Tackling bovine TB

On 18 December Defra revealed that during 2018, 32,601 badgers were killed, bringing the total number slaughtered under licence since 2013 to almost 67,000.1 ‘Effectiveness’ claims relate not to the impact on cattle TB, but rather to the ability of the contracted shooters to kill sufficient badgers to satisfy their licence requirements, which they can hardly fail to reach given that target numbers are ‘adjusted’ by Natural England part-way through the culls according to the contractors’ progress. Sixty per cent of the badgers have been killed by ‘controlled shooting’, a method rejected by both the government’s Independent Expert Panel2 and the BVA3 because of animal welfare concerns. During 2018 Natural England directly monitored just 89 (0.43 per cent) of controlled shooting events. It is deplorable that the chief veterinary officer (CVO) continues to support the roll-out of a policy that permits controlled shooting, when veterinary organisations have condemned the method on animal welfare grounds. It is particularly concerning that the CVO appears to have deflected responsibility for humaneness to Natural England’s chief scientist who, as far as we are aware, has no background in animal welfare science. It is also unacceptable for government to attribute reductions in herd bovine TB (bTB) incidents over the first four years of culling in the original ‘pilot’ cull zones to its badger culling policy.4 Independent analysis of this and more recent data from the Gloucestershire pilot cull zone5 indicate that new herd incidence is rising sharply, with 22 herd breakdowns in the 12 months to September 2017 (an increase of 29.4 per cent when compared to the 17 breakdowns reported by APHA for the previous 12 months). Analysis of the 2018 figures indicates that both incidence and prevalence are now rising even faster, with a further 24 herd breakdowns occurring between 1 January and 5 December 2018. To date, the government and its officials cite data that are two years out of date, but have declined to comment on this emerging evidence that, far from resulting in a substantial disease control benefit, badger culls may be leading to a sharp increase in bTB in cattle. Natural England’s chief scientist and the UK’s CVO continue to endorse a failing and inhumane policy, bringing their offices into serious disrepute. We urge them, and the BVA, to reconsider their support for further badger culling, and instead focus on the actual cause of bTB’s epidemic spread – a cattle skin test with a sensitivity of only 50 per cent,6,7 and the ongoing problems associated with cattle movements and on-farm biosecurity

Animal welfare impacts of badger culling operations

We are writing to express our extreme concern following recent media coverage1, 2 relating to the methodology being used by contractors to kill badgers under licence, as part of the government’s policy to control bovine TB in cattle. The coverage relates to the shooting of badgers that have been captured in live traps. Covert video footage (https://bit.ly/2Eud1iR ) from Cumbria shows a trapped badger being shot with a firearm at close range, following which it appears to take close to a minute to stop moving. The contractor clearly observes the animal during this time but makes no attempt to expedite the death of the badger and prevent further suffering, as required by the current Natural England best practice guide which states: ‘Immediately after shooting, the animal should be checked to ensure it is dead, and if there is any doubt, a second shot must be taken as soon as possible.’3 The conversation between the contractor and his companion also suggests they were considering moving the badger to another site before finally bagging the carcase, again breaching the best practice guide. While the footage only relates to the experience of a single badger, and while the degree to which the badger was conscious in the period immediately following the shot is unclear, we can by no means be certain that the badger did not suffer. It also raises serious questions about the training, competence and behaviour of contractors, in relation to both badger welfare, and biosecurity. This adds to existing concerns relating to the humaneness of ‘controlled shooting’ (targeting free-roaming badgers with rifles), which continues to be a permitted method under culling licences, in spite of the reservations expressed by both the government-commissioned Independent Expert Panel in its 2014 report,4 and the BVA, which concluded in 2015 that it ‘can no longer support the continued use of controlled shooting as part of the badger control policy’.5 (However, it has since continued to support the issuing of licences which permit the method). The BVA has consistently indicated its support for what it calls the ‘tried and tested’ method of trapping and shooting, but has thus far failed to provide comprehensive and robust evidence for the humaneness of this method. Figure1 Download figure Open in new tab Download powerpoint Natural England reported that its monitors observed 74 (just over 0.6 per cent) of controlled shooting events for accuracy and humaneness During 2017, almost 20,000 badgers were killed under licence across 19 cull zones, around 60 per cent of which were killed by controlled shooting, the remainder being trapped and shot.6 Natural England reported that its monitors observed 74 (just over 0.6 per cent) of controlled shooting events for accuracy and humaneness. No information has been provided on the extent to which trapping and shooting activities were monitored. This raises serious concerns about the extent of suffering that might be experienced by very large numbers of animals, for which contractors are not being held to account. If contractors reach their maximum culling targets set by Natural England for 2018, as many as 41,000 additional badgers could be killed.7 The extent to which these animals will suffer is once again being left in the hands of contractors, with woefully inadequate oversight, and in the face of anecdotal evidence of breaches of best practice guidance. This situation is clearly unacceptable from an animal welfare perspective and it is our view that by endorsing the policy, the BVA is contradicting the principles contained within its own animal welfare strategy.8 We therefore urge the BVA to withdraw its support for any further licensed badger culling, and the RCVS to make it clear that any veterinarian who provides support for culling activities that result in unnecessary and avoidable animal suffering could face disciplinary proceedings. The veterinary profession has no business supporting this licensed mass killing with all its inherent negative welfare and biosecurity implications, and for which the disease control benefits are, at best, extremely uncertain. We believe the continued support for the culls by veterinary bodies in the face of poor evidence for its efficacy damages the credibility of the profession, and that same support in the face of potential animal suffering on a large scale undermines its reputation. We stand ready to discuss these issues in more detail

Effect of shunted piezoelectric control for tuning piezoelectric power harvesting system responses – Analytical techniques

This paper presents new analytical modelling of shunt circuit control responses for tuning electromechanical piezoelectric vibration power harvesting structures with proof mass offset. For this combination, the dynamic closed-form boundary value equations reduced from strong form variational principles were developed using the extended Hamiltonian principle to formulate the new coupled orthonormalised electromechanical power harvesting equations showing combinations of the mechanical system (dynamical behaviour of piezoelectric structure), electromechanical system (electrical piezoelectric response) and electrical system (tuning and harvesting circuits). The reduced equations can be further formulated to give the complete forms of new electromechanical multi-mode FRFs and time waveform of the standard AC-DC circuit interface. The proposed technique can demonstrate self-adaptive harvesting response capabilities for tuning the frequency band and the power amplitude of the harvesting devices. The self-adaptive tuning strategies are demonstrated by modelling the shunt circuit behaviour of the piezoelectric control layer in order to optimise the harvesting piezoelectric layer during operation under input base excitation. In such situations, with proper tuning parameters the system performance can be substantially improved. Moreover, the validation of the closed-form technique is also provided by developing the Ritz method-based weak form analytical approach giving similar results. Finally, the parametric analytical studies have been explored to identify direct and relevant contributions for vibration power harvesting behaviours

EPidemiology Of Cardiogenic sHock in Scotland (EPOCHS):a multicentre, prospective observational study of the prevalence, management and outcomes of cardiogenic shock in Scotland

BackgroundDespite high rates of cardiovascular disease in Scotland, the prevalence and outcomes of patients with cardiogenic shock are unknown.MethodsWe undertook a prospective observational cohort study of consecutive patients with cardiogenic shock admitted to the intensive care unit (ICU) or coronary care unit at 13 hospitals in Scotland for a six-month period. Denominator data from the Scottish Intensive Care Society Audit Group were used to estimate ICU prevalence; data for coronary care units were unavailable. We undertook multivariable logistic regression to identify factors associated with in-hospital mortality.ResultsIn total, 247 patients with cardiogenic shock were included. After exclusion of coronary care unit admissions, this comprised 3.0% of all ICU admissions during the study period (95% confidence interval [CI] 2.6 to 3.5%). Aetiology was acute myocardial infarction (AMI) in 48%. The commonest vasoactive treatment was noradrenaline (56%) followed by adrenaline (46%) and dobutamine (40%). Mechanical circulatory support was used in 30%. Overall in-hospital mortality was 55%. After multivariable logistic regression, age (odds ratio [OR] 1.04, 95% CI 1.02 to 1.06), admission lactate (OR 1.10, 95% CI 1.05 to 1.19), Society for Cardiovascular Angiographic Intervention stage D or E at presentation (OR 2.16, 95% CI 1.10 to 4.29), and use of adrenaline (OR 2.73, 95% CI 1.40 to 5.40) were associated with mortality.ConclusionsIn Scotland the prevalence of cardiogenic shock was 3% of all ICU admissions; more than half died prior to discharge. There was significant variation in treatment approaches, particularly with respect to vasoactive support strategy. <br/

Variation in treatment of acute childhood wheeze in emergency departments of the United Kingdom and Ireland: An international survey of clinician practice

© 2015, BMJ Publishing Group. All rights reserved. Objective: National clinical guidelines for childhood wheeze exist, yet despite being one of the most common reasons for childhood emergency department (ED) attendance, signi ficant variation in practice occurs in other settings. We, therefore, evaluated practice variations of ED clinicians in the UK and Ireland. Design: Two-stage survey undertaken in March 2013. Stage one examined department practice and stage two assessed ED consultant practice in acute childhood wheeze. Questions interrogated pharmacological and other management strategies, including inhaled and intravenous therapies. Setting and participants: Member departments of Paediatric Emergency Research in the United Kingdom and Ireland and ED consultants treating children with acute wheeze. Results: 30 EDs and 183 (81%) clinicians responded. 29 (97%) EDs had wheeze guidelines and 12 (40%) had care pathways. Variation existed between clinicians in dose, timing and frequency of inhaled bronchodilators across severities. When escalating to intravenous bronchodilators, 99 (54%) preferred salbutamol first line, 52 (28%) magnesium sulfate (MgSO4) and 27 (15%) aminophylline. 87 (48%) administered intravenous bronchodilators sequentially and 30 (16%) concurrently, with others basing approach on case severity. 146 (80%) continued inhaled therapy after commencing intravenous bronchodilators. Of 170 who used intravenous salbutamol, 146 (86%) gave rapid boluses, 21 (12%) a longer loading dose and 164 (97%) an ongoing infusion, each with a range of doses and durations. Of 173 who used intravenous MgSO4, all used a bolus only. 41 (24%) used non-invasive ventilation. Conclusions: Signi ficant variation in ED consultant management of childhood wheeze exists despite the presence of national guidance. This reflects the lack of evidence in key areas of childhood wheeze and emphasises the need for further robust multicentre research studies

Development of an In Vivo RNAi Protocol to Investigate Gene Function in the Filarial Nematode, Brugia malayi

Our ability to control diseases caused by parasitic nematodes is constrained by a limited portfolio of effective drugs and a paucity of robust tools to investigate parasitic nematode biology. RNA interference (RNAi) is a reverse-genetics tool with great potential to identify novel drug targets and interrogate parasite gene function, but present RNAi protocols for parasitic nematodes, which remove the parasite from the host and execute RNAi in vitro, are unreliable and inconsistent. We have established an alternative in vivo RNAi protocol targeting the filarial nematode Brugia malayi as it develops in an intermediate host, the mosquito Aedes aegypti. Injection of worm-derived short interfering RNA (siRNA) and double stranded RNA (dsRNA) into parasitized mosquitoes elicits suppression of B. malayi target gene transcript abundance in a concentration-dependent fashion. The suppression of this gene, a cathepsin L-like cysteine protease (Bm-cpl-1) is specific and profound, both injection of siRNA and dsRNA reduce transcript abundance by 83%. In vivo Bm-cpl-1 suppression results in multiple aberrant phenotypes; worm motility is inhibited by up to 69% and parasites exhibit slow-moving, kinked and partial-paralysis postures. Bm-cpl-1 suppression also retards worm growth by 48%. Bm-cpl-1 suppression ultimately prevents parasite development within the mosquito and effectively abolishes transmission potential because parasites do not migrate to the head and proboscis. Finally, Bm-cpl-1 suppression decreases parasite burden and increases mosquito survival. This is the first demonstration of in vivo RNAi in animal parasitic nematodes and results indicate this protocol is more effective than existing in vitro RNAi methods. The potential of this new protocol to investigate parasitic nematode biology and to identify and validate novel anthelmintic drug targets is discussed

Evolution of Susceptibility to Ingested Double-Stranded RNAs in Caenorhabditis Nematodes

International audienceBACKGROUND: The nematode Caenorhabditis elegans is able to take up external double-stranded RNAs (dsRNAs) and mount an RNA interference response, leading to the inactivation of specific gene expression. The uptake of ingested dsRNAs into intestinal cells has been shown to require the SID-2 transmembrane protein in C. elegans. By contrast, C. briggsae was shown to be naturally insensitive to ingested dsRNAs, yet could be rendered sensitive by transgenesis with the C. elegans sid-2 gene. Here we aimed to elucidate the evolution of the susceptibility to external RNAi in the Caenorhabditis genus. PRINCIPAL FINDINGS: We study the sensitivity of many new species of Caenorhabditis to ingested dsRNAs matching a conserved actin gene sequence from the nematode Oscheius tipulae. We find ample variation in the Caenorhabditis genus in the ability to mount an RNAi response. We map this sensitivity onto a phylogenetic tree, and show that sensitivity or insensitivity have evolved convergently several times. We uncover several evolutionary losses in sensitivity, which may have occurred through distinct mechanisms. We could render C. remanei and C. briggsae sensitive to ingested dsRNAs by transgenesis of the Cel-sid-2 gene. We thus provide tools for RNA interference studies in these species. We also show that transgenesis by injection is possible in many Caenorhabditis species. CONCLUSIONS: The ability of animals to take up dsRNAs or to respond to them by gene inactivation is under rapid evolution in the Caenorhabditis genus. This study provides a framework and tools to use RNA interference and transgenesis in various Caenorhabditis species for further comparative and evolutionary studies

Computationally-Optimized Bone Mechanical Modeling from High-Resolution Structural Images

Image-based mechanical modeling of the complex micro-structure of human bone has shown promise as a non-invasive method for characterizing bone strength and fracture risk in vivo. In particular, elastic moduli obtained from image-derived micro-finite element (μFE) simulations have been shown to correlate well with results obtained by mechanical testing of cadaveric bone. However, most existing large-scale finite-element simulation programs require significant computing resources, which hamper their use in common laboratory and clinical environments. In this work, we theoretically derive and computationally evaluate the resources needed to perform such simulations (in terms of computer memory and computation time), which are dependent on the number of finite elements in the image-derived bone model. A detailed description of our approach is provided, which is specifically optimized for μFE modeling of the complex three-dimensional architecture of trabecular bone. Our implementation includes domain decomposition for parallel computing, a novel stopping criterion, and a system for speeding up convergence by pre-iterating on coarser grids. The performance of the system is demonstrated on a dual quad-core Xeon 3.16 GHz CPUs equipped with 40 GB of RAM. Models of distal tibia derived from 3D in-vivo MR images in a patient comprising 200,000 elements required less than 30 seconds to converge (and 40 MB RAM). To illustrate the system's potential for large-scale μFE simulations, axial stiffness was estimated from high-resolution micro-CT images of a voxel array of 90 million elements comprising the human proximal femur in seven hours CPU time. In conclusion, the system described should enable image-based finite-element bone simulations in practical computation times on high-end desktop computers with applications to laboratory studies and clinical imaging

Identification of dissolved organic matter size components in freshwater and marine environments

Dissolved organic matter (DOM) in the transition zone from freshwater to marine systems was analyzed with a new approach for parameterizing the size distribution of organic compounds. We used size-exclusion chromatography for molecular size analysis and quantified colored DOM (CDOM) on samples from two coastal environments in the Baltic Sea (Roskilde Fjord, Denmark and Gulf of Gdansk, Poland). We applied a Gaussian decomposition method to identify peaks from the chromatograms, providing information beyond bulk size properties. This approach complements methods where DOM is separated into size classes with pre-defined filtering cutoffs, or methods where chromatograms are used only to infer average molecular weight. With this decomposition method, we extracted between three and five peaks from each chromatogram and clustered these into three size groups. To test the applicability of our method, we linked our decomposed peaks with salinity, a major environmental driver in the freshwater-marine continuum. Our results show that when moving from freshwater to low-salinity coastal waters, the observed steep decrease of apparent molecular weight is mostly due to loss of the high-molecular-weight fraction (HMW; >2 kDa) of CDOM. Furthermore, most of the CDOM absorbance in freshwater originates from HMW DOM, whereas the absorbing moieties are more equally distributed along the smaller size range (<2 kDa) in marine samples.Peer reviewe