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Holt J.,University of Greenwich | Holt J.,Imperial College London | Leach A.W.,Imperial College London | Schrader G.,Julius Kuhn Institute | And 5 more authors.
Risk Analysis | Year: 2014

Utility functions in the form of tables or matrices have often been used to combine discretely rated decision-making criteria. Matrix elements are usually specified individually, so no one rule or principle can be easily stated for the utility function as a whole. A series of five matrices are presented that aggregate criteria two at a time using simple rules that express a varying degree of constraint of the lower rating over the higher. A further nine possible matrices were obtained by using a different rule either side of the main axis of the matrix to describe situations where the criteria have a differential influence on the outcome. Uncertainties in the criteria are represented by three alternative frequency distributions from which the assessors select the most appropriate. The output of the utility function is a distribution of rating frequencies that is dependent on the distributions of the input criteria. In pest risk analysis (PRA), seven of these utility functions were required to mimic the logic by which assessors for the European and Mediterranean Plant Protection Organization arrive at an overall rating of pest risk. The framework enables the development of PRAs that are consistent and easy to understand, criticize, compare, and change. When tested in workshops, PRA practitioners thought that the approach accorded with both the logic and the level of resolution that they used in the risk assessments. © 2013 Society for Risk Analysis.

Schuurmans J.M.,University of Amsterdam | Van Hijum S.A.F.T.,NIZO Food Research BV | Van Hijum S.A.F.T.,Radboud University Nijmegen | Handel N.,University of Amsterdam | And 4 more authors.
Plasmid | Year: 2014

Antibiotic resistance increases costs for health care and causes therapy failure. An important mechanism for spreading resistance is transfer of plasmids containing resistance genes and subsequent selection. Yet the factors that influence the rate of transfer are poorly known. Rates of plasmid transfer were measured in co-cultures in chemostats of a donor and a acceptor strain under various selective pressures. To document whether specific mutations in either plasmid or acceptor genome are associated with the plasmid transfer, whole genome sequencing was performed. The DM0133 TetR tetracycline resistance plasmid was transferred between Escherichia coli K-12 strains during co-culture at frequencies that seemed higher at increased growth rate. Modeling of the take-over of the culture by the transformed strain suggests that in reality more transfer events occurred at low growth rates. At moderate selection pressure due to an antibiotic concentration that still allowed growth, a maximum transfer frequency was determined of once per 1011 cell divisions. In the absence of tetracycline or in the presence of high concentrations the frequency of transfer was sometimes zero, but otherwise reduced by at least a factor of 5. Whole genome sequencing showed that the plasmid was transferred without mutations, but two functional mutations in the genome of the recipient strain accompanied this transfer. Exposure to concentrations of antibiotics that fall within the mutant selection window stimulated transfer of the resistance plasmid most. © 2014 Elsevier Inc.

Handel N.,University of Amsterdam | Otte S.,University of Amsterdam | Jonker M.,University of Amsterdam | Brul S.,University of Amsterdam | And 2 more authors.
PLoS ONE | Year: 2015

The spread of antibiotic resistant bacteria worldwide presents a major health threat to human health care that results in therapy failure and increasing costs. The transfer of resistance conferring plasmids by conjugation is a major route by which resistance genes disseminate at the intra- and interspecies level. High similarities between resistance genes identified in foodborne and hospital-acquired pathogens suggest transmission of resistance conferring and transferrable mobile elements through the food chain, either as part of intact strains, or through transfer of plasmids from foodborne to human strains. To study the factors that affect the rate of plasmid transfer, the transmission of an extended-spectrum β-lactamase (ESBL) plasmid from a foodborne Escherichia colistrain to the β-lactam sensitive E. coli MG1655 strain was documented as a function of simulated environmental factors. The foodborne E. coliisolate used as donor carried a CTX-M-1 harboring IncI1 plasmid that confers resistance to β-lactam antibiotics. Cell density, energy availability and growth rate were identified as factors that affect plasmid transfer efficiency. Transfer rates were highest in the absence of the antibiotic, with almost every acceptor cell picking up the plasmid. Raising the antibiotic concentrations above the minimum inhibitory concentration (MIC) resulted in reduced transfer rates, but also selected for the plasmid carrying donor and recombinant strains. Based on the mutational pattern of transconjugant cells, a common mechanism is proposed which compensates for fitness costs due to plasmid carriage by reducing other cell functions. Reducing potential fitness costs due to maintenance and expression of the plasmid could contribute to persistence of resistance genes in the environment even without antibiotic pressure. Taken together, the results identify factors that drive the spread and persistence of resistance conferring plasmids in natural isolates and shows how these can contribute to transmission of resistance genes through the food chain. Copyright: © 2015 Händel et al.

Reeuwijk N.M.,Office for Risk Assessment and Research | Venhuis B.J.,National Institute for Public Health and the Environment RIVM | de Kaste D.,National Institute for Public Health and the Environment RIVM | Hoogenboom L.A.P.,RIKILT Institute of Food Safety Wageningen UR | And 2 more authors.
Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment | Year: 2013

Herbal food supplements, claiming to enhance sexual potency, may contain deliberately added active pharmacological ingredients (APIs) that can be used for the treatment of erectile dysfunction (ED). The aim of this study was to determine whether herbal food supplements on the Dutch market indeed contain APIs that inhibit phosphodiesterase type 5 (PDE-5) inhibitors, such as sildenafil and analogous PDE-5 inhibitors. Herbal food supplements intended to enhance sexual potency (n = 71), and two soft drinks, were sampled from 2003 up to and including 2012. In 23 herbal supplements, nine different PDE-5 inhibitors were identified; in a few cases (n = 3), more than one inhibitor was indentified. The presence of these APIs was however not stated on the label. The concentrations of PDE-5 inhibitors per dose unit were analysed. Furthermore, the potential pharmacologically active properties of the detected PDE-5 inhibitors were estimated by using data from the scientific and patent literature regarding (1) in vitro PDE-5 activity, (2) reported effective doses of registered drugs with PDE-5 inhibitor activity and (3) similarity to other structural analogues. It was concluded that 18 of the 23 herbal food supplements, when used as recommended, would have significant pharmacological effects due to added APIs. Adequate use of existing regulation and control measures seems necessary to protect consumers against the adverse effects of these products. © 2013 Taylor & Francis.

Holt J.,University of Greenwich | Holt J.,Imperial College London | van der Gaag D.J.,Office for Risk Assessment and Research | Leach A.W.,Imperial College London | And 3 more authors.
EPPO Bulletin | Year: 2014

The development of methods to combine components of risk and their associated uncertainty in Pest Risk Analysis (PRA) has received attention in a number of recent European projects. Many of the risk components distinguished in the EPPO Decision-support scheme (DSS) for PRA are usually difficult to quantify, but when there is detailed knowledge of the pest and pathway, quantification may be possible to a limited extent for the pest entry section of the scheme. The European Food Safety Authority has recently commissioned a project to investigate approaches to quantitative pathway analysis for pests of commodities entering and moving within the EU (QPA-Food); a sister project concerns non-food commodities. This paper illustrates the potential for a quantitative pathway model based closely on the Entry Section of the EPPO DSS for PRA, where existing quantitative definitions of rating categories have been used as a basis to estimate the proportion and number of infested lots on a pathway. Such quantification may provide additional insights without requiring substantial changes to the information elicited via the DSS. © 2013 The Authors. Journal compilation © 2013 OEPP/EPPO.

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