Periparturient milk fever is a widespread metabolic disease within the dairy industry, with a number of potential impacts on the affected animals’ health and productivity in the subsequent lactation that can have a considerable economic impact on farmers. This thesis aimed to investigate current attitudes of both UK dairy farmers and veterinarians towards milk fever and subclinical hypocalcaemia, as well as investigating the feeding of rumen-protected rice bran during the dry period as a milk fever preventative, due to its reported potential as a calcium binder, within a commercial UK dairy herd. A retrospective study was also carried out in order to investigate associations between recorded milk fever events and other outcomes from farm records obtained from 78 UK dairy herds. The levels of agreement between three different blood sample types (serum, lithium heparin plasma, and lithium heparin whole blood) were also considered with regard to testing for concentrations of calcium, magnesium and phosphorous. Questionnaires were distributed to UK dairy farmers and veterinarians in order to assess current attitudes towards milk fever and its prevention. When choosing a prevention strategy, farmers were most concerned with its efficacy, with its ease of use being their second priority. Veterinarians placed a greater importance on metabolic disease than farmers, and it appears that vets may have an important role in education on the subject of hypocalcaemia. A retrospective study of over 59,000 lactations from 78 UK dairy herds found associations between recorded events of milk fever and an increased risk of dystocia, and an increased risk of a cow exiting the herd during the first 30 days of the lactation. Twin pregnancies were associated with a 30% reduction in the risk of milk fever. Rumen-protected rice bran was trialled against a control feed on a UK dairy herd during the dry period as a potential milk fever preventative. Serum calcium concentrations in the control group were significantly higher pre-calving than in the group that received rumen-protected rice bran. Cows fed rumen-protected rice bran were more likely to experience an elevated NEFA concentration post-calving than the control group. No feed-related differences were found in the subsequent 100 day yields. Limits of agreement were examined to investigate whether bovine serum, plasma and whole blood samples can be interchangeably used for the analysis of calcium, phosphorous and magnesium concentrations. Serum and plasma results appeared to show high levels of agreement for all three of the analytes. Whole blood results were more variable. In conclusion, the findings of this thesis provide an insight into the current attitudes within the UK dairy industry towards hypocalcaemia and its prevention. This thesis has also provided information on the effects and practicalities of feeding rumen-protected rice bran during the dry period in a commercial dairy herd and highlights the need for further research on the subject.

Weaning is a stressful period in the early life of a pig. This stress manifests as immediate weight loss coinciding with increases in intestinal transepithelial resistance. This study aims to identify the transcriptional differences in the colon between suckling and weaned animals over this period using RNA-seq. This approach identified the maximal transcriptional differences at one-day post-weaning with 353 transcripts differentially expressed compared to 78 and three transcripts at four and fourteen days post weaning respectively (q < 0.1, FC > 2). This work identified increased transcription of pro-inflammatory cytokine genes including IL1A (FC=2.63) and IL1B2 (FC = 2.98) in the colon of weaned animals at one-day post weaning, suggesting activation of the immune system. The same time points at one, four and 14 days post weaning was used to assess the transcriptional effect of supplementation with probiotic Saccharomyces cerevisiae boulardii (4.43 Log10 CFU per day from seven days of age) on the colon. A distinct effect of probiotic yeast supplementation on transcription in the colon was identified in both weaned and suckling pigs. One, 77 and one transcripts were affected by the probiotic in weaned animals at the three time points respectively compared to 197, six and two in suckling animals. However, evidence of an anti-inflammatory effect (including increased expression of IL10, FC = 2.88) was identified in weaned animals at four days post-weaning. The clear distinction between differential expression in weaned and suckling animals suggests that the transcriptional effect of Saccharomyces cerevisiae boulardii supplementation may depend on the physiological state of the host. These differences may be due to the interaction of the probiotic with the host immune system as a result of weaning related bowel disruption.

Ovine footrot is an infectious cause of lameness in sheep that has significant economic impact for the UK sheep farming industry. It is also a major concern for animal health and welfare. The causal agent is Dichelobacter nodosus, and Fusobacterium necrophorum is an opportunistic secondary pathogen that increases disease severity. The primary reservoirs for F. necrophorum in sheep were believed to be sheep faeces and the environment, however, no studies had demonstrated the presence of F. necrophorum at either of these sites. Two longitudinal studies (Study A and Study B) were conducted to determine reservoir sites of F. necrophorum in ovine footrot. Study A included 10 sheep sampled on four occasions at two week intervals. Study B included 40 sheep sampled weekly for 20 weeks. Samples collected from sheep and their environment were foot swabs, mouth swabs, faeces, soil and grass. Quantitative PCR was used to detect and quantify F. necrophorum. A multiple locus variable number tandem repeat analysis (MLVA) community typing scheme for F. necrophorum was developed and validated, and used to analyse samples from Study A and Study B. Contrary to prior assumption, the environment was not a significant reservoir of F. necrophorum. F. necrophorum persisted in sheep, primarily on feet with footrot. MLVA indicated that the strains of F. necrophorum found on the feet of sheep were closely related, and they may therefore share characteristics that make them well adapted to feet and footrot. Mouths and faeces were an intermittent reservoir for the strains of F. necrophorum involved in footrot. Mouths and faeces may therefore facilitate persistence of F. necrophorum in the absence of footrot, or facilitate transmission of F. necrophorum between flocks. Mouths were a persistent reservoir for strains of F. necrophorum not involved in footrot.

Ovine footrot (FR) is an economically important disease that causes lameness and affects sheep flocks worldwide. It is characterized by interdigital skin inflammation (interdigital dermatitis [ID]) with, or without, separation of the hoof horn from the underlying tissue (severe footrot [SFR]). The primary causative agent is the gram-negative anaerobic bacterium Dichelobacter nodosus, which is present in diseased feet and thought to be transmitted via contaminated surfaces. Periods of apparent zero prevalence of FR in a flock can be followed by disease occurrence when the climate becomes favourable for pathogen transmission. This suggests that there are sites where D. nodosus persists in the absence of disease. These sites might include healthy feet, the gingival cavity and faeces of sheep and also the environment. The aim of this thesis was to investigate persistence of D. nodosus, by investigating possible sites of survival of D. nodosus over time. Prospective longitudinal studies were used to investigate persistence. Samples were collected from sheep and from the pasture in three studies (Studies 1 and 2: England, study 3: Spain). Quantitative PCR was used to detect and quantify D. nodosus and to investigate associations between D. nodosus presence in feet, in the gingival cavity and on pasture and a range of predictor variables including climate. A multiple locus variable number tandem repeat analysis (MLVA) suitable for use on mixed DNA and environmental samples was optimized and validated to investigate D. nodosus strains within and between sites. A novel approach to characterize individual strains in a sample was designed. D. nodosus was detected in all sample types in all studies but not on all occasions. The feet of sheep were the only site where D. nodosus was detected in loads exceeding 103 cells per swab. In study 1, D. nodosus was detected in amounts exceeding103 cells in samples collected from the pasture in week 1 only, when detection frequency of D. nodosus on feet was high and the weather was wet. A minimum of 14 strains of D. nodosus were detected on the feet of sheep by MLVA. A decline in detection of D. nodosus in the environment coincided with periods of dry weather, however, dry weather did not coincide with a decline in D. nodosus loads on feet or incidence of disease. D. nodosus was more likely to be detected in the gingival cavity when a sheep had FR. It was detected in 25 % of gingival cavity samples and strain types identified in the gingival cavity were the same as the dominant strain types on the feet of sheep. In study 2, disease prevalence and D. nodosus detection frequencies were lower than in study 1. When sheep from the study group were separated from the main flock in week 1 and moved onto pasture that had been unoccupied for 10 days, D. nodosus was transferred to the study group on healthy feet. One dominant strain of D. nodosus persisted throughout an episode of disease and this strain was present on the healthy feet of sheep until up to 5 weeks before the development of lesions in high bacterial loads. There was a reduction in lesion severity and reduced detection of D. nodosus in soil in a period of dry weather. Only 1 sample from the gingival cavity was positive for D. nodosus. Two faecal sample were positive for D. nodosus, indicating for the first time that faecal shedding is possible. In study 3, there were high loads of D. nodosus on healthy feet of a sheep that was classed as susceptible when there had been no cases of FR for at least 2 month. D. nodosus was still present in the flock during the long non-transmission period in the summer. We conclude that D. nodosus is more likely to persist on the feet of sheep, whereas long-term environmental reservoirs of D. nodosus are unlikely. Future research should focus on the feet of sheep and possibly faeces as possible sites of persistence of D. nodosus in the absence of disease.

Horses are extensively exposed to various kinds of medication. However, limited information is available about how these medications are metabolised in this species. Hence, the development of strategies and methods that provide a better understanding of different metabolic pathways for different drugs is of major importance. Although, the horse is considered as a monogastric animal, it is also a hind gut fermenting animal, i.e. most of the feed is degraded in the cecum and colon. Thus, it is hypothesised that this could result in an evolutionary difference in xenobiotic metabolising enzymes between human and horses which may lead to different pharmacokinetics. Therefore, the main aim of this study is to develop an in vitro model as a preclinical testing system of newly developed substances for horses using freshly isolated, cryopreserved equine hepatocytes and liver microsomes. Fresh hepatocytes were isolated and liver microsomes were prepared using livers which were obtained from horses, post slaughter. Part of the freshly isolated hepatocytes were cryopreserved. A comparison metabolic study was carried out to compare the three in vitro systems. The intrinsic clearance (Clint) of three drugs used in equine medicine omeprazole, flunixin and phenylbutazone, was determined via the substrate depletion method. The determined Clint values were extrapolated to in vivo hepatic clearance (ClH) using two in vitro liver models, namely, well stirred and parallel tube models. To perform the extrapolation step, the values of microsomal protein per gram of liver (MPPGL) and the number of hepatocytes per gram of liver in the horse (HPGL), also known as the hepatocellularity, key scaling factors in both the well-stirred and parallel tube models, were obtained for horse. These scaling factors were determined by comparing the CYP P450 content in microsomes and cryopreserved hepatocytes against the CYP P450 content of the liver. Additionally, HPGL was also calculated from the ratio of liver protein concentration to matched hepatocyte suspension protein concentration. Effects of ageing on CYP P450 content, MPPGL and HPGL values were also investigated. Furthermore, chloramphenicol’s potential effect on the in vivo AUC for omeprazole was predicted using microsomes. In the present study, freshly isolated equine hepatocytes were successfully cryopreserved and the viability of recovered cells, after a 30% Percoll gradient, was 77 ± 11% and estimated recovery rate was approximately 27%. MPPGL and HPGL values ranged 41-73 mg/gram of liver (mean= 57 mg/gram of liver, n=39) and 146 - 320 × 106 cells/g of liver (Average = 227× 106 cells/g of liver, n=18) using CYP P450 method; and 156 - 352 × 106 cells/g of liver (Average = 232× 106 cells/g of liver) using protein method. It was found that increase in age had no effect on CYP P450/mg microsomal protein content. This study successfully predicted the in vivo clearance for omeprazole, flunixin and phenylbutazone using, both, freshly isolated and cryopreserved equine hepatocytes. Meanwhile, microsomes significantly underpredicted the in vivo hepatic clearance ClH. However, microsomes were used in present study to perform drug-drug interaction (DDI) in vitro study between omeprazole and chloramphenicol. The average of IC50 and the inhibitor constant Ki of the three horses were 17.7±5.8 μM and 15.4±5 μM, respectively. The work presented in this thesis paves the way to develop in vitro models using equine hepatocytes and liver microsomes, which are reproducible, scalable and compatible with screening platforms. These models can be applied to the improvement of predicted detection times (DT) in horse racing which may aid veterinarians to estimate accurate withdrawal times; hence, the horse welfare will be improved. Moreover, further phase II metabolism, drug induction and comparative studies can be performed.

Enteritis is a very frequent cause of morbidity and mortality in young calves and pigs. They may be infected with 54 known pathogens, particularly in the first months of their life. Simultaneous infection with multiple pathogens occurs frequently and produces a synergistic effect in terms of the severity of clinical disease. In this study two microarray platforms (Agilent and Alere) were used to detect enteric pathogens. A total of 15993 probes were designed from viral, bacterial and parasitic sequences using four different software (UPS, Picky, eArray and GoArray). The probes for the Alere platform were assessed thermodynamically individually for secondary structure formation and hybridised to their complementary sequences in silico. Specificity and sensitivity testing was done with reference strains and porcine and bovine clinical samples and were performed with both platforms. The Alere ArrayTube platform holding 201 probes was used to identify viruses in reference and clinical samples. Among eight reference virus strains, five (PEDV, TGEV, PCV-2, BVDV and PPV) were identified correctly and of these PEDV, TGEV, PCV-2 were confirmed by PCR using designed primers Two viruses, P. rotavirus A and P. bocavirus were negative by array but were confirmed by PCR, rotavirus by designed primers and bocavirus by published primers. In two hybridisations using multiplex PCR products from two separate sets each of 5 mixed pathogens, the ArrayTube detected all viruses for one set and only one virus out of two in the other set. The specificity test using three non-enteric viruses showed high background noise for Bunyamwera virus and Schmallenberg virus, however only one probe cross-hybridised with Equine influenza virus. The sensitivity of this platform showed that it can detect an amount of 2.065 x 109 copy number (2 ng) of PCV-2 and 2.420 x 105 copy number (39 pg) of TGEV present in the sample. The results of hybridised reference viral strains and clinical samples showed that random amplification was more favourable for reference strain detection compared to specific amplification. However, specific amplification performed better for clinical samples. The Agilent microarray platform, comprising 44000 probes of enteric bacteria, viruses and parasites, was subjected to hybridisation of 12 reference strains for specificity testing (four viruses, seven bacteria and one parasite). All hybridised strains were correctly detected except P. rotavirus A which showed only 7 positive probes, however with high signal intensities. A high level of cross-hybridisation was observed with this platform due to the 16S rRNA and 18S rRNA probes as these two genes were amplified in their entirety prior to hybridisation and a high degree of similarity exists between of 16S rRNA and 18S rRNA among different strains of bacteria and parasites respectively. Hybridisation of PCR products to the Agilent platform from two sets of five multiplexed pathogens showed that all ten pathogens were correctly identified. The sensitivity results of this platform showed that it can detect 2.065 x 109 copy number of PCV-2, equivalent to a viral load of 2 ng. On the other hand the detection limit of E. coli F5 was comparable to the real-time PCR technique with a minimum of 2.089 x 108 copy number of E. coli fimbrial gene present in the sample. In bovine clinical samples, the Agilent microarray was able to identify the presence of E. coli F5 in two samples out of four tested. However, in porcine clinical samples, the array successfully detected all pathogens whose presence was confirmed by PCR. Mixed infections in porcine samples were also detected by microarray, where Clostridium difficile with its toxins (toxin A tcdA and binary toxin cdt), P. rotavirus and P. kobuvirus were detected simultaneously in one sample. It also detected the presence of the C. difficile clindamycin resistance gene (ermF) in another sample. In this study microarray technology has been shown to have the potential to detect mixtures of enteric pathogens in bovine and porcine faecal samples. It also has genotyping abilities for exploration of genetic variation. However, the sensitivity and specificity could be improved with more in silico assessments of designed probes. Eventually testing with a higher number of reference strains and clinical samples is necessary.

Evidence-based veterinary medicine (EVM) has the potential to improve welfare of equine patients in primary care practice by ensuring that decision making at the point of care is underpinned by credible research. Patient focussed care requires consideration of a combination of evidence, veterinary judgement, experience and owner associated variables to ensure the best possible outcomes for the animal, whilst maximising the impact of EVM on equine health and welfare. A holistic approach to development and implementation of EVM, that involves horse owners, other equine stakeholders and veterinary surgeons, will ensure that all parties involved in decision making on behalf of equine patients are engaged in evidence-based decisions. The central aim of the thesis was to determine how advances in evidence-based veterinary medicine had the potential to achieve the greatest impact on equine health and welfare. The objectives were to: • Review methods of implementing evidence-based medicine in clinical practice and determine their suitability for veterinary medicine. • Describe the prevalence and outcome of conditions seen for ‘out of hours’ primary assessment in equine practice. • Investigate horse owner perception, understanding and approach to the most common emergency conditions. • Identify paucities in the knowledge and resources available to equine owners and highlight the information required to implement and facilitate evidence-based decision making. • Use an evidence-based approach to develop and disseminate an educational resource for horse owners to improve understanding of an emergency condition and equine welfare associated with that specific disease. The first section of the thesis aimed to identify a common emergency condition with a major welfare impact, which would become a focus for research in subsequent studies. A combination of methods were used in these chapters including a retrospective case study of ‘out of hours’ case records from two practices over a three year period, and a mixed methods online survey of opinions and experiences of equine yard owners. In the retrospective case study, colic (abdominal pain) was the most common condition seen as an ‘out of hours’ emergency at both veterinary practices, accounting for approximately a third of the ‘out of hours’ caseload. The three most common reasons for ‘out of hours’ visits for both practices were colic (35%), wounds (20%) and lameness (11%). The majority of cases seen ‘out of hours’ required a single treatment for resolution of the presenting problem (58%), whilst 26% needed multiple treatments. An online survey consisting of open and closed questions was distributed to UK livery yard owners. The survey investigated participants’ demographics and experiences, their opinion of the most common emergency conditions in the horse, and decision-making in emergency situations. Descriptive analysis of data included frequency ranking and categorisation of free text responses. There were 104 survey participants. The majority had kept horses for more than ten years (97%), and had previous experience of emergency conditions (99%), predominantly of colic (96%) and wounds (92%). Participants considered that the most common emergency conditions were colic (98%), wounds (49%) and fractures (22%), and the most concerning conditions were colic (94%), lameness (36%) and wounds (21%). Factors important in emergency decision making were: degree of pain, likelihood of condition resolving, and severity of disease. The results of these studies provided the impetus for using colic as the focus for the next phases of work within this thesis. The second section of the thesis investigated veterinary practitioners’ and horse owners’ approaches to horses with abdominal pain, with the aim of identifying where knowledge or resources were good or were variable or lacking. The subset of horses with abdominal pain from the ‘out of hours’ retrospective case series were explored to describe how these animals presented to veterinary surgeons, how they were diagnosed, treated and the outcomes. The clinical signs associated with a ‘critical’ outcome of colic were determined using univariate logistic regression. In the retrospective case series, 941 cases presented with signs of abdominal pain; 23.9% (n=225/941) cases were categorised as ‘critical’, and 18% (n=168/941) were euthanased. Fifteen variables from the case presentation significantly correlated with a critical case (p < 0.01) and were therefore incorporated into the multivariate model. The final multivariable model included three variables significantly associated with the likelihood of a case being classified as ‘critical’: increased heart rate (p < 0.01), abnormal mucous membrane colour (p < 0.01) and absence of borborygmi in at least one quadrant (p < 0.01). These were considered to be essential clinical parameters associated with the differentiation of critical cases of colic, and therefore should be included in the veterinary assessment of the condition. To investigate horse owners’ opinions and experiences, a mixed methods survey was distributed to investigate owner knowledge, experience and approaches to colic through open and closed questions and clinical scenarios. The survey also aimed to highlight knowledge and resource gaps that may affect the welfare and outcomes of horses with abdominal pain. The horse owner survey identified that owners had variable and often limited knowledge of colic and were frequently poor at recognising some of the clinical and behavioural manifestations of the condition. This study also identified the need for an all-encompassing educational resource for horse owners underpinned by scientific evidence in an accessible and functional format. Developing evidence-based resources for veterinary practitioners and horse owners was beyond the scope of what could be achieved within this thesis. Educational colic resources for horse owners (‘REACT’) were collaboratively developed and disseminated by Nottingham Equine Colic Project (including the author of the thesis) and The British Horse Society. Current evidence and literature on methods of incorporating evidence into clinical decision making were reviewed within the thesis, specifically accounting for the difficulties faced in veterinary medicine. Future work is needed to develop evidence-based resources on colic for veterinary surgeons to ensure that scientifically underpinned decisions are made at the point of care. The work contained within this thesis highlighted the importance of the owner in the recognition of disease and instigation of veterinary intervention. It is crucial that both equine owners and veterinary surgeons are considered in equal measure when investigating decision making on behalf of a horse. Owners are the gatekeepers of animal care and welfare and therefore there is a requirement that they are included in research and the development of educational material. Veterinary directed studies are commonplace, however the benefits of such research are questionable if the horse owner does not present their animal for veterinary attention. The legacy of this study will likely be the inclusion of horse owners in the development of evidence-based educational campaigns.

The aim of this study was to investigate intervention strategies that have the potential to produce treatments reducing rotavirus-related disease in swine. Rotavirus is the biggest cause of viral gastroenteritis in young swine so is a huge economic burden to farmers. Cell lines deficient for innate anti-viral mechanisms were used to passage rotavirus. This novel vaccine strategy was investigated for its ability to elicit virus that is dependent on the modified cell lines for efficient replication and growth. Rotavirus isolates dependent on modified cell lines represent promising attenuated viral vaccine candidates. Whilst no rotavirus isolates were discovered with this characteristic, analysis of the viral genome after serial passage revealed non-synonymous single nucleotide polymorphisms causing non-conserved mutations at the protein level. Rotavirus isolates with these mutations may cause cell line dependency. A second intervention strategy used computer-assisted analysis (in silico) to reveal short potentially therapeutic peptides based on possible epitopes of rotavirus capsid proteins. Each synthetic peptide was not shown to block the rotavirus-host cell interaction in vitro. Peptides with this property could be used as candidate peptide-based anti-viral blocking drugs. In addition, peptides did not block the neutralising ability of anti-rotavirus antibodies found to be present in pig serum, which would then be used as immunogens to raise neutralising antibodies against rotavirus. However, inactivated rotavirus was found to bind serum antibodies in vitro and therefore appears to hold more promise as a therapeutic strategy than the synthetic peptides. Antibodies present in sow serum were discovered to cross-react with four different lab adapted strains of rotavirus. In contrast, antibodies directed against a common porcine genotype (G5P[7]) were not crossreactive against other strains. This study has initiated research into treatments against rotavirus-related disease in swine but potential vaccine and therapeutic candidates have not yet been revealed.

Patient safety is an active field of research in medicine and the driving force behind healthcare policy and practices to ensure the delivery of safe, quality patient care. However, it is a concept in its infancy in the veterinary profession. Veterinary medical error is under reported, poorly understood and inadequately managed with consequences for patients, owners and clinicians. The aim of this thesis is to explore the causes and types of error in veterinary practice and develop solutions to improve patient safety, and by extension quality of care for veterinary patients. A mixed methodology was employed in the investigation of this aim, with data gathered by focus groups, insurance claim review and questionnaires. The findings of the study suggest that the causes of error in veterinary practice mirror those in other safety critical industries, namely individual errors and system failures. These findings led to the development of a reliable, validated safety culture survey for veterinary practice, to assess and understand the attitudes which drive safety critical behaviours of veterinary staff. This survey was then used as a pre and post training measure to assess the effectiveness of a teamwork training programme, VetTeams, as an intervention to improve safety culture, and by extension patient outcomes in veterinary practice. The outcomes of this study are a framework to inform the understanding and analysis of veterinary error, a measurement tool of veterinary safety culture and a training programme for veterinary teams which addresses the non technical skills identified as critical to preventing mistakes. The findings suggest that changing attitudes to error through an understanding of the causative factors and education in non technical skills, is essential to drive behaviour change in clinicians and enable improved delivery of clinical care.

Lameness was described by the Farm Animal Welfare Council (2009) as one of the foremost health and welfare challenges facing dairy cattle in the UK. Studies suggest UK lameness prevalence has increased over the past 30 years peaking at 36.8% in 2006-2007. The first study in this thesis aimed to investigate current lameness prevalence and related management practices in the UK. Short, structured interviews were conducted with farmers on 43 randomly selected farms in central England during spring 2014 before mobility scoring the lactating herd. Mean herd lameness prevalence was 30.1% (range 7.3%-60.6%). This represents a drop in prevalence since 2007, suggesting a corner may have been turned in control of lameness. A large proportion of farmers reported conducting their own routine trimming and treatment of lame cows. It is therefore important to ensure correct training reaches these farmers if lameness prevalence is to continue to fall. Lameness is often associated with claw horn lesions (sole ulceration and white line disease) however little information is available in the scientific literature on treatment protocols for these lesions. This second study in this thesis aims to begin to address this knowledge gap through a partially blinded, randomised, positively controlled clinical trial (RCT). Animals with an acute case of lameness (two non-lame scores followed by a lame score determined by fortnightly mobility scoring) resulting from claw horn lesions on a single, hind claw were enrolled and allocated at random one of four treatments: 1) Therapeutic trim (TRM) (positive control group), 2) therapeutic trim and foot-block (TB), 3) therapeutic trim and nonsteroidal anti-inflammatory drug (NSAID) (TN) and 4) therapeutic trim, foot-block and NSAID (TBN). One hundred and eighty-three cows were enrolled over a 13-month period. Based on a sound score (score 0) at 35 days post treatment, the number (and proportion) of successful treatments was 11 of 45 (24.4%) TRM, 14 of 39 (35.9%) TB, 12 of 42 (28.6%) TN and 23 of 41 (56.1%) TBN. A significant difference was seen between treatment groups (P=0.01). The results of this study suggest that recovery in animals treated for lameness due to claw horn lesions is maximised by treatment with a TBN. Smaller non-significant improvements were also seen in TB and TN compared with a TRM. The lesions treated in this RCT were largely mild due to the early recognition and treatment protocol used. Studies have demonstrated delays in identification of lame cows on farms and so the lesions seen in this study may not represent those treated by farmers, foot trimmers and vets in the field. The third study in this thesis aimed to investigate the impact of chronicity of lameness on treatment outcomes. The prospective, partially blinded, positively controlled RCT followed a similar protocol to the previous RCT but enrolled cows lame on the same hind leg for at least two of the last three mobility scores. Animals were randomly allocated one of three treatments: 1) therapeutic trim only, 2) therapeutic trim and shoe or 3) therapeutic trim, shoe and NSAID. Three outcomes at 42 (±4) days post treatment were analysed: (i) non-lame (score 0 or 1 at outcome), (ii) improved (lower mobility score at outcome than enrolment) and (iii) apparent leg cure (non-lame on treated leg or lame on contralateral leg at outcome). Over a 13-month period, data was collected for 189 cases of lameness from 176 cows (13 cows received treatment on both hind limbs). No significant difference between treatment groups was seen for any of the outcomes analysed. A very low response rate to treatment of around 15% was seen across all treatment groups. Data for all animals treated in this chronic lameness RCT (CLRCT) was compared to a subset of data from the acute lameness RCT (ALRCT). Analysis showed a significant difference for outcomes (i), (ii) and (iii) in animals treated for acute compared to chronic lesions (P < 0.01). In the ALRCT, 31 of 127 treated animals were lame at outcome (15 lame on the opposite hind leg to enrolment). In the CLRCT 132 of 156 treated animals were lame at outcome (60 lame on the opposite hind leg to enrolment). These findings support the need for both early and effective treatment and suggest that animals should receive appropriate treatment interventions in both hind limbs even if presenting with unilateral lameness. To have an impact on lameness prevalence, it is essential that research findings are disseminated to farmers treating cows on farms. The final study in this thesis aimed to assess the efficacy of different methods of knowledge transfer (KT) in relation to this. A prospective, qualitative and quantitative study was conducted to assess three methods of cattle lameness KT; 1) paper based/online AHDB dairy resources (positive control group), 2) resources plus facilitated discussion group, 3) resources plus on-farm visit by ‘expert’ veterinary surgeon. Prior to the KT session participants completed a semi-structured interview and observed video clips of lame and non-lame cows to select how quickly they would treat each case. Following the KT session the video exercise was repeated and a feedback form completed. Video clip responses were analysed pre-and post-session. Feedback forms were used to assess engagement and likelihood of behavioural change. Fifty-one individuals participated in the study. ‘Expert’ visits had a significant positive effect on the farmers’ awareness of the ‘correct’ maximum treatment interval advised for lame cows compared to resources alone. ‘Expert’ KT sessions were also felt to be significantly more enjoyable and useful. A narrow range of feedback scores suggest this method was also most accessible to a range of learners. The findings of this study suggest the role of the veterinary advisor remains central to the KT process. The key messages derived from the research undertaken in this thesis are the need for early identification and prompt, effective treatment of claw horn lesions in dairy cows. As the body of research grows it is imperative that suitable knowledge transfer strategies are employed to best disseminate these findings to farm-level and maximise their impact on the health and welfare of affected animals.