Cheminement des carrières de direction dans la fonction publique au Canada

Cet article présente un résumé d'une étude entreprise auprès des hauts fonctionnaires dans la fonction publique du Canada. Elle porte sur le cheminement des carrières et touche aussi à la mobilité, à l'occupation et aux sources de recrutement.Who are the most capable executives in the Federal Public Service ? What are their experience characteristics ? How mobile have they been ? What are their academic backgrounds ? How does age relate to seniority and earning power ?These and related questions must be answered if manpower at upper government levels is to be managed more effectively.A fourteen-month study recently completed by the Personnel Consulting Division, Bureau of Management Consulting Services, Ottawa, has made a major contribution towards providing these answers.In the Public Service of Canada, at the time the study was made in July, 1965, there were some 625 executives with salaries ranging from $16,000 to$30,000. These are the men and women who fill the top three or four levels in each department or agency. Officially, they are known as Senior Officers 1, 2, 3. and Deputy Ministers (Deputy Heads).Data on 591 of these executives was obtained from files and various other sources, coded and fed into a Bendix G-20 computer along with some 40 questions, the answers to which provided the following information :The typical executive is 51 years old and probably has a B.A. in Social Management Sciences (Arts, History, Political Science, Commerce, Sociology, etc.). While he could have graduated from any university in any province, the chances are greatest that he obtained his degree from the University of Toronto. He has had military service, reads a second language and joined the Public Service at a junior managerial level at 34 years of age, after having worked outside the Public Service for 11 years.At the time of his appointment to the executive level, he was 46 years of age and had 23 years of working experience. As of July 1, 1967, he had 28 years working experience and was earning $21,000 a year.BASIC PERSONAL DATAIn considering the personal data in more detail, it was found that ages ranged from 30 to 69, with an average age of 51.2. The average ages for the four levels (Senior Officer 1, 2, 3, and Deputy Minister — Deputy Head), were 50.3 52.6, 51.7 and 54.9 years respectively. The similarity of the averages implies career progression problems and also highlights the serious executive replacement problem the government faces in the next 10-15 years.A relatively high level of education was found among the government's top executives. 81$14,000 plus). Close to 20% entered directly at the executive level.SALARYAs of July 1, 1967, the average executive in the Public Service of Canada was earning $20,927 a year.It should be noted that this is a total figure because Public Servants do not receive bonusses or stock options, and there is not profit to be « profit-shared ».For the three career path categories they were :Public Service Only$21,297Private-Public 20,861Public-Private-Public 20,862Subsequent to this study, the government released proposed salary scales for the executive levels ranging from a maximum of $23,500 for Senior Executive Officers 1 up to a maximum of$40,000 for certain Deputy Ministers.APPOINTMENT TO EXECUTIVE LEVELThe average age at time of appointment to the Senior Officer 1 level was 45.6, to the SO 2 level 48, SO 3 level 47 and DM-DH 52. The similarity of these figures is interesting, since one would expect an executive to progress from the lowest to highest level. Also, based on today's standards, the ages would appear to be rather high.TRENDS IN AGE AT APPOINTMENTIt is generally believed that there has been a trend to appoint younger officers to the executive levels, but the study casts some doubt on the belief, certainly as far as government is concerned. However, more recent data obtained since the completion of the study indicates a change in the trend with the average ages of Senior Officers 1 appointed in 1966, 1967 and 1968, decreasing from 48 to 46 to 43 years respectively.EXPERIENCEThe average government executive has 28 years experience, almost two-thirds of which will have been spent in the Public Service. He will have spent about 15% in the category we called « Business and Self-Employed » and 10% in military service.However, there were indications that the more time executives spent in industry the less capable they were of adjusting to the political and Public Service atmosphere. Similarly it was found that extended career military service tended to reduce the rate of progress.RECRUITMENTPrior to July, 1967, about 76% of all appointments to the executive level were made from within the individuals present department and about 9% were from other departments. Therefore, some 85% of all appointments were from within the Public Service. Of the remaining 15%, some 10% came from Industry and 5% were recruited from Provincial Governments (2.4%), Universities (1.5%) and the Armed Forces (.3%).MOBILITYWithin the Public Service, a great interest has recently developed in the movement, or lack of movement, of management level personnel from one department to another. Traditionally, Public Servants have tended to remain in one department, rising to senior levels within what many claim to be a narrow occupational field.From the findings it appeared that moving from one department to another, within the Public Service, tended to improve the possibilities of achieving more rapid progress.A further analysis of movement after reaching the executive level showed that slightly more than 12% of all executives changed departments at least once after reaching this level and 1.3% had changed twice. This figure is changing rapidly as over 30% of the appointments made in 1968, at the executive level, resulted in movement between departments

Dispersing agents prevent negative impact of oil on uptake of sinc by duckweed (Lemna minor)

Oil spills have had extremely negative effects upon the environment, affecting both animal and plant species living in and around the contaminated water. It is known that the oil can interfere with certain plant and animal functions, potentially causing death. Means developed to remove the oil from the water include physical methods such as skimmers and chemical approaches such as adsorbents and dispersants. In the cases of the chemical treatments, some people question whether the remedy may also cause problems. Here, we confirm that the aquatic duckweed plant (Lemna) can take up zinc from its environment and show that oil in the water will inhibit that uptake. Further, we demonstrate that the negative affect the oil has upon zinc uptake by duckweed can be ameliorated by treatment with a dispersant and that the dispersant itself does not inhibit zinc uptake by duckweed. We conclude that, treatment of oil contaminated water by dispersant may be a good method to clean up the water

Correlation of baseline biomarkers with clinical outcomes and response to fulvestrant with vandetanib or placebo in patients with bone predominant metastatic breast cancer: An OCOG ZAMBONEY sub-study

AbstractBackgroundBone metastases are common in women with breast cancer and often result in skeletal related events (SREs). As the angiogenic factor vascular endothelial growth factor (VEGF) regulates osteoclast activity and is associated with more extensive bone metastases and SRE risk in metastatic breast cancer, we hypothesized that blockade of VEGF signaling could be a therapeutic strategy for inhibiting bone metastases progression and possibly prolonging overall (OS) or progression-free survival (PFS). The Zamboney trial was a randomized placebo-controlled study designed to assess whether patients with bone predominant metastatic breast cancer benefited from addition of the VEGF receptor (VEGFR) targeting agent, vandetanib, to endocrine therapy with fulvestrant. As a companion study, evaluation of biomarkers and their potential association with response to vandetanib or SRE risk was performed.MethodsBaseline overnight fasted serum from enrolled patients was analyzed for levels of various putative biomarkers including; VEGF-A, soluble (s)VEGFR2, sVEGFR3, transforming growth factor (TGF)-β1 and activinA by ELISA. Spearman correlation coefficients and Wilcoxon rank sum tests were used to investigate potential relationships between biomarker values and baseline clinical parameters. Prognostic and predictive ability of each marker was investigated using Cox proportional hazards regression with adjustments for treatment and baseline strata of serum CTx (<400 versus ≥400ng/L).ResultsOf 129 enrolled patients, serum was available for analysis in 101; 51 in vandetanib and 50 in placebo arm. Mean age amongst consenting patients was 59.8 years. Clinical characteristics were not significantly different between patients with or without serum biomarker data and serum markers were similar for patients by treatment arm. Baseline sVEGFR2 was prognostic for OS (HR=0.77, 95% CI=0.61–0.96, p=0.020), and although a modest association was observed, it was not significant for PFS (HR=0.90, 95% CI=0.80–1.01, p=0.085) nor time to first SRE (HR=0.82, 95% CI=0.66–1.02, p=0.079). When interaction terms were evaluated, sVEGFR2 was not found to be predictive of response to vandetanib, although a modest association remained with respect to PFS (interaction p=0.085). No other marker showed any significant prognostic or predictive ability with any measured outcome.ConclusionsIn this clinical trial, sVEGFR2 appeared prognostic for OS, hence validation of sVEGFR2 should be conducted. Moreover, the role of sVEGFR2 in breast cancer bone metastasis progression should be elucidated

The biological and clinical significance of emerging SARS-CoV-2 variants.

The past several months have witnessed the emergence of SARS-CoV-2 variants with novel spike protein mutations that are influencing the epidemiological and clinical aspects of the COVID-19 pandemic. These variants can increase rates of virus transmission and/or increase the risk of reinfection and reduce the protection afforded by neutralizing monoclonal antibodies and vaccination. These variants can therefore enable SARS-CoV-2 to continue its spread in the face of rising population immunity while maintaining or increasing its replication fitness. The identification of four rapidly expanding virus lineages since December 2020, designated variants of concern, has ushered in a new stage of the pandemic. The four variants of concern, the Alpha variant (originally identified in the UK), the Beta variant (originally identified in South Africa), the Gamma variant (originally identified in Brazil) and the Delta variant (originally identified in India), share several mutations with one another as well as with an increasing number of other recently identified SARS-CoV-2 variants. Collectively, these SARS-CoV-2 variants complicate the COVID-19 research agenda and necessitate additional avenues of laboratory, epidemiological and clinical research

HIV-Specific Probabilistic Models of Protein Evolution

Comparative sequence analyses, including such fundamental bioinformatics techniques as similarity searching, sequence alignment and phylogenetic inference, have become a mainstay for researchers studying type 1 Human Immunodeficiency Virus (HIV-1) genome structure and evolution. Implicit in comparative analyses is an underlying model of evolution, and the chosen model can significantly affect the results. In general, evolutionary models describe the probabilities of replacing one amino acid character with another over a period of time. Most widely used evolutionary models for protein sequences have been derived from curated alignments of hundreds of proteins, usually based on mammalian genomes. It is unclear to what extent these empirical models are generalizable to a very different organism, such as HIV-1–the most extensively sequenced organism in existence. We developed a maximum likelihood model fitting procedure to a collection of HIV-1 alignments sampled from different viral genes, and inferred two empirical substitution models, suitable for describing between-and within-host evolution. Our procedure pools the information from multiple sequence alignments, and provided software implementation can be run efficiently in parallel on a computer cluster. We describe how the inferred substitution models can be used to generate scoring matrices suitable for alignment and similarity searches. Our models had a consistently superior fit relative to the best existing models and to parameter-rich data-driven models when benchmarked on independent HIV-1 alignments, demonstrating evolutionary biases in amino-acid substitution that are unique to HIV, and that are not captured by the existing models. The scoring matrices derived from the models showed a marked difference from common amino-acid scoring matrices. The use of an appropriate evolutionary model recovered a known viral transmission history, whereas a poorly chosen model introduced phylogenetic error. We argue that our model derivation procedure is immediately applicable to other organisms with extensive sequence data available, such as Hepatitis C and Influenza A viruses

Modeling HIV-1 Drug Resistance as Episodic Directional Selection

The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance

CodonTest: Modeling Amino Acid Substitution Preferences in Coding Sequences

Codon models of evolution have facilitated the interpretation of selective forces operating on genomes. These models, however, assume a single rate of non-synonymous substitution irrespective of the nature of amino acids being exchanged. Recent developments have shown that models which allow for amino acid pairs to have independent rates of substitution offer improved fit over single rate models. However, these approaches have been limited by the necessity for large alignments in their estimation. An alternative approach is to assume that substitution rates between amino acid pairs can be subdivided into rate classes, dependent on the information content of the alignment. However, given the combinatorially large number of such models, an efficient model search strategy is needed. Here we develop a Genetic Algorithm (GA) method for the estimation of such models. A GA is used to assign amino acid substitution pairs to a series of rate classes, where is estimated from the alignment. Other parameters of the phylogenetic Markov model, including substitution rates, character frequencies and branch lengths are estimated using standard maximum likelihood optimization procedures. We apply the GA to empirical alignments and show improved model fit over existing models of codon evolution. Our results suggest that current models are poor approximations of protein evolution and thus gene and organism specific multi-rate models that incorporate amino acid substitution biases are preferred. We further anticipate that the clustering of amino acid substitution rates into classes will be biologically informative, such that genes with similar functions exhibit similar clustering, and hence this clustering will be useful for the evolutionary fingerprinting of genes

Adaptive Evolution of the Myo6 Gene in Old World Fruit Bats (Family: Pteropodidae)

PMCID: PMC3631194This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Understanding the molecular determinants driving the immunological specificity of the protective pilus 2a backbone protein of Group B Streptococcus

The pilus 2a backbone protein (BP-2a) is one of the most structurally and functionally characterized components of a potential vaccine formulation against Group B Streptococcus. It is characterized by six main immunologically distinct allelic variants, each inducing variant-specific protection. To investigate the molecular determinants driving the variant immunogenic specificity of BP-2a, in terms of single residue contributions, we generated six monoclonal antibodies against a specific protein variant based on their capability to recognize the polymerized pili structure on the bacterial surface. Three mAbs were also able to induce complement-dependent opsonophagocytosis killing of live GBS and target the same linear epitope present in the structurally defined and immunodominant domain D3 of the protein. Molecular docking between the modelled scFv antibody sequences and the BP-2a crystal structure revealed the potential role at the binding interface of some non-conserved antigen residues. Mutagenesis analysis confirmed the necessity of a perfect balance between charges, size and polarity at the binding interface to obtain specific binding of mAbs to the protein antigen for a neutralizing response

Phylodynamic Reconstruction Reveals Norovirus GII.4 Epidemic Expansions and their Molecular Determinants

Noroviruses are the most common cause of viral gastroenteritis. An increase in the number of globally reported norovirus outbreaks was seen the past decade, especially for outbreaks caused by successive genogroup II genotype 4 (GII.4) variants. Whether this observed increase was due to an upswing in the number of infections, or to a surveillance artifact caused by heightened awareness and concomitant improved reporting, remained unclear. Therefore, we set out to study the population structure and changes thereof of GII.4 strains detected through systematic outbreak surveillance since the early 1990s. We collected 1383 partial polymerase and 194 full capsid GII.4 sequences. A Bayesian MCMC coalescent analysis revealed an increase in the number of GII.4 infections during the last decade. The GII.4 strains included in our analyses evolved at a rate of 4.3–9.0×10−3 mutations per site per year, and share a most recent common ancestor in the early 1980s. Determinants of adaptation in the capsid protein were studied using different maximum likelihood approaches to identify sites subject to diversifying or directional selection and sites that co-evolved. While a number of the computationally determined adaptively evolving sites were on the surface of the capsid and possible subject to immune selection, we also detected sites that were subject to constrained or compensatory evolution due to secondary RNA structures, relevant in virus-replication. We highlight codons that may prove useful in identifying emerging novel variants, and, using these, indicate that the novel 2008 variant is more likely to cause a future epidemic than the 2007 variant. While norovirus infections are generally mild and self-limiting, more severe outcomes of infection frequently occur in elderly and immunocompromized people, and no treatment is available. The observed pattern of continually emerging novel variants of GII.4, causing elevated numbers of infections, is therefore a cause for concern