Understanding how new evidence influences practitioners' beliefs regarding dry cow therapy: A Bayesian approach using probabilistic elicitation.

This study used probabilistic elicitation and a Bayesian framework to quantitatively explore how logically practitioners' update their clinical beliefs after exposure to new data. The clinical context was the efficacy of antibiotics versus teat sealants for preventing mammary infections during the dry period. While most practitioners updated their clinical expectations logically, the majority failed to draw sufficient strength from the new data so that their clinical confidence afterwards was lower than merited. This study provides quantitative insight into how practitioners' update their beliefs. We discuss some of the psychological issues that may be faced by practitioners when interpreting new data. The results have important implications for evidence-based practice and clinical research in terms of the impact that new data may bring to the clinical community

Predicting the cost of the consequences of a large nuclear accident in the UK

Nuclear accidents have the potential to lead to significant off-site effects that require actions to minimise the radiological impacts on people. Such countermeasures may include sheltering, evacuation, restrictions on the sale of locally-grown food, and long-term relocation of the population amongst others. Countries with nuclear facilities draw up emergency preparedness plans, and put in place such provisions as distributing instructions and iodine prophylaxis to the local population. Their plans are applied in simulated exercises on a regular basis. The costs associated with emergency preparedness and the safety provisions to reduce the likelihood of an accident, and/or mitigate the consequences, are justified on the basis of the health risks and accident costs averted. There is, of course, only limited actual experience to indicate the likely costs so that much of the costing of accidents is based on calculations. This paper reviews the methodologies used, in particular the approach that has been developed in the UK, to appraise the costs of a hypothetical nuclear accident. Results of analysing a hypothetical nuclear accident at a fictitious reactor site within the United Kingdom are discussed in relation to the accidents at Three Mile Island 2, Chernobyl and Fukushima Dai-ichi

Understanding veterinarians' prescribing decisions on antibiotic dry cow therapy.

In the United Kingdom, blanket antibiotic dry cow therapy (BDCT) is commonly prescribed. An alternate strategy is selective dry cow therapy (SDCT) whereby a teat sealant is given instead of an antibiotic to cows with a low probability of infection. Switching from BDCT to SDCT can significantly reduce antibiotic use. The aims of this study were to explore how veterinarians (vets) rationalized their prescribing decisions for mammary treatments at drying off, and the barriers and motivators they perceived to implementing SDCT. Face-to-face interviews were conducted with 20 purposively recruited vets from 6 practices in England, United Kingdom. The data were analyzed qualitatively using an inductive thematic analysis. The majority of participants stated a personal preference for SDCT because it constitutes more responsible antibiotic use. On the majority of farms, the prescribing decision was taken by a senior veterinarian and BDCT was prescribed. Less experienced vets expressed a desire to be more involved in the decision-making process. The first theme, prioritizing responsible antimicrobial prescribing, encapsulated the difficulties vets expressed engaging with farmers, conflicts of interest, and vets' determination to take action. The second theme, the effect of a vet's experience on their ability to influence farmers, focused on the specific challenges faced by less experienced vets and the importance of vets being both trusted by farmers and being knowledgeable. The third theme, vets' perceptions about the risk and complexity of implementing SDCT, revealed markedly different levels of concern and fears about adverse outcomes with teat sealants versus antibiotics. The results also showed differences in perceptions about how difficult SDCT is to implement in practice. The last theme, vets' suggestions for facilitating the introduction of SDCT, was wide ranging and provided useful insight from a veterinary perspective into ways to facilitate SDCT. Initiatives that seek to alter vets' perceptions of the risks associated with switching to using SDCT are likely to prove useful in facilitating change. Our results also suggest that it is vital for senior vets to take a leading role in facilitating farms to implement SDCT. Less experienced colleagues may benefit from more help from senior vets to gain the trust of farmers and to become involved more quickly in herd-level preventive medicine. Vets must work together and take a united approach to reduce antimicrobial use

Entanglement-free Heisenberg-limited phase estimation

Measurement underpins all quantitative science. A key example is the measurement of optical phase, used in length metrology and many other applications. Advances in precision measurement have consistently led to important scientific discoveries. At the fundamental level, measurement precision is limited by the number N of quantum resources (such as photons) that are used. Standard measurement schemes, using each resource independently, lead to a phase uncertainty that scales as 1/sqrt(N) - known as the standard quantum limit. However, it has long been conjectured that it should be possible to achieve a precision limited only by the Heisenberg uncertainty principle, dramatically improving the scaling to 1/N. It is commonly thought that achieving this improvement requires the use of exotic quantum entangled states, such as the NOON state. These states are extremely difficult to generate. Measurement schemes with counted photons or ions have been performed with N <= 6, but few have surpassed the standard quantum limit and none have shown Heisenberg-limited scaling. Here we demonstrate experimentally a Heisenberg-limited phase estimation procedure. We replace entangled input states with multiple applications of the phase shift on unentangled single-photon states. We generalize Kitaev's phase estimation algorithm using adaptive measurement theory to achieve a standard deviation scaling at the Heisenberg limit. For the largest number of resources used (N = 378), we estimate an unknown phase with a variance more than 10 dB below the standard quantum limit; achieving this variance would require more than 4,000 resources using standard interferometry. Our results represent a drastic reduction in the complexity of achieving quantum-enhanced measurement precision.Comment: Published in Nature. This is the final versio

Exploring the behavioural drivers of veterinary surgeon antibiotic prescribing: a qualitative study of companion animal veterinary surgeons in the UK

Background: Multi-drug resistant bacteria are an increasing concern in both human and veterinary medicine. Inappropriate prescribing and use of antibiotics within veterinary medicine may be a contributory factor to antimicrobial resistance (AMR). The ‘One Health’ Initiative aims to work across species and environments to reduce AMR, however; little is currently known about the factors which influence antibiotic prescribing among veterinary surgeons in companion animal practice. This paper reports on qualitative data analysis of interviews with veterinary surgeons whose practice partially or wholly focuses on companion animals (N = 16). The objective of the research was to explore the drivers of companion animal veterinary surgeons’ antibiotic prescribing behaviours. The veterinary surgeons interviewed were all practising within the UK (England (n = 4), Scotland (n = 11), Northern Ireland (n = 1)). A behavioural thematic analysis of the data was undertaken, which identified barriers and facilitators to specific prescribing-related behaviours. Results: Five components of prescribing behaviours were identified: 1) confirming clinical need for antibiotics; 2) responding to clients; 3) confirming diagnosis; 4) determining dose, duration and type of antibiotic; and 5) preventing infection around surgery (with attendant appropriate and inappropriate antibiotic prescribing behaviours). Barriers to appropriate prescribing identified include: business, diagnostic, fear, habitual practice and pharmaceutical factors. Facilitators include: AMR awareness, infection prevention, professional learning and regulation and government factors. Conclusion: This paper uses a behavioural lens to examine drivers which are an influence on veterinary surgeons’ prescribing behaviours. The paper contributes new understandings about factors which influence antibiotic prescribing behaviours among companion animal veterinary surgeons. This analysis provides evidence to inform future interventions, which are focused on changing prescribing behaviours, in order to address the pressing public health concern of AMR

Gateway state-mediated, long-range tunnelling in molecular wires

If the factors controlling the decay in single-molecule electrical conductance G with molecular length L could be understood and controlled, then this would be a significant step forward in the design of high-conductance molecular wires. For a wide variety of molecules conducting by phase coherent tunneling, conductance G decays with length following the relationship G = Aexp-\b{\eta}L. It is widely accepted that the attenuation coefficient \b{\eta} is determined by the position of the Fermi energy of the electrodes relative to the energy of frontier orbitals of the molecular bridge, whereas the terminal anchor groups which bind to the molecule to the electrodes contribute to the pre-exponential factor A. We examine this premise for several series of molecules which contain a central conjugated moiety (phenyl, viologen or {\alpha}-terthiophene) connected on either side to alkane chains of varying length, with each end terminated by thiol or thiomethyl anchor groups. In contrast with this expectation, we demonstrate both experimentally and theoretically that additional electronic states located on thiol anchor groups can significantly decrease the value of \b{eta}, by giving rise to resonances close to EF through coupling to the bridge moiety. This interplay between the gateway states and their coupling to a central conjugated moiety in the molecular bridges creates a new design strategy for realising higher-transmission molecular wires by taking advantage of the electrode-molecule interface properties

Further characterization of ADAMTS-13 inactivation by thrombin

Background: The multimeric size and platelet-tethering function of von Willebrand factor (VWF) are modulated by the plasma metalloprotease, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13). In vitro ADAMTS-13 is susceptible to proteolytic inactivation by thrombin. Objectives: In this study, we aimed to characterize the inactivation of ADAMTS-13 by thrombin and to assess its physiological significance. Methods and results: By N-terminal sequencing of cleavage products, and by mutagenesis, we identified the principal thrombin cleavage sites in ADAMTS-13 as R257 and R1176. Using a library of 76 thrombin mutants, we highlighted the functional importance of exosite I on thrombin in the proteolysis of ADAMTS-13. Proteolysis of ADAMTS-13 by thrombin caused an 8-fold reduction in its affinity for VWF that contributed to its loss of VWF-cleaving function. Intriguingly, thrombin-cleaved ADAMTS-13 both bound and proteolyzed a short recombinant VWF A2 domain substrate (VWF115) normally. Following activation of coagulation in normal plasma, endogenous ADAMTS-13, but not added ADAMTS-13, appeared resistant to coagulation-induced fragmentation. An estimation of the Km for ADAMTS-13 proteolysis by thrombin was appreciably higher than the physiological concentration of ADAMTS-13. This was corroborated by the comparatively low affinity of ADAMTS-13 for thrombin (KD 95 nm). Conclusions: Together, our data suggest that ADAMTS-13 is protected from rapid proteolytic inactivation by thrombin in normal plasma. Whether this remains the case under pathological situations involving elevated/sustained generation of thrombin remains unclear