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Our aim was to assess whether there is a difference in outcomes of potential “all-cause” harm in the transfusion of whole blood (WB) compared to blood components (BC) for any bleeding patient regardless of age or clinical condition. We searched multiple electronic databases using a pre-defined search strategy from inception to 2ndMarch 2021. 1 reviewer screened, extracted, and analysed data, with verification by a second reviewer of all decisions. We used Cochrane ROB1 and GRADE to assess the quality of the evidence. We used predefined subgroups of trauma and non-trauma studies in the analysis. We included six RCTs (618 participants) which compared WB and BCtransfusion therapyin major bleeding, one trauma trial (n=107), and 5 surgical trials (non-trauma) (n=511). We GRADED evidence as very-low for all outcomes (downgraded for high and unclear risk of bias, small sample size, and wide confidence intervals around the estimate). Our primary outcome (all-cause mortality at 24-hours and 30-days) was reported in 3 out of 6 included trials. There was no evidence of a difference in mortality of WB compared to BC therapy (very-low certainty evidence). There may be a benefit of WB therapy compared to BC therapy in the non-trauma subgroup, with a reduction in the duration of oxygen dependence (1 study;n=60; mean difference 5.9 fewer hours [95% Confidence Interval [CI] -10.83, –0.99] in WB group), and a reduction in hospital stay (1 study,n=64, median difference 6 fewer days in WB group) (very-low certainty evidence). For the remaining outcomes (organ injury,mechanical ventilationand intensive care unit requirement, infection, arterial/venous thrombotic events, and haemolytic transfusion reaction) there was no difference between WB and BC therapy (wide CI, crossing line of no effect), though many of these outcomes were based on small single studies (very-low certainty evidence). In conclusion, there appears to be little to no difference in harms between WB and BC therapy, based on small studies with very low certainty of the evidence. Further large trials are required to establish the overall safety of WB compared to BC, and to assess differences between trauma and non-trauma patients.

AprV2andaprB2are variants of the apr gene ofDichelobacter nodosus, the cause of footrot in sheep. They are putative markers for severe and mild disease expression. The aim of our study was to investigate the distribution ofaprV2andaprB2in flocks with and without footrot. Our hypotheses were that both strains are present in endemically affected flocks, withaprB2andaprV2associated with mild and virulent phenotypes respectively but thatD. nodosusis not present in flocks without footrot. Alternatively,aprB2persists in flocks without footrot. Despite extensive searching over 3 years only three flocks of sheep without footrot were identified.D. nodosuswas not detected in these three flocks. In one further flock, only mild interdigital dermatitis was observed, and onlyaprB2was detected. Twenty-four flocks with endemic footrot of all severities were sampled on three occasions and all were positive forD. nodosusand theaprV2variant;aprB2was detected in only 11 of these flocks.AprB2was detected as a co-infection withaprV2in the 22% of samples positive foraprB2and was more likely in mild footrot phenotypes than severe.Dichelobacter nodosusserogroups were not associated with footrot phenotype. We conclude thatD. nodosus, evenaprB2strains, do not persist in flocks in the absence of footrot. Our results support the hypothesis thataprB2is associated with mild footrot phenotypes. Finally, we conclude that given the small number of flocks without footrot that were identified, footrot is highly endemic in English sheep flocks.

Recent research demonstrates that transfusing whole blood (WB=red blood cells (RBC)+plasma+platelets) rather than just RBC (which is current National Health Service (NHS) practice) may improve outcomes for major trauma patients. As part of a programme to investigate provision of WB, NHS Blood and Transplant undertook a 2-year feasibility study to supply the Royal London Hospital (RLH) with (group O negative, ‘O neg’) leucodepleted red cell and plasma (LD-RCP) for transfusion of trauma patients with major haemorrhage in prehospital settings.Incidents requiring such prehospital transfusion occur randomly, with very high variation. Availability is critical, but O neg LD-RCP is a scarce resource and has a limited shelf life (14 days) after which it must be disposed of. The consequences of wastage are the opportunity cost of loss of overall treatment capacity across the NHS and reputational damage.The context was this feasibility study, set up to assess deliverability to RLH and subsequent wastage levels. Within this, we conducted a quality improvement project, which aimed to reduce the wastage of LD-RCP to no more than 8% (ie, 1 of the 12 units delivered per week).Over this 2-year period, we reduced wastage from a weekly average of 70%–27%. This was achieved over four improvement cycles. The largest improvement came from moving near-expiry LD-RCP to the emergency department (ED) for use with their trauma patients, with subsequent improvements from embedding use in ED as routine practice, introducing a dedicated LD-RCP delivery schedule (which increased the units ≤2 days old at delivery from 42% to 83%) and aligning this delivery schedule to cover two cycles of peak demand (Fridays and Saturdays).

This year's Congress of the International Society of Thrombosis and Haemostasis (ISTH) was hosted virtually from Philadelphia July 17-21, 2021. The conference, now held annually, highlighted cutting-edge advances in basic, population and clinical sciences of relevance to the Society. Despite being held virtually, the 2021 congress was of the same scope and quality as an annual meeting held in person. An added feature of the program is that talks streamed at the designated times will then be available on-line for asynchronous viewing. The program included 77 State of the Art (SOA) talks, thematically grouped in 28 sessions, given by internationally recognized leaders in the field. The SOA speakers were invited to prepare brief illustrated reviews of their talks that were peer reviewed and are included in this article. The topics, across the main scientific themes of the congress, include Arterial Thromboembolism, Coagulation and Natural Anticoagulants, COVID-19 and Coagulation, Diagnostics and Omics, Fibrinogen, Fibrinolysis and Proteolysis, Hemophilia and Rare Bleeding Disorders, Hemostasis in Cancer, Inflammation and Immunity, Pediatrics, Platelet Disorders, von Willebrand Disease and Thrombotic Angiopathies, Platelets and Megakaryocytes, Vascular Biology, Venous Thromboembolism and Women's Health. These illustrated capsules highlight the major scientific advances with potential to impact clinical practice. Readers are invited to take advantage of the excellent educational resource provided by these illustrated capsules. They are also encouraged to use the image in social media to draw attention to the high quality and impact of the science presented at the congress. ispartof: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS vol:5 issue:5 ispartof: location:United States status: published

Background Fresh frozen plasma (FFP) is the accepted standard treatment for clotting factor replacement in bleeding patients during or immediately after cardiac surgery. In the United Kingdom prothrombin complex concentrate (PCC) is not licensed in this setting, although it is being used in Europe because it has a higher concentration of clotting factor levels, and it can be administered rapidly and in small volume, resulting in less volume overload during cardiac surgery. Methods PROPHESY is a pragmatic, single-centre, open-label, randomised, controlled pilot trial that will assess whether it is feasible to perform a large trial in the future that will compare PCC versus FFP in patients who are bleeding (not on warfarin) and who require blood transfusion. Over a 15-month period, 50 patients will be randomised to PCC versus FFP if they develop active bleeding within 24 h of cardiac surgery and for whom the clinician has decided to administer FFP for treatment of bleeding. Standard laboratory and point-of-care assessments will be performed as per routine practice, and additional research blood samples will be taken at three time points to assess haemostasis. Subjects will be assessed daily up to hospital discharge or 30 days or death (whichever occurs first) and will be seen in follow-up for 90 days after surgery to assess for thromboembolic complications and hospital re-admission since discharge. Quality-of-life assessment will be performed pre-surgery and at 90 days post-surgery. We will also perform qualitative research with clinical experts and patients to explore the understanding of and experience with the interventions, as well as adherence to study procedures and protocol. Discussion There have been no randomised controlled trials that have compared the safety and efficacy of FFP versus PCC in cardiac surgery patients who are bleeding. This pilot study will assess if individual components of a large trial are deliverable to assess the safety and efficacy of the two blood products in the future. Trial registration EudraCT, 2018-003041-41; ClinicalTrials.gov, NCT03715348. Registered on 29 July 2018.

There are no estimates of the heritability of phenotypic udder traits in suckler sheep, which produce meat lambs, and whether these are associated with resilience to mastitis. Mastitis is a common disease which damages the mammary gland and reduces productivity. The aims of this study were to investigate the feasibility of collecting udder phenotypes, their heritability and their association with mastitis in suckler ewes. Udder and teat conformation, teat lesions, intramammary masses (IMM) and litter size were recorded from 10 Texel flocks in Great Britain between 2012 and 2014; 968 records were collected. Pedigree data were obtained from an online pedigree recording system. Univariate quantitative genetic parameters were estimated using animal and sire models. Linear mixed models were used to analyse continuous traits and generalised linear mixed models were used to analyse binary traits. Continuous traits had higher heritabilities than binary with teat placement and teat length heritability (h2) highest at 0.35 (SD 0.04) and 0.42 (SD 0.04), respectively. Udder width, drop and separation heritabilities were lower and varied with udder volume. The heritabilities of IMM and teat lesions (sire model) were 0.18 (SD 0.12) and 0.17 (SD 0.11), respectively. All heritabilities were sufficiently high to be in a selection programme to increase resilience to mastitis in the population of Texel sheep. Further studies are required to investigate genetic relationships between traits and to determine whether udder traits predict IMM, and the potential benefits from including traits in a selection programme to increase resilience to chronic mastitis.\ud \ud

Background\ud The association between international-normalised-ratio (INR) correction and mortality in patients with major bleeding on vitamin-K-antagonists (VKA) is important for evaluating the efficacy of reversal agents for oral anticoagulants.\ud \ud Objectives\ud We evaluate if INR correction (defined as ≤1.3) following intervention in major bleeding on VKA is associated with better survival, and if there is a dose-response relationship between Vitamin K (VK) and INR correction.\ud \ud Methods\ud Data on patients' characteristics, haematological management and 30-day outcomes reported by 32 UK hospitals (October 2013–August 2016) were analysed. Associations between INR correction and: (a) 30-day mortality; (b) VK dose were estimated using multivariable logistic regression, using multiple imputation to handle missing INR values.\ud \ud Results\ud Of 1771 patients, 77%, 73% and 33% received prothrombin-complex-concentrate (PCC), VK (92% intravenous) and red cells and fresh frozen plasma transfusion respectively. Proportionally more intracranial haemorrhage (ICH) cases (87%) than non-ICH cases (69%) received PCC. VK administration did not vary by ICH group, with 10 mg (33%) and 5 mg (28%) doses being the most common. Higher doses of VK (10 mg) were more likely to correct INR than lower doses (5 mg). Post-intervention INR > 1.3 in treated patients was associated with 3.2 (95%CI: 2.1–4.9) times higher odds of death within 30 days, compared with INR ≤ 1.3, with no difference between ICH and non-ICH.\ud \ud Conclusions\ud INR correction after intervention to manage major bleeding on VKA is associated with better survival. Higher VK doses (10 mg) improve INR correction more than lower doses (5 mg) in major bleeding, but further studies are warranted to compare the relative benefits/risks of 5 mg versus 10 mg doses.

Highlights • Multiple model triangulation identifies variables that are likely true positives. • Triangulation increases confidence in which managements to recommend in practice. • Effective management of ewes can lower prevalence of lameness in ewes and lambs., Identification of factors associated with an outcome can be challenging when the number of explanatory variables is large in relation to the number of observations. Multiple model triangulation, where results from several model types are combined, improves the likelihood of identifying true predictor variables. The aim of this study was to use triangulation to identify covariates likely to be truly associated with the prevalence of lameness in sheep flocks in Great Britain. Data were collected using a questionnaire sent to 3200 sheep farmers in Great Britain in 2018. The useable response rate was 14.1 %. The geometric mean prevalence of lameness was 1.4 % (95 % CI 1.2−1.7) for ewes, and 0.6 % (95 % CI 0.5−0.9) for lambs, however, approximately 60 % flocks had >2% prevalence of lameness in ewes. Four model types were investigated, two generalised linear models (negative binomial and quasi-Poisson) built using stepwise selection, and two elastic net models (Poisson and Gaussian distributions) refined with selection stability estimation. Triangulated covariates were those selected in three or all four models – 10 for ewes and 12 for lambs. Higher prevalence of lameness in ewes was associated with 5−100% feet bleeding during routine foot trimming compared with not foot trimming, footbathing the flock to treat severe footrot (SFR) and always using formalin in footbaths, both compared with not footbathing, using FootVax™ for 3 weeks compared with always. Lower prevalence of lameness in ewes was associated with vaccinating with FootVax™ for >5 years compared with not vaccinating, peat soil compared with no peat soil, and having no lame ewes to treat. Higher prevalence of lameness in lambs was associated with 5−100% feet bleeding during routine foot trimming, always foot trimming ewes with SFR, not knowingly selecting replacement ewes from ewes that were never lame compared with always, replacement sheep purchased and homebred compared with only homebred, treating lambs >3 days after recognition of lameness compared with 0-3 days and footbathing the flock to treat interdigital dermatitis compared with not footbathing at all. Lower prevalence of lameness in lambs was associated with peat soil, flocks in Scotland versus England, an altitude of >230−500 m compared with ≤230 m, never using antibiotic injection to treat lambs with SFR compared with always, and having no lame lambs to treat. We conclude triangulation identified reliable management practices for farmers to implement to minimise lameness in sheep.

Dichelobacter nodosus is the essential pathogen in ovine footrot, an important cause of lameness in sheep that reduces productivity and welfare. The aim of this study was to investigate the feasibility of using multiple locus variable number tandem repeat analysis (MLVA) developed to investigate isolates to understand the molecular epidemiology of Dichelobacter nodosus in ovine footrot by investigation of communities of strains. MLVA sensitivity was improved by optimizing PCR conditions to 100% specificity for D. nodosus. The improved MLVA scheme was used to investigate non-cultured DNA purified from swabs (swab DNA) and cultured DNA from isolates (isolate DNA) from 152 foot and 38 gingival swab samples from 10 sheep sampled on four occasions in a longitudinal study. Isolate DNA was obtained from 6/152 (3.9%) feet and 5/6 yielded complete MLVA profiles, three strains were detected. Two of the three isolate strains were also detected in isolate DNA from 2 gingival crevice cultures. Complete MLVA profiles were obtained from swab DNA from 39 (25.7%) feet. There were 22 D. nodosus community types that were comprised of 7 single strain and 15 multi-strain communities. Six community types were detected more than once and three of these were detected on the same four sheep and the same two feet over time. There were a minimum of 17 and a maximum of 25 strain types of D. nodosus in the study. The three isolate strain types were also the most frequently detected strain types in swab DNA. We conclude that the MLVA from swab DNA detects the same strains as culture, is much more sensitive and can be used to describe and differentiate communities and strains on sheep, feet and over time. It is therefore a sensitive molecular tool to study D. nodosus strains directly from DNA without culture.

IntroductionThe incidence of severe postpartum haemorrhage (PPH) that requires blood transfusion is on the increase. Fibrinogen levels have been shown to drop early and significantly during PPH, which is associated with worse outcomes. Early fibrinogen replacement could potentially improve outcomes. No studies have investigated the clinical impact of early cryoprecipitate transfusion in PPH. Prior to performing a full-scale trial, a pilot study is needed to determine feasibility of the intervention and recruitment.MethodsACROBAT is a cluster-randomised pilot study with a qualitative evaluation. Four large London maternity units are randomised to either the intervention or control group. The intervention group will adapt their major obstetric haemorrhage procedures to administer cryoprecipitate early for primary PPH. The control group will retain their standard of care.We include women at >24 weeks gestation who are actively bleeding within 24 hours of delivery and for whom transfusion of red blood cells (RBCs) has been started. We exclude women who decline blood transfusions in advance or have inherited Factor XIII or fibrinogen deficiency. Due to the emergency nature of the intervention, informed consent for administering the intervention is waived.The primary objective is to assess the feasibility of administering cryoprecipitate within 90 min of RBC request, as compared with standard treatment where cryoprecipitate is given later or not at all. Secondary objectives include the feasibility of recruitment and data collection, reasons for and barriers to consent, preliminary maternal clinical outcomes, identification of the optimal infrastructure pathways for study delivery, and acceptability of the intervention and outcomes.Ethics and disseminationThe trial has approvals from the London—Brighton & Sussex Research Ethics Committee (ref. 18/LO/2062), the Confidentiality Advisory Group (ref. 18/CAG/0199) and Health Research Authority (IRAS number 237959). Data analysis and publication of manuscripts will start in Q3 2020.Trial registration numberISRCTN12146519.

Prolonged aPTT in Patients with Covid-19 In this study, 20% of patients with Covid-19 had a prolonged activated partial-thromboplastin time. In 90% of these cases, the cause was lupus anticoagulant...

Twenty-nine farmers with a flock prevalence of lameness >5% were visited in 2013. They participated in a facilitated discussion on treatment of footrot, and evidence-based new “best practice.” One year later, farmers were revisited and management and motivators for change were discussed. Farmers were asked how they would persuade other farmers to adopt “best practice.” Initially, most participants were resigned to having lame sheep. They believed that prototypical “good farmers” (including trusted family) practiced foot trimming, the traditional “best practice” and that the new “best practice” would be expensive and time consuming. Between 2013 and 2014 lameness prevalence reduced from 7.6 to 4.3%. The major behavioral changes were reduction in foot trimming, increased use of antibacterials to treat footrot, and treating sheep within a week of becoming lame. In 2014, participants were re-interviewed. They reported that an increased knowledge of the evidence-base, trust in the facilitator and talking to other trusted farmers who had already adopted the new “best practice” overcame concerns about the prototypical “good farmer” and motivated change. Persistent change occurred because participants observed health benefits for their sheep and that the new “best practice” had saved time and money. Participants stated that other farmers would be convinced to change to the new “best practice” because it saved time and money, ironically, these were among the original barriers to change. This is possibly an example of cognitive dissonance because farmers had become positive about the benefits of saving time and money following a change in their own behaviors.

We use the concepts of trust and knowledge to explore translation of scientific evidence about treatment of ovine footrot to students studying at agricultural colleges. We explore the role of different forms of trust (companion, competence and commitment) in facilitating relationships between students and informants. We also investigate how students acquire knowledge, and how this influences their practices for treating footrot. We find that despite being taught evidence-based practice (antibiotic treatment and no foot trimming) at college, most students would still use traditional farm practice (foot trimming) to treat footrot. Students develop tacit knowledge of traditional practices from farmers whilst working on sheep farms and these farmers have a strong influence on students' practices; students have high levels of companion trust for “known farmers". College lecturers who demonstrate competence gain students' trust, but where this does not occur there is a failure in communication between lecturer and student. Students acquire explicit classroom knowledge of evidence-based practice at college because there is limited practical experiential learning. This explicit knowledge is typically insufficient to change behaviour, unless students trust their lecturer. Our findings indicate that farming experience dominates over classroom experience and so college education alone will not ensure uptake of evidence-based practice.

The outcomes of patients developing major bleeding while on oral anticoagulants remain largely unquantified. The objectives of this study were to: (i) describe the burden of major hemorrhage associated with all available oral anticoagulants in terms of proportion of bleeds which are intracranial hemorrhages, in-hospital mortality and duration of hospitalization following major bleeding; (ii) identify risk factors for mortality; and (iii) compare the characteristics of major hemorrhage between cases treated with warfarin and direct oral anticoagulants for the subgroups of patients with atrial fibrillation or venous thromboembolism. This was a multicenter, 3-year prospective cohort study of patients aged ≥18 years on oral anticoagulants who developed major hemorrhage leading to hospitalization. The patients were followed up for 30 days or until discharge or death, whichever occurred first. In total 2,192 patients (47% female, 81% on warfarin, median age 80 years) were reported between October 2013 and August 2016 from 32 hospitals in the UK. Bleeding sites were intracranial (44%), gastrointestinal (33%), and other (24%). The in-hospital mortality was 21% (95% CI: 19%-23%) overall, and 33% (95% CI: 30%-36%) for patients with intracranial hemorrhage. Intracranial hemorrhage, advanced age, spontaneous bleeding, liver failure and cancer were risk factors for death. Compared to warfarin-treated patients, patients treated with direct oral anticoagulants were older and had lower odds of subdural/epidural, subarachnoid and intracerebral bleeding. The mortality rate due to major bleeding was not different between patients being treated with warfarin or direct oral anticoagulants. Major bleeding while on oral anticoagulant therapy leads to considerable hospital stays and short-term mortality.

It has been demonstrated that low body condition and previous occurrence of lameness increase the risk of future lameness in dairy cows. To date the population attributable fraction (PAF), which provides an estimate of the contribution that a risk factor makes toward the total number of disease events in a population, has not been explored for lameness using longitudinal data with repeated measures. Estimation of PAF helps to identify control measures that could lead to the largest improvements on-farm. The aim of this study was to use longitudinal data to evaluate the proportion of lameness that could be avoided in 2 separate herds (2 populations) through (1) reduced recurrence of previous lameness events, (2) and moving body condition score (BCS) into more optimal ranges. Data were obtained from 2 UK dairy herds: herd A, a 200-cow herd with 8 yr of data from a total of 724 cows where lameness events were based on weekly locomotion scores (LS; 1 to 5 scale), and herd B, a 600-cow herd with data recorded over 44 mo from a total of 1,040 cows where treatment of clinical cases was used to identify lameness events. The PAF for categories of BCS were estimated using a closed equation appropriate for multiple exposure categories. Simulation models were used to explore theoretical scenarios to reflect changes in BCS and recurrence of previous lameness events in each herd. For herd A, 21.5% of the total risk periods (cow-weeks) contained a lameness event (LS 3, 4, or 5), 96% of which were repeat events and 19% were recorded with BCS 16 wk before a risk period. The median PAF estimated for changes in BCS were in the region of 4 to 11%, depending on severity of lameness. Repeated bouts of lameness made a very large contribution to the total number of lameness events. This could either be because certain cows are initially susceptible and remain susceptible, due to the increased risk associated with previous lameness events, or due to interactions with environmental factors. This area requires further research.

Highlights • Investigate the role of D. nodosus and F. necrophorum in the progression of ovine FR. • Markovian model developed using bacterial load and disease severity. • The model generates probabilistic forecasts one week ahead. • All 34 rates between the 12 states of an individual foot are time homogeneous. • Results suggest primary role of D. nodosus in the initiation and progression of footrot. • Results suggest a secondary role of F. necrophorum only in severely diseased feet., Dichelobacter nodosus is a virulent, invasive, anaerobic bacterium that is believed to be the causative agent of ovine footrot, an infectious bacterial disease of sheep that causes lameness. Another anaerobe, Fusobacterium necrophorum, has been intimately linked with the disease occurrence and severity. Here we examine data from a longitudinal study of footrot on one UK farm, including quantitative PCR (qPCR) estimates of bacterial load of D. nodosus and F. necrophorum. The data is at foot level; all feet were monitored for five weeks assessing disease severity (healthy, interdigital dermatitis (ID), or severe footrot (SFR)) and bacterial load (number of bacteria/swab). We investigate the role of D. nodosus and F. necrophorum in the progress of the disease using a continuous-time Markov model with 12 different states characterising the foot. The transition rates between the adjacent states are the (34) model parameters, these are determined using Metropolis Hasting MCMC. Our aim is to determine the predictive relationship between past and future D. nodosus and F. necrophorum load and disease states. We demonstrate a high level of predictive accuracy at the population level for the D. nodosus model, although the dynamics of individual feet is highly stochastic. However, we note that this predictive accuracy at population level is only high in more diseased states for F. necrophorum model. This supports our hypothesis that D. nodosus load and status of the foot work in combination to give rise to severe footrot and lameness, and that D. nodosus load plays the primary role in the initiation and progression of footrot, while F. necrophorum load rather increases disease severity of SFR.

The aim of this study was to investigate the cost-benefit of different strategies to treat and control ovine footrot. In November 2006, 162 sheep farmers in England responded to a survey on prevalence and management of lameness. The costs of lameness per ewe per year (PEPY) were calculated for 116 flocks. Linear regression was used to model the overall cost of lameness PEPY by management method. Associations between farmer satisfaction and time and money spent managing lameness were investigated. The median prevalence of lameness was 5% (inter-quartile range, IQR, 4-10%). The overall cost of lameness PEPY in flocks with ≥10% lameness was UK £6.35 versus £3.90 for flocks with

In 2013, a questionnaire was used to gather data on risks for introduction, and factors associated with prevalence, of contagious ovine digital dermatitis (CODD). There were 1136 (28.4%) usable responses from 4000 randomly selected sheep farmers in England. CODD was present in 58% (662) of flocks, with a reported prevalence of CODD lesions of 2.3%. The geometric mean period prevalence of all lameness was 4.2% and 2.8% in CODD positive and negative flocks respectively. Factors associated with a greater risk of presence of CODD were purchasing replacement ewes, not always checking the feet of sheep before purchase, not isolating purchased sheep, foot bathing returning ewes, foot trimming the flock more than twice in the year all compared with not doing these activities and increasing log10 flock size. Farmers who vaccinated sheep with Footvax™ were less likely to report presence of CODD. Factors associated with increasing prevalence of CODD lesions were not always checking the feet of purchased sheep, flocks that mixed with other flocks and sheep that left the farm for summer grazing and later returned. In addition, flocks where farmers followed the current recommended managements for control of footrot, had a lower prevalence of CODD whilst those who used foot bathing and where feet bled during routine foot trimming had a higher prevalence of CODD. The prevalence of CODD decreased with each log10 increase in flock size. We conclude that CODD is an infectious cause of lameness in sheep of increasing importance in GB. Introduction is linked to poor biosecurity with one likely source of the pathogen being introduction of or mixing with infected sheep. As with footrot, prevalence of CODD was lower in flocks where farmers focused on individual treatment to manage lameness and avoided foot bathing and trimming feet. We conclude that most of the currently recommended biosecurity and treatment approaches to control footrot in GB are also effective for control of CODD.

© 2016 International Society for Microbial Ecology All rights reserved. Pulmonary symptoms in cystic fibrosis (CF) begin in early life with chronic lung infections and concomitant airway inflammation leading to progressive loss of lung function. Gradual pulmonary function decline is interspersed with periods of acute worsening of respiratory symptoms known as CF pulmonary exacerbations (CFPEs). Cumulatively, CFPEs are associated with more rapid disease progression. In this study multiple sputum samples were collected from adult CF patients over the course of CFPEs to better understand how changes in microbiota are associated with CFPE onset and management. Data were divided into five clinical periods: pre-CFPE baseline, CFPE, antibiotic treatment, recovery, and post-CFPE baseline. Samples were treated with propidium monoazide prior to DNA extraction, to remove the impact of bacterial cell death artefacts following antibiotic treatment, and then characterised by 16S rRNA gene-targeted high-throughput sequencing. Partitioning CF microbiota into core and rare groups revealed compositional resistance to CFPE and resilience to antibiotics interventions. Mixed effects modelling of core microbiota members revealed no significant negative impact on the relative abundance of Pseudomonas aeruginosa across the exacerbation cycle. Our findings have implications for current CFPE management strategies, supporting reassessment of existing antimicrobial treatment regimens, as antimicrobial resistance by pathogens and other members of the microbiota may be significant contributing factors.

THE UK Biotechnology and Biological Sciences Research Council (BBSRC) has funded a new Animal Welfare Research Network (AWRN) to bring together animal welfare researchers, those working in related fields and other professionals with an interest in animal welfare, including representatives from industry, charities and government. The core aims of the AWRN are to foster enhanced collaboration within the UK animal welfare research community and other relevant disciplines to: facilitate mentoring and training for early career researchers; seek new ways of supporting welfare researchers at all career stages; encourage interaction between researchers and stakeholders to identify gaps and opportunities for joint-working; and promote the impact of research outcomes. Over £100,000 has been provided by BBSRC to fund the AWRN for three years in the first instance, and it will be managed by a coordinating group of animal welfare researchers led by Professor Michael Mendl from Bristol university. Animal welfare is of high societal importance. In an EU survey, 34 per cent of approximately 29,000 citizens rated the protection of welfare in farmed animals as being of the highest importance. Within the UK this proportion was 38 per cent (EU 2007). Britain has a strong tradition of animal welfare research that dates back to the Brambell Committee's (1965) parliamentary report on the welfare of livestock kept under intensive conditions. This, in turn, was prompted by Ruth Harrison's (1964) book Animal Machines, an investigation into the rise of modern intensive farming methods. Animal welfare research is, therefore, a relatively new discipline. It uses fundamental underpinning science in studies that aim, for example, to create new and more accurate ways to scientifically assess welfare or to increase our understanding of the biological responses of animals to challenges. At the same time, strategic science studies that focus on applying findings and developing ways of implementing change and improving welfare in the real world (eg, on farm) are also an important part of the discipline. Animal welfare researchers work with a range of species including farm, laboratory, companion, zoo and even wild animals. An important objective of the AWRN is to promote greater interaction within the animal welfare research community via meetings, workshops and exchange of researchers. This will increase cohesion, awareness of the broad scope of work that is being carried out, and amalgamation of complementary skills in basic and applied research. A related objective is to create opportunities for research students and early career researchers to meet peers and colleagues, establish their own cross-institute activities and receive training from research groups with different expertise, including research areas currently outside the welfare envelope.

Understanding the coagulopathy of major-obstetric-haemorrhage (MOH) that leads to massive-transfusion (MT) is fundamental to improving outcomes. This study reports on the haematological features and transfusion management of women experiencing MT [defined as transfusion of ≥8 units of red blood cells (RBC) within 24 h of delivery]. One hundred and eighty-one cases [median (interquartile range; IQR) age 33 years (29–36)] were identified from all UK hospitals, using the UK Obstetric Surveillance System between July 2012 and June 2013. The median (IQR) estimated blood loss was 6 l (4.5–8). At presentation, the median platelet count was lowest for placenta accreta, compared with other causes, while the median prothrombin time and fibrinogen were

The aims of this study were to update the prevalence of lameness in sheep in England and identify novel risk factors. A total of 1260 sheep farmers responded to a postal survey. The survey captured detailed information on the period prevalence of lameness from May 2012–April 2013 and the prevalence and farmer naming of lesions attributable to interdigital dermatitis (ID), severe footrot (SFR), contagious ovine digital dermatitis (CODD) and shelly hoof (SH), management and treatment of lameness, and farm and flock details.\ud \ud The global mean period prevalence of lameness fell between 2004 and 2013 from 10.6% to 4.9% and the geometric mean period prevalence of lameness fell from 5.4% (95% CL: 4.7%–6.0%) to 3.5% (95% CI: 3.3%–3.7%). In 2013, more farmers were using vaccination and antibiotic treatment for ID and SFR and fewer farmers were using foot trimming as a routine or therapeutic treatment than in 2004.\ud \ud Two over-dispersed Poisson regression models were developed with the outcome the period prevalence of lameness, one investigated associations with farmer estimates of prevalence of the four foot lesions and one investigated associations with management practices to control and treat lameness and footrot. A prevalence of ID > 10%, SFR > 2.5% and CODD > 2.5% were associated with a higher prevalence of lameness compared with those lesions being absent, however, the prevalence of SH was not associated with a change in risk of lameness.\ud \ud A key novel management risk associated with higher prevalence of lameness was the rate of feet bleeding/100 ewes trimmed/year. In addition, vaccination of ewes once per year and selecting breeding replacements from never-lame ewes were associated with a decreased risk of lameness. Other factors associated with a lower risk of lameness for the first time in a random sample of farmers and a full risk model were: recognising lameness in sheep at locomotion score 1 compared with higher scores, treatment of the first lame sheep in a group compared with waiting until >5 were lame, treatment of lame sheep within 3 days, ease of catching lame sheep and quarantine for > 21 days. A previously known factor associated with a lower risk of lameness was footbathing to prevent ID. We conclude that the prevalence of lameness in sheep in England has fallen and that this might be in part because of increased uptake of managements recently reported as beneficial to control lameness. Routine foot trimming should be avoided.

A cross-sectional survey of 68 integrated Irish pig farms was conducted to determine the prevalence and risk factors for foot and limb lesions in 2948 piglets from 272 litters. One litter was selected per age category; 3–7 days, 8–14 days, 15–21 days and 22–28 days per farm. All piglets were examined for sole bruising, sole erosion, coronary band injuries, limb abrasions, alopecia, swollen limbs and swollen feet and scored from 0 to 3 based on relative size. Environmental parameters were recorded for each litter examined. A questionnaire was completed on management, health and performance factors for each farm. The overall prevalence of each lesion was calculated and multilevel mixed effect logistic regression models were used to elucidate risk factors. The prevalence (farm range) of lesions were: sole bruising = 61.5% (7–100%), sole erosion = 34.1% (0–100%), coronary band injuries = 11.3% (0–46%), limb abrasions = 55.7% (11–98%), alopecia = 24.8% (0–83%), swollen limbs = 2.4% (0–11%) and swollen feet = 4.4% (0–14%). Age was negatively associated with sole bruising (OR 0.42; CI 0.37, 0.50) and coronary band injury (OR 0.69; CI 0.60, 0.81) and positively associated with limb abrasions (OR 1.54; CI 1.12, 2.14). There was a reduced risk of sole bruising in piglets in pens with plastic slats with oval voids in the piglet area of the pen with a plastic solid area for piglets and metal slats under the crate (OR 0.32; CI 0.15, 0.70) compared with plastic stats throughout and a plastic solid area for piglets. There was an increased risk of sole erosion (OR 1.81; CI 1.07, 3.09) and foot and limb swellings (OR 1.90; CI 1.01, 3.57) in pigs in pens with metal slats only and a solid plastic area for piglets compared with plastic stats throughout and a solid plastic area for piglets. There was an increased risk of coronary band injury in pens with metal slats throughout and a metal solid area for piglets (OR 4.25; CI 1.96, 3.57) compared with plastic stats throughout and a plastic solid area for piglets. We conclude no single floor type was ideal for piglet foot and limb health with all floors influencing different lesions in different ways, however, the positive association between sole erosions, coronary band injury and foot and limb swellings and metal slats suggest that this floor type was most detrimental and most likely to be associated with joint infections that lead to severe health and welfare concerns.

Highlights • Development of a portable MLVA technique to characterise Dichelobacter nodosus. • Seventy-seven isolates from three continents typed. • Isolates from countries with a long and short history of footrot. • Allele distribution between countries matches historical accounts of sheep movement. • D. nodosus has evolved via recombinational exchanges and clonal diversification., Dichelobacter nodosus is a Gram-negative, anaerobic bacterium and the causal agent of footrot in sheep. Multiple locus variable number tandem repeat (VNTR) analysis (MLVA) is a portable technique that involves the identification and enumeration of polymorphic tandem repeats across the genome. The aims of this study were to develop an MLVA scheme for D. nodosus suitable for use as a molecular typing tool, and to apply it to a global collection of isolates. Seventy-seven isolates selected from regions with a long history of footrot (GB, Australia) and regions where footrot has recently been reported (India, Scandinavia), were characterised. From an initial 61 potential VNTR regions, four loci were identified as usable and in combination had the attributes required of a typing method for use in bacterial epidemiology: high discriminatory power (D > 0.95), typeability and reproducibility. Results from the analysis indicate that D. nodosus appears to have evolved via recombinational exchanges and clonal diversification. This has resulted in some clonal complexes that contain isolates from multiple countries and continents; and others that contain isolates from a single geographic location (country or region). The distribution of alleles between countries matches historical accounts of sheep movements, suggesting that the MLVA technique is sufficiently specific and sensitive for an epidemiological investigation of the global distribution of D. nodosus.

Previous work has hypothesised that cows in low body condition become lame. We tested this in a prospective longitudinal study. Body condition score (BCS), causes of lameness and milk yield were collected from a 600-cow herd over 44-months. Mixed effect binomial models and a continuous outcome model were used to investigate the associations between lameness, BCS and milk yield. In total, 14,320 risk periods were obtained from 1137 cows. There were 1510 lameness treatments: the most common causes of lameness were sole ulcer (SU) (39%), sole haemorrhage (SH) (13%), digital dermatitis (DD) (10%) and white line disease (WLD) (8%). These varied by year and year quarter. Body condition was scored at 60-day intervals. BCS ranged from 1 to 5 with a mean of 2.5, scores were higher in very early lactation but varied widely throughout lactation; approximately 45% of scores were 2–4 months for all causes of lameness and also specifically for SU/WLD lameness. BCS < 2.5 was associated with an increased risk of treatment for SH in the following 0–2 months but not >2–4 months. There was no such association with DD. All lameness, SU/WLD, SH and DD were significantly more likely to occur in cows that had been lame previously, but the effect of BCS was present even when all repeat cases of lameness were excluded from the analysis. Milk yield was significantly higher and fell in the month before treatment in cows lame with SU/WLD but it was not significantly higher for cows that were treated for DD compared with non-lame cows. These findings support the hypothesis that low BCS contributes to the development of horn related claw lameness but not infectious claw diseases in dairy cows. One link between low BCS and lameness is a thin digital cushion which has been proposed as a trigger for claw horn disease. Cows with BCS 2 produced more milk than cows with BCS 2.5, however, this was only approximately 100 kg difference in yield over a 305-day lactation. Given the increased risk of lameness in cows with BCS 2, the direct costs of lameness and the small variability in milk yield by BCS, preventing cows from falling to BCS < 2.5 would improve cow welfare and be economically beneficial.

Genetic heterozygosity in wild, unmanaged animal populations is often associated with protection against infectious disease. However, little is known about the relationship between heterozygosity and disease susceptibility in domesticated livestock, where disease resistance has the potential to improve animal welfare and productivity. We have investigated whether susceptibility to footrot, an important cause of poor welfare and reduced productivity in sheep, is associated with heterozygosity at 14 candidate microsatellite loci. Heterozygosity at locus BMC5221 was associated with resistance to footrot (P = 0.0034). This locus was selected based on a gene ontology classification of 'response to Gram-negative bacteria'. Sheep homozygous at BMC5221 were at increased risk of virulent footrot (OR = 4.8, 95% CI = 1.5-15.3), with a dose response relationship between homozygosity and disease severity. A highly significant homozygote deficit was observed in sheep without virulent footrot (observed = 4, expected = 21, chi(2) = 13.76, P = 0.0002) but not in sheep that had clinical disease, suggesting homozygotes were disproportionately likely to contract virulent footrot. Our results indicate that genetic heterozygosity might be important for healthy immune function in domesticated livestock. The use of gene ontology codes might prove a useful strategy to target selection of candidate markers in future studies. (C) 2011 Elsevier B.V. All rights reserved.

SUMMARYDetermining the rate of hoof horn growth in sheep is important for understanding the physiology and pathology of the foot and the impact of the environment and the treatment of diseased feet on foot health. It could lead to improved understanding of the interaction between hoof horn and pasture/barn floor characteristics and in methods for prevention and treatment of ovine foot diseases. In the current study, the hoof horn was measured using a previously tested protocol on all eight digits of 21 healthy yearling mule ewes on a farm in North Wales on four occasions over a period of 53 days. The mean hoof horn growth rate was 0·11 mm (s.e.m. 0·02) per day; the residual error variance was 0·024 and the R2 was 0·245. There were no significant differences between hoof horn growth rates in front and hind feet or between medial and lateral claws or over time.

Digital dermatitis (DD) is a contagious disease of cattle affecting the skin of the claw. The disease presents with a range of severities and can be associated with lameness. Information about the disease dynamics of DD is scarce. Parity and lactation stage have been identified as risk factors for DD and studies have also indicated that not all cows are equal regarding their risk of recurrent disease and prospects for cure from DD. The aim of this study was to investigate host heterogeneity to DD and to identify disease patterns of DD and factors associated with the development and resolution of lesions. In three commercial dairy herds, 742 lactating cows were observed for DD lesions weekly for 11 or 12 weeks. The effects of parity, lactation stage and duration of preceding episode on the hazard of transitions between healthy and lesion states were analysed using a multilevel multistate discrete-time model. One or more DD lesions were observed in 460 cows and lesions were observed in 2426 out of 10,585 observations. In total, 1755 uncensored episodes with DD lesions were observed. Early lactation was associated with a reduced risk of developing lesions compared with mid and late lactation. Lesions that developed in late lactation had a greater likelihood of resolution compared with lesions that developed during early lactation. There was a reduced risk of lesions developing in parity 3 compared with parity 1 cows, but an increased risk of lesions developing in parity 2 compared with parity 1 cows. In the present study, the mean duration of uncensored DD episodes was 1.7 weeks indicating that the duration of the majority of DD lesions might be shorter than the 42 days reported previously. The transitions between disease states suggest that DD is a dynamic disease, and that the early stage lesions are more transient than expected from previous studies. We conclude that studies with shorter observation intervals than one week are needed to fully understand and describe the individual and group dynamics of DD.

Animal health (AH) defines the outcome of their inspections of livestock holdings as full compliance with the legislation and welfare code (A), compliance with the legislation but not the code (B), non-compliance with legislation but no pain, distress or suffering obvious in the animals (C) or evidence of unnecessary pain or unnecessary distress (D). The aim of the present study was to investigate whether membership of farm assurance or organic certification schemes was associated with compliance with animal welfare legislation as inspected by AH. Participating schemes provided details of their members, past and present, and these records were matched against inspection data from AH. Multivariable multilevel logistic binomial models were built to investigate the association between compliance with legislation and membership of a farm assurance/organic scheme. The percentage of inspections coded A, B, C or D was 37.1, 35.6, 20.2 and 7.1 per cent, respectively. Once adjusted for year, country, enterprise, herd size and reason for inspection, there was a pattern of significantly reduced risk of codes C and D compared with A and B, in certified enterprises compared with the enterprises that were not known to be certified in all species.

Background A scoring scale with five ordinal categories is used for visual diagnosis of footrot in sheep and to study its epidemiology and control. More recently a 4 point ordinal scale has been used by researchers to score foot integrity (wall and sole horn damage) in sheep. There is no information on observer agreement using either of these scales. Observer agreement for ordinal scores is usually estimated by single measure values such as weighted kappa or Kendall’s coefficient of concordance which provide no information where the disagreement lies. Modeling techniques such as latent class models provide information on both observer bias and whether observers have different thresholds at which they change the score given. In this paper we use weighted kappa and located latent class modeling to explore observer agreement when scoring footrot lesions (using photographs and videos) and foot integrity (using post mortem specimens) in sheep. We used 3 observers and 80 photographs and videos and 80 feet respectively. Results Both footrot and foot integrity scoring scales were more consistent within observers than between. The weighted kappa values between observers for both footrot and integrity scoring scales ranged from moderate to substantial. There was disagreement between observers with both observer bias and different thresholds between score values. The between observer thresholds were different for scores 1 and 2 for footrot (using photographs and videos) and for all scores for integrity (both walls and soles). The within observer agreement was higher with weighted kappa values ranging from substantial to almost perfect. Within observer thresholds were also more consistent than between observer thresholds. Scoring using photographs was less variable than scoring using video clips or feet. Conclusions Latent class modeling is a useful method for exploring components of disagreement within and between observers and this information could be used when developing a scoring system to improve reliability.

The effect of Salmonella on milk production is not well established in cattle. The objective of this study was to investigate whether introduction of Salmonella into dairy cattle herds was associated with reduced milk yield and determine the duration of any such effect. Longitudinal data from 2005 through 2009 were used, with data from 12 mo before until 18 mo after the estimated date of infection. Twenty-eight case herds were selected based on an increase in the level of Salmonella-specific antibodies in bulk-tank milk from10 corrected optical density percentage (ODC%) to ≥70 ODC% between 2 consecutive three-monthly measurements in the Danish Salmonella surveillance program. All selected case herds were conventional Danish Holstein herds. Control herds (n=40) were selected randomly from Danish Holstein herds with Salmonella antibody levels consistently10 ODC%. A date of herd infection was randomly allocated to the control herds. Hierarchical mixed effect models with the outcome test-day yield of energy-corrected milk (ECM)/cow were used to investigate daily milk yield before and after the estimated herd infection date for cows in parities 1, 2, and 3+. Control herds were used to evaluate whether the effects in the case herds could be reproduced in herds without Salmonella infection. Herd size, days in milk, somatic cell count, season, and year were included in the models. Yield in first-parity cows was reduced by a mean of 1.4 kg (95% confidence interval: 0.5 to 2.3) of ECM/cow per day from 7 to 15 mo after the estimated herd infection date, compared with that of first-parity cows in the same herds in the 12 mo before the estimated herd infection date. Yield for parity 3+ cows was reduced by a mean of 3.0 kg (95% confidence interval: 1.3 to 4.8) of ECM/cow per day from 7 to 15 mo after herd infection compared with that of parity 3+ cows in the 12 mo before the estimated herd infection. We observed minor differences in yield in second-parity cows before and after herd infection and observed no difference between cows in control herds before and after the simulated infection date. Milk yield decreased significantly in affected herds and the reduction was detectable several months after the increase in bulk tank milk Salmonella antibodies. It took more than 1 yr for milk yield to return to preinfection levels.

The objective of this study was to investigate the recovery of bacteria from ewe milk after freezing for 4 or 8 weeks with and without the addition of glycerol as a cryopreservant. A total of 50 udder-half milk samples with a known range of bacterial species were selected, stored and analyzed in 5 treatment-groups: time zero, frozen for 4 weeks with, and without, glycerol; and frozen for 8 weeks with, and without, glycerol. There was a lower recovery of all bacterial species studied after freezing. Samples containing fewer than 100 cfu/mL came from ewes with a lower somatic cell count and were more likely to be bacteriologically negative after freezing than those above this threshold. The addition of glycerol increased recovery of Gram-negative bacteria after freezing, although this requires further study to draw strong conclusions. The effects on Gram-positive species were inconsistent. We conclude that whilst the addition of glycerol had a small beneficial impact on the sensitivity of detection of bacteria from frozen sheep milk, sensitivity was highest in cultures from fresh milk.

Previous studies have indicated that lame cows have a reduced milk yield both before and after they are treated. One explanation for the reduction in yield before treatment is that there is a delay to treatment, that is, cows have impaired mobility for some time before they are treated. The aim of this study was to test this hypothesis by investigating temporal associations between change in milk yield and change in mobility score. Mobility score (MS, on a scale 0 to 3), milk yield, treatments for lameness and cow activity were recorded on 312 cows in a dairy herd in Somerset, UK for 1 yr. The MS was scored every 2 wk and compared with the daily yield and activity (steps/h) averaged over the previous 16 d. Approximately 44 % of MS changed within 14 d, usually by 1 score. Overall, milk yields of cows with MS 1 were higher than those of cows with other scores. Cows with MS 2 and 3 produced 0.7 (0.35 - 0.97) kg and 1.6 (0.98 – 2.23) kg less milk / d, respectively, compared with cows with MS 1. In addition, cows with MS 1 were slightly but significantly more active than cows with MS 0, 2 or 3. Cows with MS 2 and 3 were 0.0.02 (0.01 – 0.03) and 0.03 (0.01 – 0.05) mean log steps less active than cows with MS 1. \ud There was a reduction in yield from 6 - 8 wk before becoming MS 2 0.5 (0.12 – 0.47) or 3 0.9 (0.16 – 1.65) to 4 wk after recovering from MS 2 0.42 (0.09 – 0.75) and non- significantly, score 3. The activity of cows was significantly less but quantitatively small (mean log steps 0.01) with increasing MS; the associations between activity and parity (mean 0.03 – 0.11) and month of lactation (mean 0.03 – 0.36) were quantitatively larger. Results from a multistate model indicated that once cows were lame they remained lame or become lame again despite treatment. We conclude that cows started to reduce milk production before their mobility is visibly impaired. One explanation for this is that MS is not 100% sensitive. An alternative hypothesis, using evidence from other studies, is that reduction in milk yield and development of lameness are on a common causal pathway most likely linked to loss in body condition and reduced digital cushion thickness as a result of the demands from producing high milk yields.

Cattle are infected by a community of endemic pathogens with different epidemiological properties that invoke different managerial and governmental responses. We present characteristics of pathogens that influence their ability to persist in the UK, and describe a qualitative framework of factors that influence the political response to a livestock disease. We develop simple transmission models for three pathogens (bovine viral diarrhoea virus, bovine herpesvirus and Mycobacterium avium spp. paratuberculosis ) using observed cattle movements, and compare the outcomes to an extensive dataset. The results demonstrate that the epidemiology of the three pathogens is determined by different aspects of within- and between-farm processes, which has economic, legal and political implications for control. We consider how these pathogens, and Mycobacterium bovis (the agent of bovine tuberculosis), may be classified by the process by which they persist and by their political profile. We further consider the dynamic interaction of these classifications with pathogen prevalence and with the action taken by the government.

Associations between specific host genes and susceptibility to Mycobacterial infections such as tuberculosis have been reported in several species. Bovine tuberculosis (bTB) impacts greatly the UK cattle industry, yet genetic predispositions have yet to be identified. We therefore used a candidate gene approach to study 384 cattle of which 160 had reacted positively to an antigenic skin test (‘reactors’). Our approach was unusual in that it used microsatellite markers, embraced high breed diversity and focused particularly on detecting genes showing heterozygote advantage, a mode of action often overlooked in SNP-based studies. A panel of neutral markers was used to control for population substructure and using a general linear model-based approach we were also able to control for age. We found that substructure was surprisingly weak and identified two genomic regions that were strongly associated with reactor status, identified by markers INRA111 and BMS2753. In general the strength of association detected tended to vary depending on whether age was included in the model. At INRA111 a single genotype appears strongly protective with an overall odds ratio of 2.2, the effect being consistent across nine diverse breeds. Our results suggest that breeding strategies could be devised that would appreciably increase genetic resistance of cattle to bTB (strictly, reduce the frequency of incidence of reactors) with implications for the current debate concerning badger-culling.

Our hypothesis was that pigs that develop post-weaning multisystemic wasting syndrome (PMWS) are detectable from an early age with signs of weight loss and other clinical and serological abnormalities. Therefore, the objective of this study was to investigate the temporally varying and fixed events linked with the clinical incidence of PMWS by comparing affected and unaffected pigs in a cohort of 178 male piglets. Piglets were enrolled at birth and examined each week. Samples of blood were collected at regular intervals. The exposures measured were porcine circovirus type 2 (PCV2) antibody titres in all 178 and PCV2 antigen in a subset of 75 piglets. We also observed piglet health and measured their weight, and a post-mortem examination was performed by an external laboratory on all pigs between 6 and 14 weeks of age that died. From the cohort, 14 (8%) pigs died from PMWS and 4% from other causes. A further 37 pigs between 6 and 14 weeks of age died from PMWS (30) and ileitis and other causes (7). PMWS was only apparent in pigs from 1 to 2 weeks before death when they wasted rapidly. There were no other characteristic clinical signs and no obvious gross clinical lesions post-mortem. There was no strong link with PCV2 antibody throughout life but PCV2 antigen level was higher from 4 to 6 weeks of age in pigs that died from PMWS compared with pigs that died from other causes.

Dichelobacter nodosus, a Gram-negative anaerobic bacterium, is the essential causative agent of footrot in sheep. Currently, depending on the clinical presentation in the field, footrot is described as benign or virulent; D. nodosus strains have also been classified as benign or virulent, but this designation is not always consistent with clinical disease. The aim of this study was to determine the diversity of the pgr gene, which encodes a putative proline-glycine repeat protein (Pgr). The pgr gene was present in all 100 isolates of D. nodosus that were examined and, based on sequence analysis had two variants, pgrA and pgrB. In pgrA, there were two coding tandem repeat regions, R1 and R2: different strains had variable numbers of repeats within these regions. The R1 and R2 were absent from pgrB. Both variants were present in strains from Australia, Sweden and the UK, however, only pgrB was detected in isolates from Western Australia. The pgrA gene was detected in D. nodosus from tissue samples from two flocks in the UK with virulent footrot and only pgrB from a flock with no virulent or benign footrot for >10 years. Bioinformatic analysis of the putative PgrA protein indicated that it contained a collagen-like cell surface anchor motif. These results suggest that the pgr gene may be a useful molecular marker for epidemiological studies.\ud \ud

A mathematical model of Corynebacterium pseudotuberculosis infection in sheep flocks was used to evaluate strategies for control and elimination of caseous lymphadenitis (CIA). Control strategies tested were vaccination, serological testing and removal of seropositives, clinical examination and removal of sheep with abscesses, lancing abscesses, and appropriate combinations. Three different infection rates with and without replacement of culled ewes were used to evaluate the control options. Controls were either implemented immediately after infection was detected in a flock or once CIA was at endemic equilibrium, and with different frequencies of examination or testing. Elimination of infection was defined as 99% confidence that no sheep were infected with C. pseudo tuberculosis. The control strategies were evaluated by estimating the reduction in infection or probability of elimination and the number of ewes culled from the flock.\ud \ud Lancing abscesses reduced the prevalence of infection when the initial prevalence was 0.90, but vaccination combined with clinical examination reduced infection rapidly with little impact on lamb productivity. Further research is required to develop a diagnostic test with at least 0.90 specificity and sensitivity under field conditions before any methods of control can be recommended with confidence.

The majority of intramammary infections with Escherichia coli in dairy cows result in transient infections with duration of about 10 days or less, although more persistent infections (2 months or longer) have been identified. We apply a mathematical model to explore the role of an intracellular mammary epithelial cell reservoir in the dynamics of infection. We included biological knowledge of the bovine immune response and known characteristics of the bacterial population in both transient and persistent infections. The results indicate that varying the survival duration of the intracellular reservoir reproduces the data for both transient and persistent infections. Survival in an intracellular reservoir is the most likely mechanism that ensures persistence of E. coli infections in mammary glands. Knowledge of the pathogenesis of persistent infections is essential to develop preventive and treatment programmes for these important infections in dairy cows.

Predicting that an outbreak of tail-biting is going to Occur in a group of pigs would be a useful tool for farmers. In a prospective longitudinal study, 24 groups of c.30 unclocked pigs were followed from birth to slaughter weight. Four groups had to be excluded from the analysis, the remaining groups were classified as having No Outbreak(n = 6), Underlying Outbreak (n = 8)or Severe Outbreak (n = 6) of tail-biting. The hypotheses examined were that Pigs Would be more active, perform more tail-orientated behaviours, or have their tails tucked under their body more in groups that went on to have outbreaks than in those that did not. Direct observations were made at 7, 11, 15 and 19 weeks of age and video recordings were examined for the 4 days prior to an Outbreak. All outbreaks Occurred after the behavioural observation at I I weeks of age. Activity levels were significantly higher in Severe Outbreak groups in the 4 days prior to an Outbreak, with more pigs Standing (p < 0.05) and significantly fewer pigs Sitting (p < 0.05) or Lying Inactive (p < 0.05) than in matched control groups. Comparisons of the Severe, Underlying and No Outbreak groups at 7 and 11 weeks of age, prior to any outbreaks, showed no difference in activity levels. However, at these ages, levels of Tail Interest were higher in No Outbreak groups than in those with Severe Outbreaks (p < 0.05), while the opposite was true for damaging Tail-Biting (p < 0.05). Thus high levels of damaging Tail-Biting may be a good predictor of impending outbreaks, but high levels of Tail Interest are not. Tail position also differed between groups at this age, with fewer Tails Tucked Under in No Outbreak groups (p < 0.01). Some outbreaks were predicted by multiple variables, while others had no clear predictors. In five outbreaks a small runty pig was tail bitten in the absence of a full outbreak. Whenever this happened, a full tail-biting outbreak always went on to take place sometime afterwards. The occurrence of single tail-biting events may thus be reliable indicators of future Outbreaks. In summary, measurement of pig activity has potential for predicting tail biting outbreaks on commercial farms as do levels of tails tucked under and damaging tail contact. Further work is needed to understand the relationship between different forms of tail contact and tail-biting. We highlight the difficulty in predicting all outbreaks from a single measure and conclude that tail-biting outbreaks vary considerably. The presence of an 'indicator pig' might be a useful sign that an outbreak will occur.