bluuebunny/crossref_metadata_2025 huggingface dataset:
La vie après une mission de verification de I'optimisation des ressources:le point de vue des gestionnaires
Authors: Morin Danielle
Published: January 2008

Sommaire: L'opinion des vérificateurs généraux sur la gestion des affaires publiques est bien connue. En fait, grâce aux rapports qu'ils publient régulièrement à la suite des missions de vérification de l'optimisation des ressources (vor), ils peuvent révéler au grand jour les lacunes qu'ils ont relevées dans la gestion des différentes organisations qu'ils visitent. Par contre, du côté des gestionnaires, on ne peut pas dire qu'ils se bousculent aux portes pour exprimer leur opinion sur le travail des vérificateurs généraux. La recherche que nous avons effecbée permet de lever le voile sur la face cachée de la vor, sur le point de vue des gestionnaires qui ont eu à vivre une telle expérience. En quoi le quotidien des gestionnaires publics est‐il touché par la visite des vérificateurs dans le cadre de missions de vor ? Comment les gestionnaires perçoivent‐ils le rôle des vérificateurs ? Que pensent‐ils de la performance des vérificateurs et qu'est‐ce qui les irrite lorsqu'ils interagissent avec eux ? Quels changements note‐t‐on dans les pratiques de management après une mission de vor ? Qu'en est‐il des relations de ces gestionnaires avec leurs supérieurs ou leurs subordonnés ? Et, du point de vue des gestionnaires, quel a été l'impact de la vor sur la gestion de l'organisation vérifiée ?

Abstract: The view of the auditors general on the management of public affairs is well known. In fact, through the reports they issue at regular intervals as the outcome of value for money (vfm) audits, they can bring to light the shortcomings found in the management of the various organizations they inspected. On the other hand, i't cannot be said that managers have been rushing to express their opinion on the work of the auditors general. Our research reveals the hidden face of the vfm audits by presenting the views of managers who had to go through the process. How does the vfm auditors visit affect the government officials' daily routine? How is the auditors' role perceived by managers? What do they think of the auditors' performance, and what do they find irritating when they interact with them? What changes in management practice are noted after a vfm audit? How about the relations of these managers with their superiors or subordinates? According to the managers, what was the impact of vfm audits on the management of the organization audited?
Le syndrome du SUrViVant et les fonctionnaires fédéraux du Quebec: vers une répudiation du discours managériel dominant
Authors: Rouillard Christian , Lemire Louise
Published: January 2008

Sommaire: La littérature en études managérielles et en gestion des ressources humaines concemant la décroissance organisationnelle et la réduction des effectifs maintient depuis une quinzaine d'années que leur principal effet néfaste serait le syndrome du survivant. Menace très réelle A l'accroissement de l'efficacité et de I'effi‐cience recherché par la décroissance organisationnelle, le syndrome du survivant nécessiterait d'être combattu par des pratiques de gestion des ressources humaines stratégiques pouvant éliminer ou amoindrir les symptômes couramment associés à ce syndrome. Cette recherche s'intéresse aux variations du syndrome du survivant dans des organisations de I'administration publique fédérale au Québec suite à sa sévère réduction des effectifs durant les années quatre‐vingt‐dix. Construite à partir d'un questionnaire complété par 3 307 fonctionnaires de vingt‐trois (23) ministères et agences de la Fonction publique fédérale du Canada répartis dans les seize (16) régions administratives du Québec, cette recherche suggère que le syndrome du survivant est un phénomène de faible intensité dans le cas des fonctionnaires fédéraux du Québec. Elle suggère également, suite à l'analyse factorielle et la régression linéaire, que les pratiques de gestion des ressources humaines privilégiées dans ces organisations publiques n'expliquent que très faiblement la variation des symptômes couramment associés au syndrome du survivant. En ce sens, cette recherche dément le discours pratique dominant sur le syndrome du survivant et le guide d'action managériel qui le sous‐tend, sans pour autant suggérer que la réduction des effectifs soit une décision et un processus exempt de tout effet pervers ou de conséquence non voulue.

Abstract: Mainstream literature in human resource management (hrm) and managerial studies have suggested repeatedly over the last fifteen years that the main unintended consequence of downsizing is the so‐called survivor syndrome, a potentially
Governing the multicultural city‐region
Authors: Frisken Frances , Wallace Marcia
Published: January 2008

Abstract: This article reports on a study that identified the challenges posed by large immigrant populations for the governments of eleven Greater Toronto Area municipalities and the way those challenges were being addressed by municipal agencies that provided nine local services: government‐assisted housing, land‐use planning, policing, public education, public health, public libraries, public recreation, public transit, and social services. Many of the agencies were trying to accommodate their multicultural clienteles in a variety of ways. There were large differences in agency responses, however, not only among municipalities but also among agencies providing different services within the same municipality, and even among district offices of the same municipal agencies. Moreover, municipal agencies often found it difficult or impossible to adapt to new clienteles, even when they were seriously committed to doing so, in the face of provincial government indifference, cuts in provincial and local funding, and community ambivalence or antagonism. The study concluded that municipal agencies are unlikely to devote many resources to helping the immigrant settlement process without financial and legislative support from central governments.

Sommaire: Le présent article porte sur une étude qui a cerné les défis que posent d'importantes populations d'immigrants aux gouvemements de ome municipalités de la Région du Grand Toronto, et sur la manière dont ces défis ont été relevés par des organismes municipaux assurant neuf services locaux: logement subventionné par le gouvernement, aménagement du territoire, services de police, enseignement public, santé publique, bibliothèques publiques, loisirs publics, transport en com‐mun et services sociaux. Un grand nombre de ces organismes ont essayé de répondre aux besoins de leurs clientèles multiculturelles par différents moyens. Cependant, les écarts étaient grands dans la manière d'y parvenir, non seulement parmi les municipalités mais également parmi les organismes foumissant différents services au sein de la même municipalité, et même parmi les bureaux de districts des mêmes organimes municipaux. En outre, les organismes municipaux trouvent souvent qu'il est difficile, voire même impossible, de s'adapter à de nouvelles clientèles, même lorsqu'ils se sont sérieusement engagés à le faire, face à l'indifférence du gouvemement provincial, aux compressions budgétaires à I'échelle provinciale et locale, et face à I'ambivalence ou à I'antagonisme de la colledivité. L'étude a conclu qu'il y avait de fortes chances que les organismes municipaux ne consacrent pas d'énormes ressources à I'aide au processus d'établissement des immigrants s'ils ne reçoivent pas un appui financier et législatif des gouvernements centraux.
An auditor's best friend? Standing committees on public accounts
Authors: Malloy Jonathan
Published: January 2008

Abstract: This article looks at public accounts committees (PACS) in Canadian legislatures and their relationship with legislative auditors. In most jurisdictions, there is a close relationship between the two, as PACS base their agenda on auditors' reports and interact significantly with auditors. The chief role of the committees is to provide a unique and important public forum for the further exploration of issues identified by auditors. Their effectiveness is thus not necessarily in their written reports as much as it is in their hearings and examinations of witnesses. While some committees are clearly stronger than others, for a variety of reasons, they are all potentially powerful. It is up to legislatures, governments, legislative auditors, and committees themselves to make use of PACS unique capabilities

Sommaire: Le présent article se penche sur les comités des comptes publics (CCP) dans les législatures canadiennes et leurs relations avec les vérificateurs législatifs. Dans la plupart des juridictions des provinces et territoires, il existe une relation étroite entre les deux, étant donné que les CCP fondent leur agenda sur les rapports des vérificateurs et sont en dialogue constant avec ces derniers. Le rôle principal de ces comités consiste à foumir un forum public, unique et important, dans le but d'étudier plus à fond les questions identifiées par les vérificateurs. Leur efficacité ne découle donc pas néessairement des rapports écrits, mais plutôt de leurs audiences et de l'interrogatoire des témoins. Alors que certains comités sont clairement plus forts que d'autres pour toutes sortes de raisons, ils ont tous le potentiel d'être puissants. C'est aux législatures, gouvemements, vérificateurs législatifs et aux comités eux‐mêmes qu'il revient de faire usage des capacités uniques des CCP.
RESEARCH NOTES/NOTES DE RECHERCHES: The impact of reform in Canadian state‐owned enterprises on voluntary disclosure in annual reports
Authors: Bozec Richard
Published: January 2008

Abstract: This study examines the impact of reform in Canadian state‐owned enterprises (SOES) on the level of information disclosure in their annual reports. Reform in SOES encompasses two critical stages: commercialization and privatization. Commercialization instils into SOES common principles and practices typical of the private sector. As a result, the mandate of the firm shifts away from social towards profitability objectives. Privatization refers to the legal transfer of public ownership to private hands. The author argues that SOE reform leads to greater information asymmetries between management and stakeholders (creditors and shareholders), increasing financial costs for businesses. In accounting literature, this factor is considered a component that positively influences disclosure. The study's findings support such a proposition. More precisely, the results suggest that commercialization and privatization do provide incentive for managers to disclose additional information in their annual reports. Most of the incremental disclosure is financial.

Sommaire:

Cette étude examine les répercussions de la réforme menée dans les sociétés d'État canadiennes sur le niveau d'information présentée dans leurs rapports annuels. La réforme dans les sociétés d'État comporte deux étapes critiques: la commercialisation et la privatisation. La commercialisation inculque aux sociétés d'État des principes et pratiques propres au secteur privé. I1 en résulte que le mandat de la société d'État se détourne des objectifs sociaux pour ne viser que la rentabilité. Par privatisation, on entend le transfert juridique de la propriété publique entre les mains d'intérêts privés. L'auteur prétend que la réforme dans les sociétés d'État entraîne de plus grandes asymétries dans I'information fournie par la direction et celle foumie par les parties intéressées (créanciers et actionnaires), ce qui accroît les coûts financiers pour les entreprises. Dans la documentation sur la comptabilité, ce facteur est considéré comme un élément d'influence positive sur la présentation de I'information. Les résultats de I'étude soutiennent cette thése. Plus préisiément, les
From good intentions to successful implementation: the case of patient safety in Canada
Authors: Thomas Paul G.
Published: January 2008

Abstract: Improvements to patient safety have become a major issue on Canada's already crowded health care policy agenda. This paper applies implementation theory to the practical issues involved with the adoption of patient safety reforms. It is based on a review of the literature and official reports on patient safety and on the author's experience as the chair of the Board of Directors of the Manitoba Institute for Patient Safety created in June 2004. The obstacles and possible solutions to advance the patient safety agenda are discussed. While implementation theory was found to provide a general guide, the author's experience leads him to conclude the literature on governance and organizational change offers more practical advice.

Sommaire: L'amélioration de la sécurité des patients est devenue une question majeure du programme déjà chargé des politiques en matière de soins de santé. Le présent article applique une théorie de mise en œuvre aux questions pratiques découlant de l'adoption des réformes sur la sécurité du patient. II est fondé sur une étude de publications et rapports officiels sur la sécurité du patient, ainsi que sur l'expérience de l'auteur en tant que président du conseil d'administration de l'Institut pour la sécurité des patients du Manitoba, créé en juin 2004. II passe en revue les obstacles et les solutions possibles à la promotion du programme de la sécurité des patients. Si l'auteur trouve que la théorie de la mise en œuvre fournit un guide général, son expérience le pousse à conclure que la documentation sur la gouvernance et les changements organisationnels offre davantage de conseils pratiques.
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.
Monitoring road surfaces by close proximity noise of the tire/road interaction
Authors: Paje S. E. , Bueno M. , Terán F. , Viñuela U.
Published: January 2008

Applied acoustics is becoming an important field for civil infrastructure and environmental assessment, and road maintenance or rehabilitation strategies. In this research LA2IC has developed a GPS-based measurement techniques and apparatus on a test vehicle, for monitoring the acoustical properties of different road pavement surfaces with a reference tire. A field test on PA-12 Spanish porous pavement found in Ciudad Real is developed. The test procedure, a modification based upon the close-proximity method (CPX), relies on the use of three standard microphones situated very close to the tire/road contact patch. This procedure allows the simultaneous measurement of the sound emission synchronized to a GPS receiver, which permits tracking of the position of the sound emission. Geo-referenced sound spectra for every 10m during individual passes of the test vehicle are analyzed to determine the tire/road noise emissions from tire/PA-12 pavement interaction. Noise levels of around 102dB(A), with a variability of approximately 0.6dB(A), are found at a reference vehicle speed of 85km∕h. The frequency spectrum analysis over the test section shows noticeable differences for frequencies above 1kHz, where the tire/road noise generation mechanisms are dominated by air pumping.
Factors affecting vowel formant discrimination by hearing-impaired listeners
Authors: Liu Chang , Kewley-Port Diane
Published: January 2008

The goal of this study was to measure the ability of adult hearing-impaired listeners to discriminate formant frequency for vowels in isolation, syllables, and sentences. Vowel formant discrimination for F1 and F2 for the vowels /ɪ ε æ ʌ/ was measured. Four experimental factors were manipulated including linguistic context (isolated vowels, syllables, and sentences), signal level (70 and 95dB SPL), formant frequency, and cognitive load. A complex identification task was added to the formant discrimination task only for sentences to assess effects of cognitive load. Results showed significant elevation in formant thresholds as formant frequency and linguistic context increased. Higher signal level also elevated formant thresholds primarily for F2. However, no effect of the additional identification task on the formant discrimination was observed. In comparable conditions, these hearing-impaired listeners had elevated thresholds for formant discrimination compared to young normal-hearing listeners primarily for F2. Altogether, poorer performance for formant discrimination for these adult hearing-impaired listeners was mainly caused by hearing loss rather than cognitive difficulty for tasks implemented in this study.
Gaussian representation of high-intensity focused ultrasound beams
Authors: Soneson Joshua E. , Myers Matthew R.
Published: January 2008

A method for fast numerical simulation of high-intensity focused ultrasound beams is derived. The method is based on the frequency-domain representation of the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation, and assumes for each harmonic a Gaussian transverse pressure distribution at all distances from the transducer face. The beamwidths of the harmonics are constrained to vary inversely with the square root of the harmonic number, and as such this method may be viewed as an extension of a quasilinear approximation. The technique is capable of determining pressure or intensity fields of moderately nonlinear high-intensity focused ultrasound beams in water or biological tissue, usually requiring less than a minute of computer time on a modern workstation. Moreover, this method is particularly well suited to high-gain simulations since, unlike traditional finite-difference methods, it is not subject to resolution limitations in the transverse direction. Results are shown to be in reasonable agreement with numerical solutions of the full KZK equation in both tissue and water for moderately nonlinear beams.
Laser amplification with a twist: Traveling-wave propagation and gain functions from throughout the cochlea
Authors: Shera Christopher A.
Published: January 2008

Except at the handful of sites explored by the inverse method, the characteristics—indeed, the very existence—of traveling-wave amplification in the mammalian cochlea remain largely unknown. Uncertainties are especially pronounced in the apex, where mechanical and electrical measurements lack the independent controls necessary for assessing damage to the preparation. At a functional level, the form and amplification of cochlear traveling waves are described by quantities known as propagation and gain functions. A method for deriving propagation and gain functions from basilar-membrane mechanical transfer functions is presented and validated by response reconstruction. Empirical propagation and gain functions from locations throughout the cochlea are obtained in mechanically undamaged preparations by applying the method to published estimates of near-threshold basilar membrane responses derived from Wiener-kernel (chinchilla) and zwuis analysis (cat) of auditory-nerve responses to broadband stimuli. The properties of these functions, and their variation along the length of the cochlea, are described. In both species, and at all locations examined, the gain functions reveal a region of positive power gain basal to the wave peak. The results establish the existence of traveling-wave amplification throughout the cochlea, including the apex. The derived propagation and gain functions resemble those characteristic of an active optical medium but rotated by 90° in the complex plane. Rotation of the propagation and gain functions enables the mammalian cochlea to operate as a wideband, hydromechanical laser analyzer.
High frequency broad band scattering from water-saturated granular sediments: Scaling effects
Authors: Ivakin Anatoliy N. , Sessarego Jean-Pierre
Published: January 2008

Sound backscattering from water-saturated granular sediments at frequencies from 150kHz to 8MHz at oblique incidence was studied in controlled laboratory conditions. Two kinds of sediments, medium and coarse sands, were degassed, and their surface was flattened. In these conditions, the sediment granular structure can be considered as a controlling mechanism of backscattering. Comparison of frequency dependencies of backscatter for the two sediments with different mean grain size shows the existence of a persistent scaling effect that allows description of the backscattering strength as a function of one parameter, the mean grain size/wavelength ratio.
Evidence specifically favoring the equalization-cancellation theory of binaural unmasking
Authors: Culling John F.
Published: January 2008

Three experiments investigated the roles of interaural correlation (ρ) and of the monaural power spectrum in the detection and discrimination of narrow-band-noise signals (462–539Hz) in broadband maskers (0–3kHz). The power and ρ of the target band were independently controlled, while the flanking noise was fixed and diotic. Experiments 1 and 2 involved ρ and power values that would be produced by specific values of signal-to-noise ratio (SNR) in the NoSπ binaural configuration. Listeners were required to discriminate different SNRs via a 2I-FC loudness-discrimination task. At low reference SNRs, changes in ρ fully accounted for listeners’ performance, but as reference SNR increased, additional energy in the target band played an increasing role. Experiment 2 showed that at these higher SNRs the combination of information from the power spectrum and ρ was superadditive and could not be explained by simple signal-detection models. The equalization-cancellation (EC) theory would explain these data using the output from interaural cancellation, Y, rather than ρ. Experiment 3 attempted to foil binaural processing, by fixing either ρ or Y across intervals. Consistent with EC theory, when Y was fixed, the contribution of the binaural system appeared negligible, while fixing ρ did not have this effect.
Optimal array pattern synthesis for broadband arrays
Authors: Yan Shefeng , Ma Yuanliang , Hou Chaohuan
Published: January 2008

Broadband beamformers with constant mainlobe response over the frequency of interest are desirable in many applications including underwater acoustics, ultrasonics, acoustic imaging and communications, and so on. Solutions to this problem have been presented for specific array geometry often requiring a larger number of sensors. And the array pattern synthesis error minimization is employed for the whole field of view, which leads to suboptimal designs. In this paper, a broadband array pattern synthesis approach to designing time-domain constant mainlobe response beamformer is proposed. By imposing constraints both on the mainlobe spatial response variation over frequency and on the sidelobes of the beamformer, several optimization criteria are presented and the corresponding convex second-order cone programming implementations are given. In this approach, no preliminary desired beampattern is required and the beam responses variation minimization is employed only in the mainlobe region and not in the sidelobe regions, which improves the beamformer mainlobe synthesis accuracy. Equally, one can obtain lower sidelobes at the same mainlobe synthesis accuracy. This approach is applicable to arrays with arbitrary geometry. Simulation and experimental results are presented to illustrate the effectiveness of this approach. Performance comparisons of the proposed beamformers and the existing beamformer are also provided.
Noise reduction combining time-domain ε-filter and time-frequency ε-filter
Authors: Abe Tomomi , Matsumoto Mitsuharu , Hashimoto Shuji
Published: January 2008

A time-domain ε-filter (TD ε-filter) is a nonlinear filter that can reduce noise while preserving a signal that varies drastically, such as a speech signal. Although the filter design is simple, it can effectively reduce noise. It is applicable not only to stationary noise but also to nonstationary noise. It cannot, however, be applied when the amplitude of noise is relatively large. This paper introduces an advanced method for noise reduction that applies an ε-filter to complex spectra, namely a time-frequency ε-filter (TF ε-filter). This paper also introduces noise reduction combining a TD ε-filter and a TF ε-filter. An advanced method called a variable time-frequency ε-filter is also proposed. First, the algorithm of the TD ε-filter is explained to clarify the problem. Then, the algorithms of the proposed methods are explained. By utilizing an ε-filter in the frequency domain, the proposed method can reduce not only noise that has a relatively small amplitude but also noise that has a relatively large amplitude. Experimental results are also given to demonstrate the performance of the proposed methods in comparison to the results of some conventional methods.
Phosphorothioate-Modified Oligodeoxynucleotides Inhibit Human Cytomegalovirus Replication by Blocking Virus Entry
Authors: Luganini Anna , Caposio Patrizia , Landolfo Santo , Gribaudo Giorgio
Published: January 2008

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

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

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

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

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.
Structure and cell envelope associations of flagellar basal complexes of Vibrio cholerae and Campylobacter fetus
Authors: Ferris F. G. , Beveridge T. J. , Marceau-Day M. L. , Larson A. D.
Published: January 2008

To isolate intact flagella with basal complexes from Vibrio cholerae, a rhamnolipid hemolysin from Pseudomonas aeruginosa was used to disrupt the cell envelope and flagellar sheath. The nonionic detergent, Triton X-100, provided similar results for Campylobacter fetus. Each of these basal complexes possessed, in addition to the four classical rings, concentric membrane rings (CMR's) similar to those found in Aquaspirillum serpens. Through the use of stereo imaging (which allows structures to be visualized in three dimensions) of thin sections of cells which had been sequentially treated with a number of envelope perturbants (i.e., ethylenediaminetetraacetate, lysozyme, Triton X-100, rhamnolipid hemolysin, and sodium dodecyl sulfate), we have progressively exposed the component parts of the basal organelles in V. cholerae and C. fetus. Since the action of these envelope perturbants has been well documented, we have been able to determine the associations of the exposed portions of the flagellar basal complex and the layer of the cell envelope in which they would normally reside. From our observations we have concluded that in both V. cholerae and C. fetus the L ring is embedded in the outer membrane and the P ring is associated with the peptidoglycan. The CMR's are bracketed by the L and P rings and are sandwiched between the outer membrane and the peptidoglycan. Elements of both the S and M rings appear to be associated with the plasma membrane.
Fungi of a Long Island oak–birch forest. III. Distribution and survival of ascospores in the A horizon
Authors: Zlattner Lois , Gochenaur S. E.
Published: January 2008

A 1-year survey of soil ascomycetes in the A horizon of an oak–birch forest was conducted using the selective Warcup steaming technique. Fourteen species, including two sclerotial anamorphs, belonging to seven genera were isolated. Their propagules were rare and did not exceed an average of 300 per gram of dry soil, except in the fall when numbers increased fivefold. Only Coniochaeta nepalica and an unidentified Eupenicillium species were isolated at every sampling period. Survival of ascospores of C. nepalica and the coprophilous fungus Sordaria fimicola introduced into the A horizon was tested. Both the indigenous and foreign ascospores showed no loss of viability during 210 days of incubation in soil, but approximately 15% of the Sordaria spores were ruptured as soil particles shifted during freeze–thaw cycles. The latter had no measurable effect on the much smaller ascospores of Coniochaeta.
Membrane enzymes associated with the dissimilation of some citric acid cycle substrates and production of extracellular oxidation products in chemostat cultures of Pseudomonas fluorescens
Authors: Lee Woo S. , Cooper John K. , Lynch William H.
Published: January 2008

Enzyme activities forming extracellular products from succinate, fumarate, and malate were examined using washed cell suspensions of Pseudomonas fluorescens from chemostat cultures. Membrane-associated enzyme activities (glucose, gluconate, and malate dehydrogenases), producing large accumulations of extracellular oxidation products in carbon-excess environments, have previously been found in P. fluorescens. Investigations carried out here have demonstrated the presence in this microorganism of a malic enzyme activity which produces extracellular pyruvate from malate in carbon-excess environments. Although the three membrane dehydrogenase enzymes decrease significantly in carbon-limited chemostat cultures, malic enzyme activity was found to increase fourfold under these conditions. The regulation of malate dehydrogenase and malic enzyme by malate or succinate was similar. Malate dehydrogenase increased and malic enzyme decreased in carbon-excess cultures. The opposite effect was observed in carbon-limited cultures. When pyruvate or glucose was used as the carbon source, malate dehydrogenase was regulated similarly by the available carbon concentration, but malic enzyme activity producing extracellular pyruvate was not detected. While large accumulations of extracellular oxalacetate and pyruvate were produced in malate-excess cultures, no extracellular oxidation products were detected in succinate-excess cultures. This may be explained by the lack of detectable activity for the conversion of added external succinate to extracellular fumarate and malate in cells from carbon-excess cultures. In cells from carbon-limited (malate or succinate) cultures, very active enzymes for the conversion of succinate to extracellular fumarate and malate were detected. Washed cell suspensions from these carbon-limited cultures rapidly oxidized added succinate to extracellular pyruvate through the sequential action of succinate dehydrogenase, fumarase, and malic enzyme. Succinate dehydrogenase and fumarase activities producing extracellular products were not detected in cells from chemostat cultures using pyruvate or glucose as the carbon source. Uptake activities for succinate, malate, and pyruvate also were found to increase in carbon-limited (malate or succinate) and decrease in carbon-excess cultures. The role of the membrane-associated enzymes forming different pathways for carbon dissimilation in both carbon-limited and carbon-excess environments is discussed.
Nutritional factors affecting the synthesis of an antiphagocytic factor by group E streptococci
Authors: Wessman G. E.
Published: January 2008

Effects of components of the cultural medium on formation of a group E streptococcal antiphagocytic factor (APF), as detected by an indirect bactericidal test, were studied. Bovine serum albumin (BSA) replaced serum in promoting synthesis of APF in a chemically defined medium (CDM), Todd–Hewitt broth (THB), or tryptose phosphate broth (TPB). Stimulatory factors in BSA were not retained by diafiltration membranes of nominal molecular weight cutoff limits of 10 000 or greater. Citrate, lactate, pyruvate, or oleate, often found in BSA, could not replace BSA in stimulating synthesis of APF. Cells cultured in THB were more resistant to phagocytosis by porcine leukocytes than those grown in CDM or TPB, and the addition of varying amounts of THB to CDM stimulated a measurable response in synthesis of APF. Specific substrates caused different rates of APF synthesis; in decreasing order of effectiveness were glucose or mannose, sucrose, fructose, and trehalose. Proteolytic activity, which might cause the production of phagocyte-sensitive cells by destroying APF activity during culture, was not detectable in significant amounts in subcultures of the age employed in bactericidal tests.
Effects of fibronectin on the compact colony formation in staphylococci
Authors: Usui Yukio , Ohshima Yukio , Yoshida Kosaku
Published: January 2008

Fifty-two unencapsulated strains of Staphylococcus aureus, including strains of Wood 46 and Cowan I, formed compact colonies in fibronectin – soft agar. However, 20 encapsulated strains of Staphylococcus aureus and 50 strains of Staphylococcus epidermidis showed diffuse growth in the medium. The results suggest that another possible cellular factor, other than protein A, is involved in the binding of the cell surface with fibronectin and that it would be one of factors in forming compact colonies in serum – soft agar.