Extended-spectrum B-lactamase producing Enterobacteriaceae: diagnostics and epidemiology

Kluytmans, J.A.J.W. [Promotor]Savelkoul, P.H.M. [Promotor

Assembling an Experimentalist Regime: Transnational Governance Interactions in the Forest Sector

Transnational governance initiatives increasingly face the problem of regime complexity in which a proliferation of regulatory schemes operate in the same policy domain, supported by varying combinations of public and private actors. The literature suggests that such regime complexity can lead to forum-shopping and other self-interested strategies which undermine the effectiveness of transnational regulation. Based on the design principles of experimentalist governance, this paper identifies a variety of pathways and mechanisms which promote productive interactions in regime complexes. We use the case of the EU’s Forest Law Enforcement Governance and Trade (FLEGT) initiative, interacting with private certification schemes and public legal timber regulations, including those of third countries such as the US and China, to demonstrate how an increasingly comprehensive transnational regime can be assembled by linking together distinct components of a regime complex. We argue that it is the experimentalist features of this initiative and its regulatory interactions, which accommodate local diversity and foster recursive learning from decentralized implementation experience, that make it possible to build up a flexible and adaptive transnational governance regime from an assemblage of interconnected pieces, even in situations where interests diverge and no hegemon can impose its own will

Enantiomer separation by ultrafiltration of enantioselective micelles in multistage systems

The Food and Bioprocess Engineering Group of Wageningen University, The Netherlands, is developing a new enantiomer separation system that is based on ultrafiltration (UF) of enantioselective micelles containing chiral selector molecules. Enantiomer molecules are optical isomers (mirror images), and can have different biological activities. This has forced pharmaceutical, food and agrochemical industries to develop methods for the production of optically pure compounds. This thesis shows a promising new technique to separate enantiomers at industrial scale.During the separation process, the selector molecules preferentially bind one enantiomer of a pair of enantiomers. In UF unbound enantiomers pass the membrane, while the micelles are retained. Since one single UF stage is inadequate for nearly complete (99+%) separations of both enantiomers, the separation has been studied in a cascaded system consisting of multiple UF stages. Both the equilibrium and the kinetics of (de)complexation have been modelled by a Langmuir model and a linear driving force model, respectively. The separation model has been validated by a cascaded system containing five stages and by a simulated cascade containing 60 stages.Calculations with the model have shown that a reduction in affinity allows to proportionally increase the feed concentration of the enantiomers into the cascade. An increase of the selectivity up to 10 strongly reduces the required number of stages necessary to attain a high purity of both enantiomers; higher values do not greatly reduce the number of stages. In general, the throughput of this type of separation processes can be optimized by weakening the interactions between selector and substrate.</p

Horizontal transfer of antibiotic resistance genes on abiotic touch surfaces: implications for public health

Horizontal gene transfer (HGT) is largely responsible for increasing incidence of antibiotic-resistant infections worldwide. Whilst studies have focussed on HGT in vivo, this work investigates whether the ability of pathogens to persist in the environment, particularly on touch surfaces, may also play an important role. Escherichia coli, virulent clone ST131, and Klebsiella pneumoniae encoding extended-spectrum ?-lactamase (ESBL) bla CTX-M-15 and metallo-?-lactamase bla NDM-1, respectively, exhibited prolonged survival on stainless steel with approximately 104 viable cells remaining from an inoculum of 107cfu per cm2 after one month at 21oC. HGT of bla to an antibiotic-sensitive but azide-resistant recipient E. coli occurred on stainless steel dry touch surfaces and in suspension, but not on dry copper. Conjugation frequency was approximately 10-50 times greater, occurred immediately and resulting transconjugants were more stable with ESBL E. coli as donor cell compared to K. pneumoniae but bla NDM-1 transfer increased with time. Transconjugants also exhibited the same resistance profile as donor suggesting multiple gene transfer. Rapid death, inhibition of respiration and destruction of genomic and plasmid DNA of both pathogens occurred on copper alloys accompanied by a reduction in bla copy number. Naked E. coli DNA degraded on copper at 21oC and 37oC but slowly at 4oC suggesting a direct role for the metal. Persistence of viable pathogenic bacteria on touch surfaces may not only increase risk of infection transmission but also contribute to spread of antibiotic resistance by HGT. The use of copper alloys as antimicrobial touch surfaces may help reduce infection and HGT