Pseudomonas aeruginosa Population Structure Revisited

At present there are strong indications that Pseudomonas aeruginosa exhibits an epidemic population structure; clinical isolates are indistinguishable from environmental isolates, and they do not exhibit a specific (disease) habitat selection. However, some important issues, such as the worldwide emergence of highly transmissible P. aeruginosa clones among cystic fibrosis (CF) patients and the spread and persistence of multidrug resistant (MDR) strains in hospital wards with high antibiotic pressure, remain contentious. To further investigate the population structure of P. aeruginosa, eight parameters were analyzed and combined for 328 unrelated isolates, collected over the last 125 years from 69 localities in 30 countries on five continents, from diverse clinical (human and animal) and environmental habitats. The analysed parameters were: i) O serotype, ii) Fluorescent Amplified-Fragment Length Polymorphism (FALFP) pattern, nucleotide sequences of outer membrane protein genes, iii) oprI, iv) oprL, v) oprD, vi) pyoverdine receptor gene profile (fpvA type and fpvB prevalence), and prevalence of vii) exoenzyme genes exoS and exoU and viii) group I pilin glycosyltransferase gene tfpO. These traits were combined and analysed using biological data analysis software and visualized in the form of a minimum spanning tree (MST). We revealed a network of relationships between all analyzed parameters and non-congruence between experiments. At the same time we observed several conserved clones, characterized by an almost identical data set. These observations confirm the nonclonal epidemic population structure of P. aeruginosa, a superficially clonal structure with frequent recombinations, in which occasionally highly successful epidemic clones arise. One of these clones is the renown and widespread MDR serotype O12 clone. On the other hand, we found no evidence for a widespread CF transmissible clone. All but one of the 43 analysed CF strains belonged to a ubiquitous P. aeruginosa “core lineage” and typically exhibited the exoS+/exoU− genotype and group B oprL and oprD alleles. This is to our knowledge the first report of an MST analysis conducted on a polyphasic data set

GENSEN: een computer programma voor gegeneraliseerde gevoeligheidsanalyse

De release-versie 1.0 van het programma GENSEN wordt gepresenteerd, tezamen met instructies en richtlijnen voor installatie en gebruik van de software. GENSEN voert een gegeneraliseerde gevoeligheidsanalyse uit door berekening van de discrepantie tussen acceptabele en niet-acceptabele parameters. De software is geschreven in standaard FORTRAN77 en kan op PC geinstalleerd worden.The release version 1.0 of the software program GENSEN is presented, accompanied with instructions and guidelines for its installation and use. GENSEN performs a generalized sensitivity analysis by evaluating the discrepancy between acceptable and in-acceptable parameters. GENSEN is written in standard FORTRAN77 and can be installed on PC.NOP DGM/L

DOMDIR: een computer programma ter bepaling van de dominante richtingen in de parameterruimte

De release-versie 1.0 van het programma DOMDIR wordt gepresenteerd, tezamen met instructies en richtlijnen voor installatie en gebruik van de software. DOMDIR bepaalt het belang van de model parameters op basis van een analyse van de dominante richtingen in de parameter ruimte. De software is geschreven in standaard FORTRAN77 en kan op PC geinstalleerd worden.The release version 1.0 of the software program DOMDIR is presented, accompanied with instructions and guidelines for its installation and use. DOMDIR evaluates the sensitivity of the model parameters, by studying the dominant directions in the parameter space. DOMDIR is written in standard FORTRAN77 and can be installed on PC.NOP DGM/L

RORASC: Software voor de 'rotated-random-scan' calibratie procedure

De release-versie 1.0 van het programma RORASC wordt gepresenteerd, tezamen met instructies en richtlijnen voor installatie en gebruik van de software. RORASC speelt een essentiele rol bij de 'rotated-random-scan' methode voor modelkalibratie. De software is geschreven in standaard FORTRAN77 en kan op PC geinstalleerd worden.The release version 1.0 of the software program RORASC is presented, accompanied with instructions and guidelines for its installation and use. RORASC plays an essential role in the rotated-random-scan method for modelcalibration. RORASC is written in standard FORTRAN77 and can be installed on PC.NOP DGM/L

The role of sensitivity analysis and identifiability analysis in model calibration

Abstract niet beschikbaarModel calibration is usually an important part of the modelling process. A well structured approach of this activity, supported by general guidelines and techniques, will be especially beneficial of practical applications. Particularly the study of the sensitivity and the identifiability of the parameters (e.g. model coeffients, initial conditions) has to be a relevant part of model calibration. Such a study can reveal potential problems already during the early stages of the model calibration process, and can offer useful suggestions to prevent their occurrence. It will also be useful in post-calibration studies, e.g. when analysing the problems of unsuccessful calibration runs. Several simple methods are suggested for performing these analysis for a general class of calibration problems. The advantages and disadvantages of these methodes are briefly discussed. In particular attention is given to the problem of local versus global analyses in the parameter space.Stuurgroep Verzurin

Testen van methoden en programmatuur voor verzameling-theoretische modelkalibratie en gevoeligheidsanalyses

Testen worden besproken die zijn uitgevoerd op methoden en software voor calibratie middels 'rotated-random-scanning', en voor gevoeligheidsanalyse op basis van de 'dominant direction analysis' en de 'generalized sensitivity analysis'. Deze technieken werden recentelijk op het RIVM geimplementeerd in de computer programma's RORASC, DOMDIR en GENSEN.The results are reported of testing methods and software for calibration by rotated-random scanning, and for sensitivity analysis by dominant direction analysis and generalized sensitivity analysis. These techniques have recently been implemented at the RIVM in the programs RORASC, DOMDIR and GENSEN.NOP DGM/L