bluuebunny/crossref_metadata_2025_split huggingface dataset:
The American distortion of the ombudsman concept and its influence on Canada
Authors: Rowat Donald C. 
Published: January 2008

Abstract: The essence of the original ombudsman concept as embraced by the western democracies was the independence of the ombudsman from the administrative organization being complained against. This is achieved by having the office created by law and having the ombudsman appointed by the legislature and made its agent. But as adopted and expanded in the United States, and to a lesser extent in Canada, the concept has been distorted by extending it at first to embrace so‐called ombudsmen appointed by the heads of the departments or agencies being complained against, and then to the non‐profit and profit sectors of society through similar appointment by the heads of universities, hospitals, and business corporations for internal student, patient, and employee complaints. This article shows how this development has similarly influenced Canada, and concludes with recommendations designed to restore the original concept as the desired objective and thus once again make Canada a world leader in ombudsmanship.Sommaire: L'essence du concept initial de l'ombudsman, tel qu'adopté par les démocraties occidentales, a été l'indépendance de l'ombudsman par rapport à l'organisation administrative faisant l'objet de plaintes. Cela a été rendu possible par le fait que cette position fut créée par la loi et que l'ombudsman est nommé par l'assemblée législative qui en fait son agent. Mais le concept tel qu'adopté et développé aux États‐Unis, et dans une moindre mesure au Canada, a été déformé lorsqu'il a étéélargi tout d'abord pour inclure les soi‐disant ombudsmen nommés par les chefs de ministères ou d'agences faisant l'objet de plaintes, et ensuite les secteurs à but non lucratif et lucratif de la société par le biais de nominations similaires par des chefs d'universités, d'hôpitaux et d'entreprises en ce qui concerne les plaintes internes d'étudiants, de patients et d'employés. L'auteur montre comment cette évolution a influencé le Canada et conclut en faisant des recommandations visant à restaurer le concept initial comme l'objectif désiré, et à faire ainsi à nouveau du Canada un leader mondial en matière de protection du citoyen.
Tensions entre rationalité technique et intérêts politiques: l'exemple de la mise en œuvre de laLoi sur les agences de développement de réseaux locaux de services de santé et de services sociauxau Québec
Authors: Contandriopoulos D. , Hudon Raymond , Martin Elisabeth , Thompson Daniel 
Published: January 2008

Sommaire:L'objet de cet article est constitué par les processus décisionnels entourant la mise en œuvre de laLoi sur les agences de développement de réseaux locaux de services de santé et de services sociaux(Loi 25). Nous entendons mettre en lumière les stratégies des groupes ou institutions de diverses natures qui ont fait valoir leurs préférences et ont tenté, avec un succès inégal, d'influencer les décisions relatives à cette réforme majeure de la structure du système de santé québécois. Au plan théorique, nous nous appuyons principalement sur les modèles d'analyse du lobbying qui, depuis les travaux fondateurs de Milbrath (1960, 1963), présentent cette pratique comme un processus fondamental d'échange d'information. Selon les données colligées dans les retranscriptions d'entrevues, les stratégies observées correspondent effectivement aux caractéristiques constitutives du lobbying et, dans quelques situations, à celles du patronage. La combinaison de ces divers éléments révèle que la mise en œuvre de la Loi 25 s'avère être avant tout un processus proprement politique. Ainsi, furent relégués au second plan les arguments techniques qui composaient initialement les objectifs de la Loi.Abstract:This article focuses on the decision‐making processes surrounding the implementation of Bill 25, Quebec's Act Respecting Local Health and Social Services Network Development Agencies. Our intention is to shed light on the strategies of the various groups or institutions that expressed their preferences and attempted, with varying degrees of success, to influence decisions with respect to this major reform of the Quebec health system structure. On a theoretical level, we are relying mostly on the models for analysing the lobbying process, which, since the seminal work of Milbrath (1960, 1963), have essentially presented this practice as a process for exchanging information. Based on the information gathered in the re‐transcribed interviews, the strategies observed are actually in line with the constitutive characteristics of lobbying and, in some situations, those of patronage. Ultimately, the combination of these various elements makes it obvious that the implementation of Bill 25 was, first and foremost, a clearly political process. The technical arguments on which the initial objectives of the act were centred have thereby been relegated to the backstage.
Phosphorothioate-Modified Oligodeoxynucleotides Inhibit Human Cytomegalovirus Replication by Blocking Virus Entry
Authors: Luganini Anna , Caposio Patrizia , Landolfo Santo , Gribaudo Giorgio 
Published: January 2008

ABSTRACT
Studies in animal models have provided evidence that Toll-like receptor 9 (TLR9) agonists, such as synthetic oligodeoxynucleotides (ODNs) that contain immunostimulatory deoxycytidyl-deoxyguanosine (CpG) motifs (CpG ODNs), protect against a wide range of viral pathogens. This antiviral activity has been suggested to be indirect and secondary to CpG-induced cytokines and inflammatory responses triggered through TLR9 activation. However, few studies have addressed the potential of CpG ODNs as direct antiviral agents. Here, we report on the ability of some CpG ODNs to directly suppress, almost completely, human cytomegalovirus (HCMV) replication in both primary fibroblasts and endothelial cells. Murine CMV replication was inhibited as well, whereas no inhibition was observed for herpes simplex virus type 1, adenovirus, or vesicular stomatitis virus. The antiviral activity of these ODNs was significantly reduced when they were added after virus adsorption, indicating that their action may be primarily targeted to the very early phases of the HCMV cycle. In fact, the B-class prototype CpG ODN 2006 effectively prevented the nuclear localization of pp65 and input viral DNA, which suggests that it inhibits HCMV entry. Moreover, a CpG 2006 control, ODN 2137 without CpG motifs, also showed a potent inhibitory activity on the HCMV entry phase, indicating that the anticytomegaloviral activity is independent of the CpG motif. In contrast, a phosphodiester version of CpG 2006 showed reduced antiviral activity, indicating that the inhibitory activity is dependent on the phosphorothioate backbone of the ODN. These results suggest that this yet-unrecognized activity of CpG ODNs may be of interest in the development of novel anticytomegaloviral molecules.
Linezolid and Tiamulin Cross-Resistance in
Staphylococcus aureus
Mediated by Point Mutations in the Peptidyl Transferase Center
Authors: Miller Keith , Dunsmore Colin J. , Fishwick Colin W. G. , Chopra Ian 
Published: January 2008

ABSTRACT

Oxazolidinone and pleuromutilin antibiotics are currently used in the treatment of staphylococcal infections. Although both antibiotics inhibit protein synthesis and have overlapping binding regions on 23S rRNA, the potential for cross-resistance between the two classes through target site mutations has not been thoroughly examined. Mutants of
Staphylococcus aureus
resistant to linezolid were selected and found to exhibit cross-resistance to tiamulin, a member of the pleuromutilin class of antibiotics. However, resistance was unidirectional because mutants of
S. aureus
selected for resistance to tiamulin did not exhibit cross-resistance to linezolid. This contrasts with the recently described PhLOPS
A
phenotype, which confers resistance to both oxazolidinones and pleuromutilins. The genotypes responsible for the phenotypes we observed were examined. Selection with tiamulin resulted in recovery of mutants with changes in the single-copy
rplC
gene (Gly155Arg, Ser158Leu, or Arg149Ser), whereas selection with linezolid led to recovery of mutants with changes (G2576U in 23S rRNA) in all five copies of the multicopy operon
rrn
. In contrast, cross-resistance to linezolid was exhibited by tiamulin-resistant mutants generated in a single-copy
rrn
knockout strains of
Escherichia coli
, illustrating that the copy number of 23S rRNA is the limiting factor in the selection of 23S rRNA tiamulin-resistant mutants. The interactions of linezolid and tiamulin with the ribosome were modeled to seek explanations for resistance to both classes in the 23S rRNA mutants and the lack of cross-resistance between tiamulin and linezolid following mutation in
rplC
.
Mechanism-Based Pharmacokinetic-Pharmacodynamic Models of In Vitro Fungistatic and Fungicidal Effects against
Candida albicans
Authors: Venisse Nicolas , Grégoire Nicolas , Marliat Manuella , Couet William 
Published: January 2008

ABSTRACT

Mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) models describing the fungistatic activity of fluconazole and the fungicidal activity of caspofungin were developed using dynamic in vitro models. Antifungal-drug pharmacokinetics was simulated in vitro, assuming a one-compartment model with an elimination half-life of 3 h and using a wide (1 to 10,000) range of initial concentrations. The number of CFUs over time was determined for up to 31 h and used for PK-PD modeling. A model incorporating first-order natural growth and natural death, plus a maximum number of viable
Candida
cells, was used to characterize
Candida
growth in the absence of a drug. Fluconazole was considered to inhibit
Candida
growth and caspofungin to stimulate
Candida
death according to an
E
max
pharmacodynamic model. The data were analyzed with Nonmem, using a population approach. A good fit of the data was obtained with satisfactory estimates of PK-PD parameters, especially with drug concentrations producing 50% of the maximal effect: 50% inhibitory concentrations for fluconazole growth inhibition and 50% effective concentrations for caspofungin death stimulation. In conclusion, mechanistic PK-PD models were successfully developed to describe, respectively, the fungistatic and fungicidal activities of fluconazole and caspofungin in vitro. These models provide much better information on the drug effects over time than the traditional PK-PD index based on MICs. However, they need to be further characterized.
Increasing Genetic Relatedness of Ciprofloxacin-Resistant
Streptococcus pneumoniae
Isolated in Canada from 1997 to 2005
Authors: Nichol Kimberly A. , Adam Heather J. , Karlowsky James A. , Zhanel George G. , Hoban Daryl J. 
Published: January 2008

ABSTRACT

The genetic relatedness of ciprofloxacin-resistant
Streptococcus pneumoniae
isolates collected from 1997 to 2002 (
n
= 82) and 2003 to 2005 (
n
= 123) was compared by pulsed-field gel electrophoresis (PFGE). Increased genetic homogeneity among the isolates from 2003 to 2005 (cluster analysis;
P
< 0.001) appeared to be due to expansion of existing clonal groups and to introduction of new PFGE types.
Comparison of Carbon Nutrition for Pathogenic and Commensal
Escherichia coli
Strains in the Mouse Intestine
Authors: Fabich Andrew J. , Jones Shari A. , Chowdhury Fatema Z. , Cernosek Amanda , Anderson April , Smalley Darren , McHargue J. Wesley , Hightower G. Aaron , Smith Joel T. , Autieri Steven M. , Leatham Mary P. , Lins Jeremy J. , Allen Regina L. , Laux David C. , Cohen Paul S. , Conway Tyrrell 
Published: January 2008

ABSTRACT

The carbon sources that support the growth of pathogenic
Escherichia coli
O157:H7 in the mammalian intestine have not previously been investigated. In vivo, the pathogenic
E. coli
EDL933 grows primarily as single cells dispersed within the mucus layer that overlies the mouse cecal epithelium. We therefore compared the pathogenic strain and the commensal
E. coli
strain MG1655 modes of metabolism in vitro, using a mixture of the sugars known to be present in cecal mucus, and found that the two strains used the 13 sugars in a similar order and cometabolized as many as 9 sugars at a time. We conducted systematic mutation analyses of
E. coli
EDL933 and
E. coli
MG1655 by using lesions in the pathways used for catabolism of 13 mucus-derived sugars and five other compounds for which the corresponding bacterial gene system was induced in the transcriptome of cells grown on cecal mucus. Each of 18 catabolic mutants in both bacterial genetic backgrounds was fed to streptomycin-treated mice, together with the respective wild-type parent strain, and their colonization was monitored by fecal plate counts. None of the mutations corresponding to the five compounds not found in mucosal polysaccharides resulted in colonization defects. Based on the mutations that caused colonization defects, we determined that both
E. coli
EDL933 and
E. coli
MG1655 used arabinose, fucose, and
N
-acetylglucosamine in the intestine. In addition,
E. coli
EDL933 used galactose, hexuronates, mannose, and ribose, whereas
E. coli
MG1655 used gluconate and
N
-acetylneuraminic acid. The colonization defects of six catabolic lesions were found to be additive with
E. coli
EDL933 but not with
E. coli
MG1655. The data indicate that pathogenic
E. coli
EDL933 uses sugars that are not used by commensal
E. coli
MG1655 to colonize the mouse intestine. The results suggest a strategy whereby invading pathogens gain advantage by simultaneously consuming several sugars that may be available because they are not consumed by the commensal intestinal microbiota.
Wood dust exposure and the risk of upper aero-digestive and respiratory cancers in males
Authors: Jayaprakash V , Natarajan K K , Moysich K B , Rigual N R , Ramnath N , Natarajan N , Reid M E 
Published: January 2008

Background:Wood dust (WD) has been designated a human carcinogen that can cause sino-nasal cancers. However, evidence of its association with other upper aero-digestive tract and respiratory (UADR) cancers is inconsistent.Objective:To examine the relationship between WD exposure and the risk of different histological subtypes of UADR cancers.Methods:In a hospital-based case-control study conducted at Roswell Park Cancer Institute, Buffalo, NY, USA, an examination was carried out to determine the effect of self-reported WD exposure on 1522 male UADR cancer cases (241 oral and oropharyngeal, 90 nasal cavity, nasopharyngeal and hypopharyngeal, 124 laryngeal, 809 lung and tracheal and 258 oesophagus and gastric cardia) and 1522 male controls, frequency matched on age and smoking history. Odds ratios (OR) were calculated after adjusting for relevant risk factors including tobacco smoking.Results:The results show that regular WD exposure was associated with a statistically significant increased risk of 32% for all UADR cancers (OR 1.32; 95% CI 1.01 to 1.77; p-trend = 0.05) and 69% for lung cancer alone (OR 1.69; 95% CI 1.20 to 2.36; p-trend = 0.007). WD was associated with an 82–93% increased risk of squamous cell, small cell and adenocarcinoma of the lung and more than twice the risk of developing squamous cell carcinoma of the nasal cavity, nasopharynx and hypopharynx, with a significant dose–response relationship. Oral and oropharyngeal cancers showed a non-significant increase in risk. A significant increase in risk of laryngeal and lung cancers was noted for subjects regularly exposed to WD for >20 years. Cancers of the oesophagus and gastric cardia did not show any risk associated with WD. WD was associated with a significantly greater risk of UADR cancers among people who had ever smoked than never smokers.Conclusion:WD exposure is a potential risk factor for UADR cancers, especially for cancers of the nasal cavity, nasopharynx, larynx and lung.
Observations on Inner-Scriptural Scribal Expansion in MT Ezekiel
Authors: Stromberg Jake 
Published: January 2008

AbstractTextual evidence from the Second Temple Period attests a principle by which Hebrew manuscripts were edited in light of other scriptural texts (e.g. 1QIsaa). Such inner-scriptural editing was often undertaken along lines of connection perceived between the texts before the expansion took place, so that these perceived connections served as a guide for the scribe's own work. This study argues that the same textual procedure was at work in creating the longer text of MT Ezekiel, which is 4-5% longer than LXX Ezekiel. In light of the work of E. Ulrich, this study concludes with reflections on what MT Ezekiel contributes, as an empirical example, to the discussion about the relationship between text and canon.
Der Tod des Staatsfeindes: Neues zu B3j
Authors: Timm Stefan 
Published: January 2008

AbstractRecently, it has been discovered that ostracon IFAO No. 1864 recto also bears an inscription. It says that B3j was killed as "great enemy" in the 5th year of Pharoa Siptah. This means that a connection between B3j and Moses (E. A. Knauf ) or even an identification of B3j with Moses (J. C. de Moor) is inappropriate. Whatever personage Egyptologists declare to be a "parallel" of Moses, B3j cannot be taken as one.
Persistence drives gene clustering in bacterial genomes
Authors: Fang Gang , Rocha Eduardo PC , Danchin Antoine 
Published: January 2008

Abstract

Background
Gene clustering plays an important role in the organization of the bacterial chromosome and several mechanisms have been proposed to explain its extent. However, the controversies raised about the validity of each of these mechanisms remind us that the cause of this gene organization remains an open question. Models proposed to explain clustering did not take into account the function of the gene products nor the likely presence or absence of a given gene in a genome. However, genomes harbor two very different categories of genes: those genes present in a majority of organisms – persistent genes – and those present in very few organisms – rare genes.

Results
We show that two classes of genes are significantly clustered in bacterial genomes: the highly persistent and the rare genes. The clustering of rare genes is readily explained by the selfish operon theory. Yet, genes persistently present in bacterial genomes are also clustered and we try to understand why. We propose a model accounting specifically for such clustering, and show that indispensability in a genome with frequent gene deletion and insertion leads to the transient clustering of these genes. The model describes how clusters are created via the gene flux that continuously introduces new genes while deleting others. We then test if known selective processes, such as co-transcription, physical interaction or functional neighborhood, account for the stabilization of these clusters.

Conclusion
We show that the strong selective pressure acting on the function of persistent genes, in a permanent state of flux of genes in bacterial genomes, maintaining their size fairly constant, that drives persistent genes clustering. A further selective stabilization process might contribute to maintaining the clustering.
Identification of cellular pathways affected by Sortin2, a synthetic compound that affects protein targeting to the vacuole in Saccharomyces cerevisiae
Authors: Norambuena Lorena , Zouhar Jan , Hicks Glenn R , Raikhel Natasha V 
Published: January 2008

Abstract

Background
Sortin2 is a low mass compound that interferes with vacuolar delivery of proteins in plants and yeast. The Sortin2 phenotype was tested in Arabidopsis thaliana and found to be reversible upon drug removal, demonstrating the ability of chemical genomics to induce reversible phenotypes that would be difficult to achieve using conventional genetics [1]. However, standard genetic methods can be used to identify drug target pathways in a high-throughput manner.

Results
In this study, we analyzed structure-function relationships of Sortin2 using structural analogues. The results show the key roles of sulphite substitution and a benzoic acid group. A Sortin 2 hypersensitivity screen for the induced secretion of a vacuolar cargo protein was done utilizing a yeast haploid deletion library. Using bioinformatics approaches, we highlighted functional information about the cellular pathways affected by drug treatment which included protein sorting and other endomembrane system-related processes.

Conclusion
Chemical, genomic and genetics approaches were used to understand the mode of action of Sortin2, a bioactive chemical that affects the delivery of a vacuolar protein. Critical features of Sortin2 structure necessary for bioactivity suggest a binding pocket that may recognize two ends of Sortin2. The genome-wide screen shows that Sortin2 treatment in yeast affects primarily components within the endomembrane system. This approach allowed us to assign putative functions in protein sorting for fifteen genes of previously unknown function.
Adherence to Initial Adjuvant Anastrozole Therapy Among Women With Early-Stage Breast Cancer
Authors: Partridge Ann H. , LaFountain Andrea , Mayer Erica , Taylor Brooke S. , Winer Eric , Asnis-Alibozek Aviva 
Published: January 2008

Purpose Previous research evaluating adherence to tamoxifen therapy among women with early-stage breast cancer has revealed adherence estimates ranging from 25% to 96%. No previous studies have focused on adherence to adjuvant aromatase inhibitors. Methods We used longitudinal claims data from three large commercial health programs to estimate adherence with anastrozole therapy among women with early-stage breast cancer. Adherence was defined as the proportion of days that patients had medication available over the observation period (ie, days covered); women with fewer than 80% of days covered were defined as nonadherent. Results More than 12,000 women in the databases were found to have new anastrozole prescription claims during the period of study: 1,498 women were classified as having early-stage disease in one commercial health program (Plan A) data set, 1,899 women in another program (Plan B) data set, and 8,994 women in MarketScan, a commercial data set made up of several health programs. Mean adherence over the first 12 months of therapy ranged from 82% to 88% in the three data sets. Between 19% and 28% of women had fewer than 80% of days covered. For women with 36 months of continuous eligibility, the mean adherence decreased each year, ranging from 78% to 86% in year 1 to 62% to 79% in year 3 within the three data sets. Conclusion A substantial proportion of women with early-stage breast cancer may be suboptimally adherent to adjuvant anastrozole therapy. Future research should focus on the identification of patients at risk for nonadherence with oral hormonal therapy for breast cancer and the development of interventions to improve adherence.