Evaluation of live-attenuated Salmonella vaccines expressing Campylobacter antigens for control of C. jejuni in poultry

Campylobacter jejuni is a zoonotic bacterial pathogen of worldwide importance. It is estimated that 460,000 human infections occur in the United Kingdom per annum and these involve acute enteritis and may be complicated by severe systemic sequelae. Such infections are frequently associated with the consumption of contaminated poultry meat and strategies to control C. jejuni in poultry are expected to limit pathogen entry into the food chain and the incidence of human disease. Toward this aim, a total of 840 Light Sussex chickens were used to evaluate a Salmonella enterica serovar Typhimurium ΔaroA vaccine expressing the C. jejuni amino acid binding protein CjaA as a plasmid-borne fusion to the C-terminus of fragment C of tetanus toxin. Chickens were given the vaccine at 1-day-old and two weeks later by oral gavage, then challenged after a further two weeks with C. jejuni. Across six biological replicates, statistically significant reductions in caecal C. jejuni of c. 1.4 log10 colony-forming units/g were observed at three and four weeks post-challenge relative to age-matched unvaccinated birds. Protection was associated with the induction of CjaA-specific serum IgY and biliary IgA. Protection was not observed using a vaccine strain containing the empty plasmid. Vaccination with recombinant CjaA subcutaneously at the same intervals significantly reduced the caecal load of C. jejuni at three and four weeks post-challenge. Taken together these data imply that responses directed against CjaA, rather than competitive or cross-protective effects mediated by the carrier, confer protection. The impact of varying parameters on the efficacy of the S. Typhimurium ΔaroA vaccine expressing TetC-CjaA was also tested. Delaying the age at primary vaccination had little impact on protection or humoral responses to CjaA. The use of the parent strain as carrier or changing the attenuating mutation of the carrier to ΔspaS or ΔssaU enhanced the protective effect, consistent with increased invasion and persistence of the vaccine strains relative to the ΔaroA mutant. Expression in the ΔaroA strain of a TetC fusion to Peb1A, but not TetC fusions to GlnH or ChuA, elicited protection against intestinal colonisation by C. jejuni that was comparable to that observed with the TetC-CjaA fusion. Our data are rendered highly relevant by use of the target host in large numbers and support the potential of CjaA- and Peb1A-based vaccines for control of C. jejuni in poultry. © 2009 Elsevier Ltd. All rights reserved.

UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development

It is paramount that any child or adolescent with a suspected disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD. If there is any doubt, the case should be discussed with the regional team. In most cases, particularly in the case of the newborn, the paediatric endocrinologist within the regional DSD team acts as the first point of contact. The underlying pathophysiology of DSD and the strengths and weaknesses of the tests that can be performed should be discussed with the parents and affected young person and tests undertaken in a timely fashion. This clinician should be part of a multidisciplinary team experienced in management of DSD and should ensure that the affected person and parents are as fully informed as possible and have access to specialist psychological support. Finally, in the field of rare conditions, it is imperative that the clinician shares the experience with others through national and international clinical and research collaboration. © 2011 Blackwell Publishing Ltd.

Effects of the user model on simulation-based learning of dialogue strategies

Over the past decade, a variety of user models have been proposed for user simulation-based reinforcement-learning of dialogue strategies. However, the strategies learned with these models are rarely evaluated in actual user trials and it remains unclear how the choice of user model affects the quality of the learned strategy. In particular, the degree to which strategies learned with a user model generalise to real user populations has not be investigated. This paper presents a series of experiments that qualitatively and quantitatively examine the effect of the user model on the learned strategy. Our results show that the performance and characteristics of the strategy are in fact highly dependent on the user model. Furthermore, a policy trained with a poor user model may appear to perform well when tested with the same model, but fail when tested with a more sophisticated user model. This raises significant doubts about the current practice of learning and evaluating strategies with the same user model. The paper further investigates a new technique for testing and comparing strategies directly on real human-machine dialogues, thereby avoiding any evaluation bias introduced by the user model. © 2005 IEEE.

An evaluation of a new product data model

Engineering companies face many challenges today such as increased competition, higher expectations from consumers and decreasing product lifecycle times. This means that product development times must be reduced to meet these challenges. Concurrent engineering, reuse of engineering knowledge and the use of advanced methods and tools are among the ways of reducing product development times. Concurrent engineering is crucial in making sure that the products are designed with all issues considered simultaneously. The reuse of engineering knowledge allows existing solutions to be reused. It can also help to avoid the mistakes made in previous designs. Computer-based tools are used to store information, automate tasks, distribute work, perform simulation and so forth. This research concerns the evaluation of tools that can be used to support the design process. These tools are evaluated in terms of the capture of information generated during the design process. This information is vital to allow the reuse of knowledge. Present CAD systems store only information on the final definition of the product such as geometry, materials and manufacturing processes. Product Data Management (PDM) systems can manage all this CAD information along with other product related information. The research includes the evaluation of two PDM systems, Windchill and Metaphase, using the design of a single-handed water tap as a case study. The two PDMs were then compared to PROSUS/DDM. PROSUS is the Process-Based Support System proposed by [Blessing 94] using the same case study. The Design Data Model is the product data model that includes PROSUS. The results look promising. PROSUS/DDM is able to capture most design information and structure and present it logically. The design process and product information is related and stored within the DDM structure. The PDMs can capture most design information, but information from early stages of design is stored only as unstructured documentation. Some problems were found with PROSUS/DDM. A proposal is made that may make it possible to resolve these problems, but this will require further research.