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

The effect of a concurrent cognitive task on cortical potentials evoked by unpredictable balance perturbations

BACKGROUND: Although previous studies suggest that postural control requires attention and other cognitive resources, the central mechanisms responsible for this relationship remain unclear. To address this issue, we examined the effects of altered attention on cortical activity and postural responses following mechanical perturbations to upright stance. We hypothesized that cortical activity would be attenuated but not delayed when mechanical perturbations were applied during a concurrent performance of a cognitive task (i.e. when attention was directed away from the perturbation). We also hypothesized that these cortical changes would be accompanied by alterations in the postural response, as evidenced by increases in the magnitude of anteroposterior (AP) centre of pressure (COP) peak displacements and tibialis anterior (TA) muscle activity. Healthy young adults (n = 7) were instructed to continuously track (cognitive task) or not track (control task) a randomly moving visual target using a hand-held joystick. During each of these conditions, unpredictable translations of a moving floor evoked cortical and postural responses. Scalp-recorded cortical activity, COP, and TA electromyographic (EMG) measures were collected. RESULTS: Results revealed a significant decrease in the magnitude of early cortical activity (the N1 response, the first negative peak after perturbation onset) during the tracking task compared to the control condition. More pronounced AP COP peak displacements and EMG magnitudes were also observed for the tracking task and were possibly related to changes in the N1 response. CONCLUSION: Based on previous notions that the N1 response represents sensory processing of the balance disturbance, we suggest that the attenuation of the N1 response is an important central mechanism that may provide insight into the relationship between attention and postural control

Trunk Sway Measures of Postural Stability During Clinical Balance Tests: Effects of Age

Background. The major disadvantage of current clinical tests that screen for balance disorders is a reliance on an examiner's subjective assessment of equilibrium control. To overcome this disadvantage we investigated, using quantified measures of trunk sway, age-related differences of normal subjects for commonly used clinical balance tests. Methods. Three age groups were tested: young (15-25 years; n = 48), middle-aged (45-55 years; n = 50) and elderly (65-75 years; n = 49). Each subject performed a series of fourteen tasks similar to those included in the Tinetti and Clinical Test of Sensory Interaction in Balance protocols. The test battery comprised stance and gait tasks performed under normal, altered visual (eyes closed), and altered proprioceptive (foam support surface) conditions. Quantification of trunk sway was performed using a system that measured trunk angular velocity and position in the roll (lateral) and pitch (fore-aft) planes at the level of the lower back. Ranges of sway amplitude and velocity were examined for age-differences with ANOVA techniques. Results. A comparison between age groups showed several differences. Elderly subjects were distinguished from both middle-aged and young subjects by the range of trunk angular sway and angular velocity because both were greater in roll and pitch planes for stance and stance-related tasks (tandem walking). The most significant age group differences (F = 30, p < .0001) were found for standing on one leg on a normal floor or on a foam support surface with eyes open. Next in significance was walking eight tandem steps on a normal floor (F = 13, p < .0001). For gait tasks, such as walking five steps while rotating or pitching the head or with eyes closed, pitch and roll velocity ranges were influenced by age with middle-aged subjects showing the smallest ranges followed by elderly subjects and then young subjects (F = 12, p < .0001). Walking over a set of low barriers also yielded significant differences between age groups for duration and angular sway. In contrast, task duration was the only variable significantly influenced when walking up and down a set of stairs. An interesting finding for all tasks was the different spread of values for each population. Population distributions were skewed for all ages and broadened with age. Conclusions. Accurate measurement of trunk angular sway during stance and gait tasks provides a simple way of reliably measuring changes in balance stability with age and could prove useful when screening for balance disorders of those prone to fal

New Insights on Emotional Contributions to Human Postural Control

It has been just over 20 years since the effects of height-induced threat on human postural control were first investigated. Raising the height of the support surface on which individuals stood increased the perceived consequences of instability and generated postural control changes. Since this initial work, converging evidence has accumulated supporting the efficacy of using height-induced threat to study the effects of emotions on postural control and confirming a direct influence of threat-related changes in arousal, anxiety, and fear of falling on all aspects of postural control, including standing, anticipatory, and reactive balance. In general, threat-related postural changes promote a greater physical safety margin while maintaining upright stance. We use the static balance literature to critically examine the current state of knowledge regarding: (1) the extent to which threat-related changes in postural control are sensitive to threat-related changes in emotions; (2) the underlying neurophysiological and cognitive mechanisms that may contribute to explaining the relationship between emotions and postural control; and (3) the generalizability of threat-related changes across different populations and types of threat. These findings have important implications for understanding the neuromechanisms that control healthy balance, and highlight the need to recognize the potential contributions of psychological and physiological factors to balance deficits associated with age or pathology. We conclude with a discussion of the practical significance of this research, its impact on improving diagnosis and treatment of postural control deficits, and potential directions for future research

Assessing the probability of introduction and transmission of lumpy skin disease virus within the United Kingdom

Several emerging exotic diseases are currently oscillating on the eastern borders of the European Union (EU) including the bovine pathogen Lumpy skin disease virus (LSDV). Given the recent transboundary spread of LSDV into the EU, assessing the probability of further expansion is an important part of EU surveillance and can inform policy regarding risk mitigation priorities. This qualitative assessment focuses on the probability of introduction and onward transmission of LSDV into the United Kingdom (UK) for the time period June 2017 to June 2018. Overall the probability of introduction was considered, at most, to be very low. The probability of onward transmission was considered highest for vector mediated routes either via contact of an infected vector with susceptible cattle or contact of a competent native vector with an infected cattle. Factors with high uncertainty were identified to emphasise their impact on the assessment conclusions and for future research requirements. Medium to high uncertainty surrounds the probability of introduction to the UK via several of the routes assessed, in particular, the species of vectors involved and the illegal/legal import of meat and milk products; all estimates made consequential to these probabilities are therefore underpinned by high uncertainty. Whilst the assessment was UK centric the knowledge gaps are relevant to the probability of introduction and spread of LSDV in any geographical region. The value of estimating uncertainty lies in the identification of research required to make conclusions more robust

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

Postural threat increases sample entropy of postural control

IntroductionPostural threat elicits modifications to standing balance. However, the underlying neural mechanism(s) responsible remain unclear. Shifts in attention focus including directing more attention to balance when threatened may contribute to the balance changes. Sample entropy, a measure of postural sway regularity with lower values reflecting less automatic and more conscious control of balance, may support attention to balance as a mechanism to explain threat-induced balance changes. The main objectives were to investigate the effects of postural threat on sample entropy, and the relationships between threat-induced changes in physiological arousal, perceived anxiety, attention focus, sample entropy, and traditional balance measures. A secondary objective was to explore if biological sex influenced these relationships.MethodsHealthy young adults (63 females, 42 males) stood quietly on a force plate without (No Threat) and with (Threat) the expectation of receiving a postural perturbation (i.e., forward/backward support surface translation). Mean electrodermal activity and anterior–posterior centre of pressure (COP) sample entropy, mean position, root mean square, mean power frequency, and power within low (0–0.05 Hz), medium (0.5–1.8 Hz), and high-frequency (1.8–5 Hz) components were calculated for each trial. Perceived anxiety and attention focus to balance, task objectives, threat-related stimuli, self-regulatory strategies, and task-irrelevant information were rated after each trial.Results and DiscussionSignificant threat effects were observed for all measures, except low-frequency sway. Participants were more physiologically aroused, more anxious, and directed more attention to balance, task objectives, threat-related stimuli, and self-regulatory strategies, and less to task-irrelevant information in the Threat compared to No Threat condition. Participants also increased sample entropy, leaned further forward, and increased the amplitude and frequency of COP displacements, including medium and high-frequency sway, when threatened. Males and females responded in the same way when threatened, except males had significantly larger threat-induced increases in attention to balance and high-frequency sway. A combination of sex and threat-induced changes in physiological arousal, perceived anxiety, and attention focus accounted for threat-induced changes in specific traditional balance measures, but not sample entropy. Increased sample entropy when threatened may reflect a shift to more automatic control. Directing more conscious control to balance when threatened may act to constrain these threat-induced automatic changes to balance

Activity of ceftolozane/tazobactam against surveillance and ‘problem’ Enterobacteriaceae, Pseudomonas aeruginosa and non-fermenters from the British Isles

Background: We assessed the activity of ceftolozane/tazobactam against consecutive isolates collected in the BSAC Bacteraemia Surveillance from 2011 to 2015 and against ‘problem’ isolates sent to the UK national reference laboratory from July 2015, when routine testing began. Methods: Susceptibility testing was by BSAC agar dilution with resistance mechanisms identified by PCR and interpretive reading. Results: Data were reviewed for 6080 BSAC surveillance isolates and 5473 referred organisms. Ceftolozane/tazobactam had good activity against unselected ESBL producers in the BSAC series, but activity was reduced against ertapenem-resistant ESBL producers, which were numerous among reference submissions. AmpC-derepressed Enterobacter spp. were widely resistant, but Escherichia coli with raised chromosomal AmpC frequently remained susceptible, as did Klebsiella pneumoniae with acquired DHA-1-type AmpC. Carbapenemase-producing Enterobacteriaceae were mostly resistant, except for ceftazidime-susceptible isolates with OXA-48-like enzymes. Ceftolozane/tazobactam was active against 99.8% of the BSAC Pseudomonas aeruginosa isolates; against referred P. aeruginosa it was active against 99.7% with moderately raised efflux, 94.7% with strongly raised efflux and 96.6% with derepressed AmpC. Resistance in P. aeruginosa was largely confined to isolates with metallo-β-lactamases (MBLs) or ESBLs. MICs for referred Burkholderia spp. and Stenotrophomonas maltophilia were 2–4-fold lower than those of ceftazidime. Conclusions: Ceftolozane/tazobactam is active against ESBL-producing Enterobacteriaceae; gains against other problem Enterobacteriaceae groups were limited. Against P. aeruginosa it overcame the two most prevalent mechanisms (up-regulated efflux and derepressed AmpC) and was active against 51.9% of isolates non-susceptible to all other β-lactams, rising to 80.9% if ESBL and MBL producers were excluded

Molybdenum oxide on Fe2O3 Core-Shell catalysts: Probing the nature of the structural motifs responsible for methanol oxidation catalysis

A series of MoOx-modified Fe2O3 catalysts have been prepared in an attempt to make core–shell oxidic materials of the type MoOx/Fe2O3. It is conclusively shown that for three monolayers of Mo dosed, the Mo stays in the surface region, even after annealing to high temperature. It is only when the material is annealed above 400 °C that it reacts with the iron oxide. We show by a combination of methods, and especially by XAFS, that at temperatures above 400 °C, most of the Mo converts to Fe2(MoO4)3, with Mo in a tetrahedral structure, whereas below that temperature, nanocrystalline MoO3 is present in the sample; however, the active catalysts have an octahedral MoOx layer at the surface even after calcination to 600 °C. This surface layer appears to be present at all temperatures between 300 and 600 °C, and it is the nanoparticles of MoO3 that are present at the lower temperature that react to form ferric molybdate, which underlies this surface layer. It is the MoOx layer on the Fe2(MoO4)3 underlayer that makes the surface active and selective for formaldehyde synthesis, whereas the iron oxide surface itself is a combustor. The material is both activated and improved in selectivity due to the dominance of the methoxy species on the Mo-doped material, as opposed to the much more stable formate, which is the main intermediate on Fe2O3