Assessing the impact of a cattle risk-based trading scheme on the movement of bovine tuberculosis infected animals in England and Wales

The adoption of bovine tuberculosis (bTB) risk-based trading (RBT) schemes has the potential to reduce the risk of bTB spread. However, any scheme will have cost implications that need to be balanced against its likely success in reducing bTB. This paper describes the first stochastic quantitative model assessing the impact of the implementation of a cattle risk-based trading scheme to inform policy makers and contribute to cost–benefit analyses. A risk assessment for England and Wales was developed to estimate the number of infected cattle traded using historic movement data recorded between July 2010 and June 2011. Three scenarios were implemented: cattle traded with no RBT scheme in place, voluntary provision of the score and a compulsory, statutory scheme applying a bTB risk score to each farm. For each scenario, changes in trade were estimated due to provision of the risk score to potential purchasers. An estimated mean of 3981 bTB infected animals were sold to purchasers with no RBT scheme in place in one year, with 90% confidence the true value was between 2775 and 5288. This result is dependent on the estimated between herd prevalence used in the risk assessment which is uncertain. With the voluntary provision of the risk score by farmers, on average, 17% of movements was affected (purchaser did not wish to buy once the risk score was available), with a reduction of 23% in infected animals being purchased initially. The compulsory provision of the risk score in a statutory scheme resulted in an estimated mean change to 26% of movements, with a reduction of 37% in infected animals being purchased initially, increasing to a 53% reduction in infected movements from higher risk sellers (score 4 and 5). The estimated mean reduction in infected animals being purchased could be improved to 45% given a 10% reduction in risky purchase behaviour by farmers which may be achieved through education programmes, or to an estimated mean of 49% if a rule was implemented preventing farmers from the purchase of animals of higher risk than their own herd. Given voluntary trials currently taking place of a trading scheme, recommendations for future work include the monitoring of initial uptake and changes in the purchase patterns of farmers. Such data could be used to update the risk assessment to reduce uncertainty associated with model estimates

Multiple exon skipping strategies to by-pass dystrophin mutations.

Manipulation of dystrophin pre-mRNA processing offers the potential to overcome mutations in the dystrophin gene that would otherwise lead to Duchenne muscular dystrophy. Dystrophin mutations will require the removal of one or more exons to restore the reading frame and in some cases, multiple exon skipping strategies exist to restore dystrophin expression. However, for some small intra-exonic mutations, a third strategy, not applicable to whole exon deletions, may be possible. The removal of only one frame-shifting exon flanking the mutation-carrying exon may restore the reading frame and allow synthesis of a functional dystrophin isoform, providing that no premature termination codons are encountered. For these mutations, the removal of only one exon offers a simpler, cheaper and more feasible alternative approach to the dual exon skipping that would otherwise be considered. We present strategies to by-pass intra-exonic dystrophin mutations that clearly demonstrate the importance of tailoring exon skipping strategies to specific patient mutations

Using network analysis to identify seasonal patterns and key nodes for risk-based surveillance of pig diseases in Italy

The description of the pattern of livestock movements between herds provides essential information for both improving risk-based surveillance and to understand the likely spread of infectious diseases. This study provides a description of the temporal pattern of pig movements recorded in Italy on a 4-year period (2013–2016). Data, provided by the National Livestock registry, were described by social network analysis and the application of a walk-trap algorithm for community detection. Our results show a highly populated community located in Northern Italy, which is the focal point of the Italian industrial pig production and as a general pattern an overall decline of medium and backyard farms and an increase in the number of large farms, in agreement with the trend observed by other EU pig-producing countries. A seasonal pattern of all the parameters evaluated, including the number of active nodes in both the intensive and smaller production systems, emerged: that is characterized by a higher number of movements in spring and autumn, linked with the breeding and production cycle as pigs moved from the growing to the finishing phase and with periods of increased slaughtering at Christmas and Easter. The same pattern was found when restricting the analysis to imported pig batches. Outbreaks occurring during these periods would have a greater impact on the spread of infectious diseases; therefore, targeted surveillance may be appropriate. Finally, potential super-spreader nodes have been identified and represent 0.47% of the total number of pig holdings (n = 477). Those nodes are present during the whole study period with a similar ranking in their potential of being super-spreaders. Most of them were in Northern Italy, but super-spreaders with high mean out-degree centrality were also located in other Regions. Seasonality, communities and super-spreaders should be considered when planning surveillance activity and when applying disease control strategies

Using multi-criteria risk ranking methodology to select case studies for a generic risk assessment framework for exotic disease incursion and spread through Europe

We present a novel approach of using the multi-criteria pathogen prioritisation methodology as a basis for selecting the most appropriate case studies for a generic risk assessment framework. The approach uses selective criteria to rank exotic animal health pathogens according to the likelihood of introduction and the impact of an outbreak if it occurred in the European Union (EU). Pathogens were evaluated based on their impact on production at the EU level and international trade. A subsequent analysis included criteria of relevance to quantitative risk assessment case study selection, such as the availability of data for parameterisation, the need for further research and the desire for the case studies to cover different routes of transmission. The framework demonstrated is flexible with the ability to adjust both the criteria and their weightings to the user's requirements. A web based tool has been developed using the RStudio shiny apps software, to facilitate this

Maximising data to optimise animal disease early warning systems and risk assessment tools within Europe

Timely and reliable data and information availability and sharing is essential for early warning, prevention and control of transboundary diseases. While there are a growing number of global datasets capable of providing information for use in early warning systems and risk assessment (RA) tools, there are currently time-consuming data cleansing and harmonisation activities which need to be carried out before they can be reliably used and combined. Thus, using global datasets as they stand can lead to errors in RA parameterisation and results due to inherent biases in the data, e.g. missing disease prevalence data treated as a zero may inadvertently penalise those countries which do report disease outbreaks as opposed to those countries which are affected by a pathogen but do not report outbreak data. It is therefore of great importance that data are clearly provided and easy to understand and that data providers strive for greater harmonisation of database standards. In this paper the datasets utilised in the SPARE (’Spatial risk assessment framework for assessing exotic disease incursion and spread through Europe’) project are described and discussed in terms of key criteria: accessibility, availability, completeness, consistency and quality. It is evident that most databases exist as information portals and not exclusively for RA purposes. Another striking issue from this assessment is the need for enhanced data sharing specifically with regards to data on illegal seizures, arthropod vector/wildlife abundance, intra-country livestock movement and national animal disease surveillance. It is hoped that the outcomes of this work will promote discussion and exchange between data providers, including the development of standardised data exchange protocols. The transformation of datasets to a common format is a considerable challenge but recommendations could and should be made on the standardisation of datasets and reporting in order to achieve a unified approach across Europe

Nonrigid chiral soliton for the octet and decuplet baryons

Systematic treatment of the collective rotation of the nonrigid chiral soliton is developed in the SU(3) chiral quark soliton model and applied to the octet and decuplet baryons. The strangeness degrees of freedom are treated by a simplified bound-state approach which omits the locality of the kaon wave function. Then, the flavor rotation is divided into the isospin rotation and the emission and absorption of the kaon. The kaon Hamiltonian is diagonalized by the Hartree approximation. The soliton changes the shape according to the strangeness. The baryons appear as the rotational bands of the combined system of the soliton and the kaon.Comment: 11 pages(LaTex), 1 figures(eps

Assessing the impact of tailored biosecurity advice on farmer behaviour and pathogen presence in beef herds in England and Wales

The term ‘biosecurity’ encompasses many measures farmers can take to reduce the risk of pathogen incursion or spread. As the best strategy will vary between settings, veterinarians play an important role in assessing risk and providing advice, but effectiveness requires farmer acceptance and implementation. The aim of this study was to assess the effectiveness of specifically-tailored biosecurity advice packages in reducing endemic pathogen presence on UK beef suckler farms. One hundred and sixteen farms recruited by 10 veterinary practices were followed for three years. Farms were randomly allocated to intervention (receiving specifically-tailored advice, with veterinarians and farmers collaborating to develop an improved biosecurity strategy) or control (receiving general advice) groups. A spreadsheet-based tool was used annually to attribute a score to each farm reflecting risk of entry or spread of bovine viral diarrhoea virus (BVDV), bovine herpesvirus-1 (BHV1), Mycobacterium avium subsp. paratuberculosis (MAP), Leptospira interrogans serovar hardjo (L. hardjo) and Mycobacterium bovis (M. bovis). Objectives of these analyses were to identify evidence of reduction in risk behaviours during the study, as well as evidence of reductions in pathogen presence, as indications of effectiveness. Risk behaviours and pathogen prevalences were examined across study years, and on intervention compared with control farms, using descriptive statistics and multilevel regression. There were significant reductions in risk scores for all five pathogens, regardless of intervention status, in every study year compared with the outset. Animals on intervention farms were significantly less likely than those on control farms to be seropositive for BVDV in years 2 and 3 and for L. hardjo in year 3 of the study. Variations by study year in animal-level odds of seropositivity to BHV1 or MAP were not associated with farm intervention status. All farms had significantly reduced odds of BHV1 seropositivity in year 2 than at the outset. Variations in farm-level MAP seropositivity were not associated with intervention status. There were increased odds of M. bovis on intervention farms compared with control farms at the end of the study. Results suggest a structured annual risk assessment process, conducted as a collaboration between veterinarian and farmer, is valuable in encouraging improved biosecurity practices. There were some indications, but not conclusive evidence, that tailored biosecurity advice packages have potential to reduce pathogen presence. These findings will inform development of a collaborative approach to biosecurity between veterinarians and farmers, including adoption of cost-effective strategies effective across pathogens

Levothyrox® new and old formulations: are they switchable for millions of patients?

International audienceIn France, more than 2.5 million patients are currently treated with levothyroxine, mainly as the marketed product Levothyrox ®. In March 2017, at the request of French authorities, a new formulation of Levothyrox ® was licensed, with the objective of avoiding stability deficiencies of the old formulation. Before launching this new formulation, an average bioequivalence trial, based on European Union recommended guidelines, was performed. The implicit rationale was the assumption that the two products, being bioequivalent, would also be switchable, allowing substitution of the new for the old formulation, thus avoiding the need for individual calibration of the dosage regimen of thyroxine, using the thyroid-stimulating hormone level as the endpoint, as required for a new patient on initiating treatment. Despite the fact that both formulations were shown to be bioequivalent, adverse drug reactions were reported in several thousands of patients after taking the new formulation. In this opinion paper, we report that more than 50% of healthy volunteers enrolled in a successful regulatory average bioequivalence trial were actually outside the a priori bioequivalence range. Therefore, we question the ability of an average bioequivalence trial to guarantee the switchability within patients of the new and old levothyroxine formulations. We further propose an analysis of this problem using the conceptual framework of individual bioequivalence. This involves investigating the bioavailability of the two formulations within a subject, by comparing not only the population means (as established by average bioequivalence) but also by assessing two variance terms, namely the within-subject variance and the variance estimating subject-by-formulation interaction. A higher within individual variability for the new formulation would lead to reconsideration of the appropriateness of the new formulation. Alternatively, a possible subject-by-formulation interaction would allow a judgement on the ability, or not, of doctors to manage patients effectively during transition from the old to the new formulation

Instability of the hedgehog shape for the octet baryon in the chiral quark soliton model

In this paper the stability of the hedgehog shape of the chiral soliton is studied for the octet baryon with the SU(3) chiral quark soliton model. The strangeness degrees of freedom are treated by a simplified bound-state approach, which omits the locality of the kaon wave function. The mean field approximation for the flavor rotation is applied to the model. The classical soliton changes shape according to the strangeness. The baryon appears as a rotational band of the combined system of the deformed soliton and the kaon.Comment: 24 pages, LaTeX, 8 eps file