba diving. The prices at all the shops are basically the same. The local diving is at Hol Chan Marine Reserve, a 30 min boat ride away. A little further out is Spanish Bay, Caye Chapel, and some other sites. Long distance trips to Turneffe Atoll and the famous Blue Hole are regularly available.
[edit] Snorkeling
Short "half-day" snorkeling tours are offered by numerous local businesses for approximately $70Bz per person. They usually leave at 10:30AM and 2:30PM. Stops include the local reef, the Coral Garden, and Shark and Ray Alley.
Looking out towards the reef
Longer "full-day" snorkeling tours are offered by numerous local businesses, for approximately $130Bz. They usually leave around 10AM and return around 4:30PM. Stops include the Coral Garden, Shark and Ray Alley, and Hol Chan Marine Reserve. Be sure to check whether your tour guide will include lunch, since some only include snacks. Some of them include lunch, snacks, and a Rum Punch "happy hour" on the way back. With all operators, check to make sure they have equipment that is in good shape.
The creation of Swallow Caye Wildlife Sanctuary - a manatee reserve near Belize City is due to the efforts of a Caye Caulker local named Chocolate. He offers guided tours to the Manatee reserve approximately every other day, as do a few other tour operators. Be warned that you don't get to swim with the manatees in the sanctuary and some days may be more difficult to see them. Most manatee tours include one or two snorkeling stops. Manatees can be seen all year long, and in the summer months can be seen near Hol Chan Marine Reserve as well as other local areas. The younger ones are curious and will swim close to you, unlike the more mature manatees, which generally avoid people (for good reason).
• Chocolate (tours), (At the north end of Front Street, near Ragamuffin Tours). Tours to Swallow Caye Wildlife Sanctuary and manatree habitats, tours are normally run every 2nd day. edit
• Carlos Tours is located next to Cafe Amore, 1 block south of the Sandbox restaurant. An eco-friendly tour and quite respectful of the reef. The locals living on the island will say that his tours are one of the best. The tour includes 4 stops: Hol Chan Marine Reserve, San Pedro on Ambergris Caye for lunch (not provided), Shark-Ray Alley, & Coral Gardens. The price is $90Bz. Carlos will take multiple underwater pictures during the trip and can supply them on a CD after the trip for $30Bz. This is much better than getting $40Bz underwater disposable camera.
• Red Mangrove Eco Adventures, Front Street, Caye Caulker, [7]. Eco friendly small group snorkel tours to local sites and Turneffe Atoll. edit
• Seagull Adventures, about a block from the Front Pier, offers snorkeling tours to more distant locations that most other tour guides will only go to for diving. Examples include Blue Hole (about $230Bz per person), Tourneffe Atoll (about $120Bz per person), etc. Ask the owner a few days in advance to find out what the schedule is. The best time to catch her is in the evening, around 6PM, during the day she's usually gone on the snorkeling trips.
• Juni's, sailing/snorkling trips to hol chan marine reserve. Authentic experience on a beautiful self built sailing boat. Small groups to maximum of 6 people. Only for those who respect the ocean, the fish and the locals. If you like drinking and smoking with 20+ people on a sailing boat, then don't go to Juni. Go to raggamuffin instead. Find Juni in his office behind the police station, best before 9.30AM and after 5.30PM, or at his boat Trinity at the dock. Experience yourself, and direct nice and friendly people to him if you can.
[edit] Diving
Caye Caulker is popular with divers and there are several dive shops on the island. Contact them a few days in advance to find out what their schedule is. PADI certified dive shops are available offering both recreational diving and open water courses. These courses normally take 3-4 days, providing the weather is fair. The certification includes 2 shallow-water dives, and 4 open-water dives. All dives are done in the ocean.
The local dive shops all offer dive trips to the Blue Hole, Hol Chan Marine Reserve, Caye Caulker Marine Reserve, Spanish Bay, Turneffe North, and Turneffe Elbow, prices vary depending on the dive site.
• Belize Diving Services, (Near the soccer field in the northern half of the town), [8]. PADI Resort facility. Small groups, safety conscious and is the only dive shop to offer technical diving services. edit
• Big Fish Diving, (Located at the southern part of the island opposite of Quan's Shopping Center). EXPELLED from PADI. edit
• Frenchies, (Located in the northern part of the island towards the Split), [9]. Run by a Belizean. Very friendly and laid back. PADI Certified. edit
• Scuba Sensation, (Located in the middle of the island before the police station). PADI Certified. edit
There are also operators on nearby Ambergris Caye that can pick you up if the local shops aren't going where you want.
The cost of various trips varies according to the distance from Caye Caulker. Typical costs are:
• Local dives (Hol Chan, Spanish Bay): $US90 (2 tank dives)
• Turneffe Atoll: $US150 (3 tank dives)
• Blue Hole: $US150 (3 tank dives) plus $US40 park permit
[edit] Sea Kayaks
• Tsunami Adventures, extreme north end of Front St., [10]. This is a great way to explore the northern mangrove forest. Head for the leeward side of the island (the west side) for smoother water and to avoid paddling into the wind. Cost for a two-person kayak is $15Bz per hour for the first hour, then $10Bz for each additional hour.
[edit] Other Activities
You can also book various activities at many places on the island, such as
• Sailing tours. With the Ragga muffin tour you can do a sailing trip of three days (two nights). Sleeping on little islands, snorkeling, fishing your own meal, a wonderfull experience.
• Cave tubing (on the mainland).
• Manatee watching Tours normally include a snorkeling stop at Sergeant's Caye (on the barrier reef) and a short visit to St. George's Caye. There are many tour operators out of Caye Caulker, San Pedro and Belize City who do manatee watching trips. Visit Swallow Caye Wildlife Sanctuary that was set up by Chocolate Heredia, Belizean native and award winning conservationist. 9,000 acres of sea and mangrove became a protected area in July of 2002. For more information see the Friends of Swallow Caye. [11]
[edit][add listing] Buy
Like most of Belize, most shops accept US Dollars, US$1 equals $2 Belizian. Prices will be posted in Belizian dollars, but always confirm before making a purchase.
There are 2 ATMs on the island. One ATM is for local cards only and another ATM accepts foreign cards. Often on weekends, ATMs run out of money, so stock up on your money in Belize City.
Gift shops along the Front Street sell mainly t-shirts, hammocks and souvenirs. Vendors can be found along the main street selling a variety of crafts and jewelry.
• Caribbean Colors Art Gallery, Front Street. Art gallery on Caye Caulker.
• Chocolate's Gift Shop, Front Street near the split. Sells beautiful sarongs and clothing from Bali. Nice sarongs and silver jewelry.
• Chan's Mini Mart, Middle Street. For your grocery needs during your stay in Caye Caulker. edit
• Seleni Camal, near the Split (table under a palm tree, in front of ReMax, across from the Miramar Hotel). daylight. Seleni etches beautiful work in slate, in particular representations of the Mayan calendar and panels representing Mayan gods. edit
[edit][add listing] Eat
This article or section does not match our manual of style or needs other editing. Please plunge forward, give it your attention and help it improve! Suggested fixes: Please assist to develop the accuracy of this article by placing the establishments already listed here into the most appropriate of the 3 available price categories. Any new Eat listings should also go into the most appropriate of the the three price categories available: Budget, Mid-range or Splurge
[edit] Budget
• Auntie's Fast Food is on the Middle Street. It offers delicious Belizean and Chinese take out with a relatively low price. Famous dishes include Stew Chicken, Baked Chicken, Rice and Bean and Cow Foot Soup.
• Meldy's also on Middle Street is tops for breakfast. The varying menu includes stew chicken with beans and crisp, fluffy fry jacks; juevos rancheros; luscious pancakes layered with banana slices and honey; fresh fruit, and good coffee. Meldy treats her customers like members of her family! Dishes range from 8 - 12 Bz.
• The Bamboo Grill next to Rasta Pasta has good fish and shrimp dishes, but chicken is also available. Features swings instead of chairs at some tables and the bar. Friendly hostess.
This guide uses the following price ranges for a typical meal for one, including soft drink:
Budget up to $9 Bz
Mid-range up to $--Bz
Splurge over $--Bz
• Glenda's, Back Street near the microwave tower, serves eggs, bacon, a cinnamon roll, and coffee for just $US3.50.
• Syd's is on Middle Street and is famous for a plate of juicy fried chicken surrounded by amazing french fries, for about 9 Bz. But show up before 1-2 because he sometimes runs out of those chicken dinners.
• The Sandbox, located right near the Front Pier, has good food at reasonable prices. This is a place on the island where you can get a veggie burger.
• Femi's Bar and Lounge, Front Street, a little south of the Lazy Lizard. Great lunch, dinner, and drink specials on a pier overhanging the sea.
• Fran's - Roger's sister, her fare is similar to that of Jolly Roger's, for the same price. Located across the street from the Miramar Hotel.
• Caye Caulker Bakery, Back Street, just North of Chan's Grocery. Opens at 7:30AM. Serving a mixture of sweet and savory foods. The ham and cheese turnover (if available) is exceedingly delicious and is a filling breakfast on its own.
• Pirates located near the supermarkets offers cheap food for the budget traveller. A generous portion of Chicken and Chips can be had for $7Bz.
• Pizza Caulker is on the way to the ATMs (about two blocks away), has an interesting vibe and very accommodating owner and staff. Pizza is fresh and spiced well with Belizean hot sauce added in, and starts at $9 BZ/ large* slice or from $17-35 BZ for a pie (depending on size and toppings). Happy hour: strong, yet well-balanced rum drinks- 2/$8 BZ for happy hour. Opportunity to meet many people- he's a bartender (and owner) who brings everyone together. They also deliver. On Tripadvisor and Facebook for more info.
[edit] Mid-range
• Agave, (Front Street, north of Dock Street), [12]. Bar and grill offering contemporary seafood dishes for between $20Bz-$40Bz edit
• Amor y Café, [13]. Owned by a Dutch woman, this is a great (though small) breakfast place on Front Street just south of Dock Street. They offer home-made bread, yoghurt and fruit juices. edit
• Jolly Roger, Front Street. For $25Bz you can get catch of the day (lobster, snapper, baracuda) with garlic bread, mashed potatoes, rum punch and a small desert. The grilled seafood is delicious (like everywhere else), but the lack of hygiene and running water means you need a robust digestive system and a bit of luck if you want to avoid food poisoning. edit
• Roses Grill and Bar, Calle Al Mar Street (Straight down the street off the main dock), +5012260407 (), [14]. 11:00 a.m. to 10:00 p.m.. Serving fresh catches of the day like Fishes, Barracudas, Crab Claws, Kabobs, Conch Octpus and even Lobsters so fresh they're crawling off the display table. It's definitely worth the try. $20-$50Bz. edit
[edit] Splurge
• Don Corleone, Front Street. Italian restaurant. edit
• Habaneros, Front Street. Lunch and dinner. edit
[edit][add listing] Drink
There is not much to do in the night in regards to partying. Holidays and long weekends are when events and dances are held on the island by individual committees of the island.
Sunset at the Lazy Lizard
• I&I Reggae Bar, (Located on the southern part of the island). Nice vibes and hang out spot to meet with friends or meet new friends. Great place to relax on a hammock or swing with a cocktail. From the top deck you can see the whole island, eerily peaceful at night. edit
• Oceanside Night Club, (On the front street). Karaoke nights Wednesdays, Thursdays and Saturdays, and Lady's Nights. Has dancing and/or live music from time to time, and can be a popular destination on weekend nights before midnight. edit
• The split is the place where hurricane Hattie split the island in two in 1961, a bit of dredging and currents subsequently formed the split. There is a bar just next to the split called the Lazy Lizard. Good place for a binch while watching large tarpons and rays just swimming by. Happy hour starts at 5PM and offers two rum drinks for $5Bz; try the "Panty Ripper" included in this deal.
• The Sports Bar (they have a couple of TVs tuned to ESPN) is right across from Rasta Pasta and the Police Station and occasionally has live music. The food is pretty good and it's a nice place to grab a beer in the shade on a hot day. They frequently have a jam session on Friday afternoons, from 3 to 6 or so. You may hear a riotous mix of music and thoroughly enjoy yourself watching the dancers.
• Sunset View - a disco on the back side of the island just north of the soccer field. It is only open from 11PM on weekends (it doesn't get going until 1AM), but you will see a different side of the island. DJs spin reggae, punta, and other caribbean music and the locals cut loose and dance in a surprisingly large room. Be prepared to be one of the few tourists there, but it is great fun if you like music and dancing.
[edit][add listing] Sleep
• Caye Caylker offers a good spread of high quality lodging facilities ranging from budget accommodation to higher end hotels and serviced apartments. Many high quality lodging facilities are available for US$20-30 per night. Don't get ripped off by the rental companies charging US$60 or more per night, do some thorough research first to ensure they are not run down, and a complete ripoff.
• Anchorage Hotel, (on the southern point of town). Possibly has the nicest beach on the island. The rooms have A/C, TV, hot water and fridge, and are all in one concrete building with a great ocean view. US$50-60. edit
• Blue Wave Guesthouse, (near the split, across from Ragamuffin Tours), [15]. Rooms with balcony, cableTV, private bathroom. Nice and new. $60Bz per night. edit
• Caye Reef, (on the beachfront facing the reef, on the breezy eastern side of the island near the split), +501 226 0382 (), [16]. Boutique apartment hotel with 6 spacious units accommodating 2-6 guests. Swimming pool, roof top hot tub, spectacular views, balcony, A/C, cable, WiFi, safe, fully equipped kitchen, telephone. US$160+ per unit per night. edit
• Chila's Cabin, (on the northern part of the island towards the split next to Don Corleone), +501 630 3668, [17]. Ideal for the budget traveler. On the beach front. Nice sea view, private hot/cold shower, cableTV, fridge, coffee pot, microwave, toaster, balcony with hammock. Split unit A/C, 1 double bed, WiFi and complementary bicycles. Good for a couple or a single person and safe for females traveling alone. US$55. edit
• Colinda Cabanas (Previously known as Lorraines Guest House), (beside The Anchorage Resort, a 10 min walk south along the beach from the water taxi), +501 226 0383, [18]. checkin: 12 noon; checkout: 10AM. Renovated in 2011 and renamed Colinda Cabanas. Beachfront location facing the reef with frequent easterly breeze. All bathrooms have hot and cold reverse osmosis purified water. All cabanas have a fridge and coffee pot. The cabanas up on stilts have a porch and hammock. A 175 ft dock with palapa and hammocks, safe swimming area. Private ocean view cabana-US$25, A/C beachfront suite-US$100. edit
• Da Real McCaw, [19]. Great place, quiet, hammocks on porches right across from beach. US$40-70 two beds. edit
• Iguana Reef Inn, [20]. Hotel with private pool, beach, dock, free continental breakfasts, safes and small refrigerators in each room, A/C, free Wifi and shower. They have their own bar. No children under 10 years old allowed. edit
• Oasi, [21]. 3-room guest house located south of downtown, near the airstrip. Each suite has a kitchen, porch with hammock and free use of bicycles. edit
• Tree Tops Guesthouse, (just before Tom's Hotel), +501 226 0240, [22]. checkin: 1PM; checkout: 11AM. Immaculately clean and very comfortable rooms, with charming garden just 50 yards from the waters edge. US$55-110. edit
• The Tropics Hotel offers an alternative for those on a budget who don't mind getting cosy. A "Sunset" room costs $55Bz and comes with a shower and two double beds to share.
• Yuma's House Belize ((also known as Tina's Backpacker's Hostel)), (east side of the island), +501 206 0019 (), [23]. The islands hostel, between 2 of the water taxis on the beach. It has new management and the rooms have been renovated. A social place and this is the way a hostel should be. edit
• Ignacio's Cabins, (southern part of the island along the water, ask at Mario's tour agency). Cheap cabins, especially if you're 2 or 3 people, they also rent kayaks and snorkel gear for the day. The owner, Ruben, is really friendly and helpful, as are all his family, they're willing to push down the prices and haggle a little, at least in low season, and half the cabins have a spectacular view looking directly out onto the ocean. Rooms are basic but breezy and comfortable. Two night stay minimum though. edit
• Popeye's Resort, (*'''Popeye's Resort'' you will find near the water taxi terminals (to the right, 1-2 blocks, depending on taxi).). checkin: 11:00 am; checkout: 10:00 am. Clean, comfortable, rooms. Private cabanas for just $40 US close to the ocean. On the upper end you could get a King bed suite, with futon sitting area, refrigerator, and balcony overlooking the sea for just $90 US. A/C is included in all rooms. Staff is very accommodating. Has private dock. $40-90 USD. edit
• Dirty Mc Nasty, 1 crocodile st. (western end of Crocodile Street (4 blocks north of boat pier)), +1 501-636-7512. checkout: 10am. Quite new Backpacker's place. Clean rooms, good matresses, enough space. 6 Dorm rooms with 6 beds and 4 private rooms available. Public kitchen. This place is missing a hangout zone. from BZD 27.25. (17.746607,-88.024409) edit
[edit] Contact
Caye Caulker has internet access, but the island is served by a single hard line to the mainland and is therefore prone to bandwidth problems and interruptions.
There are a few internet cafes and Wi-Fi hotspots on the island.
• Cayeboard Connection is open from 8AM-9PM.
• Caye Caulker Cyber Cafe open from 8AM-10PM.
• The Island Link Internet Cafe & Ice Cream Parlor is open from 8AM-9PM. They also have delicious ice creams and is owned by a local Caye Caulker native.
• Young's Internet Cafe on the back street
[edit] Get out
Water taxis [24] leave the island for Belize City from early in the morning till the end of the day.
This is a usable article. It has information for getting in as well as some complete entries for restaurants and hotels. An adventurous person could use this article, but please plunge forward and help it grow!
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Contents >> Measuring progress - an ABS approach
Introduction - why the ABS developed Measures of Australia's Progress
Recent years have seen growing public interest in assessing whether life in Australia and other countries is getting better, and whether the level of (or pace of improvement in) the quality of life can be sustained into the future. Although most regard Gross Domestic Product (GDP) as an important measure of progress, there are many who believe that it should be assessed in conjunction with other measures of progress. This is the prime reason the ABS looked for an alternative approach.
A national statistical agency like the ABS has an important role to play in providing the statistical evidence that will allow assessments of progress to be made by users - those who formulate and evaluate policy, researchers and the community. Through its publications, electronic releases of data and other means, the ABS provides a rich array of statistics relevant to assessing progress. But the very size of the information base means that it is not so accessible to many people. Moreover, most ABS products provide a window into one or a few aspects of life in Australia - say, health, education, income, water - whereas a comprehensive assessment of progress demands that these aspects of life are examined together.
Measures of Australia's Progress (MAP) provides a digestible selection of statistical evidence that will allow Australians to make their own assessment of whether life in Australia is getting better. MAP is not intended as a substitute for the full array of statistics - indeed, the ABS hopes that many readers will be led to read our other publications on the aspects of society, the economy and the environment that particularly interest them.
There are many different views of what progress means and how it might be measured. Some issues that arise when developing a publication like MAP include -
• What core concept is being addressed by MAP?
• What model or other view of the real world underlies the statistical evidence presented in MAP? - in particular, how does MAP deal with the complex interactions within and between society, the economy and the environment?
• On what basis were the selection and presentation of statistical evidence decided? How did the ABS decide what aspects of national life should be included, and what statistical indicators should be used to encapsulate those aspects? What presentational model did the ABS adopt and why?
• Any assessment of whether life is getting better is unavoidably based on values and preferences, so whose values and preferences are reflected in MAP, and at what points during the writing (and reading) are they applied?
Different approaches to these issues might be taken by, say, a policy agency or an academic researcher or an interest group or a private citizen. This essay sets out the approach that the ABS thinks appropriate for a national statistical agency.
Notions of progress
Thinking about progress and allied concepts (such as wellbeing and the good society) has exercised philosophers from the time of Socrates. Answering the question 'Is life getting better?' is not straightforward. It is clear, however, that to understand progress one must examine many aspects of people's lives - their health, the quality of their environment, their incomes, their work and leisure, their security from crime, and so on. So progress is multidimensional. Moreover, the dimensions of progress are intertwined. To earn more income, people may need to work longer hours and so have less leisure time. Increased industrial activity may generate more money to spend on health care, but it might also lead to more air pollution and hence to poorer health.
For this publication, we have chosen to adopt progress as our primary concept. Progress here encompasses more than improvements in the material standard of living or other changes in the economic aspects of life; it also includes changes in the social and environmental areas. It encompasses:
• The major direct influences on the changing wellbeing of the Australian population.
• The structure and growth of the Australian economy.
• The environment - important both as a direct influence on the wellbeing of Australians and the Australian economy, and because people value it in its own right.
While most would agree on the desirability of progress in, say, health, work or environmental protection, there is no universally accepted view of the relative importance of these aspects of Australian life. This publication contains an array of objective measures of progress; readers can apply their own subjective valuations to decide whether that array of measures implies that Australia is, on balance, progressing and at what rate. The measures (or indicators) can be loosely associated with one of the three broad domains of progress (economy, society and environment), although some relate to several domains. But the number of indicators associated with a domain is not a measure of the domain's relative importance to overall national progress.
• Just three headline indicators - national income, national wealth and productivity - are used to encapsulate economic progress. They consolidate major flows and stocks relevant to national progress.
• There is no similarly compact set of indicators to encapsulate progress in the social and environmental domains. When seeking indicators of social progress, we have examined the various areas of social concern; when seeking indicators of environmental progress, we have examined the various environmental subsystems or resources.
This publication focuses on aspects of progress that are, in principle, susceptible to some objective measurement (e.g. life expectancy and educational qualifications). We have avoided aspects that are either intrinsically subjective (e.g. happiness) or, while somewhat more objective, do not at present have generally agreed measures (e.g. political freedom). These aspects of life are important to Australians, but they do not yet lend themselves to statistical expression. Moreover, people's subjective wellbeing should be influenced to some degree by the changes in objective wellbeing that are included here.
Various temporal perspectives are provided within the publication. The major focus is on the history of progress over the past ten years in key economic, social and environmental aspects of Australian life. But a snapshot of the current (or, more strictly, recent) condition of the Australian economy, society and environment is also provided.
We have not made forecasts or entered into any direct discussion of sustainability. But we have, for some aspects of progress, reported on whether Australian stocks of assets (human, natural, produced and financial, and social assets) are being maintained.
Many aspects of progress relate to one another, and it is important to understand some of those links when assessing overall progress. The issues of concern that are considered span important aspects of life in Australia and enable readers to assess the country's capacity to maintain a healthy economy, society and environment.
What is meant by "national progress"?
Progress is one of a cluster of related concepts that also includes wellbeing, welfare, quality of life, sustainability and even happiness.
• Wellbeing or welfare, which is generally used to mean the condition of being well, contented and satisfied with life. It typically includes material, physical, social and spiritual aspects of life.
• Quality of life, which is linked strongly to (sometimes as synonymous with) wellbeing and canalso be used in a collective sense to describe how well a society satisfies people's wants and needs.
• Sustainability, which considers whether an activity or condition can be maintained indefinitely. Although it has most commonly been used when considering the human impact on environmental systems (as in ‘sustainable fishing’), it can also be extended to economic and social systems.
The ABS provides statistics relevant to some of these concepts as they bear upon some aspects of life in Australia - see, for example, Measuring Wellbeing (ABS cat. no. 4160.0), Australian Social Trends (ABS cat. no. 4102.0) and Environment by Numbers (ABS cat. no. 4617.0).
The distinguishing features of MAP are that it adopts progress as its central concept and that it tries to take a comprehensive view of progress, embracing the social, economic and environmental aspects of Australian life.
MAP does not provide a tight definition of progress; MAP I expressed its aim as ‘providing statistical evidence about whether life in Australia is getting better’. Some readers of MAP have argued that the ABS should make explicit its definition of national progress, and even that the ABS should describe the future state towards which Australia should be progressing. In the ABSs view, specifying such a desired future state would be inappropriate for a national statistical agency. It is, however, possible to say some more about the notion of progress that underlies the design of MAP. Also, as discussed later, different Australians have different views of what constitutes progress.
Alternative core concepts
Core concept Publication and author(a)
Wellbeing/ Quality of Life Quality of Life Counts, United Kingdom
Department of the Environment
Transport and the Regions
Progress The Genuine Progress Indicator, The
Australia Institute
Sustainability Are We Sustaining Australia: A Report
Against Headline Sustainability
Indicators for Australia, Australian
Commonwealth
(a) See Appendix II for more information.
Approaches to measuring progress
Most attempts at measuring progress begin with a model or paradigm. A paradigm provides a context for the dimensions of progress that one is trying to measure. It helps to identify gaps in the available measures. It can also be used to place a given approach within the discourse on progress, welfare, sustainability, etc.
There are two steps to applying the chosen paradigm. First, one defines and applies a mechanism for choosing what aspects of progress are to be measured. Second, one decides how each aspect is to be measured and how the measures are to be presented.
Mechanisms for choosing aspects of progress
The ABS considered three broad approaches to choosing what aspects of progress to measure:
• Referring to international standards or practice.
• Referring to current policy issues and debates.
• Referring to the views of stakeholders and the general Australian public.
International standards or practice. Some international statistical initiatives, such as the United Nations' Human Development Index (HDI), consider only a very few issues of concern common to all nations and so take quite a narrow view. (The HDI uses life expectancy, education and command over resources needed for a decent living (income) to assess development.) Others use a larger number of issues. But some issues of concern in Australia are almost uniquely Australian (salinity, for example, affects few other countries; and while much of western Europe is preoccupied with road congestion, this is not (yet) a major issue here - at least not when compared to the scale of congestion problems in the UK, for example). We examined international standards and publications when listing aspects of progress. But because of this publication's Australian focus, we did not judge it necessary to confine our list to aspects of progress for which international comparisons are possible. On occasion we refer to other countries' data when they are useful for setting Australian progress in context (in the area of health, for example), and an article compares some key progress indicators across OECD countries.
Policy issues. Some statistical initiatives aim to choose measures which relate directly to government policy - the European System of Social Indicators, for example. Many aspects of progress included in this publication are potentially useful for assessing policy. However, they were not chosen with that in mind. Measures of Australia's Progress is meant to inform public discussion of national progress, rather than be used as a scorecard for government policy.
Public opinion. Other projects in this field have asked the public about what aspects of progress should be measured. Approaches used or suggested include:
• Appealing to the choices and emphases expressed in current government policy (on the ground that policy reflects preferences expressed by the electorate).
• Using opinion polls and other attitudinal data to assess the relative importance that people place on different aspects of national life.
• Using polling or otherwise, to make a direct, summary assessment of whether Australians feel that life has got better or worse.
Alternative values and preferences
Whose values and preferencesPublication and author(a)
Community prioritesTasmania Together, Tasmanian Parliament
Government policy prioritiesThe European System of Social Indicators, The European Union
International prioritiesThe Human Development Index, United Nations
(a) See Appendix II for more information.
The treatment of values, preferences and emphases
Any overall assessment about whether life is getting better unavoidably appeals to values and preferences.
Most obviously, values and preferences are invoked when readers survey any body of statistical evidence and make their assessments about the direction and pace of progress. For example, faced with statistics revealing that the life expectancy of Australians has lengthened during the past decade, average income has risen and more land has been degraded by salinity, one reader may judge that there has been progress and another that there has been regress. Even if all or most Australians attached much the same relative value to different aspects of life, it would be difficult to arrive at a one-line or summary judgment about whether life has got better or worse. Arriving at such a one-line judgment would be even more vexed in the face of widely diverging values and preferences.
Some commentators on MAP have argued that issues of value and preference must also be faced by the writers of such a publication. How, for example, does one decide which aspects of national life should be included, or which statistical indicators should be used to encapsulate those aspects? How does one decide on the balance of the publication across the various aspects of national life? Choices of this kind must be made — otherwise, the ABS would simply point readers to the full array of statistical publications and invite them to make their own selection of evidence and assign their own weightings. Such a course may be suitable for experts, but would be unhelpful to most people.
In the ABSs view, these approaches may be appropriate for other investigators and other purposes, but they are not appropriate for a national statistical agency.
We have not polled members of the public directly, but we have gathered broad views about what should be measured - first, by directly consulting stakeholders and experts in the fields of economic, social and environmental measurement; second, by distilling the views expressed during the ABS regular user group discussions regarding what data should be collected and published; and third, during a wide-ranging consultation process (in 2001 when the first issue of Measures of Australia's Progress was being written, and in further consultations after it was released).
Whichever mechanism is used, it is important to remember that society's views of progress, and of what is important, change over time, and that there are also some aspects of progress - governance and democracy, for example - that are seen as important now, but for which there are no agreed statistical measures yet. The issue of ongoing statistical development is discussed in more detail at the end of this section.
Deciding how measures of progress should be presented
Three broad approaches to presenting the chosen indicators of progress were considered - the one-number approach; the integrated accounting approach; and the suite-of-indicators approach.
Alternative presentations
PresentationPublication and author(a)
Suite of indicatorsQuality of Life Counts, United Kingdom Department of the Environment Transport and the Regions
One numberThe Genuine Progress Indicator, The Australia Institute
Integrated accounting frameworkSESAME, Statistics Netherlands
(a) See Appendix II for more information.
The one-number approach combines data about progress across a number of fronts (such as health, wealth and the environment) into a single composite indicator. Such composite indicators can be set in contrast with narrower indicators such as GDP. The ABS considers that it is more appropriate for others to develop such composite measures (see box overleaf).
The accounting framework approach presents social, economic and environmental data in one unified system of accounts, measured in various units. Potentially this is a powerful tool for analysts, and a detailed set of accounts will complement indicators. However, such a complex system may be too difficult to interpret for anyone wishing quickly to form an overall view about Australian progress. Most importantly, Australia is still a long way from being able to develop such a system, although some environmental accounts (e.g. energy) have been developed to link the economy and the environment. The Dutch System of Economic and Social Accounting Matrices and Extensions (SESAME) is one of the most mature sets of integrated accounts - more details of SESAME are in Appendix II.
The suite-of-indicators approach sets out key aspects of progress side-by-side and discusses the links between them; readers make their own evaluations of whether the indicators together imply that Australia is on balance progressing and at what rate. This is the approach used in Measures of Australia's Progress. The approach makes no overall assessment about whether the array of statistical indicators presented implies that life is getting better or worse. Instead, the suite of indicators leaves each individual reader to apply their own values and preferences to the evidence, and to arrive at their own overall assessment of national progress.
The ABS already publishes sets of indicators relating to economic, social and environmental concerns. Measures of Australia's Progress brings together all three domains by providing a set of headline indicators of progress that are tracked over time. In our view, this approach strikes a balance between the potential oversimplification of the one-number approach and the complexity of the accounting framework approach. The approach has been used by other countries, for example in the United Kingdom where the government produced a publication Quality of Life Counts.
One-number approaches to measuring progress
Although a good deal of effort has been put into trying to develop a single measure of progress (most notably the Genuine Progress Indicator, and the Human Development Index), consensus about the merits of the approach and about particular implementations still appears a long way off. There is no doubt that composite indicators are appealing. The demand for an alternative to that important indicator, GDP, is an argument in favour of a one-number approach.
However, difficulties arise when one wishes to combine several indicators into one number. The components of composite indicators are usually measured in different units - life expectancy (in years), income (in dollars), air pollution (in particles per volume of air), etc. Some compilers of composite indicators express the components in index form, then calculate a weighted or unweighted mean; others convert the components to a common unit of measurement, typically some estimate of their economic value or cost. But neither technique removes the basic issue - namely, that any composite indicator is based on some judgment regarding the relative weights to be applied to the components. Is a one-year increase in average life expectancy to be weighted more heavily than, less heavily than or equally with a 5% decrease in greenhouse gas emissions?
There is, therefore, a danger that a composite index will oversimplify a complex system and give potentially misleading signals.
There is still a debate about extending the scope of economic valuation into non-economic areas. Although attaching dollar values to changes in life expectancy, say, is usually done for methodological convenience, it might send the wrong signals. For example, E.F. Schumacher wrote, "To press non-economic values into the framework of the economic calculus...is a procedure by which the higher is reduced to the level of the lower and the priceless given a price".
Potential shortcomings of the suite-of-indicators approach
Although we adopted the suite-of-indicators approach, it is not without its problems.
• The choice of indicators could not be made using statistical criteria alone; it has required us to exercise judgment albeit based on the views of experts. Any of thousands of measures of progress could have been chosen, but we present just 13 headline dimensions, most of which use one headline indicator. Although we explain the criteria we have used to select indicators, there is an irreducible element of judgment, both in choosing the dimensions of progress to include and in choosing the statistical measures for those dimensions ofprogress.
• We have not included indicators for every aspect of progress that some Australians regard as significant. Some (such as a happiness indicator) are not included because such areas of progress are inherently subjective. Some (such as a single indicator for family and community) are not identified because there is not yet a consensus about the concept that one should measure. Some (such as a human capital indicator) are not yet included because ABS data construction work or other statistical development is still in progress.
Choosing the progress indicators
The progress indicators presented in this publication were chosen in four key steps.
• First, we defined three broad domains of progress (social, economic and environmental).
• Second, we made a list of potential progress dimensions within each of the three domains.
• Third, we chose a subset of dimensions for which we would try to find indicators.
• Fourth, we chose an indicator (or indicators) to give statistical expression to each of those dimensions.
This was an iterative process and several steps were revisited after listening to the views of the many people we consulted during the publication's development. More information about our selection of dimensions and indicators is provided in the section - A framework for measuring progress.
Domains of progress
Most commentators consider that progress relates to issues clustered around broad areas of concern (domains of progress). Each domain in turn comprises a number of dimensions of progress. Domain boundaries can be drawn in several ways.
• The two-domain view: human concerns and environmental concerns.
• The three-domain view: economic concerns, societal concerns, and environmental concerns.
• The four-domain view: concerns about aggregate material wellbeing and economic development, society and equity, democracy and human rights, and the environment and nature.
We adopted the three-domain view when developing the publication, although the dimensions are arranged around four areas that relate to the individual, the economy, the environment and people's interactions with others.
From domains to dimensions
Economy. We began with the systems of economic accounting that guide the ABS program of economic statistics, and concentrated on the major stock and flow variables represented in those systems.
Society. We began by considering key dimensions of social concern, which are underlaid by a view of fundamental human needs and aspirations. The ABS program of social statistics is guided by a social concerns framework, the design of which has drawn on many other frameworks and initiatives, such as those developed by the UN, the OECD and the European Union.
Environment. We began by considering major ecosystems and environmental resources that are recognised in international frameworks such as the System of Economic and Environmental Accounting.
The choice of a view is largely a matter of presentational convenience; the view is a tool to help choose areas of concern and identify progress indicators. The view we have adopted does not purport to be a model of a world in which the environment, economy and society can be separated. The three domains comprise one system: the economy depends on a functioning society which in turn depends on a functioning environment and economy. And although some concerns can, for the convenience of discussion, be attached loosely to the economy, the society or the environment, they are all of importance to other domains - education and training, and work, for example, are of both social and economic importance; air quality is of economic, social and environmental importance.
Dimensions of progress
To identify the major dimensions, the three domains were considered in detail and partitioned into a number of dimensions of progress to ensure that the important aspects of economic, social and environmental progress were considered.
Once a list of dimensions of progress that might be presented had been compiled, we selected the subset that would be presented. A balance had to be struck - if we showed too many indicators, readers would not be able to assimilate them; if we showed too few, important aspects of progress would be omitted, and the overall picture might be biased. Ten to twenty indicators seemed about right, and the choice of those 10-20 headline dimensions was guided by a wide variety of people from inside and outside the ABS.
During the design of MAP, our selection of aspects of life and indicators were guided by past and current ABS consultations. The ABS has a systematic program of consulting users of statistics about our statistical frameworks, surveys, products and analyses. Through this program, thousands of government agencies, academic researchers, businesses and business councils, community organisations and individual Australians have told the ABS what they think it is important that we measure. Our initial choices were tested through several further rounds of consultation undertaken specifically for MAP.
The final choice of indicators was made by the ABS after taking account of the full spectrum of views. In so far as such selections are value-driven, they are distilled from the values and emphases expressed by the user community.
Indicators of progress
Our next step was to find indicators to express these dimensions of progress. Our selection of indicators was guided by expert advice and by the criteria described in the box overleaf.
Such a small set of indicators cannot paint a full picture of progress, and so supplementary indicators are included. Some supplementary indicators give more information about dimensions of progress that are already represented by a headline indicator; others extend beyond the dimensions covered by the headline indicators.
We recognise that our sifting process means that this publication is both partial and selective - partial because not every dimension of progress is included, and selective because progress in each included dimensions is measured using just one or two indicators.
The set of headline indicators plays a special role in MAP, and particular considerations of values and preferences arise. MAP presents several hundred indicators overall; to assist readers in gaining a quick understanding of the bigger picture about national progress, MAP presents a more compact suite of fourteen headline indicators, covering the fifteen dimensions (some dimensions have more than one indicator, and some have none).
Headline indicators are distinguished from others by their capacity to encapsulate major features of change in the given aspect of Australian life. And an additional criterion was applied to them - namely, that most Australians would agree that each headline indicator possessed a 'good' direction of movement (signalling progress, when that indicator is viewed alone) and a 'bad' direction of movement (signalling regress, when that indicator is viewed alone). This good-direction / bad-direction distinction raises unavoidably the question of values and preferences.
Once the ABS had drafted its initial list of candidate headline indicators, it undertook extensive consultation to test whether the list accorded with users' views. Some commentators have disagreed with our choice of headline indicators in MAP I, usually on the grounds of knock-on effects or interactions - that is, the good/bad direction of change may be ambiguous when one takes into consideration the real-world associations between movements in the headline indicator and movements in other indicators. Whether a reader agrees with the ABS choice of headline indicators or not, he or she is free to peruse the whole suite of several hundred indicators in MAP and to assign high weight, low weight or no weight to each, as his or her own values and preferences dictate.
Some readers of MAP have tried to infer an ABS view about the relative importance of the different aspects of Australian life from the number of aspects discussed under the social, economic and environmental headings, or from the number of headline indicators or the number of indicators overall. No such inference can or should be drawn. It is not for the national statistical agency to say what relative importance should be accorded to, say, changes in health, income or air quality. The ABS based its decision about how many indicators to present not on relative value but on statistical grounds - is it possible to find one or a few indicators that would encapsulate the changes in the given aspect of life? Is it possible to sum or otherwise combine indicators?
To illustrate - changes in national wealth can be summarised well in one indicator (real net worth per capita), whereas half a dozen indicators are needed to depict significant changes in knowledge and innovation.
The place of values and preferences in MAP is well illustrated by its treatment of income distribution and equity. Many Australians believe that a more even distribution of income would represent progress; some would argue that, other things equal, any shift to more even distribution would be an improvement; others would argue only for a somewhat more even distribution than at present - say, one that reduces extreme disparities between high and low incomes. Other Australians would not accept that more even distribution of income would represent progress. Thus, when developing MAP, the ABS decided that measures of income distribution should appear only as supplementary indicators, not as headline indicators. Likewise, associated with many other dimensions of progress, MAP compares and contrasts the circumstances of different groups in the population.
Criteria for choosing progress indicators
When deciding which statistical indicators should be used to encapsulate each aspect of Australian life, we did not have such a comprehensive or longstanding corpus of users' advice to rely upon. For some aspects - health, crime, income, productivity and air quality, for example - there was already some broad consensus regarding indicators that would meet MAPs criteria. But for other aspects - social attachment, knowledge and innovation and biodiversity, for example - the effort to develop statistical indicators is more recent, and stakeholder agreement has not yet been reached. Thus, during the development of MAP, the ABS undertook wide-ranging consultation with experts and the general community of users regarding the indicators that would be ideal for each aspect of Australian life and the best approximations to those ideal indicators that are currently available. For the newer or less settled aspects, MAP generally provides an array of indicators and invites readers to form a view about progress.
Our first step was to take each dimension of progress in turn, and to ask ‘Why is this dimension particularly important to Australia's progress? What are the key facets of progress in that dimension that any headline indicator should seek to express?’
There were usually several competing indicators that might be included. We chose among them by reference to criteria, such as the following.
Indicators should focus on the outcome rather than, say, the inputs or other influences that generated the outcome, or the government and other social responses to the outcome. For example, an outcome indicator in the health dimension should if possible reflect people's actual health status and not, say, their dietary or smoking habits, or public and private expenditure on health treatment and education. Input and response variables are of course important to understanding why health outcomes change, but the outcome itself must be examined when one is assessing progress.
It was also judged important that movements in any indicator could be associated with progress by most Australians. For instance, one might consider including the number of divorces as an indicator for family life. But an increase in that number is ambiguous - it might reflect, say, a greater prevalence of unhappy marriages, or greater acceptance of dissolving unhappy marriages.
Applying this criterion depends crucially on interpreting movements in one indicator, assuming that the other indicators of progress are unchanged. For example, some would argue that economic growth has, at times, brought environmental problems in its wake, or even that the problems were so severe that the growth was undesirable. Others would argue that strong environmental protection might be retrograde to overall progress because it hampers economic growth. However, few would argue against economic growth or strong environmental protection if every other measure of progress was unaffected: that is, if growth could be achieved without environmental harm, or if environmental protection could be achieved without impeding economic growth. Of course, although keeping other things equal might be possible in theory, it seldom, if ever, occurs. The links between indicators are important, and Measures of Australia's Progress discusses these links once trends in the individual indicators have been analysed.
Other criteria included an indicator's availability at a national level and as a time series. A full list of our criteria for headline progress indicators is in Appendix I.
Deciding what attributes to measure
Once the ABS had decided on the suite-of-indicators presentation style and on the domains and dimensions of progress, there were still choices to be made regarding the characteristics or attributes of each dimension that should be measured. This is best explained through an example - say, the Health dimension. A comprehensive statistical compendium about health in Australia might present data on:
• health outcomes / the health status of the Australian people - e.g. life expectancy or the occurrence of disease or disability
• health risk factors / pressure points - e.g. patterns of diet, exercise, smoking and occupation that might point to future health outcomes
• financial and other resources (or inputs) expended on health improvement - e.g. government and private current and capital expenditures, the health workforce
• process measures - e.g. the number of peoplereceiving health treatments
• performance metrics - e.g. productivity, efficiency and effectiveness ratios for health service delivery.
Whenever the available statistics support it, MAP focuses on outcomes, that is on things that provide direct measures of whether life in Australia has been getting better. For our headline health indicator, we sought a measure that encapsulates major elements of health outcomes for the whole Australian population. And the best available single measure at present is life expectancy at birth, which is supplemented by other aspects of outcomes such as the burden of disease.
For this and other dimensions of progress, statistics on other attributes are also presented in MAP. But the aim is always to assist the reader to make an overall assessment of historical trends in outcomes or of key influences on outcomes. So for example, the data on life expectancy trends and the burden of disease are supplemented by data on risk factors such as obesity, exercise and smoking - to assist readers who are interested in forming a judgment about past influences on (and the likely future course of) health outcomes.
For several environmental dimensions, outcome-based data are supplemented by discussions of the programs and resources directed to environmental amelioration, such as conservation reserves, revegetation and other efforts to address salinity, rates of water use, and so on.
The data on educational attainments are supplemented by process measures such as school retention rates that influence past and future trends in attainment.
The data on income and wealth are supplemented by performance metrics such as competitiveness that exert a key influence on past and future improvements in material wellbeing.
The treatment of linkages
A change in one aspect of national life is almost always associated with changes in others. Even if the linkages between the different aspects were relatively simple ('when this variable goes up by such-and-such an amount, that variable goes down by such-and-such an amount'), the occurrence of linkages poses problems for anyone developing a publication like MAP. And, of course, real-world linkages are much more complex.
One must decide how to present linkages between aspects of progress to the reader. To present particular linkages rigorously (and to present the full network of linkages comprehensively), one would need to provide a model of interactions between and within Australian society, economy and environment. The ABS puts considerable effort into developing statistical frameworks and data models that encapsulate the characteristics of entities (individuals, households, businesses, government agencies and other organisations) and the transactions, interactions and relationships between them. That work is informed by and seeks to assist 'scientific' models of the world; but developing such scientific models is not the business of a statistical agency. And a full-blown presentation of such models would be unsuitable for a publication like MAP.
On the other hand, ignoring linkages between the different aspects of progress could mislead readers of MAP into believing that an assessment of past progress can be achieved by a simple summation of changes in the indicators, or that a vision of future progress can be achieved by sketching a desirable or probable trajectory for each of the indicators. To forestall such an oversimplified view, the introductory chapters of MAP include a general discussion of 'How the progress indicators relate to one another'; and the chapter on each dimension of progress includes a short discussion of links to other dimensions. These discussions have been distilled from the large body of Australian and overseas research, and have been tested through user review.
Continuing development
These headline indicators form a core set of statistics for reporting on Australian progress. But the we have chosen will change over time, because, for example:
• Thinking may change about what is important to national progress.
• There may be conceptual developments relating to one or more dimensions of progress (such as social cohesion).
• There may be statistical developments that allow us to measure aspects of progress for which we do not at present construct indicators (such as human capital).
The commentary accompanying each headline indicator discusses what an ideal progress indicator might be for each dimension. The conceptually ideal indicators may, in some cases, help guide the continuing development of Measures of Australia's Progress.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Catalogue Number
6301.0 - Average Weekly Earnings, Australia, Preliminary, Nov 2000
Latest ISSUE Released at 11:30 AM (CANBERRA TIME) 05/02/2001
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MEDIA RELEASE
February 05, 2001
Embargoed: 11:30 AM (AEST)
10/2001
Wage Cost Index replaces Average Weekly Earnings as ABS principal wages indicator
In a move designed to increase the focus on its Wage Cost Index series for the tracking of wage and salary movements, and reduce the focus on its Average Weekly Earnings series, the Australian Bureau of Statistics (ABS) today announced changes to the publication schedules for these statistics.
The ABS has brought forward the timing of its Wage Cost Index publication and will cease the production of its preliminary Average Weekly Earnings statistics. The final Average Weekly Earnings publication will continue to be released each quarter to its current timetable.
Australian Statistician, Dennis Trewin, said the initiative was taken because he was concerned about the attention that was being given to the Average Weekly Earnings series as indicators of change in wage rates.
"Although they are often used that way, the Average Weekly Earnings series are significantly affected by changes in the composition of the work force which undermine their use as indicators of change in wage rates," he said.
"While the Average Weekly Earnings series continue to provide a reliable measure of the average wage bill, because they reflect factors such as the upward shift in the skill level of the work force, they do not represent changes in wage costs on a 'constant quality' basis.
"The Average Weekly Earnings series can also be affected by the rolling-in of some entitlements into wages and salaries as a result of some workplace agreements."
Mr Trewin said the Wage Cost Index series (cat. no. 6345.0) provide each quarter direct measures of change in wage and salary rates on a 'constant quality' basis and are, in his opinion, far superior measures of this change.
"The publication timetable for the Wage Cost Index will be brought forward from the March quarter 2001 issue (due out on 16 May 2001) so that it will become the first quarterly release on wage movements," he said.
The preliminary Average Weekly Earnings series (cat. no.6301.0) will be discontinued after the November 2000 issue, which will be released on 9 February 2001. The final Average Weekly Earnings publication (cat. no.6302.0) will continue to be released - the November 2000 issue will be released on 1 March 2001, and the February 2001 issue on 17 May 2001, one day after the Wage Cost Index publication.
The changes that are being made relate to the publication of these statistical series only. The source collections will continue in the same way and the same level of statistical detail will be available as now.
Mr Trewin advised that the Average Weekly Earnings series will continue, as they are useful for analysis purposes, and are frequently used for indexation and contract escalation.
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Research article
Perceptions and behaviors related to hand hygiene for the prevention of H1N1 influenza transmission among Korean university students during the peak pandemic period
Jae-Hyun Park1, Hae-Kwan Cheong1*, Dae-Yong Son2, Seon-Ung Kim2 and Chang-Min Ha2
Author Affiliations
1 Department of Social and Preventive Medicine, Sungkyunkwan University College of Medicine, Suwon, Korea
2 Sungkyunkwan University College of Medicine, Suwon, Korea
For all author emails, please log on.
BMC Infectious Diseases 2010, 10:222 doi:10.1186/1471-2334-10-222
The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2334/10/222
Received:24 March 2010
Accepted:28 July 2010
Published:28 July 2010
© 2010 Park et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
This study was performed to better assess the perceptions, motivating factors, and behaviors associated with the use of hand washing to prevent H1N1 influenza transmission during the peak pandemic period in Korea.
Methods
A cross-sectional survey questionnaire was completed by 942 students at a university campus in Suwon, Korea, between December 1 and 8, 2009. The survey included questions regarding individual perceptions, motivating factors, and behaviors associated with hand washing for the prevention of H1N1 influenza transmission.
Results
Compared to one year prior, 30.3% of participants reported increasing their hand washing frequency. Female students were more likely to practice more frequent hand washing. Women also perceived the effectiveness of hand washing to be lower, and illness severity and personal susceptibility to H1N1 infection to be higher. Study participants who were female (OR: 1.79-3.90) who perceived of hand washing to be effective (OR: 1.34-12.15) and illness severity to be greater (OR: 1.00-3.12) washed their hands more frequently.
Conclusions
Korean students increased their frequency of hand hygiene practices during the pandemic, with significant gender differences existing in the attitudes and behaviors related to the use of hand hygiene as a means of disease prevention. Here, the factors that affected hand washing behavior were similar to those identified at the beginning of the H1N1 or SARS pandemics, suggesting that public education campaigns regarding hand hygiene are effective in altering individual hand hygiene habits during the peak periods of influenza transmission.
Background
In April 2009, a new strain of influenza virus - A/H1N1 - began appearing in several different countries around the world. The World Health Organization (WHO) raised the influenza pandemic alert level to Phase 5 on April 29, 2009, and later to Phase 6, indicating that a full global pandemic was under way. By May 23, 2009, 12,022 H1N1 cases and 83 deaths had been confirmed in 43 countries [1]. In Korea, the first H1N1 influenza infection case was confirmed on May 3, 2009, and the first H1N1-related death occurred on August 15, 2009. By the beginning of September 2009, H1N1 cases had increased dramatically, with 4,293 cases and 3 deaths confirmed by the end of September 2009. The H1N1 infection rate peaked two months later in November 2009, at which time approximately 9,000 new cases of A/H1N1 influenza were being confirmed each day. By the end of the month, a total of 104 deaths had resulted from H1N1-related causes [2], leading the Korean government to declare a public "Emergency Response Level." At that time, approximately one half of all patients seeking treatment for "common cold-like symptoms" were found to have H1N1 influenza[3].
As no vaccine for H1N1 Influenza had been developed, the Korean government attempted to mitigate the spread of disease by reducing transmission. Infected individuals were identified, isolated, and treated, while public health campaigns were initiated to educate the general public about preventive behaviors that reduce the risk of transmission. The specific techniques recommended included sneezing into a tissue and washing hands regularly with soap and water [4]. Given that the evidence regarding the preventive effectiveness of wearing a facemask is inconclusive [5], hand hygiene was considered the easiest and most effective measure [6] to prevent the spread of influenza A/H1N1.
Previously, multiple studies were undertaken to identify the factors that most effectively motivated people to adopt specific hand hygiene behaviors. Data collected during the SARS pandemic and at the onset of the H1N1 epidemic had already ascertained several such factors, including the perceived effectiveness of hand hygiene [7,8], the perceived susceptibility to illness [8-10], the perceived severity of the illness [8], and levels of anxiety associated with infection [7,11]. However, most of the previous studies were preformed during the recent SARS pandemic, and several studies were conducted at the outset of the H1N1 influenza pandemic [12,13].
The current study was designed to qualify recent hand-washing behaviors, changes in hand-washing behaviors, relationship between hand washing frequency and flu-like symptom as well assess the perceptions, attitudes, and motivating factors regarding hand washing during the peak period of the H1N1 influenza pandemic through the use of a cross-sectional survey model.
Methods
Participants and Procedures
For this study, subjects were recruited by convenience sampling from Sungkyunkwan University, a public university located in Suwon, Korea with an enrollment of 8,485 male students and 2,600 female students. Inclusion criteria included current enrollment as a student and willingness to participate in a research study. Without exception, all students who agreed to participate completed the questionnaire. Subjects were recruited from university residence halls and the campus library during a one-week period between 12/01/09 and 12/8/09. Individuals who agreed to participate were given the study questionnaire to complete on their own. In total, 942 students (738 males, 204 females) completed the questionnaire, with the proportion of male participants to female participants accurately reflecting the student body demographics at Sungkyunkwan University. Pilot surveys were conducted prior to the study in order to confirm that participants could understand the survey questions and to ensure the validity of the questionnaire content. with face or content validity of the questionnaires. Using the results of this pilot study, the survey questionnaire was amended to create a final version. This study was approved by the Samsung Medical Center IRB (No: 2009-12-030) in Korea.
Measurements
The study questionnaire was designed to assess recent hand-washing behaviors, changes in hand-washing behaviors, information encountered regarding hand washing, perceived effectiveness of hand washing in preventing infection with H1N1 influenza, perceived severity of H1N1 influenza, perceived susceptibility to H1N1 influenza infection, and recent flu-like symptoms. The study questionnaire was modeled after other similar questionnaires used in prior SARS or H1N1 studies [12,13], and was subsequently modified to reflect the current situation of the H1N1 epidemic in Korea. The variables, matched questions, and answer categories included in the survey questionnaire (see Additional file 1) are summarized in Table 1. Subject gender, age, and residence type (university residence hall versus other) was also recorded. Additionally, participants were asked if any acquaintances (e.g. family members, friends, etc) were currently experiencing flu-like symptoms.
Additional file 1. Questionnaire.
Format: DOC Size: 48KB Download file
This file can be viewed with: Microsoft Word Viewer
Table 1. Variables and matched questions in the questionnaire
Statistical analyses
Using chi-squared tests, the following variables were examined for differences by gender: recent hand washing frequency, changes in hand washing frequency, information encountered about hand washing, perceived effectiveness of hand washing, perceived severity of H1N1 influenza, and perceived susceptibility to H1N1 infection, and recent flu-like symptoms. Additionally, each variable was evaluated for correlation with all other variables using the chi-squared test to identify trends. To identify factors related to the frequency of hand washing, both chi-square tests and multiple logistic regression models were used. For the logistic regression modeling, additional independent variables were selected based on data from several previous studies, including gender, presence flu-like symptoms among subject acquaintances, information encountered about hand washing, perceived effectiveness of hand washing, perceived illness severity, and perceived illness susceptibility. Chi-squared tests were also used to evaluate the relationship between recent hand washing frequency and recent flu-like symptoms by gender, with multiple logistic regression modelling employed to adjust for gender, age, type of residence, and presence of flu-like symptoms among acquaintances. Recent hand washing frequency was re-classified #4, 5-7, #8, given the frequency of each category and statistical stability in multiple logistic regression models. All of the multiple logistic regression models were validated by the average receiver operating characteristics and the p-value for the Hosmer-Lemeshow goodness-of-fit test. The software program SPSS 15.0 was used to for all data analysis. Two-tailed p-values ≥ 0.05 were considered statistically significant.
Results
General study subject demographics
General participant demographics are outlined in Table 2. A total of 942 participants were enrolled, of which 78.3% were male. Male students were more likely to live in university residence halls, while more female students were more likely to have acquaintances that had experienced flu-like symptoms in the recent past.
Table 2. General demographics, reported hand washing behaviors, and perceived effectiveness, severity, and susceptibility of the participants
Changes in hand washing frequency
The reported frequency of hand washing behavior was greater in women than men (Table 2). While 34.4% of male students reported washing their hands five times a day, 57.4% of female students reported washing their hands with this same frequency. Additionally, 30.3% of participants reported increasing their personal frequency of hand washing within the last year. After stratifying by gender, both groups reported an increased frequency of hand washing compared with one year ago, with these trends reaching statistical significance by Chi-square analysis (Figure 1).
Figure 1. Changes in reported daily hand washing frequency (%).
Information encountered and perceptions related to the effectiveness of hand washing, severity of the illness, and susceptibility to H1N1 influenza
A majority of participants reported encountering information regarding hand washing (males: 91.2%, females: 94.6%) and perceived hand washing as an effective measure to prevent H1N1 influenza transmission (Table 2). Men were more likely to perceive hand washing as an effective preventive measure (P = 0.006). Regarding perception of H1N1 influenza severity, while 56.1% of subjects believed that infection with H1N1 influenza would produce mild symptoms similar to those of the common cold, women were more likely to perceive infection with H1N1 influenza as potentially fatal (P < 0.001) (Table 2). Roughly half of the participants (59.5%) rated their personal susceptibility to H1N1 influenza as "low" or "somewhat low," although female students were more likely to perceive their personal susceptibility to H1N1 to be higher (p = 0.002).
Intervariable Correlations
Having an acquaintance with recent flu-like symptoms was positively correlated with reporting recent flu-like symptoms (P < 0.001), information encountered (P < 0.001), and perceived severity (P = 0.026). Reporting recent flu-like symptoms was negatively correlated with hand washing frequency (P = 0.034) and positively correlated with information encountered (P = 0.038) and perceived personal susceptibility (P < 0.001). Hand washing frequency was positively correlated with perceived effectiveness (P = 0.002) and perceived severity (P = 0.001). Information encountered was positively correlated with perceived severity (P = 0.013). Perceived severity was positively correlated with perceived susceptibility (P = 0.001) (Table 3).
Table 3. Correlations with each variable
Factors related to frequency of hand washing
In both univariate and multivariate logistic regression analyses, women were found to wash their hands more frequently than men (Table 4). Participants who perceived hand washing as more effective washed their hands more frequently, as did those who perceived the severity of H1N1 influenza to be higher. However, no significant relationships were identified between hand washing frequency and the following variables: having an acquaintance with recent flu-like symptoms, the degree of information encountered about hand washing, and the perceived susceptibility to infection. Interaction terms were tested, however no interaction effects between independent variables were found. The p-value for the Hosmer-Lemeshow test was 0.465.
Table 4. Logistic regression analysis: factors related to recent reported increases in hand washing frequency (≥5 times a day/<4 times a day).
Relationship between subjects with recent flu-like symptoms and hand washing frequency
In men, flu-like symptoms were more prevalent in participants with less frequent hand washing habits. However, no such relationship between recent flu-like symptoms and hand washing frequency was identified in women. After adjusting for age, residence type, and having an acquaintance with flu-like symptoms by multivariate logistic regression, men with frequent hand washing behavior were found to be less likely to experience flu-like symptoms. However, no such relationship was observed in women. The p-value for the Hosmer-Lemeshow test was 1.000 for males and 0.296 for females (Table 5).
Table 5. Relationship between recent flu-like symptoms and reported hand washing frequency.
Discussion
Our study demonstrates that, during the peak pandemic periods of H1N1 influenza, most subjects reported increasing their personal frequency of hand washing in order to prevent infection. Similar findings were also reported in studies conducted at the beginning of the H1N1 influenza pandemic in Hong Kong [12]. In a study from the United Kingdom (UK), 28% of subjects reported changing their hand washing behavior as a result of H1N1 influenza [13]. When viewed together, the data from all of these studies imply that behaviors preventative of infection - such as hand washing - become more prevalent during pandemics.
Here, we found that, during the H1N1 pandemic, men reported washing their hands less frequently than women. Several previous studies have also concluded that women are more likely to follow behavioral recommendations (such as hand washing) to prevent the transmission of H1N1 influenza, SARS, or other infectious diseases [7,8,11,13]. Our results also show that the majority of subjects had encountered information about hand washing (males: 91.2%, females: 94.6%) and most perceive hand washing to be an effective measure in preventing the transmission of H1N1 influenza (males: 95.7%, females: 96.1%). These results suggest that the recent public campaigns regarding H1N1 infection prevention conducted through mass media and public education have been successful in terms of public knowledge acquisition. Similar findings were observed in other studies performed during the H1N1 influenza pandemic both in Hong Kong [12] and the UK [13]. However, in the present study, we demonstrate that gender significantly affects perceptions of hand washing effectiveness. Specifically, men are more likely to perceive hand hygiene to be an effective preventive measure against H1N1 infection. Interestingly, several previous studies conducted in Hong Kong during the SARS pandemic concluded exactly the opposite: these studies found that, when compared with women, men were less likely to believe that preventive behaviors were efficacious in controlling SARS [11,14,15]. While such differences could result from differences in study population demographics, profound differences may also exist in perceptions of hand washing between the two countries. Regardless, these conflicting findings highlight the need for additional cross-national comparative studies similar to one previous study conducted during the SARS pandemic [16].
Notably, our data indicate that gender also affects the participants' perceived severity of the H1N1 influenza as well as their own personal susceptibility to the disease. Not only were perceptions of illness severity higher among women, female participants were also more likely to perceive their own personal susceptibility to H1N1 influenza as higher. With regards to these findings, several previous studies conducted during the SARS pandemic [16] also reported similar gender-specific results. As for the perceived severity of illness and perceived susceptibility to H1N1 influenza, this study shows similar perceptions to a study conducted at the beginning of the H1N1 influenza pandemic in Hong Kong [12]; In the Hong Kong study, 64.0% of participants indicated that an H1N1 influenza infection would have "no impact" or "only a minor impact" on their daily life, while 59.7% of men and 42.9% women in our study held these beliefs. Furthermore, only 7.0% of men and 10.3% of women in our cohort, and 10% of participants from the Hong Kong study indicated believing that their personal probability of contracting H1N1 was "high" or "very high."
In this study, study participants who were female, who perceived the overall severity of the illness to be greater and hand washing to be effective in preventing disease washed their hands more frequently. Notably, these data correspond with results from multiple previous studies in regard to the relationship between the frequency of hand washing and female gender [7,8,11,12,17], perceived efficacy of hand washing [12], and perceived severity of the illness [12]. However, information contact was not corrected with hand washing in this study. We contend that due to a ubiquitous media campaign, the public was already well informed about H1N1 influenza (males: 91.2%, females: 94.6%) by the time our survey was conducted, and thus any effect of obtaining information on hand washing behavior was likely minimized. Similar findings were observed in a previous study from the UK [12], where the perceived susceptibility to the illness had no additional effect on hand washing not already documented by previous studies [8-10,12,18].
Lastly, we examined the relationship between hand washing frequency and flu-like symptoms. Although we did not confirm H1N1 infection by viral culture or PCR, we preliminarily identified a relationship between hand washing behaviors and flu-like symptoms in men. However, as this study is cross-sectional in design, we were not able to determine causality between the variables. Nonetheless, despite being unable to confirm a causal relationship between hand hygiene and H1N1 virus transmission, the correlations identified in this study suggest a possible preventive effect of hand hygiene.
This study has notable several limitations. First, we were unable to distinguish H1N1 influenza infection from other upper respiratory tract infections among individuals who reported flu-like symptoms, as we did not use laboratory confirmation techniques. Symptom-based outcomes often lack specificity for influenza virus infections [5,19], as they allow for variable interpretations. In our self-administered questionnaire, 'flu-like symptoms' could be construed differently by different students. However, as the survey period occurred during the peak period of the H1N1 influenza pandemic, public attention and information about H1N1 influenza can be assumed to be high. Consequently, the reliability and validity of using a descriptor like 'flu-like symptoms' may not have significantly skewed our data. Second, even though the relationship between hand hygiene and flu-like symptoms may have mixed effects on H1N1 influenza and the common cold, the contact and inhalation transmission hypotheses are relatively similar for both diseases, suggesting an overall importance of hand hygiene. Furthermore, as the survey was conducted during the peak period of the H1N1 influenza pandemic, the importance of improved hand hygiene should be emphasized. A third limitation is inherent to the study design: the use of convenience sampling - as opposed to random sampling - imposes some inherent selection bias and diminishes the internal validity. To maintain internal validity, we attempted to match the gender ratio of participants in our study with that of the general university population. Our study is further limited by the cross-sectional study design, which prevents the identification of any causal relationships, even though associations between the variables and reverse cause-effect relationships may exist. Lastly, the participants in our study were exclusively composed of students from a single university in Korea. As this does not represent the general Korean population, caution should be exercised when comparing these results with other studies.
Despite these limitations, our study provides invaluable insight into the general perceptions and preventive behaviors relating to H1N1 influenza among young Koreans during the peak of the H1N1 influenza pandemic. Korean students were found to increase their frequency of hand hygiene during the pandemic, and gender differences were apparent in attitudes and behaviors related to the prevention of influenza through the use of hand hygiene. Here, the factors that affected hand washing behavior were similar to those identified at the beginning of the H1N1 or SARS pandemics, suggesting that public education campaigns regarding hand hygiene are effective in altering individual hand hygiene habits during the peak periods of influenza transmission. Further studies conducted during different periods of pandemic influenza transmission are necessary to better describe changing patterns in public perceptions of illness, preventive behaviors, and outcomes of pandemic influenza transmission.
Conclusion
Korean students increased their frequency of hand hygiene during the pandemic, and gender differences were apparent in attitudes and behaviors related to the prevention of influenza by hand hygiene. Here, the factors that affected hand washing behavior were similar to those identified at the beginning of the H1N1 or SARS pandemics, suggesting that public education campaigns regarding hand hygiene are effective in altering individual hand hygiene habits during the peak periods of influenza transmission.
Abbreviations
(WHO): World Health Organization; (SARS): Severe acute respiratory syndrome; (UK): United Kingdom.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
JHP contributed to the conception of study and interpretation, and writing the manuscript. HKC participated in the conception of the study and drafting of the manuscript. DYS participated in the design and data collection. SUK participated in the design and statistical analysis. CMH participated in the design, data collection and statistical analysis. All authors read and approved the final manuscript.
References
1. World Health Organization: Influenza A(H1N1) e update 31. [http://www.who.int/csr/don/2009_05_17/en/index.html] webcite
2009 May 17 [accessed 17.05.09]
2. The Korea Centers for Disease Control and Prevention, Republic of Korea [http://www.cdc.go.kr/] webcite
2009 November 30 [accessed 04.02.10]
3. Minister for Health, Welfare and Family Affairs, Republic of Korea [http://www.mohw.go.kr/front/al/sal0301ls.jsp?PAR_MENU_ID=04&MENU_ID=0403] webcite
2009 November 2 [accessed 04.02.10]
4. Minister for Health, Welfare and Family Affairs, Republic of Korea [http://www.mohw.go.kr/front/al/sal0301ls.jsp?PAR_MENU_ID=04&MENU_ID=0403] webcite
2009 August 20 [accessed 04.02.10]
5. Cowling BJ, Fung RO, Cheng CK, Fang VJ, Chan KH, Seto WH, Yung R, Chiu B, Lee P, Uyeki TM, Houck PM, Peiris JS, Leung GM: Preliminary findings of a randomized trial of non-pharmaceutical interventions to prevent influenza transmission in households.
PLoS ONE 2008, 3:e2101. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
6. Morrison LG, Yardley L: What infection control measures will people carry out to reduce transmission of pandemic influenza? A focus group study.
BMC Public Health 2009, 9:258. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
7. Lau JTF, Yang X, Tsui H, Kim JH: Monitoring community responses to the SARS pandemic in Hong Kong: from day 10 to day 62.
J Epidemiol Community Health 2003, 57:864-70. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
8. Tang CSK, Wong C-Y: Factors influencing the wearing of facemasks to prevent the severe acute respiratory syndrome among Chinese in Hong Kong.
Prev Med 2004, 39:1193. Publisher Full Text
9. Tang CSK, Wong C-Y: An outbreak of the severe acute respiratory syndrome: predictors of health behaviors and effect of community prevention measures in Hong Kong, China.
Am J Public Health 2003, 93:1887-8. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
10. Leung GM, Quah S, Ho LM, Ho SY, Hedley AJ, Lee HP, Lam TH: A tale of two cities: community psychobehavioral surveillance in Hong Kong and Singapore during the severe acute respiratory syndrome pandemic.
Infect Control Hosp Epidemiol 2004, 25:1033-41. PubMed Abstract | Publisher Full Text
11. Leung GM, Ho LM, Chan SK, Ho SY, Bacon-Shone J, Choy RY, Hedley AJ, Lam TH, Fielding R: Longitudinal assessment of community psychobehavioral responses during and after the 2003 outbreak of severe acute respiratory syndrome in Hong Kong.
Clin Infect Dis 2005, 40:1713-20. PubMed Abstract | Publisher Full Text
12. Lau JT, Griffiths S, Choi KC, Tsui HY: Widespread public misconception in the early phase of the H1N1 influenza pandemic.
J Infect 2009, 59(2):122-7. PubMed Abstract | Publisher Full Text
13. Rubin GJ, Amlôt R, Page L, Wessely S: Public perceptions, anxiety, and behaviour change in relation to the swine flu outbreak: cross sectional telephone survey.
BMJ 2009, 2(339):b2651. Publisher Full Text
14. Lau JT, Yang X, Tsui HY, Pang E: SARS related preventive and risk behaviours practised by Hong Kong-mainland China cross border travellers during the outbreak of the SARS pandemic in Hong Kong.
J Epidemiol Community Health 2004, 58(12):988-996. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
15. Lau JT, Yang X, Pang E, Tsui HY, Wong E, Wing YK: SARS-related perceptions in Hong Kong.
Emerg Infect Dis 2005, 11(3):417-424. PubMed Abstract | Publisher Full Text
16. de Zwart O, Veldhuijzen IK, Elam G, Aro AR, Abraham T, Bishop GD, Voeten HA, Richardus JH: Brug: Perceived threat, risk perception, and efficacy beliefs related to SARS and other (emerging) infectious diseases: results of an international survey.
J Int J Behav Med 2009, 16(1):30-40. Publisher Full Text
17. Nobile CG, Montuori P, Diaco E, Villari P: Healthcare personnel and hand decontamination in intensive care units: knowledge, attitudes, and behaviour in Italy.
J Hosp Infect 2002, 51(3):226-232. PubMed Abstract | Publisher Full Text
18. Brewer NT, Chapman GB, Gibbons FX, Gerrard KD, McCaul KD, Weinstein ND: Meta-analysis of the relationship between risk perception and health behavior: the example of vaccination.
Health Psychol 2007, 26:136-45. PubMed Abstract | Publisher Full Text
19. Call SA, Vollenweider MA, Hornung CA, Simel DL, McKinney WP: Does this patient have influenza?
JAMA 2005, 293:987-97. PubMed Abstract | Publisher Full Text
Pre-publication history
The pre-publication history for this paper can be accessed here:
http://www.biomedcentral.com/1471-2334/10/222/prepub
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You are here: Home / Data and maps / Maps and graphs / Separate collection of biodegradable waste fractions in the Flemish Region of Belgium
Separate collection of biodegradable waste fractions in the Flemish Region of Belgium
Created : Nov 12, 2009 Published : Jun 23, 2009 Last modified : Nov 29, 2012 11:35 AM
Municipalities are required to organise separate collection of either biowaste or garden waste (in combination with home composting of biowaste).
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Difference between revisions of "Conferences"
From Forensics Wiki
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(Research Conferences and Workshops)
(Research Conferences and Workshops)
Line 21: Line 21:
;CanSecWest
;CanSecWest
:http://cansecwest.com/
:http://cansecwest.com/
;Computer and Enterprise Investigations Conference (CEIC)
:http://www.ceicconference.com/
;Conference on Digital Forensics, Security and Law
;Conference on Digital Forensics, Security and Law
Revision as of 08:01, 12 August 2011
This is a list of conferences in the computer forensics field, and was originally taken from Brian Carrier's list of conferences and journals at http://www.digital-evidence.org/publish/index.html and used with his permission. Brian no longer maintains those listings and points back to this Wiki.
For Dates and Locations of upcoming conferences and training events, see the pages titled Upcoming events (Calls for papers, Conferences and On-Demand Training) and Scheduled Training Courses (Training Classes/Courses scheduled for specific dates/locations).
Research Conferences and Workshops
Research conferences that are related to digital investigation and forensics.
American Academy of Forensic Science
http://www.aafs.org/default.asp?section_id=meetings&page_id=aafs_annual_meeting
Australian Digital Forensics Conference
http://scissec.scis.ecu.edu.au/conferences2008/index.php?cf=2
BlackHat Japan Briefings & Training
http://japan.blackhat.com/
BlackHat Federal Briefings & Training
http://www.blackhat.com/html/bh-link/briefings.html
CanSecWest
http://cansecwest.com/
Conference on Digital Forensics, Security and Law
http://www.digitalforensics-conference.org/
CyberCrime Summit (Last found in 2010)
http://www.cybercrimesummit.com/index.htm
Department of Defense CyberCrime Conference
http://www.dodcybercrime.com/
Detection of Intrusions and Malware & Vulnerability Assessment (DIMVA)
www.dimva.org/
e-Forensics (Last found in 2010)
http://www.e-forensics.eu/
E-Crime and Computer Evidence (NOTE - Can't find any since 2006)
http://www.ecce-conference.com
EuSecWest
http://eusecwest.com/
EuroForensics-Forensics Sciences Conference and Exhibition
http://www.euroforensics.com/
FIRST Conference
http://www.first.org/conference
French-Speaking Days on Digital Investigations - Journées Francophones de l'Investigation Numérique
http://www.afsin.org/
IFIP International Information Security Conference
http://sec2008.dti.unimi.it/index.php
IFIP WG 11.9 International Conference on Digital Forensics
http://www.ifip119.org/Conferences/
International Conference on Availability, Reliability and Security
http://www.ares-conference.eu/conf/
International Conference on Information and Communication Technologies in Forensics (ICTinForensics)
http://www.ICTinForensics.org
International Conference on IT-Incident Management & IT-Forensics
http://www.imf-conference.org
International Symposium on Recent Advances in Intrusion Detection
http://www.ll.mit.edu/IST/RAID2008/
Mobile Forensics Conference
http://www.mobileforensicsconference.com/
Open Source Software for Computer and Network Forensics (Last seen in 2008)
http://conferenze.dei.polimi.it/ossconf/index.php
Open Web Application Security Project
http://www.owasp.org/index.php/Main_Page
PacSec Conference
http://pacsec.jp/
SANS WhatWorks Summit in Forensics and Incident Response
http://www.sans.org/forensics09_summit/index.php
Security OPUS Information Security Conference
http://www.securityopus.com/index.php
Sleuthkit and Open Source Forensics Conference
http://www.basistech.com/about-us/events/open-source-forensics-conference/
Systematic Approaches to Digital Forensic Engineering (SADFE)
http://conf.ncku.edu.tw/sadfe/
USENIX Annual Technical Conference
http://www.usenix.org/events/
USENIX Security Symposium
http://www.usenix.org/events/
Virus Bulletin Conference
http://www.virusbtn.com/conference/index
Training Conferences
ChicagoCon - White Hats Come Together in Defense of the Digital Frontier
http://www.chicagocon.com
Computer and Enterprise Investigations Conference (CEIC)
http://www.ceicconference.com/
HTCIA International Training Conference and Expo
http://www.htcia.org/index.shtml
IACIS Computer Forensic Training Event
http://www.cops.org/training
Mobile Forensics World Training
http://www.MobileForensicsWorld.org/Training.aspx
Regional Computer Forensics Group Conference (RCFG)
http://www.rcfg.org
SANS Computer Forensics, Investigation, and Response
http://forensics.sans.org/events/
Techno Forensics Conference
http://www.techsec.com/
Techno-Security Conference
http://www.techsec.com/
See also
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Books
From Forensics Wiki
Revision as of 15:21, 7 August 2011 by Ahoog (Talk | contribs)
Jump to: navigation, search
Contents
General books about forensics
Title Author ISBN Publisher Publication Date Comment
Principles and Practice of Criminalistics: The Profession of Forensic Science Keith Inman and Norah Rudin 0849381274 CRC Press Aug 29, 2000 Highly Recommended
Forensic Science Handbook, Volume I (2nd Edition) Richard E. Saferstein, Ed. 0130910589 Prentice Hall Jun 5, 2001
Forensic Science Handbook, Volume II (2nd Edition) Richard E. Saferstein, Ed. 013112434X Prentice Hall Oct 8, 2004
Forensic Science Handbook, Volume III Richard E. Saferstein, Ed. 0133253902 Prentice Hall Apr 22, 1993
Forensic Science: An Introduction to Scientific and Investigative Techniques, Second Edition Stuart James and Jon J Nordby 0849327474 CRC Press Feb 10, 2005
Ethics in Forensic Science: Professional Standards for the Practice of Criminalistics Peter D Barnett 0849308607 CRC Press Jun 27, 2001
Wiley Encyclopedia of Forensic Science (Five Volume Set) Allan Jamieson (Ed) and Andre Moenssens (Ed) 0470018267 Wiley Jun 29, 2009
Books about computer forensics
Title Author ISBN Publisher Publication Date Comment
File System Forensic Analysis Brian Carrier 0321268172 Addison-Wesley Mar 27, 2005 (Highly recommended)
Android Forensics: Investigation, Analysis and Mobile Security for Google Android Andrew Hoog 1597496510 Syngress June 2011
iPhone and iOS Forensics: Investigation, Analysis and Mobile Security for Apple iPhone, iPad and iOS Devices Andrew Hoog and Katie Strzempka 1597496596 Syngress June 2011
Forensic Discovery Dan Farmer and Wietse Venema 0321703251 Addison-Wesley Dec 28, 2009 HTML version of the book is freely available online.
Digital Evidence and Computer Crime Second Edition Eoghan Casey 0121631044 Academic Press Mar 22, 2004
Handbook of Digital Forensics and Investigation Eoghan Casey 0123742676 Academic Press Nov 09, 2009
Incident Response & Computer Forensics, Second Edition Kevin Mandia, Chris Prosise & Matt Pepe 007222696X McGraw-Hill/Osborne Jul 17, 2003
Windows Forensics and Incident Recovery Harlan Carvey 0321200985 Addison Wesley Professional Jul 21, 2004
Forensic Examination of Digital Evidence: A Guide for Law Enforcement NCJ 199408 National Institute of Justice April 2004 Special Report
Electronic Crime Scene Investigation: A Guide for First Responders NCJ 187736 National Institute of Justice July 2001 NIJ Guide
Investigating Computer-Related Crime Peter Stephenson 0849322189 CRC Press Sep 28, 1999
Investigator's Guide to Steganography Gregory Kipper 0849324335 Auerbach Publications Oct 27, 2003
Cyber Forensics: A Field Manual for Collecting, Examining, and Preserving Evidence of Computer Crimes Albert J Marcella, Jr. and Robert S Greenfield 0849309557 Auerbach Publications Jan 23, 2002
Investigating Computer Crime Franklin Clark and Ken Diliberto 0849381584 CRC Press Jul 11, 1996
Windows Forensic Analysis
Windows Forensic Analysis DVD Toolkit, Second Edition
Harlan Carvey 159749156X
1597494224
Syngress (Elsevier) May 21, 2007
Jun 11, 2009
CD and DVD Forensics Paul Crowley and Dave Kleiman(Technical Editor) 1597491284 Syngress Nov 8, 2006
Mastering Windows Network Forensics and Investigation Steven Anson and Steve Bunting 0470097620 Sybex April 02, 2007
iPhone Forensics Jonathan Zdziarski 0596153589 O'Reilly Sep 12, 2008
Mac OS X, iPod, and iPhone Forensic Analysis DVD Toolkit Ryan R. Kubasiak, Sean Morrissey and Jesse Varsalone (Tech. Ed.) 1597492973 Syngress Dec 08, 2008
Books in other languages
German
Title Author ISBN Publisher Publication Date Comment
Computer-Forensik, 2nd edition Alexander Geschonneck 3898643794 2006 Errata and blog of the author
Italian
Title Author ISBN Publisher Publication Date Comment
Computer Forensics 1st edition Andrea Ghirardini and Gabriele Faggioli 8850325932 Apoge May 17, 2007 EAN 9788850325931
Portuguese
Title Author ISBN Publisher Publication Date Comment
Perícia Forense Aplicada à Informática 1st edition Andrey Rodrigues de Freitas 8574522260 Brasport 2006
Russian
Title Author ISBN Publisher Publication Date Comment
Форензика – компьютерная криминалистика N. N. Fedotov
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Changes related to "Introduction to Steganography: Steganography and Data Exfiltration"
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Trevor Baxendale - Alphabetical Bibliography
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Other views: Summary Awards Chronological
Novels Omnibus Shortfiction Essays Interior Art
Copyright (c) 1995-2011 Al von Ruff.
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Bibliography: Epilogue (Twilight World)
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Title: Epilogue (Twilight World)
Author: Poul Anderson
Year: 1961
Type: SHORTFICTION
Storylen: shortstory
Series: Tomorrow's Children
Series Number: 4
Language: English
ISFDB Record Number: 663185
User Rating: This title has fewer than 5 votes. VOTE
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Nutrients 2013, 5(1), 97-110; doi:10.3390/nu5010097
Review
Selenium in Bone Health: Roles in Antioxidant Protection and Cell Proliferation
Grand Forks Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Grand Forks, ND 58202, USA
* Author to whom correspondence should be addressed.
Received: 28 November 2012; in revised form: 17 December 2012 / Accepted: 3 January 2013 / Published: 10 January 2013
(This article belongs to the Special Issue Dietary Selenium and Health)
Download PDF Full-Text [477 KB, uploaded 10 January 2013 11:27 CET]
Abstract: Selenium (Se) is an essential trace element for humans and animals, and several findings suggest that dietary Se intake may be necessary for bone health. Such findings may relate to roles of Se in antioxidant protection, enhanced immune surveillance and modulation of cell proliferation. Elucidation of the mechanisms by which Se supports these cellular processes can lead to a better understanding of the role of this nutrient in normal bone metabolism. This article reviews the current knowledge concerning the molecular functions of Se relevant to bone health.
Keywords: antioxidant; bone health; cell proliferation
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Cite This Article
MDPI and ACS Style
Zeng, H.; Cao, J.J.; Combs, G.F., Jr. Selenium in Bone Health: Roles in Antioxidant Protection and Cell Proliferation. Nutrients 2013, 5, 97-110.
AMA Style
Zeng H, Cao JJ, Combs GF, Jr. Selenium in Bone Health: Roles in Antioxidant Protection and Cell Proliferation. Nutrients. 2013; 5(1):97-110.
Chicago/Turabian Style
Zeng, Huawei; Cao, Jay J.; Combs, Gerald F., Jr. 2013. "Selenium in Bone Health: Roles in Antioxidant Protection and Cell Proliferation." Nutrients 5, no. 1: 97-110.
Nutrients EISSN 2072-6643 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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OCCU-EVOLVE 14.0(WORK SESSION)-Agenda notes May 25, 2012
Posted by & filed under .
OCCU-EVOLVE 14.0(WORK SESSION)-Agenda and notes May 25, 2012
Facilitated by Sumumba, Robert, and Holly and Lauren
Location-Liberty Plaza
Introductions/Reportbacks Agenda-Robert Hernandez OTS, Lauren OTS, Sumumba National Gathering, MRG Proposal- Holly Health Care for the 99%, Mission Statement OBW-20 minutes-all items discussed…
I. Review last week’s notes-Sumumba-5minutes
II. What is Occu-Evolve (Brief overview for new comers)-5minutes-Sumumba
III. Upcoming Actions- For Housing 99%Hollis 5-28-12, June17, 2012(Proposals -consensed upon),
IV. Point Person discussion/Needs Campaign/Tabling-Proposal Rules for consenting -Brief discussion led by Sumumba
V. Ego Discussion(Ethics explaining) -10 minutes-Sumumba-tabled
VI. 10 Questions Part 1-group discussed first 4 points of 10 point discussion. No resolutions, but it was agreed that we’d work on the other questions as a follow up in coming weeks.-Hollie facilitated
VII. Actionable Items: following up on the 10 questions..-Hollie
VII. Announcements-10minutes-Occupic hosted by Occupy Astoria/Long Island City…Occu-Evolve members will be there…
VIII. Leisure Caucus? -none
IX. **NEXT MEETING location Occu-Picnic** and then internal meeting concerning needs of members sometime during week.
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My favourites
OpenWebMail
Community rating:
Notes:
Great product! My email provider EuMX.net offers this as their primary webmail client. It has all features I need: email, calendar, addressbook, filespace and above that it is fast!
What is a Stack?
It's a list of software used to accomplish something. LAMP is an example.
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Copyright © 2013 Black Duck Software, Inc. and its contributors, Some Rights Reserved. Unless otherwise marked, this work is licensed under a Creative Commons Attribution 3.0 Unported License . Ohloh ® and the Ohloh logo are trademarks of Black Duck Software, Inc. in the United States and/or other jurisdictions. All other trademarks are the property of their respective holders.
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CMD sent two reporters to track ALEC in Oklahoma
Click here to help support our future investigations.
John Shadegg
From SourceWatch
Jump to: navigation, search
John Shadegg previously served the 3rd Congressional district of Arizona
John Barden Shadegg, a Republican, is a former U.S. Representative for the 3rd Congressional district of Arizona, having served 1995 to 2011.[1][2]
Contents
Record and controversies
Iraq War
Shadegg voted for the Authorization for Use of Military Force Against Iraq Resolution of 2002 that started the Iraq War.[3]
For more information see the chart of U.S. House of Representatives votes on the Iraq War.
SKIL Act of 2007
The Securing Knowledge Innovation and Leadership Act, or the SKIL Bill, is targeted at increasing legal immigration of scientific, technology, engineering, and mathematics (STEM) workers into the United States by increasing the quotas on the H-1B visa, eliminating green card caps for certain advanced degree holders, and streamlining the processing of employment-based green cards.
Rep. John Shadegg (R-Ariz.) introduced the House version (H.R.1930) of the SKIL Act on April 17, 2007.
As of April 2007, the SKIL Bill was referred to the House Judiciary Committee.
Main article: SKIL Act of 2007
Term limits
When Shadegg was first elected as part of the "Republican revolution" in 1994, he supported the application of term limits to all members of Congress. However, after the limits were struck down on constitutional grounds, Shadegg ran again and won election for a sixth term in 2004. [1]
Constituent memo
On June 12, 2006, Shadegg sent reelection supporters an opinion piece on the federal investigation surrounding House Appropriations Committee chairman Jerry Lewis (R-Calif.). He wrote, “The debate continues on earmark reform … and, in my ongoing effort to illustrate the potential for abuse in the congressional spending process, created by unlimited earmarks, you may find the following commentary by John Fund at the Wall Street Journal informative.” The piece which Shadegg referred to condenses newspaper reports concerning the relationship of Lewis to a political action committee run by his stepdaughter (Small Biz Tech PACand) and the lobbying firm of Bill Lowery (Copeland Lowery Jacquez Denton & White), a close friend and former colleague. [2]
Bio
Shadegg was born October 22, 1949 in Phoenix, Arizona. He was educated at the University of Arizona B.A. 1972 J.D. 1975, served in the Arizona Air National Guard from 1969 to 1975, and was a lawyer, a special counsel to the Arizona state House Republican caucus from 1991-1992, special assistant attorney general in the State of Arizona 1983-1990, and an advisor to the United States Sentencing Commission before entering the House.
He has established a reputation in Congress as a leading advocate for reduced government spending, federal tax relief, and the re-establishment of state and individual rights.
Shadegg was recently elected Chairman of the House Republican Policy Committee, the fifth-ranking position in the House Leadership below the Majority Leader. He is the only member of the Republican Class of 1994 currently serving in leadership. He was a key player on the leadership team of former House Majority Leader Tom DeLay.
Shadegg claims to have never met DeLay associate and lobbyist Jack Abramoff. In 2005, he did return US$ 6,900 he received from parties linked to Abramoff. [3] Shadegg explained that he accepted through a former associate who, unbeknownst to him, had become affiliated with Abramoff. [4]
From 2000 to 2002, Congressman Shadegg served as chairman of the Republican Study Committee (RSC), the largest conservative organization in the U.S. House of Representatives. Under Shadegg's leadership, the organization grew from 40 to more than 70 members, and became the most influential and respected force in the U.S. House shaping conservative policy for the country.
On January 13, 2006 Shadegg officially joined the race for the House Majority Leader as a compromise alternative candidate to Representatives Roy Blunt and John Boehner. On Feb. 2, after Shadegg came third in the first ballot, his supporters switched to second place Boehner, ensuring Boehner's election on the second ballot. Shadegg is also the son of Steve Shadegg of Arizona, 1964 campaign manager for Republican presidential nominee Barry Goldwater.
2006 elections
In 2006, the Democrats nominated Herb Paine to face Shadegg in his November 2006 bid for reelection. (See U.S. congressional elections in 2006) [5] Shadegg easily retained his seat with nearly 60% of the vote.
Retirement
On February 11, 2008, Shadegg issued a statement on his website announcing his decision not to seek reelection in 2008. [4] Shadegg served 7 terms in the House of Representatives, starting in 1995. After Tom Delay’s resignation from the House in 2006, Shadegg unsuccessfully challenged for the Republican leadership of the House, losing to John Boehner and Roy Blunt. [5] Shadegg plans on returning to the private sector. [6]
2008 election
On February 21, at the urging of his Republican colleagues, Shadegg reversed his decision not to run for reelection. “146 of my colleagues in the U.S. House signed a letter asking me to reconsider, an unprecedented event,” Shadegg said in a statement. Shadegg said he was “stunned” and “humbled” by the response he received on Capitol Hill and, after careful consideration, decided he would run for another term.[7]
2010 election
Shadegg decided again to retire and did not run for reelection in 2010.[2]
Committees and affiliations
Committees
Committee assignments in the 109th Congress (2005-2006)
Coalitions and caucuses
• Chair, House Republican Policy Committee, 2005-present
• Chair, Republican Study Committee, 2000-2002
• Special Counsel, Arizona House Republican Caucus, 1991-1992
• Chair, 'It's Time' Anti-Tax Initiative
Boards and other affiliations
• Board Member, Arizona State University Law Society
• Vestry, Christ Church of the Ascension
• Former President, Crime Victim Foundation
• Founding Member, Friends of Lake Powell
• Founding Director, Goldwater Institute for Public Policy
• Former Chair, Juvenile Justice Advisory Board
• Advisory Board, Salvation Army
• Victim's Bill of Rights Task Force.
More background data
Wikipedia also has an article on John Shadegg. This article may use content from the Wikipedia article under the terms of the GFDL.
Articles and resources
References
1. John Shadegg profile, The Washington Post, accessed January 2011.
2. 2.0 2.1 Erin Kelly, "Retiring Rep. John Shadegg awaits new challenge", The Arizona Republic, December 5, 2010.
3. Roll call vote, Authorization for Use of Military Force Against Iraq Resolution of 2002.
4. John Shadegg, “Congressman John Shadegg Opts Not To Seek Re-Election ", “Congressman Shadegg’s House Website”, February 11, 2008
5. Chris Kahn, AP, “Ariz. Rep. Shadegg Not Seeking 8th Term", “The Washington Post”, February 12, 2008
6. Diana Marrero and Matthew Benson, “Rep. Shadegg won’t seek re-election", “The Arizona Republic”, February 12, 2008
7. Jackie Kucinich, "Shadegg listens to pleas from colleagues, will run again," The Hill, February 21, 2008.
Resources
Local blogs and discussion sites
Articles
Corresponding article on Wikipedia and Cause Caller. (If Cause Caller link does not work, pick from its list of senators and representatives.)
Current Office: U.S. House of Representatives
111th Congress
Leadership Position:
Committees Chaired:
Committees,
Ranking Member On:
Caucuses:
Committees:
110th Congress
Leadership Position:
None
Committees Chaired:
Committees,
Ranking Member On:
Caucuses:
Committees: House Committee on Energy and Commerce, House Committee on Energy and Commerce/Subcommittee on Energy and Air Quality, House Committee on Energy and Commerce/Subcommittee on Environment and Hazardous Materials, House Committee on Energy and Commerce/Subcommittee on Health, House Select Committee on Energy Independence and Global Warming,
Congressional Career
First Elected to Current Office:
November 1, 1994
First Took Current Office:
January 3, 1995
Next Election:
November 2, 2010
Term Ends:
Freshman Member?
No
Previous Political Work?
Special Assistant Attorney General, 1983 - 1990,
Other Party Membership:
District Offices:
1. 301 East Bethany Home Road, Suite C-178, Phoenix, AZ 85012
Phone: 602-263-5300 / Fax: 602-248-7733
Campaign Contact:
Website:
Webform Email: / Email:
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1.
Phone: / Fax:
Zip Code Affiliations:
Misc:
Date of Birth: October 22, 1949
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Traffic news and updates for the M18
Avoid the traffic jams on your route - enter your origin and destination and we'll calculate the best route.
ORIGIN
DESTINATION
M18 Traffic News
TODAY53°F
Sun54°F
Mon54°F
Tue54°F
INCIDENTS
1
ROADWORKS
0
The following traffic incidents, roadworks and road closures are reported within 25 miles of the M18:
HIDE ROADWORKS
SHOW ROADWORKS
M18 INFORMATION
Motorway Information
Motorway
M18
Description
Linking the M1 at Rotherham to the M62 near Goole.
Counties
South Yorkshire, East Riding of Yorkshire
Length
1967 – present
Existed Since
Constructed 1967–1979
Completed
Major junctions
Nearby Roads
Text TRAFFIC M18 to 68899 for live M18 traffic news
Please wait... traffic map loading
Traffic M1 North J38-J39
No Delay
On the M1 northbound between junctions J38 (Huddersfield) and J39 (Denby Dale), minor traffic delays can be expected at peak times due to barrier repairs closing one lane, from 8 pm on 17 May 2013 to 5 am on 18 May 2013.
Reported: 18/05/2013 10:10:04
Traffic M1
Traffic Conditions by SMS
Get the latest traffic M18 news and travel information and conditions by mobile phone to ensure you're one step ahead of the traffic jams. It's quick and easy.
Simply text TRAFFIC plus the postcode, city or road/motorway to 68899.
EXAMPLE:
TO:
TRAFFIC M25
TRAFFIC BIRMINGHAM
TRAFFIC BS11AA
68899
Texts cost £1 plus your standard network SMS charge.
More Information
M18 Motorway Services
Report a traffic jam
Comments refresh every minute
M18 Traffic Tweets
Local Petrol Stations
The above petrol and fuel prices can be found at petrol stations in the Doncaster area, and include unleaded, diesel, super and LPG fuel prices.
Regional Weather Forecast
Tomorrow's weather (Sunday) in Doncaster will be cloudy with light rain with a maximum daytime temperature of 53°f and a nighttime temperature of 39°f (12°c/4°c). Wind will be coming in from the W, reaching 9mph. On Monday it'll be sunny intervals , with 8 miles per hour wind from the NE. Daytime temperatures will reach 54°f, and during the night the temperature will drop to around 43°f (12°c/6°c).
Wind from the N will reach mph in Doncaster on Tuesday), with cloudy with light rain in the area. The temperature during the day will reach 54°f, and 50°f overnight (12°c/10°c). Wednesday's weather will be white cloud in Doncaster, with daytime temperatures reaching a maximum of 54°f, and night-time temperatures reaching a low of 40°f (12°c/4°c).
Doncaster
19 MAY
MAX 53° (12°c)
MIN 39° (4°c)
WIND 9mph (W)
20 MAY
MAX 54° (12°c)
MIN 43° (6°c)
WIND 8mph (NE)
21 MAY
MAX 54° (12°c)
MIN 50° (10°c)
WIND 15mph (N)
22 MAY
MAX 54° (12°c)
MIN 40° (4°c)
WIND 16mph (N)
Local Radio Stations
The following radio stations may broadcast traffic and travel news & bulletins for the local area. Use the 'Traffic' function on your RDS radio (marked TA, TP, TI or Traffic) and you will be automatically switched to travel and traffic conditions.
101.8 FMBranch FM (Dewsbury)
www.branchfm.co.uk/
102.0 FMDearne FM (Doncaster)
www.dearnefm.co.uk/
102.2 FMLincs FM (Lincoln)
www.lincsfm.co.uk/
102.7 FMRadio Leeds (Leeds)
www.bbc.co.uk/leeds/local_radio/index.sh
102.9 FMHallam FM (Sheffield)
www.hallamfm.co.uk/
103.2 FMMansfield FM (Mansfield)
www.mansfield103.co.uk/
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Breakdown Recovery
If you've broken down or had an accident on the M18 then you may need to call out a breakdown recovery service for roadside assistance. Use our service to help find the best deals from the top providers, including The AA, The RAC and Green Flag and others.
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Person:Samuel May (7)
Watchers
Browse
Samuel Joseph May
b.12 SEP 1797 Boston, MA
m. 28 DEC 1784
1. Charles May1785 - 1786
2. Catherine May1786 -
3. Charles May1788 -
4. Louisa May1789 - 1791
5. Eliza Sewall May1790 - 1791
6. Louisa May1792 - 1828
7. Samuel Joseph May1794 - 1795
8. Edward May1795 - 1802
9. Samuel Joseph May1796 - 1797
10. Samuel Joseph May1797 -
11. Elizabeth Sewall May1798 -
12. Abigail May1800 - Abt 1877
13. Louisa Caroline Greenwood May1810 -
Facts and Events
Name Samuel Joseph May
Gender Male
Birth? 12 SEP 1797 Boston, MA
Reference Number? 03-1308x
the text in this section is copied from an article in Wikipedia
Samuel Joseph May (September 12, 1797 – July 1, 1871) a radical American reformer during the nineteenth century, championed multiple reform movements including education, women’s rights, and abolitionism. He was born on September 12, 1797 in an upper class Boston area. May was the son of Colonel Joseph May, a merchant, and Dorothy Sewell, who was descended from or connected to many of the leading families of colonial Massachusetts, including the Quincys and the Hancocks. His sister was Abby May Alcott, mother of novelist Louisa May Alcott. In 1825, he married Lucretia Flagge Coffin with whom he had five children. The oldest died as a toddler, but May saw this event as a sacrifice he had to make for the purity of his own soul.
This page uses content from the English Wikipedia. The original content was at Samuel Joseph May. The list of authors can be seen in the page history. As with WeRelate, the content of Wikipedia is available under the Creative Commons Attribution/Share-Alike License.
References
1. Samuel Joseph May, in Wikipedia: The Free Encyclopedia. (Online: Wikimedia Foundation, Inc.).
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Place:Dale, Outagamie, Wisconsin, United States
Watchers
NameDale
TypeTown
Coordinates44.267°N 88.667°W
Located inOutagamie, Wisconsin, United States
source: Getty Thesaurus of Geographic Names
source: Family History Library Catalog
the text in this section is copied from an article in Wikipedia
Dale is a town in Outagamie County, Wisconsin, United States. The population was 2,731 at the 2010 census. The census-designated place of Dale and the unincorporated community of Medina are located in the town.
Research Tips
This page uses content from the English Wikipedia. The original content was at Dale, Wisconsin. The list of authors can be seen in the page history. As with WeRelate, the content of Wikipedia is available under the Creative Commons Attribution/Share-Alike License.
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Proton
Jump to: navigation, search
Proton
<tr> <td align="center" colspan="2">
The quark structure of the proton.</td> </tr> <tr> <th>Classification:</th> <td>Baryon</td> </tr><tr> <th>Composition:</th> <td>2 up, 1 down</td> </tr><tr> <th>Family:</th> <td>Fermion</td> </tr><tr> <th>Group:</th> <td>Quark</td> </tr><tr> <th>Interaction:</th> <td>Gravity, Electromagnetic, Weak, Strong</td> </tr><tr> <th>Antiparticle:</th> <td>Antiproton</td> </tr><tr> <th>Theorized:</th> <td>William Prout (1815)</td></tr><tr> <th>Discovered:</th> <td>Ernest Rutherford (1919)</td><tr> <th>Symbol:</th> <td>Template:SubatomicParticle, Template:SubatomicParticle, Template:SubatomicParticle</td> </tr><tr> <th>Mass:</th> <td>1.6726×10^−27 kg Template:Val/delimitnum(80) Template:Val/units Template:Val/delimitnum(13) Template:Val/units</td> </tr><tr> <th>Mean lifetime:</th> <td>>Template:Val/delimitnum×10Template:Su Template:Val/units (stable)</td> </tr><tr> <th>Electric charge:</th> <td>1.60217653(14)×10^−19 C</td> </tr><tr> <th>Spin:</th> <td>½</td> </tr>
Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
In physics, the proton (Greek πρώτον / proton = first) is a subatomic particle with an electric charge of one positive fundamental unit 1.60217653(14)×10^−19 C, a diameter of about 1.65x10^-15 m [1], and a mass of (938.27231 MeV/c2) (1.00727646688(13) u), (1.6726x10^-27 kg), or about 1836 times the mass of an electron.
History
Ernest Rutherford is generally credited with the discovery of the proton. In 1918 Rutherford noticed that when alpha particles were shot into nitrogen gas, his scintillation detectors showed the signatures of hydrogen nuclei. Rutherford determined that the only place this hydrogen could have come from was the nitrogen, and therefore nitrogen must contain hydrogen nuclei. He thus suggested that the hydrogen nucleus, which was known to have an atomic number of 1, was an elementary particle.
See also: William Prout and Prout's hypothesis
Prior to Rutherford, Eugene Goldstein had observed canal rays, which were composed of positively charged ions. After the discovery of the electron by J.J. Thomson, Goldstein suggested that since the atom is electrically neutral there must be a positively charged particle in the atom and tried to discover it. He used the "canal rays" observed to be moving against the electron flow in cathode ray tubes. After the electron had been removed from particles inside the cathode ray tube they became positively charged and moved towards the cathode. Most of the charged particles passed through the cathode, it being perforated, and produced a glow on the glass. At this point, Goldstein believed that he had discovered the proton.[2] When he calculated the ratio of charge to mass of this new particle (which in case of the electron was found to be the same for every gas that was used in the cathode ray tube) was found to be different when the gases used were changed. The reason was simple. What Goldstein assumed to be a proton was actually an ion. He gave up his work there, but promised that "he would return." However, he was widely ignored.
Description
Protons are spin −1/2 fermions and are composed of three quarks[3], making them baryons. The two up quarks and one down quark of the proton are held together by the strong force, mediated by gluons.
Protons and neutrons are both nucleons, which may be bound by the nuclear force into atomic nuclei. The nucleus of the most common isotope of the hydrogen atom is a single proton (it contains no neutrons). The nuclei of heavy hydrogen (deuterium and tritium) contain neutrons. All other types atoms are composed of two or more protons and various numbers of neutrons. The number of protons in the nucleus determines the chemical properties of the atom and thus which chemical element is represented; it is the number of both neutrons and protons in a nuclide which determine the particular isotope of an element.
Antiproton
Main article: antiproton
The antiparticle of the proton is the antiproton. It was discovered in 1955 by Emilio Segrè and Owen Chamberlain, for which they were awarded the 1959 Nobel Prize in Physics.
CPT-symmetry puts strong constraints on the relative properties of particles and antiparticles and, therefore, is open to stringent tests. For example, the charges of the proton and antiproton must sum to exactly zero. This equality has been tested to one part in 10^8. The equality of their masses is also tested to better than one part in 10^8. By holding antiprotons in a Penning trap, the equality of the charge to mass ratio of the proton and the antiproton has been tested to 1 part in 9 x 10^11. The magnetic moment of the antiproton has been measured with error of 8 x 10^-3 nuclear Bohr magnetons, and is found to be equal and opposite to that of the proton.
High-energy physics
Due to their stability and large mass (relative to electrons), protons are well suited to use in particle colliders such as the Large Hadron Collider at CERN and the Tevatron at Fermilab. Protons also make up a large majority of the cosmic rays which impinge on the Earth's atmosphere. Such high-energy proton collisions are more complicated to study than electron collisions, due to the composite nature of the proton. Understanding the details of proton structure requires quantum chromodynamics.
See also
References
1. Weisstein, Eric (1996–2007). Proton—from Eric Weisstein's World of Physics. Wolfram Research, Inc.. Retrieved on 2007-01-16.
2. Gilreath, Esmarch S.: "Fundamental Concepts of Inorganic Chemistry.", page 5. New York: McGraw–Hill, 1958.
3. Adair, Robert K.: "The Great Design: Particles, Fields, and Creation.", page 214. New York: Oxford University Press, 1989.
External links
Wikimedia Commons has media related to:
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RAR-related orphan receptor beta
Jump to: navigation, search
RAR-related orphan receptor B
250px
PDB rendering based on 1k4w.
Available structures: 1k4w, 1n4h, 1nq7
Identifiers
Symbol(s) RORB; NR1F2; ROR-BETA; RZRB; bA133M9.1
External IDs OMIM: 601972 MGI1343464 Homologene38250
RNA expression pattern
250px
More reference expression data
Orthologs
Human Mouse
Entrez 6096 225998
Ensembl ENSG00000198963 ENSMUSG00000036192
Uniprot Q92753 Q8R1B8
Refseq NM_006914 (mRNA)
NP_008845 (protein)
NM_001043354 (mRNA)
NP_001036819 (protein)
Location Chr 9: 76.3 - 76.49 Mb Chr 19: 19 - 19.06 Mb
Pubmed search [1] [2]
RAR-related orphan receptor beta (ROR-beta), also known as NR1F2 (nuclear receptor subfamily 1, group F, member 2) is a nuclear receptor encoded by the RORB gene.
The protein encoded by this gene is a member of the NR1 subfamily of nuclear hormone receptors. It is a DNA-binding protein that can bind as a monomer or as a homodimer to hormone response elements upstream of several genes to enhance the expression of those genes. The specific functions of this protein are not known, but it has been shown to interact with NM23-2, a nucleoside diphosphate kinase involved in organogenesis and differentiation.[1]
References
Further reading
• Beeson WM, Perry TW, Zurcher TD (1977). "Effect of supplemental zinc on growth and on hair and blood serum levels of beef cattle.". J. Anim. Sci. 45 (1): 160-5. PMID 885817.
• Giguère V, Tini M, Flock G, et al. (1994). "Isoform-specific amino-terminal domains dictate DNA-binding properties of ROR alpha, a novel family of orphan hormone nuclear receptors.". Genes Dev. 8 (5): 538-53. PMID 7926749.
• Carlberg C, Hooft van Huijsduijnen R, Staple JK, et al. (1994). "RZRs, a new family of retinoid-related orphan receptors that function as both monomers and homodimers.". Mol. Endocrinol. 8 (6): 757-70. PMID 7935491.
• Greiner EF, Kirfel J, Greschik H, et al. (1996). "Functional analysis of retinoid Z receptor beta, a brain-specific nuclear orphan receptor.". Proc. Natl. Acad. Sci. U.S.A. 93 (19): 10105-10. PMID 8816759.
• Paravicini G, Steinmayr M, André E, Becker-André M (1996). "The metastasis suppressor candidate nucleotide diphosphate kinase NM23 specifically interacts with members of the ROR/RZR nuclear orphan receptor subfamily.". Biochem. Biophys. Res. Commun. 227 (1): 82-7. doi:10.1006/bbrc.1996.1471. PMID 8858107.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791-806. PMID 8889548.
• Park HT, Baek SY, Kim BS, et al. (1997). "Developmental expression of 'RZR beta, a putative nuclear-melatonin receptor' mRNA in the suprachiasmatic nucleus of the rat.". Neurosci. Lett. 217 (1): 17-20. PMID 8905729.
• André E, Conquet F, Steinmayr M, et al. (1998). "Disruption of retinoid-related orphan receptor beta changes circadian behavior, causes retinal degeneration and leads to vacillans phenotype in mice.". EMBO J. 17 (14): 3867-77. doi:10.1093/emboj/17.14.3867. PMID 9670004.
• Greiner EF, Kirfel J, Greschik H, et al. (2000). "Differential ligand-dependent protein-protein interactions between nuclear receptors and a neuronal-specific cofactor.". Proc. Natl. Acad. Sci. U.S.A. 97 (13): 7160-5. PMID 10860982.
• Gawlas K, Stunnenberg HG (2001). "Differential binding and transcriptional behaviour of two highly related orphan receptors, ROR alpha(4) and ROR beta(1).". Biochim. Biophys. Acta 1494 (3): 236-41. PMID 11121580.
• Gawlas K, Stunnenberg HG (2001). "Differential transcription of the orphan receptor RORbeta in nuclear extracts derived from Neuro2A and HeLa cells.". Nucleic Acids Res. 29 (16): 3424-32. PMID 11504880.
• Stehlin C, Wurtz JM, Steinmetz A, et al. (2001). "X-ray structure of the orphan nuclear receptor RORbeta ligand-binding domain in the active conformation.". EMBO J. 20 (21): 5822-31. doi:10.1093/emboj/20.21.5822. PMID 11689423.
• Sumi Y, Yagita K, Yamaguchi S, et al. (2002). "Rhythmic expression of ROR beta mRNA in the mice suprachiasmatic nucleus.". Neurosci. Lett. 320 (1-2): 13-6. PMID 11849752.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899-903. doi:10.1073/pnas.242603899. PMID 12477932.
• Stehlin-Gaon C, Willmann D, Zeyer D, et al. (2003). "All-trans retinoic acid is a ligand for the orphan nuclear receptor ROR beta.". Nat. Struct. Biol. 10 (10): 820-5. doi:10.1038/nsb979. PMID 12958591.
• Humphray SJ, Oliver K, Hunt AR, et al. (2004). "DNA sequence and analysis of human chromosome 9.". Nature 429 (6990): 369-74. doi:10.1038/nature02465. PMID 15164053.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
6220.0 - Persons Not in the Labour Force, Australia, Sep 2005
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 17/03/2006
Page tools: Print Page Print All RSS Search this Product
NOTES
ABOUT THIS PUBLICATION
This publication presents information about people aged 15 years and over who are not in the labour force: that is, neither employed nor unemployed. The data measure the potential supply of labour not reflected in employment and unemployment statistics.
Statistics in this publication were obtained from the Persons Not in the Labour Force survey, conducted throughout Australia in September 2005 as a supplement to the Australian Bureau of Statistics (ABS) monthly Labour Force Survey (LFS).
This survey provides information about people aged 15 years and over who were not in the labour force. The survey collected details about whether they wanted to work, reasons why they were not actively looking for work, their availability for work, and their main activity while not in the labour force.
Many people not in the labour force could be considered to have some attachment to the labour force. For example they may want a job, but for a variety of reasons are not actively looking for work or are not currently available to start a job. There is an expectation that many of these people will move into the labour force in the short term, or could do so if labour market conditions changed.
NOTES ABOUT THE ESTIMATES
The scope of the Persons Not in the Labour Force survey was expanded in September 2005 to include all people aged 15 years and over. Previously the scope was restricted to people aged 15-69 years. This change has resulted in an extra 1.6 million people coming within the scope of this survey. Users need to exercise care when comparing the estimates in this publication with previous publications. Direct comparisons should only be made where the populations are the same.
ROUNDING
As estimates have been rounded, discrepancies may occur between sums of the component items and totals.
INQUIRIES
For further information about these and related statistics, contact the National Information and Referral Service on 1300 135 070 or Labour Market Section on Canberra (02) 6252 7206.
SUMMARY COMMENTARY
CONCEPTUAL FRAMEWORK
PERSONS NOT IN THE LABOUR FORCE AGED 15 YEARS AND OVER
Persons not in the labour force can be divided into those who are marginally attached to the labour force, and those who are not. Persons who are marginally attached to the labour force may satisfy some, but not all, of the criteria required to be classified as unemployed.
Persons not in the labour force are considered to be marginally attached to the labour force if they:
• want to work and are actively looking for work but are not available to start work in the reference week, or
• want to work and are not actively looking for work but are available to start work within four weeks.
Persons not in the labour force are not marginally attached to the labour force if they:
• do not want to work, or
• want to work but are not actively looking for work and are not available to start work within four weeks.
SUMMARY OF FINDINGS
OVERVIEW
In September 2005, there were 5,453,500 people aged 15 years and over who were not in the labour force. This represented 34% of the civilian population aged 15 years and over. Just under one-quarter (21%) of persons not in the labour force wanted to work and 61% of persons not in the labour force were women.
The proportion of people who were not in the labour force varied according to age. In the 15-19 years age group, where there are high levels of participation in education, the proportion was 41% for men and 38% for women. In all other age groups, there were more women than men not in the labour force. The proportion of women not in the labour force decreased from 27% for those aged 25-34 years to 23% for those aged 45-54 years, before increasing sharply to 43% for those aged 55-59 years, and 98% for those aged 70 years and over. For men in the same age groups, the proportion not in the labour force increased from 7% for those aged 25-34 and 35-44 years, to 11% for those aged 45-54 years, 24% for those aged 55-59 years, and 93% for those aged 70 years and over .
Persons not in the labour force, proportion of the civilian population
MARGINAL ATTACHMENT
Of the 840,300 people with marginal attachment to the labour force in September 2005, 771,100 or 92% were not actively looking for work but were available to start work within four weeks. The remainder were actively looking for work but were not available to start work in the reference week.
Some 17% of women and 13% of men not in the labour force were marginally attached to the labour force. Seventy two per cent of women with marginal attachment to the labour force would have preferred part-time work, while 16% preferred full-time work. For men, 49% preferred part-time work and 34% preferred full-time work. The remainder had no preference, or were undecided.
Approximately 59% of people with marginal attachment to the labour force 'intended to enter' the labour force within 12 months, 18% 'might enter' the labour force within 12 months, and 19% 'did not intend to enter' the labour force within 12 months
Of those with marginal attachment to the labour force, 80% previously had a job. Thirty two per cent of those who had a job stated that their last job was less than 12 months ago, and 21% reported their last job was between 1 and 3 years ago.
Main reason for not actively looking for work
The main reasons for not actively looking for work most commonly reported by men were 'attending an educational institution' (34%) and 'own ill health or physical disability' (20%). The most commonly reported main reasons for not actively looking for work for women were 'caring for children' (31%) and 'attending an educational institution' (18%).
Discouraged job seekers
At September 2005 there were 63,100 discouraged job seekers aged 15 years and over. There was a 23% decline in the number of discouraged job seekers aged 15-69, from 82,000 in September 2004 to 59,300 in September 2005. Women accounted for most of this decrease, with 53,600 women who were discouraged job seekers in September 2004 and 37,500 in September 2005.
The characteristics of discouraged job seekers aged 15 years and over in September 2005 included:
• 61% were women
• 29% of men and 21% of women had looked for work in the previous 12 weeks.
• 64% of men and 57% of women intended to enter the labour force in the next 12 months
• 85% had worked before.
The main reasons reported by discouraged job seekers for not actively looking for work were 'considered too old by employers' (39%), 'no jobs in locality or line of work' (27%) and 'lacked necessary schooling, training, skills or experience' (14%). Fifty per cent of men gave the reason 'considered too old by employers' compared with 32% of women. For women, 29% gave the reason 'no jobs in locality or line of work' and 17% gave the reason 'lacked necessary schooling, training, skills or experience'.
PEOPLE WITHOUT MARGINAL ATTACHMENT
Of the 4,613,200 people aged 15 years and over who were without marginal attachment to the labour force in September 2005, the majority (88%) were people who did not want to work, while a further 5% were permanently unable to work. Of those people who did not want to work, 38% (31% of women, 50% of men) reported their main activity as 'retired or voluntarily inactive', 28% (41% of women, 7% of men) as 'home duties or caring for children', and 12% (9% of women, 16% of men) as 'attending an educational institution'.
There were 325,000 people who wanted to work but were neither actively looking for work nor available to start work within four weeks. Of these, 69% were women, forty-four per cent reported their main activity as 'home duties or caring for children' and 28% as 'attending an educational institution'. Twenty-eight per cent reported that they had a job less than 12 months ago.
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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Friday, 20 July 2012
Protecting Madiba's legacy
Natacha Rey
Afro Leo is pleased to post this guest piece by Natacha Rey on how to protect famous personalities using IP:
When is asked to think of a famous brand they are likely to answer quickly with names such as Coca-Cola, Nike and Virgin. However, the name Nelson Mandela is not likely to feature at all. The reason for this is not that Nelson Mandela is not “famous” or well-known, but rather because people have not been educated to understand that Nelson Mandela is in fact a brand. This is why it is difficult but not impossible to protect his name as a “brand”. The brand “Nelson Mandela” is of course much more than just his name. It includes every association with him, including his legacy.
So, how does one go about protecting the value of his brand?
Quite simply, its value is protected in the same way that one would protect any other brand – through trade mark registration, copyright, design and patent laws, in addition to rights in personality.
1. Trade mark protection could be sought for the word marks “NELSON MANDELA”, nicknames such as “MADIBA” and “TATA”, associations such as “46664”as well as his signature and possibly a portrait image of Nelson Mandela. Some difficulties can arise because he is so famous so it is important that the names are controlled as trade marks. This appears to have been achieved through licence agreements between the Trustees of the Nelson Mandela Trust and organisations such as the Nelson Mandela Foundation, the Nelson Mandela Children’s Fund and the 46664 Organisation.
2. The historical speeches that Nelson Mandela has delivered to the public, the literary works he has authored, the photographs of him and various artworks depicting him are all protected by copyright. To the extent possible, he should try to obtain ownership of such copyright.
3. Contrary to what one might think, the law of designs is not completely irrelevant to the Nelson Mandela brand. The new and aesthetic designs of paraphernalia (such as key-rings, t-shits, caps, shoes and accessories) bearing the Nelson Mandela brand may be protectable by design registration.
4. From a patent perspective, while the jury’s still out on the patentability of a human being and their DNA, one wonders whether the idea of cloning a person as remarkable and unique as Nelson Mandela might tip the balance in favour of the protagonists.
The most important thing to remember when building a personal brand that you wish to protect is the necessity to educate the public that is in fact a brand. Your personal brand is an asset and if protected correctly, it can grow to be a valuable one
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1,309 reputation
49
bio website 000fff.org
location Copenhagen, Denmark
age 39
visits member for 3 years, 6 months
seen Mar 29 at 14:42
stats profile views 191
My name is Thomas Petersen. I am co-founder and partner in Hello a digital creative agency out of Copenhagen serving clients around the world. Besides that I am investor in a fish restaurant in the danish version of the Meatpacking district. I also do public speeches about a wide range of areas from digital design to the future of media. I have more than 14 years of professional experience in designing digital experiences especially for startups. You can learn more about me on @hello_world or write me a mail at thomas.petersen@gmail.com
63 Answers
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Research article
Antinociceptive interaction of (±)-CPP and propentofylline in monoarthritic rats
Francisco Morales1, Luis Constandil1, Teresa Pelissier2, Alejandro Hernández1 and Claudio Laurido1*
Author Affiliations
1 Laboratory of Neurobiology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Ave. Libertador B. O'Higgins 3363, Casilla 40 Correo 33, Santiago 917002, Chile
2 Program of Molecular and Clinical Pharmacology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Independencia 1027, P.O. Box 70000 Santiago 7, Santiago, Chile
For all author emails, please log on.
Arthritis Research & Therapy 2012, 14:R196 doi:10.1186/ar4030
The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/14/4/R196
Received:15 December 2011
Revisions received:19 July 2012
Accepted:14 August 2012
Published:24 August 2012
© 2012 Morales et al.; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Introduction
Multiple studies have shown that glial cells of the spinal cord, such as astrocytes and microglia, have close contact with neurons, suggesting the term tripartite synapse. In these synapses, astrocytes surrounding neurons contribute to neuronal excitability and synaptic transmission, thereby increasing nociception and thus the persistence of chronic pain. Conversely, the N-methyl-D-aspartate (NMDA) receptor is crucial in the generation and maintenance of chronic pain. It has multiple sites of modulation. One is the site of recognition of extracellular neurotransmitter (glutamate), which can be blocked by competitive antagonists such as (3-(2-carboxipiperazin-4)1-propyl phosphonic acid), (±)-CPP, resulting in a blockade of the calcium current and thus the intracellular transduction process. In the present study, we investigated whether the potential antinociceptive effect of glial inhibition produced by propentofylline (PPF) can be enhanced when combined with an NMDA-receptor inhibitor such as (±)-CPP.
Methods
We used Sprague-Dawley monoarthritic rats. The monoarthritis was induced by injection of complete Freund adjuvant in the right tibiotarsal joint. Four weeks later, rats were treated with PPF (1, 10, 30, and 100 μg/10 μl) intrathecally (i.t.) for 10 days, injected once with (±)-CPP (2.5, 5, 12.5, 25, 50, and 100 μg/10 μl, i.t.), or both treatments combined. The antinociceptive effect was evaluated on day 11 for PPF and immediately to (±)-CPP, by assessing the vocalization threshold to mechanical stimulation of the arthritic paw.
Results
The data indicate that intrathecal administration of increasing concentrations of (±)-CPP or PPF produced a significant dose-dependent antinociceptive effect with respect to monoarthritic rats receiving saline. The linear regression analysis showed that the dose that produces 30% of maximal effect (ED30) for i.t. (±)-CPP was 3.97 μg, and 1.42 μg for i.t. PPF. The administration of the PPF and (±)-CPP combination in fixed proportions of ED30 produced a dose-dependent antinociceptive effect, showing an interaction of the supraadditive type.
Conclusions
The results suggest that glia inhibitors can synergically potentiate the effect of glutamate blockers for the treatment of chronic inflammatory pain.
Introduction
Pain is a sensory modality that, in its acute form, performs the physiological role of alerting the individual of real or potential tissue damage. It is the immediate consequence of the pain-pathways activation (nociceptive system), ongoing in a temporal fashion, and usually resolves when the painful stimulus is removed. Conversely, when pain lasts, even after the lesion has been healed, or when pain is originated without apparent tissue damage and lasts for more than 6 months, it is considered pathologic and called chronic pain [1].
The information collected by the nociceptors is driven by primary afferent fibers to the spinal cord where they synapse and transmit nociceptive information to projection neurons located in the dorsal horn of the spinal cord. These projection neurons relay the information to supraspinal centers through ascending pathways. The first-order neurons release a number of neurotransmitters, among others, glutamate and substance P. Substance P stimulates NK-1 receptors that produce a slow and prolonged depolarization in the projection neuron. Glutamate binds to AMPA receptors, increasing depolarization. When nociceptive stimulation frequency is greater, it generates a membrane depolarization that triggers the release of ion Mg2+ from the NMDA receptor [2], promoting the entry of Ca2+ and the subsequent activation of the enzyme nitric oxide synthase, generating nitric oxide production (NO). NO is a gas that diffuses rapidly through the cell membrane and acts as an excitatory retrograde messenger in the neurons that generate it, as in the presynaptic elements and adjacent astrocytes. This event, classified as positive feedback, has an important role in the development of synaptic neuroplasticity mechanisms, as has been shown for hippocampal LTP [3] and spinal potentiation known as spinal cord windup, generated against a high and low frequency of C-fiber stimulation, respectively. As a result, the perception of pain increases significantly, a potentiation phenomenon in the origin of the generation of chronic pain.
The NMDA receptors are tetramers [4] that can be assembled in different configurations. The NR1 subunit is essential for the functionality of the receptor, whereas the NR2 subunits determine the biophysiologic properties of the channel, like the conductance and the average time of opening or blocking sensitivity to Mg2+ [5]. The cloning of the receptor subunits revealed that the NR1 subunit has a glycine-binding site, whereas the NR2 subunit has a glutamate-binding site, which can be blocked by competitive antagonists such as (±)-CPP, resulting in a blockade of the Ca2+ current, and therefore the intracellular transduction process, as well as the inhibition of the windup phenomenon [6]. Moreover, a number of other NMDAR antagonists, such as ketamine and ifenprodil acting on different receptor sites, have been shown to present antinociceptive effects in models of inflammatory and neuropathic pain [7-11]. This indicates that the (±)-CPP could be used as an analgesic, because this receptor is involved in the induction and maintenance of central sensitization.
As mentioned earlier, the NMDA receptor is important in the establishment of chronic pain; however, today we know other factors that can modulate this pain, such as glial cells [12]. In the last decade, numerous studies have shown that glial cells of the spinal cord have a close communication with neurons, proposing the term tripartite synapse [13]. This synapse contributes to the modulation of neuronal excitability and synaptic transmission by increasing nociception and thus the persistence of chronic pain. It has been found that astrocytes and microglia in the dorsal horn of the spinal cord are active against a variety of conditions that cause chronic pain and hyperalgesia, such as subcutaneous swelling, subcutaneous administration of inactivated mycobacterium [14], and trauma peripheral nerve [15], among others [16].
Once activated glial cells release several neuroactive molecules capable of inducing or magnifying the pain, such as NO, prostaglandins, arachidonic acid, excitatory amino acids (glutamate, aspartate, cysteine), quinolinic acid, and growth factors, as well as variety of proinflammatory cytokines, such as interleukin-1β, interleukin-6, and tumor necrosis factor [17]. Glial cells and neurons have receptors for cytokines. It is accepted that cytokines have a role as neuromodulators in the central nervous system, specifically at the level of second-order nociceptive neurons. In this regard, it has been reported that IL-1β is able to increase the C-fiber response and windup activity in the spinal cord [18] at the level of nociceptive afferent terminals, where IL-1β increases the release of substance P and glutamate [19].
In this context, it is apparent that the main strategy to suppress the communication between glia and spinal neurons is through the possibility of pharmacologically disrupting the glial function. In this regard, different drugs have been identified that inhibit the activity of glia, including propentofylline (PPF) [20]. PPF has inhibitory effects on the activity of phosphodiesterase types I, II, and IV and on adenosine extracellular transporters in glial cells [21], thereby modifying intracellular cyclic nucleotide homeostasis, leading to a decrease of the production of proinflammatory cytokines and free radicals in these cells. This is supported by studies in which has been found an inhibition of the release of tumor necrosis factor and interleukin 1, as well as the formation of oxygen radicals, in microglia cultures activated by LPS treatment and subsequently challenged with PPF. Moreover, increased cAMP-dependent signaling has been shown to increase the expression of antiinflammatory cytokine IL-10 [22]. Therefore, PPF may increase the production of antiinflammatory cytokines and, in turn, downregulates the production of proinflammatory cytokines.
PPF also functions as a reuptake inhibitor of adenosine [23]. This is potentially important because adenosine has been proposed to play a role in neuropathic pain. Adenosine presynaptically inhibits the release of substance P and glutamate, and postsynaptically decreases the action of substance P and glutamate [24]. Inhibition of substance P and glutamate release can attenuate central sensitization and, consequently, could decrease pain.
Because NMDA receptors and glia have an important role in the pathophysiology of chronic pain, we propose to evaluate whether the coadministration of (±)-CPP and PPF could enhance the analgesic effect of each drug on chronic inflammatory pain, by using an isobolographic analysis. The ultimate goal of drug combination is to obtain effective analgesia with a reduction in the incidence and severity of side effects, which can be achieved by using lower doses of the drugs [25].
Materials and methods
Animals
In total, 152 male monoarthritic Sprague-Dawley rats (225 to 250 g) were used in this study. The experimental groups were constituted by six animals in each group. All animals were obtained from the facilities of the Faculty of Medicine of the University of Chile, held in a light-dark cycle of 12/12 hours, starting at 8:00 AM, food and water ad libitum. After each experiment, rats were killed by using an overdose of urethane (3 g/kg, intraperitoneal, i.p.)
The experiments were conducted in accordance with the "Guide for the Care and Use of Laboratory Animals of National Institutes of Health (NIH)" [26] and the rules of the International Association for the Study of Pain (IASP) "Models of animal pain and ethics in experimental animals" [27] and "Ethical standards in research and management of pain." Furthermore, the experimental protocols were approved by the Bioethics Committee of the Universidad de Santiago de Chile.
Induction of monoarthritis
Monoarthritic rats were used as a model of chronic inflammatory pain. Monoarthritis was induced in rats of 120 to 150 g by the method described by Butler et al., [28]. In brief, rats were inoculated with a volume of 50 μl of Freund adjuvant, in the right ankle joint. The adjuvant consisted of a solution of 60 mg of Mycobacterium butiricum, 6 ml of mineral oil, 4 ml of sodium chloride (0.9%), and 1 ml of Tween 80. Subsequently, this mixture was autoclaved at 120°C for 20 minutes and stored at room temperature until use. Before injection, the solution was homogenized by constant stirring. The injection of adjuvant produces a localized arthritic syndrome that becomes stable around the fourth week after inoculation, and establishes a persistent pain with hyperalgesia of the tibiotarsal joint, which is maintained for a period exceeding 2 months. Around 90% to 95% of the injected rats developed mechanical hyperalgesia. Monoarthritic rats were used between the fourth and the fifth weeks after induction of monoarthritis.
Intrathecal injection
(±)-CPP (Tocris) was administered at single doses of 2.5, 7.5, 12.5, 25, 50, and 100 μg/10 μl. PPF (Sigma) was administered in repeated doses of 1, 10, 30, and 100 μg/10 μl, once daily for a period of 10 days. The two drugs were administered via i.t. injection in a volume of 10 μl and dissolved in saline; i.t. injection consists of administering the drug into the subarachnoid space between lumbar vertebrae L5 and L6 [29], by using a Hamilton syringe with a needle 26G × 1/2 inch'. The access to the subarachnoid space is evidenced by a slight movement in the tail of the rat as a result of the needle mechanical stimulation penetrating the meninges of the spinal cord. The daily PPF i.t. injection was done under brief halothane anesthesia (2 minutes).
Experimental groups
To evaluate the antinociceptive effect of both drugs individually on monoarthritic rats, the vocalization threshold to mechanical stimulation (Randall-Selitto test) was used. The animals were separated in a first stage of experimentation into two groups: (a) intrathecal administration of (±)-CPP: 2.5, 7.5, 12.5, 25, 50, or 100 μg/10 μl (n = 6 for each dose); and (b) daily i.t. administration of increasing PPF concentrations of 1, 10, 30, or 100 μg/10 μl (n = 8 for each dose) for 10 days.
To evaluate the antinociceptive effect of the PPF and (±)-CPP combination, we conducted a second series of experiments. Both drugs were diluted in decreasing doses (1/3, 1/10, and 1/100) in relation to its ED30. Five groups were used:
1. Daily administration of ED30 of PPF i.t. for 10 days. At day 11, an i.t. injection of ED30 of (±)-CPP was done (n = 6).
2. Daily administration of ED30 of PPF i.t. for 10 days. At day 11, an i.t. injection of 1/3 of ED30 of (±)-CPP was done (n = 6).
3. Daily administration of ED30 of PPF i.t. for 10 days. At day 11, an i.t. injection of 1/10 of ED30 of (±)-CPP was done (n = 6).
4. Daily administration of ED30 of PPF i.t. for 10 days. At day 11, an i.t. injection of 1/30 of ED30 of (±)-CPP was done (n = 6).
5. Daily administration of ED30 of PPF i.t. for 10 days. At day 11, an i.t. injection of 1/100 of the ED30 of (±)-CPP was done (n = 6).
Controls were provided by normal and monoarthritic rats receiving saline, as follows:
1. Normal group of the same age of monoarthritic rats, receiving i.t. injection of saline before testing (n = 6).
2. Monoarthritic saline group, pooled from saline controls for the (±)-CPP, PPF, and combined (±)-CPP/PPF series, receiving i.t. daily injection of saline for a period of 10 days, followed by an i.t. injection of saline at day 11, or a single injection at day 11 (n = 16). The three groups were pooled because they showed no significant differences in vocalization threshold between them at any time of testing.
Mechanical hyperalgesia
This behavioral test consists of adding a continuous and increasing pressure with a taper ending in blunt tip on the posterior knee joint of the rat to generate a nociceptive behavior. The response is evidenced by a vocalization or withdrawal reflex of the limb in response to stimulation. The pressure on the joint is increased gradually (linearly) up to 570 g, a value that does not harm the animal. The equipment used for this test was called analgesiometer Ugo Basile. Each animal was tested 2 times at 5, 15, 30, and 60 min for monoarthritic rats treated with (±)-CPP or the combination of PPF and (±)-CPP, and at 15, 30, and 60 min for monoarthritic PPF-treated rats. After the experiment, all rats were killed with an overdose of urethane. Grams of pressure, which expresses rat nociceptive behavior, were saved for later analysis. The data were expressed as percentage change to baseline and were then averaged over the different groups and different times. Later, the area under the curve (AUC) was calculated, by using the Microcal Origin V 6.0 program, and the groups were compared statistically.
Isobolographic analysis
The evaluation of the interaction between both drugs was performed by using isobolographic analysis [25]. The isobologram is a graphic method that consists of calculating the theoretic additive dose for each level of effect and their statistical comparison with the combination dose that produces the same effect experimentally. Equieffective doses of both drugs alone are needed to calculate the expected dose in a combination. To this end, we determined the dose that produces 30% of maximal effect (ED30) by using a linear regression analysis from the dose-response curve of six increasing doses of (±)-CPP and the previously mentioned for increasing doses of PPF. Once we obtained the ED30 of both drugs, a graph was constructed by placing in the y-axis of the ED30 point of (±)-CPP and the x-axis point of the ED30 of PPF. The union of two points by a straight line (isobolo), also known as a line of additivity or no interaction, helped to establish the type of interaction (synergism or antagonism) of both compounds. The interaction between both drugs was carried out by an administration of 1, 1/3, 1/10, 1/30, and 1/100 of the ED30 (±)-CPP, and PPF. The coadministration was performed through intrathecal PPF ED30 daily for 10 days. The antinociception was assessed on day 11 with the Randall-Selitto test and then followed by i.t. administration of ED30 (±)-CPP; antinociception was assessed by the same test. Then the ED30 of the association of both drugs (ED30 experimental), from a dose-response curve, was obtained by linear regression analysis. This dose was compared statistically with the dose that theoretically represents the simple addition of effects, obtained by the following formula:
Where R is the power ratio between the two drugs given alone, P1 is the proportion of the drug (PPF) in the mixture, and P2 is the proportion of drug 2 ((±)-CPP) in the mixture.
The graphic region in which is located the experimental value (ED30 experimental) in relation to the theoretic value (ED30 theoretic additivity) determines the type of interaction: If the value is located under the line of additivity and is statistically different from the theoretic value, the type of interaction is synergistic or supraadditive (effect greater than the sum of the individual effects of drugs); if located next to the line of additivity and not statistically different from the theoretic value, the interaction is simple additivity (equal effect of the sum of each drug); conversely, if the experimental value lies above the line of additivity and is statistically different from the theoretic nature of the interaction, it is subadditive or antagonistic. At the same time, we calculated the interaction index (I.I.) between the drugs, obtained from the following formula:
This index, when less than 1 corresponds to a synergistic interaction, when equal to 1, corresponds to an additive interaction, and when greater than 1 is an antagonistic interaction [30].
Statistical analysis
The results were expressed as mean percentage of antinociceptive effect ± standard error of the mean (SEM) for each experimental group, from baseline obtained before the injection of saline or each of the drugs under study, as appropriate. The quantification of the antinociceptive effect (%AE) of the drugs tested were calculated as a percentage change in AUC from baseline (basal) for each rat, and set a maximum pressure cut-off of 570 g in the Randall-Selitto, according to the following formula:
(1)
(2)
Where AUCpre and AUCpost are approximate integrals of the curves obtained by the method of trapezoids and pre-post drug injection, respectively, according to Eq. 1. The AUCdrug effect values are the integrals of the real effect of the drug. The antinociceptive effect (AE) was calculated according to Eq. 2, where the AUCcut-off corresponds to the area of maximum pressure possible on the animal.
To analyze the time-course of the antinociceptive effect of increasing doses of i.t. (±)-CPP and PPF, two-way ANOVA was performed. It allowed us to assess both intergroup comparisons (vocalization-threshold changes under different treatments) and intragroup comparisons (vocalization thresholds along the time), followed by the Bonferroni multiple comparisons test. To analyze the percentage antinociception obtained from the area under the time-course curves, one-way ANOVA was used, followed by Tukey-Kramer multiple comparisons test. To assess differences for the theoretic ED30 and experimental ED30, the two-tailed Student t test was used. All statistical analyses were performed with the Prism 3.0 software (GraphPad Software, Inc., San Diego CA, USA).
Results
Dose-response of (±)-CPP on mechanical nociception in monoarthritic rats
The administration of (±)-CPP (2.5, 5, 12.5, 25, 50, or 100 μg/10 μl) increased the vocalization threshold measured at 5, 15, 30, and 60 min after injection compared with rats receiving saline (Figure 1A), well above the pre-monoarthritis threshold. Areas under curves indicate that rats administered with saline showed a percentage of antinociception of 1.1% ± 1.4%, whereas rats administered with increasing doses of (±)-CPP showed a percentage of antinociception of 26.0% ± 2.4%, 33.9% ± 4.5%, 43.2% ± 5.0%, 47.8% ± 5.2%, 54.4% ± 6.8%, and 67.0% ± 6.8%, respectively (Figure 1B). In all cases, they were significantly higher than the percentages represented by the saline, showing a dose-dependent increase in trend. The linear regression analysis of the percentage AE showed that the ED30 was 3.97 μg, with a 95% confidence interval (95% CI) of 2.35 to 6.7 μg.
Figure 1. Antinociceptive effect of (±)-CPP in monoarthritic rats. (A) Time-course of the antinociceptive effect of increasing doses of i.t. (±)-CPP (2.5, 5.0, 12.5, 25, 50, and 100 μg/rat). Vocalization thresholds were measured before (left arrow), and then 28 days after monoarthritis induction, and after a single injection of CPP. Open symbols, values from monoarthritic rats. Solid symbols, values from normal rats receiving saline under a similar protocol. The right arrow corresponds to CPP or saline injection. Values are expressed as mean ± standard error of the mean (SEM); n = 6 rats per group. Two-way ANOVA indicates a significant effect for the (±)-CPP Treatment factor (F(6, 175) = 39.32; ANOVA P < 0.0001), as well as for the Time factor (F(5, 175) = 56.64; ANOVA P < 0.0001). Bonferroni multiple comparisons post hoc test showed that vocalization thresholds of all (±)-CPP treated rats (2.5, 5.0, 12.5, 25, 50, and 100 μg/rat) were significantly higher (p < 0.05) than the corresponding threshold of saline-treated animals (symbols omitted). In addition, Bonferroni multiple comparisons post hoc test showed that vocalization thresholds of rats after receiving the four highest doses of (±)-CPP were significantly higher (*P < 0.05) than the threshold measured before monoarthritis induction. (B) Ordinate indicates percentage antinociception obtained from the area under the time-course curves from (A) (see Materials and methods). Data are expressed as mean ± standard error of the mean (SEM), and were analyzed by using one-way ANOVA followed by Tukey-Kramer multiple comparisons test (*P < 0.05; **P < 0.01; ***P < 0.001; compared with monoarthritic rats receiving saline).
Dose-response of PPF on mechanical nociception in monoarthritic rats
Unlike the study with (±)-CPP, the PPF was administered over a longer term (that is, once daily for 10 consecutive days) to ensure that the glia became inactive. At day 11 of saline or PPF treatment, the animals were challenged with a single dose of saline (10 μl) and studied at 0, 15, 30, and 60 minutes after injection. The effect of PPF was evaluated by comparing the treatments as independent groups.
The administration of saline i.t. for 10 days in monoarthritic rats produced an average threshold of vocalization at zero time of 174 ± 9.2 g. After the injection of saline challenge, this vocalization threshold was unchanged at 0, 15, 30, and 60 minutes after injection (Figure 2A). In the groups treated with 1, 10, 30, and 100 μg/10 μl PPF for 10 days, the vocalization threshold at 0 time was 183 ± 6.3, 226 ± 13.5, 288 ± 10.0, and 310 ± 8.8 g, respectively, which remained without modifications during the 60 minutes of measurement. These data show that PPF produced dose-dependent increases in the vocalization threshold in monoarthritic rats, the two higher doses raising the threshold above those observed in the premonoarthritis condition.
Figure 2. Antinociceptive effect of PPF in monoarthritic rats. (A) Time course of the antinociceptive effect of daily repeated injections of PPF in monoarthritic rats. Vocalization thresholds were measured before (left arrow), and then 28 days after monoarthritis induction, and 10 days after repeated injection of PPF (right arrows) (Time 0). Empty symbols represent values from monoarthritic rats. Solid symbols represent values from normal rats receiving saline under a similar protocol. Values are expressed as mean ± standard error of the mean (SEM); n = 6 rats per group. Two-way ANOVA indicates a significant effect for the PPF treatment factor (F(4, 125) = 132.20; ANOVA P < 0.0001) as well as for the time factor (F(4, 125) = 7.55; ANOVA P < 0.0001). Bonferroni multiple comparisons post hoc test showed that vocalization thresholds of rats receiving the three highest doses of PPF (10, 30, and 100 μg/rat) were significantly higher (P < 0.05) than the corresponding thresholds of saline-treated animals (symbols omitted). In addition, Bonferroni multiple comparisons post hoc test showed that vocalization thresholds of rats after receiving the highest doses of PPF were significantly higher (*P < 0.05) than the threshold measured before monoarthritis induction. (B) Ordinate indicates percentage antinociception obtained from the area under the time-course curves from (A) (see Materials and methods). Data are expressed as mean ± standard error of the mean (SEM), and were analyzed by using one-way ANOVA followed by Tukey-Kramer multiple comparisons test (***P < 0.001, compared with monoarthritic rats receiving saline).
Area under curves indicates that monoarthritic rats injected with increasing doses of PPF (1, 10, 30, or 100 μg/10 μl) showed a percentage of antinociception of 32.8% ± 1.0%, 39.4% ± 2.4%, 50.1% ± 1.8%, and 54.4% ± 1.6%, respectively (Figure 2B), which were significantly higher than that observed in saline controls. Linear regression analysis allowed calculation of an ED30 of 1.42 μg with a 95% CI of 0.88 to 2.27 μg.
Dose-response of the combination of PPF and (±)-CPP: isobolographic study
In a second series of experiments, (±)-CPP and PPF were administered together in a proportion obtained from their respective ED30, which made possible to calculate the theoretic additive dose, generating a series of theoretic doses shown in Table 1.
Table 1. Fixed proportions, equieffective and theoretically additive, used for the combination of both drugs
In the five groups treated with increasing doses of the PPF/(±)-CPP combination (according to Table 1), the vocalization threshold increased for all doses, starting at 5 minutes, and remained elevated until 60 minutes after injection (Figure 3A). For the three higher doses of the combination, the vocalization threshold remained above the premonoarthritis threshold throughout the testing period.
Figure 3. Antinociceptive effect of PPF/(±)-CPP combination in monoarthritic rats. (A) Time course of the antinociceptive effect of daily repeated injections of PFF followed by a single injection of (±)-CPP in monoarthritic rats. Vocalization thresholds were measured before (left arrow) and then 28 days after monoarthritis induction, and after 10 repeated and a single injection of PPF and (±)-CPP, respectively (right arrows) (Time 0). Open symbols represent values from monoarthritic rats. Solid symbols represent values from normal rats receiving saline under a similar protocol. Values are expressed as mean ± standard error of the mean (SEM); n = 6 rats per group. Two-way ANOVA indicates a significant effect for the PPF/(±)-CPP treatment factor (F(5, 180) = 51,78; ANOVA P < 0.0001) as well as for the time factor (F(5, 180) = 44.37; ANOVA P < 0.0001). Bonferroni multiple comparisons post hoc test showed that vocalization thresholds of all PPF/(±)-CPP treated rats were significantly higher (P < 0.05) than the corresponding threshold of saline-treated animals (symbols omitted). In addition, Bonferroni multiple-comparisons post hoc test showed that vocalization thresholds of rats after receiving the highest doses of PPF/(±)-CPP were significantly higher (*P < 0.05) than the threshold measured before monoarthritis induction. (B) Ordinate indicates percentage antinociception obtained from the area under the time-course curves from (A) (see Materials and methods). Data are expressed as mean ± standard error of the mean (SEM), and were analyzed by using one-way ANOVA followed by Tukey-Kramer multiple comparisons test (**P < 0.01; ***P < 0.001; compared with monoarthritic rats receiving saline).
The %AE (Figure 3B) indicates that monoarthritic rats injected with equieffective doses of the PPF/(±)-CPP combination showed a percentage of antinociception of 29.1% ± 5.0%, 32.1% ± 1.9%, 40.8% ± 7.9%, 36.9% ± 7.4%, and 45.0% ± 3.6%, which were significantly higher than that observed in saline controls. Linear regression analysis showed that the ED30 for the PPF/(±)-CPP combination was 0.063 μg with a 95% CI of 0.012 to 0.334 μg.
The combined effect of both drugs was analyzed by constructing an isobologram graph (Figure 4), which shows that the antinociceptive activity induced by coadministration of fixed proportions of the ED30 for PPF and (±)-CPP produced a greater antinociceptive effect than a simple additivity in monoarthritic rats. This result is achieved because the ED30 point for the combination is under the curve of isobolo and statistically different from the ED30 theoretically additive, indicating that the effect of the combination of both drugs is supraadditive (t = 2.879; P < 0.001, two-tailed Student t test). The interaction index between PPF and (±)-CPP was 0.024.
Figure 4. Isobologram for the coadministration of PPF and (±)-CPP at fixed-ratio combinations. The white circle on the straight line represents the point of theoretic activity calculated with a confidence limit of 95%, whereas the black circle under the straight line corresponds to the experimental point obtained with the monoarthritic rats (95% confidence limit). The experimental point was significantly different from the theoretically calculated point (mean ± SEM; ***P < 0.001, two-tailed Student t test), indicating supraadditive synergy in the Randall-Selitto test.
Discussion
The results of this study show that the analgesic effect observed by combining PPF (a glial cells inhibitor) and (±)-CPP (an NMDA-receptor antagonist) on the paw-pressure test is supraadditive, in rats with chronic inflammatory pain. The ED30 obtained for (±)-CPP was 3.97 μg, and for PPF, 1.42 μg, whereas the ED30 of the combination was 0.063 μg, which was significantly lower than that expected by simple additivity. The ED50 was not used because the maximum effect of the drugs administered separately did not exceed 60% of the maximum effect.
As pointed out elsewhere [31-34], a supraadditive effect of combining two drugs producing the same effect could occur only if the mechanisms of action involved are totally or partially different (that is, "purely mutually nonexclusive" or "partially or nonpurely nonexclusive," as defined by Chou [31]), but not when the mechanism of action is the same for the two combined drugs. In the case of combining PPF and (±)-CPP, the mechanisms of action are partially independent and therefore consistent with the supraadditive effect found in the present study.
Some evidence supports that the administration of PPF to cultures of microglia from neonatal rat brain, activated by lipopolysaccharides, inhibits secretion of tumor necrosis factor (TNF-α), interleukin 1 (IL-1), and oxygen radicals [21]. Similar results obtained from microdialysis in the lumbar spinal cord of rats submitted to sciatic nerve chronic constriction injury have been reported [35]. It seems that inhibition by PPF of glial proinflammatory cytokine secretion is mediated by the cAMP-PKA pathway, because PPF effects are mimicked by dibutyryl-cAMP [36], and cAMP-PKA signaling represses proinflammatory cytokine gene expression in microglia [37]. However, the mechanisms of action of PPF are not yet clear. For instance, PPF has been shown to reinstate the decreased expression of glutamate transporters GLT-1 and GLAST produced for the L5 nerve transection in mice [38], thus promoting glial glutamate uptake and thereby glutamate excitotoxicity, therefore decreasing nociception by a mechanism different from proinflammatory cytokine repression. Furthermore, it has been reported that PPF decreases hyperalgesia induced by intracisternal BDNF administration [39], which may constitute another different mechanism from the previously mentioned. BDNF synthesis is increased not only in primary afferents during chronic pain [40,41] but also in second-order nociceptive neurons [42,43] and glial cells [44,45] of the dorsal horn. It has been claimed that BDNF promotes pain through two different mechanisms: (a) by potentiating the glutamatergic transmission in the spinal cord via increased glutamate release and enhanced synaptic efficacy at the postsynaptic level [46], and (b) by reducing the expression of the KCC2 transporter in dorsal horn neurons, which leads to a shift in the transmembrane anion gradient that causes normally inhibitory anionic synaptic currents to be excitatory; this latter mechanisms has been reported to be triggered only by glial-derived BDNF neurotrophin [44]. Because expression of the KCC2 transporter was found to be significantly reduced in spinal cord slices of rats with chronic inflammatory pain [47], it is likely that in the present study, PPF could reduce hyperalgesia by depressing glial BDNF release, thereby restoring the normal transmembrane anion gradient.
Conversely, it is accepted that the NMDA receptor is crucial in the transfer of nociceptive information in the spinal cord, specifically between the first and second nociceptive projection neurons [48]. Studies using antagonists of NMDA receptors have demonstrated their effectiveness as antinociceptive drugs in animal models of central hypersensitivity induced by cutaneous application of the chemical irritant mustard oil, tested with brief electrical stimulation of the sural nerve and challenged with MK-801 and (±)-CPP [49]. For example, MK-801 (an uncompetitive antagonist of the NMDA receptor) prevents skin and tactile hyperalgesia induced by muscle noxious C-fiber stimuli [7,50], and (±)-CPP (a competitive antagonist of the glutamate-binding site on the NMDA receptor) specifically blocks the action of glutamate, thus producing analgesia in different pain models [12,51]. In the present study, we demonstrated that increasing doses of (±)-CPP have a dose-dependent antinociceptive effects in monoarthritic rats.
Thus, it seems clear that PPF and (±)-CPP act through different mechanisms, but it is also clear that PPF and (±)-CPP can functionally interact because PPF lowers glial release of BDNF, thus avoiding the potentiating effect of the glial-derived BDNF on the glutamatergic transmission in the spinal cord. Therefore, the antihyperalgesic mechanisms of action of PPF and (±)-CPP are only partially independent, because PPF- and (±)-CPP-dependent effects can converge at the NMDA-receptor functionality, thus supporting supraadditive interactions when combined in equieffective doses.
Conclusions
We showed for the first time that the glial inhibitor PPF can synergistically potentiate the effect of (±)-CPP, a drug that inhibits NMDA-receptor activity, thus opening the field of associating glial inhibitors to NMDA-receptor blockers in the pharmacologic treatment of chronic inflammatory pain. Glial inhibitors [52,53] and NMDA antagonists [54,55] have been associated with opioid therapy in a variety of painful conditions, but glial inhibitors and NMDA antagonists have not still assayed in combination clinical studies.
Abbreviations
ANOVA: analysis of variance; AUC: area under curve; (±)-CPP: 3-(2-carboxipiperazin-4)1-propyl phosphonic acid; IL-1β: interleukin-1beta; NO: nitric oxide; PPF: propentofylline; TNF-α: tumor necrosis factor-alpha.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
FM, TP, and CL performed most of the experiments. TP performed experiments in inducing monoarthritis. LC, TP, AH, and CL conceived the study and participated in the design, in the interpretation of results, and in drafting the manuscript. All authors read and approved the final manuscript.
Acknowledgements
This study was supported by grants DICYT 011043LF, FONDECYT 1070115, and CEDENNA FB0807.
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29. Mestre C, Pelissier T, Fialip J, Wilcox G, Eschalier A: A method for perform direct transcutaneous intrathecal injection in rats.
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31. Chou T-C: Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies.
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36. Si Q, Nakamura Y, Ogata T, Kataoka K, Schubert P: Differential regulation of microglial activation by propentofylline via cAMP signaling.
Brain Res 1998, 23:97-104.
37. Cho S, Kim Y, Cruz MO, Park EM, Chu CK, Song GY, Joh TH: Repression of proinflammatory cytokine and inducible nitric oxide synthase (NOS2) gene expression in activated microglia by N-acetyl-O-methyldopamine: protein kinase A-dependent mechanism.
Glia 2001, 33:324-333. PubMed Abstract | Publisher Full Text
38. Lashbrook JM, Ossipova MH, Hunterb JC, Raffacd RB, Tallaridad RJ, Porrecaa F: Synergistic antiallodynic effects of spinal morphine with ketorolac and selective COX1 and COX2 inhibitors in nerve-injured rats.
Pain 1999, 82:65-72. PubMed Abstract | Publisher Full Text
39. Constandil L, Goich M, Hernández A, Bourgeais L, Cazorla M, Hamon M, Villanueva L, Pelissier T: Cyclotraxin-B, a new TrkB antagonist, and glial blockade by propentofylline, equally prevent and reverse cold allodynia induced by BDNF or partial infraorbital nerve constriction in mice.
J Pain 2012, 13:579-589. PubMed Abstract | Publisher Full Text
40. Tarsa L, Bałkowiec-Iskra E, Kratochvil J, Jenkins VK, McLean A, Brown S, Smith JA, Baumgartner C, Balkowiec A: Tooth pulp inflammation increases BDNF expression in rodent trigeminal ganglion neurons.
Neuroscience 2010, 167:1205-1215. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
41. Lin YT, Ro L-S, Wang H-L, Chen J-C: Up-regulation of dorsal root ganglia BDNF and trkB receptor in inflammatory pain: an in vivo and in vitro study.
J Neuroinflammation 2011, 8:126. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
42. Onda Y, Murata Y, Rydevik B, Larsson K, Kikuchi S, Olmarker K: Infliximab attenuates immunoreactivity of brain-derived neurotrophic factor in a rat model of herniated nucleus pulposus.
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43. Pezet S, McMahon S: Neurotrophins: mediators and modulators of pain.
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44. Coull JM, Beggs M, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter M, De Konink Y: BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain.
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45. Tokumine J, Kakinohana O, Cizkova D, Smith DW, Marsala M: Changes in spinal GDNF, BDNF, and NT-3 expression after transient spinal cord ischemia in the rat.
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46. Merighi A, Salio C, Ghirri A, Lossi L, Ferrini F, Betelli C, Bardoni R: BDNF as a pain modulator.
Progr Neurobiol 2008, 85:297-317. Publisher Full Text
47. Zhang W, Liu L-Y, Xu TL: Reduced potassium-chloride co-transporter expression in spinal cord dorsal horn neurons contributes to inflammatory pain hypersensitivity in rats.
Neuroscience 2008, 152:502-510. PubMed Abstract | Publisher Full Text
48. Raigorodsky G, Urca G: Involvement of N-methyl-D-aspartate receptors in nociception and motor control in the spinal cord of the mouse: behavioral, pharmacological and electrophysiological evidence.
Neuroscience 1990, 36:601-610. PubMed Abstract | Publisher Full Text
49. Woolf CJ, Thompson SW: The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states.
Pain 1991, 44:293-299. PubMed Abstract | Publisher Full Text
50. Ma QP, Woolf CJ: Noxious stimuli induce an N-methyl-D-aspartate receptor-dependent hypersensitivity of the flexion withdrawal reflex to touch: implications for the treatment of mechanical allodynia.
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51. Kristensen JD, Karlsten R, Gordh T, Berge OG: The NMDA antagonist 3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid ((±)-CPP) has antinociceptive effect after intrathecal injection in the rat.
Pain 1994, 56:59-67. PubMed Abstract | Publisher Full Text
52. Goldstein FJ: Adjuncts to opioid therapy.
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53. Hameed H, Hameed M, Christo PJ: The effect of morphine on glial cells as a potential therapeutic target for pharmacological development of analgesic drugs.
Curr Pain Headache Rep 2010, 14:96-104. PubMed Abstract | Publisher Full Text
54. Kalso E: Improving opioid effectiveness: from ideas to evidence.
Eur J Pain 2005, 9:131-135. PubMed Abstract | Publisher Full Text
55. Lossignol DA, Obiols-Portis M, Body JJ: Successful use of ketamine for intractable cancer pain.
Support Care Cancer 2005, 13:188-193. PubMed Abstract | Publisher Full Text
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{
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"url": "ccsenet.org/journal/index.php/ibr/article/view/12363/0",
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"warc_url": "http://ccsenet.org/journal/index.php/ibr/article/view/12363/0"
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Why Small Business Owners Should Not Worry about“Money Left on the Table” in IPOs!
Roger Su, Keith Hooper, Amitabh S. Dutta, Ronghua Yi
Abstract
Purpose – this study aims to investigate how those directors of listed companies to make profits when their firms were listed to public.
Design/methodology/approach –This is an empirical study; we adopted the formula from Ritter (2001) for this research.
Findings -this study finds that directors of issuing companies usually get benefits from the money left on the table due to two factors. First, they usually retain larger percentage of shares before or after the companies going public; second, the first-day closing market price is normally higher than the initial file price ranges (defined as the expected price per share by issuing companies just before the firms go public). Originality/value - the findings may be used for future academic research literatures which focus on IPO or primary market. This research would help individual investors better understanding primary market especially IPO market.
Full Text: PDF
This work is licensed under a Creative Commons Attribution 3.0 License.
International Business Research ISSN 1913-9004 (Print), ISSN 1913-9012 (Online)
Copyright © Canadian Center of Science and Education
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{
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"provenance": "cccc-CC-MAIN-2013-20-0000.json.gz:60118",
"uncompressed_offset": 47570328,
"url": "ccsenet.org/journal/index.php/jsd/article/view/1225",
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"warc_filename": "<urn:uuid:01fcd2a2-6987-4e5c-904a-5934b8ae58da>",
"warc_url": "http://ccsenet.org/journal/index.php/jsd/article/view/1225"
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On the Problems and Recommendations of the Inland Port Container in the Inspection and Quarantine
Jian Xu, Fengli Zeng
Abstract
Container transport with its high efficiency, convenience, security features becomes an important tool of China Foreign Trade Transportation. Container goods transport is also the main carriers of the inland port international logistics. This article discusses problems and improved measures of the inland port containers in the inspection and quarantine.
Full Text: PDF
This work is licensed under a Creative Commons Attribution 3.0 License.
Journal of Sustainable Development ISSN 1913-9063 (Print) ISSN 1913-9071 (Online)
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{
"content_type": "text/html",
"provenance": "cccc-CC-MAIN-2013-20-0000.json.gz:60137",
"uncompressed_offset": 81184708,
"url": "dotnetkicks.com/stories/20793/Visual_Studio_2010_CTP_Download_Temporary_Down",
"warc_date": "2013-11-22T14:34:51.000Z",
"warc_filename": "<urn:uuid:01fcd2a2-6987-4e5c-904a-5934b8ae58da>",
"warc_url": "http://dotnetkicks.com/stories/20793/Visual_Studio_2010_CTP_Download_Temporary_Down"
}
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Error!
Success!
Visual Studio 2010 CTP Download Temporary Down
0
kicks
Visual Studio 2010 CTP Download Temporary Down (Unpublished)
As that I’m was downloading Visual Studio 2010 and the download just stop working, therefore I did a search about it and found on Othmane Blog informing that the download build being rebuild. And that the VHD will be available on Friday morning. Be ready download again from zero at Microsoft Connect Visual Studio 2010 CTP site, that is downloading another 7.5GB (my slow ISP L).
Kicked By:
Drop Kicked By:
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{
"content_type": "text/html",
"provenance": "cccc-CC-MAIN-2013-20-0000.json.gz:60150",
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"url": "googlesystem.blogspot.com/2005/11/google-local-mobile.html",
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An unofficial blog that watches Google's attempts to move your operating system online.
Send your tips to gostips@gmail.com.
November 7, 2005
Google Local Mobile
Google launched a mobile version of its Google Local service that will allow users to search for businesses or services in a specific geographical location and view the search results plotted on a map. Google Local for mobile works with most new Java-enabled (J2ME) mobile phones.
While Google’s focus will be on expanding its services for mobile phone users such as the Google Local and Google Maps services, Yahoo is also hoping to increase its presence in the mobile phone industry with the announcement that it will be releasing a Yahoo Mobile phone next year the Wall Street Journal reported on Monday.
More: Google and Yahoo strengthen mobile offering
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{
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Rideshare
From Hitchwiki
Jump to: navigation, search
Rideshare systems can be used as an alternative to real hitchhiking.
Contents
One Time Ridesharing Projects
Train Ticket Sharing
Structural Car-Pooling based
How to name this?
• Myoto is a system in Belgium with special cards for hitchhikers. Drivers can then easily recognize the hitchhiker as part of this service. See also this discussion
Rideshare applications
• carpooling.com connects drivers and passengers so they can share their rides. Drivers can post empty seats and passengers can book a seat online like a bus or a train ticket. Access to user profile info and user ratings ensure a pleasant ride for all. Application is available in 45 countries on iPhone and Android in 7 languages.
• At Crash at Mine there are plans to create a free open API for rideshare websites and a system for RSS streams based on this. There's also a nice survey of carpool services.
• Carticate is an application for the iphone that allows you to connect with other drivers. It is a 'location based mobile social network for ride sharing, ride combining, and car pooling', or also 'carticipation.' Launched in August 2008.
• Avego is an application that runs on mobile devices and matches drivers and passengers who are going the same way. "Avego Stops", the best places to pick up and drop off riders. It also wants to connect it with a social networking website. Launched in September 2008.
• Zimride combines the technology of Google Maps with the social networking power of Facebook to find rides for people at 25 public and private institutions across the United States. Zimride is now taking their rideshare algorithm to Zipcar to make hitching a ride even more efficient source.
• Ridejoy "social transportation" website that helps connect drivers and passengers doing long distance rideshare. Pulls in information from Facebook like photo, age range, work/education history, and mutual friends so ride matches feel more comfortable with each other. Launched Summer 2011.
News
• 12 November 2008. The ridesharing website PickupPal was struck down by a Canadian court in a case brought against them by bus giant Trentway-Wagar. The company took PickupPal to the Highway Transport Board complaining that it was against the law. link
• 17 December 2008. The US based company Dell started a ride-share experiment for their employees. In cooperation with the Rideshare website Ridesnearme.com they set up an application which is basically a mash-up of Google maps with employees submitting their home locations. Employees can use this to better figure out which coworkers to commute with and the most efficient routes. link
• Although still evolving as a real resource for riders, Twitter is being touted in some circles as the next big thing in realtime ridesharing. Known to fans as twitchhiking, this form of ride-sharing asks travelers to rely on the social networking site's popularity as well as the kindness of fellow tweeters. From: Product Service Systems: The Future of Mobility Services link
See also the Future of Hitchhiking
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For the half-year to 30 June 2013, the IPKat's regular team is supplemented by contributions from guest bloggers Stefano Barazza, Matthias Lamping and Jeff John Roberts.
Two of our regular Kats are currently on blogging sabbaticals. They are Birgit Clark and Catherine Lee.
Sunday, 18 May 2008
Silver bullet or rubber dagger?
"Community Designs – a Silver Bullet or a Rubber Dagger? What is happening in the Community courts?" This was the title of a talk, hosted by law firm Linklaters in a packed auditorium. The audience was eager to hear presentations on Community designs from Dr Henning Hartwig (Bardehle Pagenberg Dost Altenburg Geissler, Munich) and Henry Carr QC (11 South Square).
Dr Hartwig, one of the first lawyers to enforce Community designs before a national court, has published a Europe-wide up-to-date collection of emerging national case law on Community designs, while Henry Carr was counsel for the successful party in the leading case of Procter & Gamble Company v Reckitt Benckiser (UK) Ltd [2007] EWCA Civ 936, the first UK trial in respect of a Community design (noted by the IPKat here). The ECJ is yet to give any guidance in this area.
Dr Hartwig opened the presentation with a review of selected cases from Germany, France and (non-EU) Switzerland to illustrate the principles and requirements adopted by certain Member States for enforcing and protecting a Community design. While there were sometimes differing national standpoints, a clear tendency is emerging towards a more harmonized and reliable system.
Of particular interest was the analysis of Article 6 of Community Design Regulation 6/2002 and the test for “individual character”. Dr Hartwig explained the correct test should be a one-to-one comparison of the registered application (as published in the OHIM bulletin, not as sold in the market) with the prior art, in particular the piece of prior art that comes closest to the claimant’s design. As for what constitutes relevant prior art, it is anything “made available to the public” which given the accessibility of information through search engines, Dr Hartwig considered to have wide scope.
How to perform the one-to-one comparison is, however less clear: should the court consider first the similarities of two designs, or their differences? Dr Hartwig preferred the former approach, and if sufficient similarity is found, infringement should only be denied if the differences are great enough.
Henry Carr asked the crowd to review the Procter & Gamble “Febreze” product (the Community design registration) and the Reckitt & Beckiser “Airwick” product (the alleged infringement, said to be one of the last in circulation). A show of hands revealed that the vast majority of the audience considered the Airwick design to infringe. Accordingly Mr Carr took on the task of persuading the audience that this was not the case.
First, Mr Carr set out the case for Procter & Gamble. Counsel had argued that, where there had been a significant departure from the prior art (the Febreze design had received industry awards for its unique shape) and plenty of design freedom (there were lot of aerosol sprayers in the prior art, very different to the product in issue), the scope of protection for a design should be wide. He had also argued that this tied with the language of the Regulation, Recital 14 and Article 10 CDR which require a consideration of a “different overall impression” which being so worded should give rise to a wide scope of protection. It was this consideration of “overall impression” however, which Mr Carr believed led to a “sea change” towards a decision for non-infringement.
Both parties had agreed that the scope of protection given by Article 10 CDR extended to designs which give the same overall impression. The assessment of overall impression involved, as Dr Hartwig had explained earlier, a detailed feature analysis, quite distinct from the “doctrine of imperfect recollection” in trade mark law. It was here that Mr Carr had played a “Gerald Ratner” defence, describing how each feature of the Airwick design was “simply inferior” to the equivalent in the Febreze design. This argument had not only been amusing but persuasive. It was also consistent with Lewison J’s analysis of the Febreze design as having a “smooth and dynamic feel, flowing lines, and an elegant sense of movement” which, if taken as Lewison J’s overall impression of the Febreze design, was very different to the “few kind words” about the alleged infringement. The expert for P&G who was the designer of the Febreze design had also been quick to support Mr Carr’s disparaging remarks about the Airwick design (a lesson, Mr Carr added, not to call the designer as an expert unless one has to).
In the question and answer session that followed, Dr Hartwig commented that he did not think highly of the feature analysis applied by the Court of Appeal, remarking that it had been, at best, “unlucky” and with a better analysis of features, a German court would have been convinced of infringement.
However, Mr Carr also felt policy decisions had been significant to the decision. Mr Carr warned the audience that as Community designs are non-examined IP rights, given a wide scope of monopoly they would be “too powerful” as the onus would be on competitors to spend money and time invalidating them. Moreover, as Community designs can extend to functional features as well as aesthetic ones, their monopoly can be greater than that granted for patents: function need not even be inventive and the monopoly can last 25 years including renewals. Granting a wide scope of protection would be anti-competitive and would discourage innovation.
Mr Carr was also asked where such a narrow interpretation left unregistered design rights. Mr Carr considered these rights to still be dangerous given that a claimant can apply for protection of the whole as well as any aspect of a design. Even if a design gives a different overall impression to the design-in-issue, there may still be a strong case on a very limited important part.
A show of hands at the end of the session revealed few audience members had (or dared to admit that they had) been persuaded by Mr Carr’s arguments for non-infringement of the Febreze design. However, Mr Carr proposed that whether or not one finds infringement is essentially one of policy: how wide should the scope of Community design protection be? Whether the Community design should act as a rubber dagger or a silver bullet was the question left with the audience [the IPKat thanks Georgina Warnett for preparing this post].
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2013-05-18T09:27:52.000Z
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[maemo-developers] [maemo-developers] Telepathy-SIP status
From: Jorge Salamero Sanz bencer at cauterized.net
Date: Wed Jan 24 14:54:47 EET 2007
On Wednesday 24 January 2007 12:52, Laurent GUERBY wrote:
> Note that Gizmo works in SIP mode :
>
> http://www.gizmoproject.com/learnmore-nokia.html
>
> There is a version for N770 and one for N800 (I tested the N800 version
> with my ISP provided SIP).
yes but:
1.- it is non-free
2.- it isn't integrated with the maemo environment
3.- it needs gizmo account anyway
More information about the maemo-developers mailing list
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56vejj7w7fcw3kgvtgjwuztqqqjpzpca
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#noemail: Are technology's early adopters abandoning their email?
Image credits: Orin Zebest
(7 votes)
Could you live without your email?
Yes. I'd love to just shut the whole thing down.
10.1% (59 votes)
Yes. In fact, I already did.
2.6% (15 votes)
No. It is the lifeblood of my communications.
49% (287 votes)
No. Too many people contact me there. Wish I could though.
27.3% (160 votes)
Maybe. I've been considering it.
11.1% (65 votes)
Co-author: Paul Jones
Most people--including my parents--have email. But now, just as mom and dad (and, though more rarely, grandma and grandpa) are getting on the email bandwagon, it seems a fair number of folks are jumping right off. And I don’t mean great-aunts who decided it was too difficult or dirty.
The most recent--and closest--notice was a post from Paul Jones, the director of Ibiblio.org and a professor at UNC-Chapel Hill. Professor Jones also happens to be my former boss, a prolific writer and speaker, a bit of an internet celebrity, and a good friend. And because of his extensive help reviewing and providing the basis for this piece, a co-author.
He posted the opening salvo of the email-less on May 3, and it went like this:
“Giving up email beginning June 1, 2011. You will be able to reach me on Facebook and on most socialnetworking sites as smalljones including Twitter, Gtalk, AIM, Skype, Quora, Hunch, LinkedIn, DropBox, YouTube, XtraNormal and here on this blog.”
Professor Jones isn’t the first person to ponder divesting. He’s following the lead of several other tech pioneers (his friends and influencers, the way he’s one of mine)--Donald Knuth, the Stanford professor and author. And Luis Suarez, a community builder and social evangelist at IBM. They’ve both written extensively about their reasoning, process, and success since abandoning the inbox.
Jones has conversed with Red Hat thinker Michael Tiemann about the attempt. He’s opened it up for comment on his blog. And we’ve been watching, fascinated. We asked him if he’d mind talking about it a bit more, or if we followed along and shared it with our readers. Thus, this article (and perhaps others that look at the result) was born.
How did we do it, without email? Email is usually part of the writing process at opensource.com. Drafts traded, updates made, all by emailed correspondence. I had to change routine for this article, but it wasn’t difficult. The process was, in fact, quite smooth. I caught the tweeted updates about Jones’ blog posts (which also showed up in my RSS feed) on my Android phone. We used Facebook to connect, chat, and exchange messages. Google Docs came into play to compose the piece, share it, discuss it, and work on the interview portion. We didn’t trade a single piece of real email1
How the others have fared
Knuth’s been email-free (well, ok, sort of--he has a secretary to receive email and pass along any important information) since 1990. While working on one of the exhaustive volumes of The Art of Computer Programming, Knuth found himself losing too much time wading through spam and unsolicited mail.
Knuth’s solution is probably not practical for everyone. Most of us don’t have a secretary. If we miss the important notice from HR about our benefits, well--no one’s going to print it out and pass it on, and we might get an unpleasant surprise next time we go to the doctor.
But, at the lowest level, Knuth has done the same thing Suarez has--and Jones is attempting: He shifted one form of communication (email) to another (snail mail and direct communication through his assistant).
Suarez’s approach, however, is a bit more reasonable for the rest of us. Like Jones, he moved the conversations he was having through email to other venues--and often found (as he suspected he would) the new method more appropriate and efficient. Quick responses got moved to chat; more elaborate conversations reverted to that old-tech method--the phone call.
Admittedly, Suarez is not exactly email-free, merely email-reduced. After three years, he was able to reduce his inbox count by more than 90 percent--down to an average of 17 emails per week, instead of the hundreds he was having to sift through before.
But it’s a far cry from what people expected. Like Jones, Suarez had his share of detractors. He’s commented in several of his talks, and in blog posts, that coworkers expected his email-free experiment to be short-lived. Others, more negative, speculated it could cost him his job. None of these things have happened.
The open source problem (and other motivations)
The level of concern--and outright anger--about such a communications change is interesting. Do people resent their own email ball-and-chain so much that, like with other bad environments, they want company in their misery? Or are they simply worried that their emails will go unanswered, or that the new venue for communication will result in more work on their part, or less choice about how they can respond?
Choice is important--especially for Professor Jones, and for opensource.com. Free and open source software (FOSS) advocates would like as much of their technology (if not all of it) to be developed and licensed in open ways. With email, as Jones points out, that choice is dubious--few people take the time to investigate the infrastructure behind their email or behind their internet service, nor that of the people they communicate with. It’s possible to choose open source alternatives often, but nearly impossible to not make use of a proprietary tool somewhere down the line.
The social media universe is wide. For almost every proprietary tool (Facebook), there is a open one (identi.ca, based on a free software package called StatusNet), but the crux of the matter is adoption. If you want to talk to friends who exclusively use FB, or see their posts, pictures, and updates, you have to sign up for the service. Open APIs and plug-ins to other platforms alleviate some of this lock-in, but not all, and they’re dependant upon the user actually using them.
People congregate around a useful social tool. Which tool this is changes, both as technologies develop and per user group. Adults over 55, to cull an example from research and our own anecdotal experience, tend to use email more than they do social apps or online shopping. It would be less likely, for example, for mom to maintain something like a Facebook account or an identi.ca profile. And she probably wouldn’t use both--she would see it as useless duplication of effort, and not have the technical savvy (or desire) to integrate the services.
But bringing up the generational split introduces another interesting wrinkle. Young people still make up a vast majority of the internet’s denizens. The choices people will have in the future depend largely on what tools they--and those that come after--rally around. And in late 2010, Pew Internet and the American Life project found that teens--the generation after Y Millennials--were growing even less likely to use email--only 11 percent of teens (12-17) used email to keep in daily contact with their peers. This is down from 14 percent, over three years (from November 2006 to September 2009). Contrast this with social networking--in 2006, 21 percent used IMs and FB to connect with pals. But 2009, it rose to 25 percent. But the real winner is direct text messaging--27 percent used it in 2006, but over half (54 percent) used texts three years later.
Can we leave our inboxes behind, and follow teens to texts and social networks? What if none of your age-bracket contemporaries choose to subscribe to the same services or use web-enabled phones? How do you pick which social media platforms to invest in?
Next: We interview Paul Jones about his decision to abandon email.
More info
1 I’m not counting the automated emails sent by Google Docs, since neither of us really composed them as email, and they were technically alerts I could have routed through one of several other interfaces.
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2013-05-18T09:29:26.000Z
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xcuugkcvziostep2o2wxztmyor7724ez
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I might show facts as plain as day: but, since your eyes are blind, you'd say, Where? What? and turn away. Rossetti, Christina
This quote is about facts · Search on Google Books to find all references and sources for this quotation.
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Christina Georgina Rossetti (December 5, 1830 December 29, 1894) was an English poet and the sister of artist Dante Gabriel Rossetti as well as William Michael Rossetti and Maria Francesca Rossetti. Their father, Gabriele Rossetti, was a political asylum seeker from Naples, and their mother, Frances Polidori, was the sister of Lord Byron's friend and physician, John William Polidori.
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The way of paradoxes is the way of truth. To test Reality we must see it on the tight-rope. When the Verities become acrobats we can judge them. Wilde, Oscar
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Oscar Fingal O'Flahertie Wills Wilde (October 16, 1854 November 30, 1900) was an Anglo-Irish playwright, novelist, poet, and short story writer. One of the most successful playwrights of late Victorian London, and one of the greatest celebrities of his day, known for his barbed and clever wit, he suffered a dramatic downfall and was imprisoned after being convicted in a famous trial of "gross indecency" for homosexual acts.
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If courtesans and strumpets were to be prosecuted with as much rigor as some silly people would have it, what locks or bars would be sufficient to preserve the honor of our wives and daughters? Mandeville, Bernard
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Do good to your friends to keep them, to your enemies to win them. Franklin, Benjamin
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Benjamin Franklin (January 17, 1706 April 17, 1790) was one of the most prominent of Founders and early political figures and statesmen of the United States. Considered the earliest of the Founders, Franklin was noted for his curiosity, ingenuity and diversity of interests. His wit and wisdom is proverbial to this day. More than anyone he shaped the American Revolution despite never holding national elective office. As a leader of the Enlightenment he had the attention of scientists and intellectuals all across Europe. As agent in London before the Revolution, and Minister to France during, he more than anyone defined the new nation in the minds of Europe. His success in securing French military and financial aid was decisive for American victory over Britain. He invented the lightning rod; he invented the notion of colonial unity; he invented the idea of America; historians hail him as the "First American". The city of Philadelphia, Pennsylvania will mark Franklin's 300th Birthday in January 2006, with a wide array of exhibitions, and events citing Franklin's extraordinary accomplishments throughout his illustrious career.
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A three -- to four -- to five-hour experience with nothingness. Glezer, Frederic
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Unlike any other business in the United States, sports must preserve an illusion of perfect innocence. The mounting of this illusion defines the purpose and accounts for the immense wealth of American sports. It is the ceremony of innocence that the fans pay to see -- not the game or the match or the bout, but the ritual portrayal of a world in which time stops and all hope remains plausible, in which everybody present can recover the blameless expectations of a child, where the forces of light always triumph over the powers of darkness. Lapham, Lewis H.
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It's easy! Just pick the product you like and click-through to buy it from trusted partners of Quotations Book. We hope you like these personalized gifts as much as we do.
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Reject your sense of injury and the injury itself disappears. Aurelius, Marcus
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212 - The Extra Degree
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2013-05-18T09:38:23.000Z
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vi5h7w6a5mx3wi6tmlk65vfz7dnx32cv
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The one extra degree makes the difference. This simple analogy reflects the ultimate definition of excellence. Because it's the one extra degree of effort, in business and life, that can separate the good from the great. This powerful book by S.L. Parker and Mac Anderson gives great examples, great quotes and great stories to illustrate the 212° concept. A warning - once you read it, it will be hard to forget. Your company will have a target for everything you do ... 212°
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The Thresher (Houston, Tex.), Vol. 8, No. 2, Ed. 1 Friday, September 22, 1922
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dc.coverage.spatial United States - Texas - Harris County - Houston
dc.coverage.temporal New South, Populism, Progressivism, and the Great Depression, 1877-1939
dc.date.accessioned 2012-11-07T02:15:14Z
dc.date.available 2012-11-07T02:15:14Z
dc.date.issued 1922-09-22
dc.identifier.uri http://hdl.handle.net/1911/65043
dc.description four pages : ill. ; page 20 x 15 in.
dc.description.abstract A weekly student newspaper from the Rice Institute in Houston, Texas that includes campus news and commentaries along with advertising.
dc.language eng
dc.publisher Rice University
dc.relation.ispartof This digitized newspaper is also presented online at the Portal to Texas History, at http://texashistory.unt.edu/ark:/67531/metapth229926/
dc.relation.ispartofseries This Issue appears in Vol. 8 of the Rice Thresher.
dc.rights This material is in the public domain and may be freely used, with attribution. This work is licensed under a Creative Commons Attribution 3.0 Unported License.
dc.rights.uri http://creativecommons.org/licenses/by/3.0/
dc.subject.lcsh Harris County (Tex.) -- Newspapers
Houston (Tex.) -- Newspapers
Houston (Tex.) -- Periodicals
Student publications -- Texas -- Houston
College student newspapers and periodicals -- Texas -- Houston
dc.title The Thresher (Houston, Tex.), Vol. 8, No. 2, Ed. 1 Friday, September 22, 1922
dc.digitization.specifications Page images were scanned by the UNT Portal to Texas History from microfilm as 8-bit grayscale at 400 dpi and saved as TIF masters, with OCR'd PDF access copies.
dc.source.collection Rice Thresher, Fondren Library, Rice University, Houston, Tex.
dc.citation.volumeNumber 8
dc.citation.issueNumber 2
dc.identifier.digital thr19220922
dc.contributor.publisher Rice Institute
dc.type.genre Newspaper
dc.type.dcmi Text
dc.identifier.citation (1922). "The Thresher (Houston, Tex.), Vol. 8, No. 2, Ed. 1 Friday, September 22, 1922." vol. 8. no. 2,
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2902.0 - Census Update (Newsletter), Apr 1998
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1301.6 - Tasmanian Year Book, 1983
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07/09/2007 Note: The data cube '6553.0 Appendix 6: SIH 2005-06 Data Item Listing' has been revised to correct minor label errors.
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Manovo-Gounda-St Floris National Park, Central African Republic
Manovo-Gounda-St Floris National Park, Central African Republic
Gounda's river. Manovo-Gounda-St Floris National Park. Source: José Tello
This article has been reviewed by the following Topic Editor: Langdon D. Clough
Manovo-Gounda-St Floris National Park (8° 05'-9° 50'N, 20° 28'-22° 22'E) is a World Heritage Site. The importance of this park is in its wealth of flora and fauna. Its vast savannas shelter a wide variety of species: black rhinoceros, elephant, cheetah, leopard, wild dog, red-fronted gazelle and buffalo; a wide range of waterfowl species also occurs in the northern floodplains.
Threats to Site
The site was added to the List of World Heritage in Danger following reports of illegal grazing and poaching by heavily armed hunters, who may have harvested as much as 80% of the park's wildlife. The shooting of four members of the park staff in early 1997 and a general state of deteriorating security brought all development projects and tourism to a halt. The government of the Central African Republic proposed to assign site management responsibility to a private foundation. The preparation of a detailed state of conservation report and rehabilitation plan for the site was recommended by the World Heritage Committee at its 1998 session.
Geographical Location
The Park occupies most of the eastern end of Bamingui-Bangoran province in the north of the country. Its boundary on the north is the international border with Chad on the River (Bahr) Aouk and R.Kameur; on the east, the R.Vakaga, on the west the R.Manovo about 40 kilometers (km) east of Ndéle, and in the south the ridge of the Massif des Bongo. The Ndéle-Birao road runs through the park. 8° 05'-9° 50'N, 20° 28'-22° 22'E
Country Flag and Map of the Central African Republic where the Manovo-Counds-St Floris National Park is located (Source: U.S. Department of State)
Date and History of Establishment
• 1993: Part of the area originally designated Oubangui-Chari National Park (13,500 hectares (ha)), renamed Matoumara National Park in 1935;
• 1940: Renamed St. Floris National Park (40,000 ha);
• 1960: St Floris National Park enlarged to 100,700 ha, and to 277,600 in 1974
• 1979: Manoco-Gounda-St. Floris National Park designated, including St Floris National Park and the former Safarafric hunting/tourism concession
Area
1,740,000 ha. Contiguous on the north to the Réserve de faune de l'Aouk-Aoukalé (330,000 ha), and on the east to the Réserve de faune de l'Ouandjia-Vakaga (130,000 ha). A proposed Réserve de faune du Bahr Oulou lying between these two reserves would also be contiguous, if designated.
Land Tenure
Government property. In 1984 a renewable twenty year agreement between the government and Manovo S.A made that company responsible for managing the park and exploiting its tourist potential.
Altitude
400 meters (m) to 800 m.
Physical Features
The park comprises three main zones: the grassy floodplain of the Bahr Aouk and Bahr Kameur rivers in the north, a gently undulating transitional plain of bushy or wooded savanna with occasional small granite inselbergs, and the Chaine des Bongo plateau in the south. The seasonally flooded lowlands have fine, deep, alluvial soils, where the drainage may be poor. The plain has coarse, well-drained, generally ferruginous and relatively infertile soils. Particularly in depressions, these develop a lateritic pan on which woody vegetation is sparse or absent. The massif is chiefly highly dissected sandstone, rising from the plain in a 100-200 m escarpment. Five major rivers thread through the park from the massif in the south east to the Bahr Aouk - Bahr Kameur floodplain in the north: the Vakaga on the eastern boundary, the Goro, Gounda, Koumbala, and the Manovo on the western boundary. The basins of the three central rivers all lie within the Park. However, their flow may be intermittent near the end of the dry season, and may only reach the Bahr Aouk and Bahr Kameur during the wettest months.
Climate
The climate is tropical, semi-humid Sudano-Guinean, with a mean annual rainfall of between 950 and 1,700 millimeters (mm), mainly falling between June and November, rainfall being much higher in the upland areas. December to May is hot and dry and grass fires are common in the late winter. Temperatures are much higher in the northern floodplain than on the plateau.
Vegetation
African Savanna which has a tropical climate (Source: Fullerton College)
The park is the largest savanna park in west and central Africa. It covers a broad range of habitat types ranging on a gradient from Sudano-Sahelian grassy savanna on the northern floodplains through bushy savanna, treed savanna and Sudanese wooded savanna, over the undulating land to its south threaded by gallery forest, to Sudano-Guinean savanna-woodland on the plateau in the southeast. Wooded savannas cover 70% of the area.
From riverside swamps the vegetation grades from sandy grassland of perennial grass communities, sedges and annual forbs covering the most heavily flooded areas, to seasonally flooded flat river valleys where the trees and shrubs are confined to patches of higher ground and have to be both flood and fire resistant. Predominant grassland species include perennials such as Vossia cuspidata, Echinochloa stagnina, Jardinea congoensis, Setaria anceps, Hyparrhenia rufa, and Eragrostis sp., their distributions depending on the duration and depth of seasonal flooding. In this impeded drainage tree savanna Pseudocedrela kotschyi and Terminalia macroptera with Combretum glutinosum. grow in soil of varying depths over ironstone. In less wet soils mixed open wooded savanna with a sparse shrub layer carries the same species plus Terminalia laxiflora, Combretum glutinosum and Anogeissus leiocarpus around seasonal streams and isolated low points. All the grassy savannas are heavily used by wildlife, especially ungulate herds. They are interspersed with less common types which form a mosaic related to soil and topography. These include Combretum scrub or ironstone meadow, ringed by stunted vegetation, where the laterite pan is close to the surface, bare isolated inselbergs and termite mounds which can shelter quite dense growth.
Wide stretches of the transitional plains are covered by wooded savanna of Terminalia laxiflora with Crossopteryx febrifuga and Butyrospermum parkii, heavily used by the larger mammals such as elephant, during the dry season. South of this is Isoberlinia doka - Monotes kerstingi woodland with little shrub layer or grass that is less used by animals. A dense dry forest of Anogeissus leiocarpus and Khaya senegalensis grows along the edges of the plains, particularly along the Gounda and Koumbala Rivers, and in small islands within the plains. This forest is under threat: Anogeissus leiocarpus is not fire resistant, which, with low rainfall, may be contributing to its decline. The gallery forests in deep high-banked valleys are attractive to monkeys and birds. In the south, the range of habitats is extended. There are broken rocky areas used by baboons, wooded savanna on the plateau, bamboo open savanna and clear forest with dense understory around the sources of the rivers, used by shyer ungulates.
Fauna
The fauna of the Park reflects its transitional position between east and west Africa, the Sahel and the forested tropics. It contains the richest fauna in the country, including some 57 mammals, which have been well protected in the past. In this it resembles the riches of the east African savannas. Faunal studies include those by Spinage, Buchanan & Schacht, and Barber et al., as well as aerial studies reported by Loevinsohn et al. and Loevinsohn. However, their reports cover mainly the northern area of and around St. Floris.
Several mammal species of particular concern to conservationists occur within the park: black rhinoceros Diceros bicornis (E), now reduced to fewer than ten animals, the small forest elephant Loxodonta africana cyclotis (V), which may number 2,000-3,000 individuals, leopard Panthera pardus, cheetah Acinonyx jubatus (V) and wild dog Lycaon pictus (E). Unfortunately, poaching of black rhinoceros and elephant has been heavy, and has decimated leopard and crocodile. Snares catch other species like lions and hyaenas indiscriminately. Red-fronted gazelle Gazella rufifrons (V) is the only gazelle found in the park, on its northeastern edge.
Baboon (Papio anubis), the most common primate (Source: Smithsonian Institution)
Within the St. Floris region, the most abundant large mammals seem to be kob Kobus kob, hartebeest Alcelaphus buselaphus and grey duiker Sylvicapra grimmia, with other fairly abundant ungulates including waterbuck Kobus ellipsiprymnus, oribi Ourebia ourebi, topi Damaliscus lunatus, reedbuck Redunca redunca, roan antelope Hippotragus equines and giant eland Taurotragus derbianus; also buffalo Syncerus caffer, warthog Phacochoerus aethiopicus and hippopotamus Hippopotamus amphibius. The most common primate recorded by Barber et al. was baboon Papio anubis, with lower numbers of patas and tantalus monkeys (Cercopithecus patas and C. tantalus), and low numbers of black and white colobus monkeys Colobus guereza in the dry forest. Other conspicuous large mammals include lion Panthera leo, giraffe Giraffa camelopardalis. Less common animals in the area include golden cat Felis aurata, red-flanked duiker Cephalophus rufilatus, yellow-backed duiker C. sylvicultor and aardvark Orycteropus afer. Few nocturnal species have been studied, but serval Felis serval may be common, also lesser bush baby Galago senegalensis. De Brazza's monkey Cercopithecus neglectus, greater white-nosed monkey Cercopithecus nictitans and bush pig Potamochoerus porcus have been discovered here since 1980, and Buchanan has also recorded rock hyrax Procavia ruficeps more than 200 km west of the nearest known population. The Nile crocodile Crocodylus niloticus is quite common.
Some 320 species of birds have been identified, with at least 25 species of raptor including bataleur Terathopius ecaudatus, and African fish eagle Cumcuma vocifer. There are large seasonal populations of marabou stork Leptoptilos crumeniferus and pelicans Pelecanus onocrotalus and P. rufescens. The floodplains of the north of the Park are fairly important for both waterbirds and shorebirds. Shoebill Balaeniceps rex (K) nests there. On the plains, ostrich Struthio camelus seem fairly common, moving to woodland to lay their eggs. Several species of bee-eater and kingfisher are present along the rivers.
Local Human Population
Most of the area has been sparsely inhabited since the beginning of the century having been a no-man's-land between opposing sultanates. However, nomadic cattle herders from the Nyala area of Sudan and from Chad, with between 30-40,000 head, enter the park during the winter as part of their dry season range, in a traditional transhumance. In the past, drought has also driven them there. There is sparse and limited agriculture around the park boundaries.
Visitors and Visitor Facilities
Access to the southern part of the park is relatively easy though there are few facilities for visitors. The infrastructure may be improved if it is agreed between the Government and the concessionaire, Manova S.A. This has responsibility for managing tourism within the park, and hunting in the buffer zones for 20 years from 1984, under an agreement with the government. However, in 1996, tourism stopped because the Park was no longer safe for travelers.
Scientific Research and Facilities
An aerial count of larger mammals in parts of the park was carried out by Loevinsohn for FAO. and again the next year as part of a larger project to improve management of [[fauna in the north of the country. An ecological survey of the St. Floris National Park was carried out by US Peace Corps biologists in 1977 and 1978. The report of this survey includes both general descriptions and species lists, and makes several recommendations. Further research was carried out in the newly-designated park in 1979 to extend much of the work to cover also the Gounda-Koumbala region. Between 1981 and 1984, Peace Corps biologists studied the ecology of elephants in the center of the park, with special reference to diet, distribution and the impact of poaching. Other activities by the research team included observations on poaching and other illegal activities, a botanical survey, noting rare or previously unidentified in the park species, and monitoring rhinoceros activity. A research center is planned at Camp Koumbala.
Conservation Value
The Park is one of the major biogeographic crossroads of central Africa. A remarkable range of north-central African savanna ecosystems shelter the country’s richest variety of animals, including black rhinoceroses, elephants, cheetahs, leopards, wild dogs, red-fronted gazelles and buffaloes, and the northern floodplains harbor several species of waterfowl.
Conservation Management
The park was said in the past to be the best protected area in the country. Over several years, FAO worked within the Central African Republic to improve wildlife management. As part of this work, Spinage made a preliminary survey of the St. Floris National Park, producing a number of recommendations for improving its management. Recommendations were also made by a series of subsequent studies. Until 1985, development was supported by the Fonds d'Aide et Coopération. Much investment was made to improve the tourist infrastructure. The tourism concessionaire, Manova S.A. also carried out limited park management such as grading tracks and burning to improve game-viewing, but it is unclear how much this was coordinated with the Park management. Most of the present management effort goes into limiting poaching and preventing grazing within park boundaries. Some army support is provided for anti-poaching work, but this has been sporadic and of short-term value.
In 1988 the EEC and FED started a ten-year project costing US$27million to enhance the integrity of the Park, and access into it, also to aid research and develop staff and facilities. Nevertheless, marauding continued. In 1997, the government of the Central African Republic was to give site responsibility to a private foundation which was trying to raise funds to provide staff and equipment for the park. In 2001 an IUCN mission visited the site to prepare for fund-raising and produce a realistic work plan for the next two years plan for the Park's rehabilitation, and the integration of local communities in participatory management. The government was also encouraged to seek the cooperation of neighboring states in limiting poaching.
Management Constraints
The most significant human impact on the park is the professional poaching of large mammals, particularly rhinoceros and elephant. This is facilitated by a main national route which crosses the park. Some poachers come from within the country but most are from Chad and Sudan, well supplied with automatic weapons since the civil wars in those countries. In 1997 uncontrolled poaching reached emergency levels, with heavily armed groups entering the park, setting up camp, and transporting bushmeat out by camel train. Four park staff were killed, and there was no effective anti-poaching force. 80% of the park's wildlife is said to have been harvested by poachers. The numbers of many animals in the area have fallen sharply. The elephant population decreased by 75% between 1981 and 1984, as few as ten rhinoceros remained by 1988, and the giraffe population has declined. Meanwhile, the staff is extremely short of the manpower and equipment needed to manage so large an area and has few firearms and only one vehicle.
Two other factors cause concern: fire, whether initiated by grazers, poachers, hunters or guards, and grazing. Most illegal grazing occurs during the dry season, with huge numbers of cattle moving from the Nyala region of Sudan and from Chad which compete with the wildlife and can introduce disease. This is also affecting the composition of grasslands, with perennial species giving way under grazing pressure to annuals and herbs.
Staff
The park is currently under the administration of one manager and one assistant with five guards, supplemented on occasions by army personnel for anti-poaching patrols. The concessionaire employs ten people on management oriented tasks.
Budget
Little site-specific information is available. The 1988 EEU/FED grant of US$27million to control poaching and grazing for ten years was to be succeeded in 1997 by funding from a private foundation to continue the work. In 2001 the World Heritage Bureau approved a grant of US$150,000 for an emergency rehabilitation plan.
IUCN Management Category
• II National Park
• Natural World Heritage Site, inscribed in 1988. Natural Criteria ii, iv.
• Listed as World Heritage in Danger in 1997 because of very heavy poaching and insecurity.
Further Reading
• Barber, K., Buchanan, S. & Galbreath, P. (1980). An Ecological Survey of the St Floris National Park, Central African Republic. IPAD, US National Parks Service, Washington D.C.
• Buchanan, S. & Schacht, W. (1979). Ecological investigations in the Manovo-Gounda-St Floris National Park ISBN: B0007AWI2G. Ministre des Eaux, Forêts, Chasses et Pêches, Bangui. CAR
• CAR (1987). Nomination of the Parc National du Manovo-Gounda-St Floris for Inscription on the World Heritage List. Ministre du Tourisme, des Eaux, Forêts, Chasses et Pêches, Bangui. Central African Republic.
• CAR (1992). Sauvegarde de Manovo-Gounda St Floris. Patrimoine Mondial. Report of the Haut Commissaire de la Zone Franche Ecologique to UNESCO.
• Douglas-Hamilton, I., Froment, J., & Doungoubé, G. (1985). Aerial survey of wildlife in the North of the Central African Republic. Report to CNPAF, WWF, IUCN, UNDP and FAO.
• IUCN, (1988). World Heritage Nomination - Technical Evaluation. Report to WWF.
• IUCN/WWF Project 3019. Elephant Research and Management, Central African Republic. Various reports.
• IUCN (1997) State of Conservation of Natural World Heritage Properties. Report prepared for the World Heritage Bureau, 21st session, UNESCO, Paris. 7pp.
• Loevinsohn, M. (1977). Analyse des Résultats de Survol Aérien 1969/70. CAF/72/010 Document de Travail No.7. FAO, Rome.
• Loevinsohn, M.,Spinage, C. & Ndouté, J. (1978). Analyse des Résultats de Survol Aérien 1978. CAF/72/010 Document de Travail No.10. FAO, Rome.
• Pfeffer, P. (1983). Un merveilleux sanctuaire de faune Centrafricain: le parc national Gounda-Manovo-St.Floris. Balafon, 58. Puteaux, France.
• Spinage, C. (1976). Etudes Préliminaires du Parc National de Saint-Floris. CAF/72/010. FAO Rome.
• Spinage, C.(1981). Résumé des Aires de Faune Protégées et Proposées pour être Protégées. CAF/78/006 Document de terrain No.2. FAO, Rome.
• Spinage, C. (1981). Some faunal isolates of the Central African Republic. African Journal of Ecology 19(1-2): 125-132.
• Temporal, J-L. (1985). Rapport Final d'Activités dans le Parc National Manovo-Gounda-St Floris. Rapport du projet. Fonds d'Aide et Coopération.
• UNESCO World Heritage Committee (1997). Report on the 20th Session of the World Heritage Committee, Paris.
• UNESCO World Heritage Committee (1998). Report on the 21st Session of the World Heritage Committee, Paris.
• UNESCO World Heritage Committee (2001). Report on the 24th Session of the World Heritage Committee, Paris.
• UNESCO World Heritage Committee (2002). Report on the 25th Session of the World Heritage Committee, Paris
Disclaimer: This article is taken wholly from, or contains information that was originally published by, the United Nations Environment Programme-World Conservation Monitoring Centre (UNEP-WCMC). Topic editors and authors for the Encyclopedia of Earth may have edited its content or added new information. The use of information from the United Nations Environment Programme-World Conservation Monitoring Centre (UNEP-WCMC) should not be construed as support for or endorsement by that organization for any new information added by EoE personnel, or for any editing of the original content.
Citation
United Nations Environment Programme-World Conservation M (Lead Author);Langdon D. Clough (Topic Editor) "Manovo-Gounda-St Floris National Park, Central African Republic". In: Encyclopedia of Earth. Eds. Cutler J. Cleveland (Washington, D.C.: Environmental Information Coalition, National Council for Science and the Environment). [First published in the Encyclopedia of Earth July 8, 2008; Last revised Date July 31, 2012; Retrieved May 18, 2013 <http://www.eoearth.org/article/Manovo-Gounda-St_Floris_National_Park,_Central_African_Republic>
The Author
The UNEP World Conservation Monitoring Centre (UNEP-WCMC) is a collaboration between the United Nations Environment Programme, the world's foremost intergovernmental organization, and WCMC 2000, a UK-based charity. Our Vision A world where biodiversity counts Our Mission To evaluate and highlight the many values of biodiversity and put authoritative biodiversity knowledge at the centre of decision-making Our Goal To be an internationally recognised Centre of Excellence for the synthe ... (Full Bio)
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About this Journal Submit a Manuscript Table of Contents
Current Gerontology and Geriatrics Research
Volume 2013 (2013), Article ID 928603, 6 pages
http://dx.doi.org/10.1155/2013/928603
Research Article
Unexplained Falls Are Frequent in Patients with Fall-Related Injury Admitted to Orthopaedic Wards: The UFO Study (Unexplained Falls in Older Patients)
1Geriatric and Gerontology Institute, University of Modena and Reggio Emilia, Modena 41121, Italy
2Geriatric Department, Azienda Policlinico Federico II, Naples 80131, Italy
3Unit of Gerontology and Geriatric Medicine, Department of Critical Care Medicine and Surgery, University of Florence and Azienda Ospedaliero Universitaria Careggi, Florence 50134, Italy
4Geriatric Unit, Santa Chiara Hospital, Trento 38122, Italy
5Department of Geriatrics, Azienda Sanitaria Locale 4, Chiavari 16043, Italy
6Division of Geriatrics, Ospedale S Maria Nuova, Reggio Emilia 42123, Italy
Received 24 July 2012; Revised 13 January 2013; Accepted 16 January 2013
Academic Editor: Arnold B. Mitnitski
Copyright © 2013 Mussi Chiara et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
To evaluate the incidence of unexplained falls in elderly patients affected by fall-related fractures admitted to orthopaedic wards, we recruited 246 consecutive patients older than 65 (mean age years, range 65–101). Falls were defined “accidental” (fall explained by a definite accidental cause), “medical” (fall caused directly by a specific medical disease), “dementia-related” (fall in patients affected by moderate-severe dementia), and “unexplained” (nonaccidental falls, not related to a clear medical or drug-induced cause or with no apparent cause). According to the anamnestic features of the event, older patients had a lower tendency to remember the fall. Patients with accidental fall remember more often the event. Unexplained falls were frequent in both groups of age. Accidental falls were more frequent in younger patients, while dementia-related falls were more common in the older ones. Patients with unexplained falls showed a higher number of depressive symptoms. In a multivariate analysis a higher GDS and syncopal spells were independent predictors of unexplained falls. In conclusion, more than one third of all falls in patients hospitalized in orthopaedic wards were unexplained, particularly in patients with depressive symptoms and syncopal spells. The identification of fall causes must be evaluated in older patients with a fall-related injury.
1. Introduction
Falls in older people are a major public health concern in terms of morbidity, mortality, and health and social services costs [1].
Falls are the leading cause of injury-related visits to emergency department in the United States. Trauma is the fifth leading cause of death in people starting from 65 years, and falls are responsible for 70% of accidental death in people starting from 75 years.
More than a third of older adults falls each year [2]. About one-third of community-dwelling elderly people and up to 60% of nursing home residents fall each year; one half of these “fallers” have multiple episodes [3]. Nearly all hip fractures occur as a fall result [4]. Fall-related injuries among older adults, especially among older women, are associated with substantial economic costs, mostly because of hip fractures and their subsequent disability [5].
Data regarding fall types in patients admitted to orthopaedic wards because of fall-related injury are lacking: the UFO study (Unexplained Falls in Older Patients) was made to assess the incidence and the clinical characteristics of unexplained falls in this specific group of elderly subjects affected by fall-related fractures.
2. Methods
2.1. Definition of Fall
We defined four different types of falls: “accidental” (fall explained by a definite accidental cause), “medical” (fall caused directly by a specific medical disease, e.g., hypoglycemia, drugs, drop and attack, transient ischemic attack, myocardial infarction, arrhythmic drugs, orthostatic hypotension), “dementia-related” (fall in a patient with previous diagnosis of moderate-severe dementia), and “unexplained” (nonaccidental falls, not related to a clear medical or drug-induced cause, where no apparent cause has been found) [6].
2.2. Protocol
All enrolled patients were starting from 65 years and consecutively admitted to orthopaedic wards because of fall-related injury, without any exclusion criteria.
All patients (or relatives if the patient had diagnosis of dementia) gave informed written consent.
Centers involved in the study (the appendix) designated and instructed a trained investigator who used to manage falls and syncope to run the study.
All subjects were asked to complete their clinical history, with a specific questionnaire about fall characteristics, pharmacologic anamnesis considering all drugs taken in the last month, clinical and neurological examination, routine blood chemistry tests, and 12-lead ECG.
Moreover, we performed a multidimensional geriatric evaluation including Mini Mental State Examination-(MMSE) [7] to assess cognitive performance, Geriatric Depression Scale (GDS) [8], to screen the presence of affective disorders, basal (BADL) [9] and instrumental (IADL) activities of daily living [10], to evaluate disability, and Cumulative Illness Rating Scale to define comorbidity (CIRS) [11].
2.3. Statistical Analysis
Data analysis was performed using SPSS, 14th version (SPSS, Chicago, IL, USA). The test was used to compare proportions in univariate analysis of dichotomic variables and to calculate odds ratio and the 95% confidence intervals. Student’s -test for independent samples was used to compare continuous variables. Variables significantly associated with the outcome of interest in univariate analyses were entered into a multivariate logistic regression model (backward stepwise) to assess their independent association with the outcome. A value <0.05 was considered statistically significant.
3. Results
246 patients (mean age years, 82% females) were submitted to the basal evaluation. We divided patients into two groups, according to age: 65–79 years (), ≥80 (). Most patients () were admitted because of a fall-related hip fracture.
Clinical characteristics of the studied sample are shown in Table 1.
Table 1: Clinical characteristics.
Patients older than 80 years were more likely to be self-dependent and obtained lower MMSE scores; they were more likely to show depressive symptoms, and they had lower values of BMI. No differences were found in the two groups in terms of biochemical values, except for hemoglobin that was significantly lower in older subjects. 17 patients (8.1%) had syncope as a cause of fall. According to the anamnestic features of the event, older patients had a lower tendency to remember the fall (Table 2).
Table 2: Clinical history.
Data regarding drugs taken in the last 30 days are shown in Table 3: 184 of 246 enrolled patients were taking at least one drug (74.7%). Older patients were more likely to take diuretics, and no other difference was found between the two groups.
Table 3: Drugs taken in the previous month.
4. Fall Types
The different fall types are described in Table 4.
Table 4: Different fall types (suggestive diagnosis).
Younger patients had a higher number of falls documented as accidental (48.1% versus 36.5%, ), while older patients were more frequently affected by dementia, as expected. No other differences were found for the other fall types (Table 4).
Clinical characteristics of patients with different fall types are shown in Table 5. Patients with dementia-related falls were significantly older than patients with accidental falls ( versus , ); they were more likely to have a higher degree of comorbidity (CIRS score: versus , ) and of disability (lost BADL: versus , ; lost IADL: versus , ), and, as expected, they obtained lower MMSE scores (). Patients with unexplained falls were less self-dependent with respect to patients with medical fall causes (lost BADL: versus , , lost IADL: versus , ) and to patients with dementia-related falls (lost BADL: versus , ; lost IADL: versus , ).
Table 5: Clinical patient features with different fall types.
Patients with falls related to medical causes reached higher levels of comorbidity than patients with accidental falls (CIRS score: versus , ), and they lost a higher number of BADL ( versus , ) and IADL ( versus , ). These latter ones referred to a significantly higher number of anamnestic falls in the last year with respect to patients with accidental (), dementia-related (), and unexplained () falls. Moreover, they showed worse cognitive performances at MMSE with respect to patients with accidental () and unexplained () falls.
Patients with unexplained falls lost a higher number of IADL with respect to patients with accidental falls (lost IADL: versus , ), and they showed a higher number of depressive symptoms, expressed as GDS score ().
No differences were found between the four groups as far as the use of different classes of drugs is concerned.
History in different syncope types is illustrated in Figure 1. Patients with accidental falls remember more often the event, as expected. Witness presence is less than 50% in all the fall types.
Figure 1: History in different syncope types.
5. Multivariate Analysis
We drew four multivariate models (logistic regression, method backward stepwise) separately, considering the four fall types as independent variables. We considered in the models the variables that were significantly different between the four groups at the univariate analysis. No predictive factor was found for medical and dementia-related falls. Younger age, low GDS values, and no syncopal spells were independent accidental falls predictors (Table 6(A)), while a higher GDS and syncopal spells were independent predictors of unexplained falls (Table 6(B)). Other variables in the multivariate analysis considered in the model, but not significant, were comorbidity (expressed by means of the Cumulative Illness Rating Score) and the number of lost activities and instrumental activities of daily living.
Table 6: Multivariate analysis: types of fall predictors.
6. Discussion
According to our knowledge, there is no study about causes of falls leading an old patient to an orthopaedic ward in Italy. Our study demonstrates that these patients are very old and frail because of severe comorbidity and polytherapy. The percentage of patients affected by dementia is quite high (12.6%). The majority of our patients were admitted to hospital because of hip fracture. Hip fractures are very common, and their incidence was not reduced in the last ten years [12]. Moreover 14.8% of patients with hip fractures experienced a second hip fracture in a followup of 4.2 years [13]. For all of these reasons it may be very useful to study the fall etiology to reduce recurrence.
Our study found a high number of patients with unexplained falls (37%), when the study of Kenny et al. found a significantly lower number of unexplained falls (15%). This difference is explained by the fact that they also considered younger patients (older than 50) admitted to an emergency department, and not to an orthopaedic ward [14]. Unexplained falls can lead to more serious consequences, like hip fractures. Scuffham et al. demonstrated that unspecified falls, although not so frequent as the accidental ones, lead to a significant higher number of hospital accesses and are responsible for 53% of total costs related to falls [15].
A number of different strategies and interventions for each case are effective, but population-based strategies have not yet been evaluated, particularly in frail old patients, admitted to orthopaedic wards. Multidisciplinary, multifactorial intervention programmes inclusive of risk-factor assessment, screening, cause identification by means of diagnostic flow charts, and appropriate intervention proved to be effective [16], and they are useful to identify the causes of fall in the elderly. This topic is mandatory in older patients in order to abolish risk factors and to build a correct prevention programme. Unfortunately we found that only previous syncope and higher GDS score were predictive factors of unexplained falls. For this reason, all patients with fall-related injury must be evaluated for the possible fall cause. A recent meta-analysis showed that in patients with injury-related falls a multifactorial assessment and a targeted intervention do not reduce fall recurrence, whereas the same programme seems to be effective in patients who fall without getting an injury [17].
In our “faller” cohort, as shown in Table 3, our patients took a great number of antihypertensive drugs (60.1%) which are well-known fall and syncope risk factors [18]. In a multivariate analysis a previous syncope is a predictor of unexplained falls, while it is a negative predictor of accidental falls. We can speculate that unexplained falls may be caused by syncope more often than normally considered in clinical practice.
Our study demonstrates the need to study deeply and correctly patients with falls at the very beginning of the story (e.g., when they are admitted to the orthopaedic ward because of the fall). Unfortunately, at the moment, this is very difficult to achieve because of cultural and organizational problems. Future studies may be conducted to evaluate the correct strategy for patients with unexplained falls, probably in a postacute setting such as a rehabilitation unit.
One limitation to this study is the observational design and the absence of an active “prevention and treatment time.” In the literature it is well known that the presence of a team applying comprehensive geriatric assessment and rehabilitation, including prevention, detection, and treatment of fall risk factors, can successfully prevent inpatient falls and injuries, even in those with dementia [19]; this group of old patients is at the highest risk of developing postsurgical complications like delirium [20].
In conclusion, all these data demonstrate that patients admitted to orthopaedic wards after a fall-related injury are frail and affected by severe comorbidity and that unexplained falls are frequent in these patients. These results underline the absolutely relevant role of geriatric evaluation and intervention in older patients admitted to orthopaedic wards. Further studies are necessary to evaluate the impact of diagnostic protocol in patients with unexplained falls.
Appendix
Centers and Investigators Participating to the Study
(1)Florence, Syncope Unit, Department of Geriatric Cardiology, University of Florence and Azienda Ospedaliero Universitaria Careggi. Investigators: Andrea Ungar, Annalisa Landi, Alice Maraviglia, Niccolò Marchionni, Giulio Masotti, Alessandro Morrione, and Martina Rafanelli.(2)Modena, Chair of Geriatrics, University of Modena and Reggio Emilia: Chiara Mussi, and Gianfranco Salvioli.(3)Trento, Division of Geriatrics, Santa Chiara Hospital: Gabriele Noro, and Gianni Tava.(4)Reggio Emilia, Division of Geriatrics, Santa Maria Nuova Hospital: Loredana Ghirelli.(5)Naples, Department of Geriatrics, Federico II University: Pasquale Abete, Vincenzo Del Villano, Gianluigi Galizia, and Franco Rengo.(6)Grosseto, Division of Geriatrics, Walter De Alfieri, Fabio Riello.(7)Chiavari, Department of Geriatrics, Paolo Cavagnaro.
Acknowledgment
This paper is done on behalf of the Italian Group of Syncope in the Elderly of the Italian Society of Gerontology (GIS Group).
References
1. J. A. Rizzo, R. Friedkin, C. S. Williams, J. Nabors, D. Acampora, and M. E. Tinetti, “Health care utilization and costs in a medicare population by fall status,” Medical Care, vol. 36, no. 8, pp. 1174–1188, 1998. View at Scopus
2. G. F. Fuller, “Falls in the elderly,” American Family Physician, vol. 61, no. 7, pp. 2159–2168, 2000. View at Scopus
3. C. H. Hirsch, L. Sommers, A. Olsen, L. Mullen, and C. H. Winograd, “The natural history of functional morbidity in hospitalized older patients,” Journal of the American Geriatrics Society, vol. 38, no. 12, pp. 1296–1303, 1990. View at Scopus
4. L. Nyberg, Y. Gustafson, D. Berggren, B. Brännström, and G. Bucht, “Falls leading to femoral neck fractures in lucid older people,” Journal of the American Geriatrics Society, vol. 44, no. 2, pp. 156–160, 1996. View at Scopus
5. J. A. Stevens, P. S. Corso, E. A. Finkelstein, and T. R. Miller, “The costs of fatal and non-fatal falls among older adults,” Injury Prevention, vol. 12, no. 5, pp. 290–295, 2006. View at Publisher · View at Google Scholar · View at Scopus
6. T. Masud and R. O. Morris, “Epidemiology of falls,” Age and Ageing, vol. 30, no. 4, pp. 3–7, 2001. View at Publisher · View at Google Scholar · View at Scopus
7. M. F. Folstein, S. E. Folstein, and P. R. McHugh, “‘Mini mental state’. A practical method for grading the cognitive state of patients for the clinician,” Journal of Psychiatric Research, vol. 12, no. 3, pp. 189–198, 1975. View at Publisher · View at Google Scholar · View at Scopus
8. J. A. Yesavage, T. L. Brink, T. L. Rose et al., “Development and validation of a geriatric depression screening scale: a preliminary report,” Journal of Psychiatric Research, vol. 17, no. 1, pp. 37–49, 1982. View at Publisher · View at Google Scholar · View at Scopus
9. S. Katz, A. B. Ford, R. W. Moskowitz, B. A. Jackson, and M. W. Jaffe, “Studies of illness in the aged. The index of ADL: a standardized measure of biological and psychosocial function,” The Journal of the American Medical Association, vol. 185, pp. 914–919, 1963. View at Scopus
10. M. P. Lawton and E. M. Brody, “Assessment of older people: self-maintaining and instrumental activities of daily living,” Gerontologist, vol. 9, no. 3, pp. 179–186, 1969. View at Scopus
11. Y. Conwell, N. T. Forbes, C. Cox, and E. D. Caine, “Validation of a measure of physical illness burden at autopsy: the cumulative illness rating scale,” Journal of the American Geriatrics Society, vol. 41, no. 1, pp. 38–41, 1993. View at Scopus
12. M. Piirtola, T. Vahlberg, R. Isoaho, P. Aarnio, and S. L. Kivelä, “Incidence of fractures and changes over time among the aged in a Finnish municipality: a population-based 12-year follow-up,” Aging—Clinical and Experimental Research, vol. 19, no. 4, pp. 269–276, 2007. View at Scopus
13. S. D. Berry, E. J. Samelson, M. T. Hannan et al., “Second hip fracture in older men and women: the framingham study,” Archives of Internal Medicine, vol. 167, no. 18, pp. 1971–1976, 2007. View at Publisher · View at Google Scholar · View at Scopus
14. R. A. M. Kenny, D. A. Richardson, N. Steen, R. S. Bexton, F. E. Shaw, and J. Bond, “Carotid sinus syndrome: a modifiable risk factor for nonaccidental falls in older adults (SAFE PACE),” Journal of the American College of Cardiology, vol. 38, no. 5, pp. 1491–1496, 2001. View at Publisher · View at Google Scholar · View at Scopus
15. P. Scuffham, S. Chaplin, and R. Legood, “Incidence and costs of unintentional falls in older people in the United Kingdom,” Journal of Epidemiology and Community Health, vol. 57, no. 9, pp. 740–744, 2003. View at Publisher · View at Google Scholar · View at Scopus
16. D. A. Skelton and C. J. Todd, “Thoughts on effective falls prevention intervention on a population basis,” Journal of Public Health, vol. 13, no. 4, pp. 196–202, 2005. View at Publisher · View at Google Scholar · View at Scopus
17. S. Gates, J. D. Fisher, M. W. Cooke, Y. H. Carter, and S. E. Lamb, “Multifactorial assessment and targeted intervention for preventing falls and injuries among older people in community and emergency care settings: systematic review and meta-analysis,” The British Medical Journal, vol. 336, no. 7636, pp. 130–133, 2008. View at Publisher · View at Google Scholar · View at Scopus
18. S. Mayor, “NICE issues guideline to prevent falls in elderly people,” The British Medical Journal, vol. 329, no. 7477, article 1258, 2004. View at Scopus
19. M. Stenvall, B. Olofsson, M. Lundström et al., “A multidisciplinary, multifactorial intervention program reduces postoperative falls and injuries after femoral neck fracture,” Osteoporosis International, vol. 18, no. 2, pp. 167–175, 2007. View at Publisher · View at Google Scholar · View at Scopus
20. B. D. Robertson and T. J. Robertson, “Current concepts review: postoperative delirium after hip fracture,” Journal of Bone and Joint Surgery Series A, vol. 88, no. 9, pp. 2060–2068, 2006. View at Publisher · View at Google Scholar · View at Scopus
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39 Bible Verses about False Deacons
Revelation 8:1-13 ESV / 3 helpful votes
When the Lamb opened the seventh seal, there was silence in heaven for about half an hour. Then I saw the seven angels who stand before God, and seven trumpets were given to them. And another angel came and stood at the altar with a golden censer, and he was given much incense to offer with the prayers of all the saints on the golden altar before the throne, and the smoke of the incense, with the prayers of the saints, rose before God from the hand of the angel. Then the angel took the censer and filled it with fire from the altar and threw it on the earth, and there were peals of thunder, rumblings, flashes of lightning, and an earthquake. ...
Revelation 7:1-17 ESV / 3 helpful votes
After this I saw four angels standing at the four corners of the earth, holding back the four winds of the earth, that no wind might blow on earth or sea or against any tree. Then I saw another angel ascending from the rising of the sun, with the seal of the living God, and he called with a loud voice to the four angels who had been given power to harm earth and sea, saying, “Do not harm the earth or the sea or the trees, until we have sealed the servants of our God on their foreheads.” And I heard the number of the sealed, 144,000, sealed from every tribe of the sons of Israel: 12,000 from the tribe of Judah were sealed, 12,000 from the tribe of Reuben, 12,000 from the tribe of Gad, ...
James 1:1-27 ESV / 3 helpful votes
James, a servant of God and of the Lord Jesus Christ, To the twelve tribes in the Dispersion: Greetings. Count it all joy, my brothers, when you meet trials of various kinds, for you know that the testing of your faith produces steadfastness. And let steadfastness have its full effect, that you may be perfect and complete, lacking in nothing. If any of you lacks wisdom, let him ask God, who gives generously to all without reproach, and it will be given him. ...
Romans 16:7 ESV / 3 helpful votes
Greet Andronicus and Junia, my kinsmen and my fellow prisoners. They are well known to the apostles, and they were in Christ before me.
John 15:7 ESV / 3 helpful votes
If you abide in me, and my words abide in you, ask whatever you wish, and it will be done for you.
John 15:6 ESV / 3 helpful votes
If anyone does not abide in me he is thrown away like a branch and withers; and the branches are gathered, thrown into the fire, and burned.
John 15:5 ESV / 3 helpful votes
I am the vine; you are the branches. Whoever abides in me and I in him, he it is that bears much fruit, for apart from me you can do nothing.
John 15:4 ESV / 3 helpful votes
Abide in me, and I in you. As the branch cannot bear fruit by itself, unless it abides in the vine, neither can you, unless you abide in me.
John 14:18 ESV / 3 helpful votes
“I will not leave you as orphans; I will come to you.
John 14:1 ESV / 3 helpful votes
“Let not your hearts be troubled. Believe in God; believe also in me.
John 12:46 ESV / 3 helpful votes
I have come into the world as light, so that whoever believes in me may not remain in darkness.
Luke 22:1-71 ESV / 3 helpful votes
Now the Feast of Unleavened Bread drew near, which is called the Passover. And the chief priests and the scribes were seeking how to put him to death, for they feared the people. Then Satan entered into Judas called Iscariot, who was of the number of the twelve. He went away and conferred with the chief priests and officers how he might betray him to them. And they were glad, and agreed to give him money. ...
Matthew 1:18 ESV / 3 helpful votes
Now the birth of Jesus Christ took place in this way. When his mother Mary had been betrothed to Joseph, before they came together she was found to be with child from the Holy Spirit.
Hebrews 9:1-28 ESV / 2 helpful votes
Now even the first covenant had regulations for worship and an earthly place of holiness. For a tent was prepared, the first section, in which were the lampstand and the table and the bread of the Presence. It is called the Holy Place. Behind the second curtain was a second section called the Most Holy Place, having the golden altar of incense and the ark of the covenant covered on all sides with gold, in which was a golden urn holding the manna, and Aaron's staff that budded, and the tablets of the covenant. Above it were the cherubim of glory overshadowing the mercy seat. Of these things we cannot now speak in detail. ...
Hebrews 8:1-13 ESV / 2 helpful votes
Now the point in what we are saying is this: we have such a high priest, one who is seated at the right hand of the throne of the Majesty in heaven, a minister in the holy places, in the true tent that the Lord set up, not man. For every high priest is appointed to offer gifts and sacrifices; thus it is necessary for this priest also to have something to offer. Now if he were on earth, he would not be a priest at all, since there are priests who offer gifts according to the law. They serve a copy and shadow of the heavenly things. For when Moses was about to erect the tent, he was instructed by God, saying, “See that you make everything according to the pattern that was shown you on the mountain.” ...
1 Timothy 3:8 ESV / 2 helpful votes
Deacons likewise must be dignified, not double-tongued, not addicted to much wine, not greedy for dishonest gain.
1 Corinthians 10:1-33 ESV / 2 helpful votes
For I want you to know, brothers, that our fathers were all under the cloud, and all passed through the sea, and all were baptized into Moses in the cloud and in the sea, and all ate the same spiritual food, and all drank the same spiritual drink. For they drank from the spiritual Rock that followed them, and the Rock was Christ. Nevertheless, with most of them God was not pleased, for they were overthrown in the wilderness. ...
1 Corinthians 9:1 ESV / 2 helpful votes
Am I not free? Am I not an apostle? Have I not seen Jesus our Lord? Are not you my workmanship in the Lord?
John 14:1-31 ESV / 2 helpful votes
“Let not your hearts be troubled. Believe in God; believe also in me. In my Father's house are many rooms. If it were not so, would I have told you that I go to prepare a place for you? And if I go and prepare a place for you, I will come again and will take you to myself, that where I am you may be also. And you know the way to where I am going.” Thomas said to him, “Lord, we do not know where you are going. How can we know the way?” ...
Joel 2:1-32 ESV / 2 helpful votes
Blow a trumpet in Zion; sound an alarm on my holy mountain! Let all the inhabitants of the land tremble, for the day of the Lord is coming; it is near, a day of darkness and gloom, a day of clouds and thick darkness! Like blackness there is spread upon the mountains a great and powerful people; their like has never been before, nor will be again after them through the years of all generations. Fire devours before them, and behind them a flame burns. The land is like the garden of Eden before them, but behind them a desolate wilderness, and nothing escapes them. Their appearance is like the appearance of horses, and like war horses they run. As with the rumbling of chariots, they leap on the tops of the mountains, like the crackling of a flame of fire devouring the stubble, like a powerful army drawn up for battle. ...
Hosea 6:6 ESV / 2 helpful votes
For I desire steadfast love and not sacrifice, the knowledge of God rather than burnt offerings.
Hosea 5:2 ESV / 2 helpful votes
And the revolters have gone deep into slaughter, but I will discipline all of them.
Isaiah 43:1-28 ESV / 2 helpful votes
But now thus says the Lord, he who created you, O Jacob, he who formed you, O Israel: “Fear not, for I have redeemed you; I have called you by name, you are mine. When you pass through the waters, I will be with you; and through the rivers, they shall not overwhelm you; when you walk through fire you shall not be burned, and the flame shall not consume you. For I am the Lord your God, the Holy One of Israel, your Savior. I give Egypt as your ransom, Cush and Seba in exchange for you. Because you are precious in my eyes, and honored, and I love you, I give men in return for you, peoples in exchange for your life. Fear not, for I am with you; I will bring your offspring from the east, and from the west I will gather you. ...
Psalm 22:1-31 ESV / 2 helpful votes
To the choirmaster: according to The Doe of the Dawn. A Psalm of David. My God, my God, why have you forsaken me? Why are you so far from saving me, from the words of my groaning? O my God, I cry by day, but you do not answer, and by night, but I find no rest. Yet you are holy, enthroned on the praises of Israel. In you our fathers trusted; they trusted, and you delivered them. To you they cried and were rescued; in you they trusted and were not put to shame. ...
1 Samuel 16:11 ESV / 2 helpful votes
Then Samuel said to Jesse, “Are all your sons here?” And he said, “There remains yet the youngest, but behold, he is keeping the sheep.” And Samuel said to Jesse, “Send and get him, for we will not sit down till he comes here.”
Judges 6:34 ESV / 2 helpful votes
But the Spirit of the Lord clothed Gideon, and he sounded the trumpet, and the Abiezrites were called out to follow him.
Judges 6:33 ESV / 2 helpful votes
Now all the Midianites and the Amalekites and the people of the East came together, and they crossed the Jordan and encamped in the Valley of Jezreel.
Judges 6:30 ESV / 2 helpful votes
Then the men of the town said to Joash, “Bring out your son, that he may die, for he has broken down the altar of Baal and cut down the Asherah beside it.”
Judges 6:16 ESV / 2 helpful votes
And the Lord said to him, “But I will be with you, and you shall strike the Midianites as one man.”
Judges 6:15 ESV / 2 helpful votes
And he said to him, “Please, Lord, how can I save Israel? Behold, my clan is the weakest in Manasseh, and I am the least in my father's house.”
Judges 6:4 ESV / 2 helpful votes
They would encamp against them and devour the produce of the land, as far as Gaza, and leave no sustenance in Israel and no sheep or ox or donkey.
Judges 6:1-40 ESV / 2 helpful votes
The people of Israel did what was evil in the sight of the Lord, and the Lord gave them into the hand of Midian seven years. And the hand of Midian overpowered Israel, and because of Midian the people of Israel made for themselves the dens that are in the mountains and the caves and the strongholds. For whenever the Israelites planted crops, the Midianites and the Amalekites and the people of the East would come up against them. They would encamp against them and devour the produce of the land, as far as Gaza, and leave no sustenance in Israel and no sheep or ox or donkey. For they would come up with their livestock and their tents; they would come like locusts in number—both they and their camels could not be counted—so that they laid waste the land as they came in. ...
Joshua 6:1-27 ESV / 2 helpful votes
Now Jericho was shut up inside and outside because of the people of Israel. None went out, and none came in. And the Lord said to Joshua, “See, I have given Jericho into your hand, with its king and mighty men of valor. You shall march around the city, all the men of war going around the city once. Thus shall you do for six days. Seven priests shall bear seven trumpets of rams' horns before the ark. On the seventh day you shall march around the city seven times, and the priests shall blow the trumpets. And when they make a long blast with the ram's horn, when you hear the sound of the trumpet, then all the people shall shout with a great shout, and the wall of the city will fall down flat, and the people shall go up, everyone straight before him.” ...
Deuteronomy 16:1 ESV / 2 helpful votes
“Observe the month of Abib and keep the Passover to the Lord your God, for in the month of Abib the Lord your God brought you out of Egypt by night.
Numbers 10:1-36 ESV / 2 helpful votes
The Lord spoke to Moses, saying, “Make two silver trumpets. Of hammered work you shall make them, and you shall use them for summoning the congregation and for breaking camp. And when both are blown, all the congregation shall gather themselves to you at the entrance of the tent of meeting. But if they blow only one, then the chiefs, the heads of the tribes of Israel, shall gather themselves to you. When you blow an alarm, the camps that are on the east side shall set out. ...
Numbers 9:4-5 ESV / 2 helpful votes
So Moses told the people of Israel that they should keep the Passover. And they kept the Passover in the first month, on the fourteenth day of the month, at twilight, in the wilderness of Sinai; according to all that the Lord commanded Moses, so the people of Israel did.
Exodus 19:1-25 ESV / 2 helpful votes
On the third new moon after the people of Israel had gone out of the land of Egypt, on that day they came into the wilderness of Sinai. They set out from Rephidim and came into the wilderness of Sinai, and they encamped in the wilderness. There Israel encamped before the mountain, while Moses went up to God. The Lord called to him out of the mountain, saying, “Thus you shall say to the house of Jacob, and tell the people of Israel: You yourselves have seen what I did to the Egyptians, and how I bore you on eagles' wings and brought you to myself. Now therefore, if you will indeed obey my voice and keep my covenant, you shall be my treasured possession among all peoples, for all the earth is mine; ...
Exodus 12:2 ESV / 2 helpful votes
“This month shall be for you the beginning of months. It shall be the first month of the year for you.
Exodus 12:1-51 ESV / 2 helpful votes
The Lord said to Moses and Aaron in the land of Egypt, “This month shall be for you the beginning of months. It shall be the first month of the year for you. Tell all the congregation of Israel that on the tenth day of this month every man shall take a lamb according to their fathers' houses, a lamb for a household. And if the household is too small for a lamb, then he and his nearest neighbor shall take according to the number of persons; according to what each can eat you shall make your count for the lamb. Your lamb shall be without blemish, a male a year old. You may take it from the sheep or from the goats, ...
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Category:Tea Party Movement
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This is a category for articles about the right-wing "Tea Party movement" which emerged in 2009. The movement is disparate with many tendencies and groups, from grassroots populist volunteers to powerful, corporate-funded right wing lobby groups such as Freedom Works. It shares an opposition to Democratic liberalism and the Barack Obama administration. This category below includes politicians who are supported or endorsed, or who benefit from the movement, such as Scott Brown, but who do not necessarily self-identify with it. This category is meant to also include media who promote the movement and its objectives, such as Fox News, and media that have produced good investigations or analysis of it.
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James H. Miller
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This article is part of the Coal Issues portal on SourceWatch, a project of CoalSwarm and the Center for Media and Democracy. See here for help on adding material to CoalSwarm.
Learn more from the Center for Media and Democracy's research on climate change.
James H. Miller is president and chief executive officer of PPL. He joined the company in February 2001 as president of PPL Generation, a subsidiary that controls more than 11,000 megawatts of electrical generation capacity in the United States. He was promoted to executive vice president of PPL Corporation in January 2004 and to chief operating officer in September 2004.[1]
Before joining PPL, Miller was executive vice president of USEC Inc., an international supplier of enriched uranium to nuclear utilities. Previously, he was president of two subsidiaries of ABB Group: ABB Environmental Systems, which supplied air pollution control equipment to the power industry, and ABB Resource Recovery Systems, which designed, built and operated waste-to-energy plants. He also served as president of the former UC Operating Services, a subsidiary of Constellation Energy and Louisville Gas and Electric Co. He got his start in the electricity industry at the former Delmarva Power & Light Co., where he held engineering and management positions.[1]
Miller received his undergraduate degree in electrical engineering from the University of Delaware and served in the U.S. Navy nuclear submarine program.[1]
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Affiliations
Miller is a member of the following boards:[1]
PPL power portfolio
Out of its total 12,611 MW of electric generating capacity in 2005 (1.18% of the U.S. total), PPL produced 47.4% from coal, 20.6% from nuclear, 17.8% from oil, 7.5% from hydroelectricity, and 7.1% from natural gas. PPL owns power plants in Connecticut, Illinois, Maine, Montana, New York, and Pennsylvania; 67.6% of the company's generating capacity comes from power plants in Pennsylvania.[2]
Existing coal-fired power plants
PPL owned 13 coal-fired generating stations in 2005, with 5,982 MW of capacity. Here is a list of PPL's coal power plants:[2][3][4]
Plant Name State County Year(s) Built Capacity 2007 CO2 Emissions 2006 SO2 Emissions
Colstrip MT Rosebud 1975, 1976, 1984, 1986 2314 MW 16,783,000 tons 14,298 tons
Montour PA Montour 1972, 1973 1625 MW 8,964,000 tons 129,357 tons
Brunner Island PA York 1961, 1965, 1969 1559 MW 9,118,000 tons 93,545 tons
Martins Creek PA Northampton 1954, 1956 312 MW 3,007,000 tons 30,058 tons
Corette MT Yellowstone 1968 173 MW 1,498,000 tons 4,401 tons
In 2006, PPL's 5 coal-fired power plants emitted 39.4 million tons of CO2 (0.65% of all U.S. CO2 emissions) and 272,000 tons of SO2 (1.81% of all U.S. SO2 emissions).
Resources
References
1. 1.0 1.1 1.2 1.3 James H. Miller, PPL, accessed December 2008.
2. 2.0 2.1 Existing Electric Generating Units in the United States, 2005, Energy Information Administration, accessed April 2008.
3. Environmental Integrity Project, Dirty Kilowatts: America’s Most Polluting Power Plants, July 2007.
4. Dig Deeper, Carbon Monitoring for Action database, accessed June 2008.
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This article is a stub. You can help by expanding it.
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Place:Boggabilla, New South Wales, Australia
Watchers
NameBoggabilla
TypeTown
Coordinates28.6°S 150.35°E
Located inNew South Wales, Australia
source: Getty Thesaurus of Geographic Names
source: Family History Library Catalog
the text in this section is copied from an article in Wikipedia
Boggabilla is a small town in the far north of inland New South Wales, Australia in Moree Plains Shire. In 2006, the town had a population of 647, of which 56% identified as Aboriginal or Torres Strait Islander descent.
The name Boggabilla comes from Gamilaraay bagaaybila, literally "full of creeks". The same "creek" element is found in the name of Boggabri.
Research Tips
This page uses content from the English Wikipedia. The original content was at Boggabilla, New South Wales. The list of authors can be seen in the page history. As with WeRelate, the content of Wikipedia is available under the Creative Commons Attribution/Share-Alike License.
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Place:Destelbergen, Oost-Vlaanderen, Belgium
Watchers
NameDestelbergen
TypeMunicipality
Coordinates51.05°N 3.8°E
Located inOost-Vlaanderen, Belgium
source: Getty Thesaurus of Geographic Names
source: Family History Library Catalog
the text in this section is copied from an article in Wikipedia
Destelbergen is a municipality located in the Belgian province of East Flanders. The municipality comprises the towns of Destelbergen proper and Heusden and was created on January 1, 1977 by the fusion of these two municipalities. Its western border touches the municipality of Ghent and Melle and is formed by an ancient silted up branch of the river Scheldt.
Curiosities worth seeing are the many residential castles, a Gaulish farmhouse, and the Damvallei nature reserve.
On January 1, 2011 Destelbergen had a total population of 17,636. The total area is 26.56 km² which gives a population density of 664 inhabitants per km².
Research Tips
This page uses content from the English Wikipedia. The original content was at Destelbergen. The list of authors can be seen in the page history. As with WeRelate, the content of Wikipedia is available under the Creative Commons Attribution/Share-Alike License.
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Place:Fowlerville, Livingston, Michigan, United States
Watchers
NameFowlerville
TypeVillage
Coordinates42.65°N 84.067°W
Located inLivingston, Michigan, United States
source: Getty Thesaurus of Geographic Names
source: Family History Library Catalog
the text in this section is copied from an article in Wikipedia
Fowlerville is a village in Livingston County in the U.S. state of Michigan. It is located in the northeast portion of Handy Township, but is politically independent from the township. The population was 2,886 at the 2010 census.
Research Tips
This page uses content from the English Wikipedia. The original content was at Webberville, Michigan. The list of authors can be seen in the page history. As with WeRelate, the content of Wikipedia is available under the Creative Commons Attribution/Share-Alike License.
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Connected Democracy is Philosophically Blind
With respect to the use of technology by the Dean campaign, Tom Mangan writes:
I just finished Ed Cone's piece, which seems to be missing one critical point: anything perceived good guy Howard Dean can do with technology can be replicated by his enemies (it's possible I glazed over this part, it's long article). Team Bush has $200 million and six months to play catch-up. It also has talk radio, the Fox Network and all the warbloggers on its side, plus the population's inherent tendency to side with the current prez during wartime. The Web knows no politics, it just offers politicians another way to get people to the polls. All Dean's "he gets it!" cheerleaders are gonna have some crow to digest if somebody really repellant uses all these tools to get elected in the future
From Prints the chaff
Referenced Fri Nov 21 2003 14:07:01 GMT-0700
Tom's right. There's no trade secret in what Dean's doing and indeed, to be effective, it would be hard to keep it a secret. Campaigns don't really work so much on secret information as much as they do on effective operations. I think this is how we want it. We want the playing field to be as even as possible so that the message and the ability to execute are what takes center stage. This hasn't always been the case with broadcast style democracy, maybe with connected democracy we will move more in this direction.
I disagree with Tom on his last point. I don't think someone odious will get elected because of some technology spin. They'll get elected because their message resonates with people and people vote for them. Happens all the time. Course my definition of "odious" may differ considerably from yours. :-)
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Web IM / Presence has been released..it's prett cool.
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Web IM / Presence has been released..it's prett cool. (Unpublished)
Many of you may have alread seen Angus's blog and the introduction of a web IM/Presence control on the left side. For those who haven't...check it out :) So for anyone who uses Messenger and has thought to themself.."gee, it'd be really handy to be able to have a messenger control on my site so people can talk to me without having Messenger", your wishes have been granted. I'll be doing an article about setting this up in the next couple of days..so watch this space... If you want to have a play yourself here's the cutdown version of what to do:
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Be not afraid of the Visitor, the big, bad Composite, or their little
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Be not afraid of the Visitor, the big, bad Composite, or their little (Unpublished)
Over and over again the Composite and Visitor patterns come up as good solutions to a certain range of problems, but these patterns are often a source of almost superstitious fear to those developers who aren't familiar with them. From past experience developers don't necessarily grok these patterns at the first exposure. Design patterns that are useful for processing heterogeneous lists and object hierarchies without resorting to an uncontrolled proliferation of "if/then" branches.
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Graves County, KentuckyEdit This Page
From FamilySearch Wiki
United States Kentucky Graves County
Guide to Graves County Kentucky genealogy. Birth records, marriage records, death records, census records, family history, and military records.
Kentucky
Online Records
Graves County, Kentucky
Map
Location in the state of Kentucky
Location of Kentucky in the U.S.
Facts
Founded 1823
County Seat Mayfield
Courthouse
Adopt-a-wiki page
This page adopted by:
KYGenWeb Project
who welcome you to contribute.
Adopt a page today
Contents
Graves County Kentucky Courthouse
Beginning Dates for Graves County, Kentucky Government Records
Birth* Marriage Death* Census Deeds Wills
1852 1888 1852 1830 1888 1888
*Many years between 1852 and 1911 are missing
Graves County Courthouse, Mayfield, Ky. Courtesy: Collection: County Court Houses, Flickr by Jimmy Emerson. Used by permission.
Graves County Courthouse
201 E College Street
Mayfield, KY 42066
Phone: 270.247.1733[1]
Graves County Kentucky History
Parent County
1823--Graves County was created in 1823 from Hickman County.
County seat: Mayfield [2]
Boundary Changes
Record Loss
1864, 1896--Had disasters which destroyed some records.
1897--Court house burned to the ground but material survived this also.
Graves County Kentucky Places/Localities
Populated Places
Baltimore Dublin Kansas Stubblefield
Bell City Fairbanks Lowes Symsonia
Boaz Fancy Farm Lynnville Tri City
Boydsville Farmington Mayfield Vealsburg
Browns Grove Feliciana Payne Viola
Camp Beauregard Folsomdale Pilot Oak Water Valley
Clear Springs Golo Pottsville West Viola
Cooksville Hickory Pryorsburg Westplains
Cuba Hicksville Roper Wheel
Dogwood Holifield Sedalia Wingo
Dublin Kaler South Highland
Neighboring Counties
Graves County Kentucky Genealogy Resources
African American Research
The following have information concerning African American research. Both should be used:
Biographies
Cemeteries
Kentucky cemetery records often identify birth, death, relationship, and military information, as well as religious affiliation.
Census
Historical populations
Census Pop.
18302,504
18407,465198.1%
185011,39752.7%
186016,23342.4%
187019,39819.5%
188024,13824.4%
189028,53418.2%
190033,20416.4%
191033,5391.0%
192032,483−3.1%
193030,778−5.2%
194031,7633.2%
195031,364−1.3%
196030,021−4.3%
197030,9393.1%
198034,04910.1%
199033,550−1.5%
200037,02810.4%
http://ukcc.uky.edu/~census/21083.txt
For tips on accessing Graves County, Kentucky census records online, see: Kentucky Census.
Church
Court
Genealogy
• [Sassin] Allen, Cameron. "Francois Sasin/Sassin of Manakin Town: The First Six Generations of the Sassin/Sasseen Family in America," The Virginia Genealogist, Vol. 37, No. 1 (Jan.-Mar. 1993):3-17; Vol. 37, No. 2 (Apr.-Jun. 1993):99-116; Vol. 37, No. 3 (Jul.-Sep. 1993):193-205; Vol. 37, No. 4 (Oct.-Dec. 1993):259-271. Digital version at American Ancestors ($). FHL Book 975.5 B2vg v. 37 (1993).
Land
Local Histories
Maps
Military
Miscellaneous
Newspapers
Obituaries
Probate
Taxation
Vital Records
Birth
• 1852-1859 - Graves County Birth Index 1852-1859. Batch C517391 at FamilySearch - free.[3]
• 1874-1875 - Graves County Birth Index 1874-1875. Batch C517392 at FamilySearch - free.[3]
• 1875-1876 - Graves County Birth Index 1875-1876. Batch C517393 at FamilySearch - free.[3]
Marriage
• 1852-1859 - Graves County Marriage Index 1852-1859. Batch M517391 at FamilySearch - free.[3]
• 1852-1907 - Graves County Marriage Index 1852-1907. Batch M517396 at FamilySearch - free.[3]
• 1875-1876 - Graves County Marriage Index 1875-1876. Batch M517394 at FamilySearch - free.[3]
• 1876-1879 - Graves County Marriage Index 1876-1879. Batch M517395 at FamilySearch - free.[3]
Unsorted
Graves County Kentucky Genealogy Societies and Libraries
Family History Centers
Graves County Kentucky Genealogy Websites
Graves County Kentucky Genealogy References
1. Handybook for Genealogists: United States of America, 10th ed. (Draper, Utah: Everton Pub., 2002), Graves County, Kentucky page 270, At various libraries (WorldCat); FHL Book 973 D27e 2002.
2. The Handybook for Genealogists: United States of America,10th ed. (Draper, UT:Everton Publishers, 2002).
3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Genealogical Society of Utah, Parish and Vital Records List (July 1998). Microfiche. Digital version at https://familysearch.org/learn/wiki/en/images/0/0b/Igikentuckygl.pdf.
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• This page was last modified on 28 March 2013, at 22:00.
• This page has been accessed 3,458 times.
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