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The main aim of this study was to estimate the genetic parameters of test day records of British Holstein-Friesian heifers and to determine how best to use these parameters for generic prediction of lactation performance from test day records. The possibility of reducing the frequency of recording to less often than monthly and procedures for the inclusion of part records in genetic evaluations were also investigated. Estimates of genetic parameters of test day and lactation records were obtained from data on 47736 heifers in 7973 herds, progeny of 40 proven and 707 young sires, using multivariate restricted maximum likelihood methods with a sire model. Average values of heritability estimates for test day records of milk, fat and protein yields and fat and protein contents were 0.36, 0.23, 0.29, 0.36 and 0.36, respectively. Generally, heritability estimates for test day records were lowest at the start and highest in mid and late lactation. Heritability estimates for lactation records of these traits wre 0.49, 0.39, 0.43, 0.63 and 0.47, respectively. Average values of genetic correlations between adjacent TD records of these traits were high (0.92 to 0.97), and the correlations decreased as the interval between tests increased. Genetic correlations of lactation milk yield with fat and protein yields and contents were 0.72, 0.94, -0.56 and -0.53, respectively. Estimates of genetic correlation of test day records with corresponding lactation traits were also high (0.76 to 0.99), being highest in mid lactation.

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The examination of impression smears stained with Giemsa's stain showed schizonts and piroplasms were present in all lymphoid and non lymphoid organs in calves infected with <I>T. annulata </I>or <I>T. parva. </I>Analysis of tissue sections immunocytochemically labelled with monoclonal antibodies, reported to recognise schizonts, and counterstained with Harris's Haematoxylin detected schizonts within lesions in all calves and distinguished macroschizonts from microschizonts. The phenotypic analysis of schizont infected cells by immunocytochemical labelling of leucocyte surface markers in tissues indicated <I>T. annulata </I>resided within cells from the myeloid lineage which expressed CD11b, the membrane receptor for iC3b. <I>T. parva </I>resided within cells from the T cell lineage which expressed CD3; this parasite was also shown to inhabit CD11b cells which may have been B cells. The phenotypic analysis of uninfected cells in parasitised lymphoid organs in <I>T. annulata </I>or <I>T. parva </I>infected calves showed uninfected CD11b cells were markedly increased in medulla areas whereas uninfected CD3 cells were markedly decreased in thymic dependent areas as compared with lymphoid organs in normal cattle. The examination of parasitised non lymphoid organs showed an infiltration of larger numbers of uninfected CD11b cells and uninfected CD3<SUP>+</SUP> cells as compared with non lymphoid organs in normal cattle. The assessment of apoptosis in a prescapular lymph node draining the site of inoculation in a calf infected with <I>T. annulata </I>(Hisar) with TdT-mediated-dUTP-biotin nick end labelling showed more apoptotic cells were detected in this lymph node than in a prescapular lymph node in a normal calf. The effect of nitric oxide on uninfected and <I>T. annulata </I>infected bovine macroschizont cell lines cultured <I>in vitro </I>was examined because peripheral blood mononuclear cells harvested from calves infected with <I>T. annulata </I>(Hisar) had produced nitric oxide <I>in vitro, </I>nitric oxide had been reported to induce apoptosis under other circumstances and damaged tissues in calves infected with <I>T. annulata </I>had been infiltrated with macrophages, a potential source of nitric oxide. Incubation of uninfected and parasitised bovine macroschizont cell lines with S-nitroso-N-acetyl-DL-penicillamine, a nitric oxide donor, resulted in an increase of apoptosis in uninfected and parasitised bovine macroschizont cell lines and caused malformation and elimination of schizonts as compared with uninfected and parasitised bovine macroschizont cell lines incubated in medium alone. It was postulated that macrophage derived nitric oxide could be detrimental to the host by inducing tissue damage and beneficial to the host by controlling the parasite.

The majority of lameness in dairy herds occurs during the winter housing period when management is at its most intensive. This study assessed the impact of different dietary and management regimes at the system, calving season, and individual level. Observational studies of behaviour and subjective assessment of lameness disease types were carried out on two herds of high genetic merit Holstein-Friesian cows. The herds were housed under identical conditions but differed in their dietary and management regimes. One herd, unit 1, was kept on a low dietary concentrate input regime and milked twice daily whilst the other herd, unit 2, was fed large amounts of supplementary concentrate over lactation and milked three times daily. Assessment of clinical disease in each unit showed that there were more lameness cases on the high input regime, unit 2; however unit 1 showed a higher incidence of diseases related to claw horn disorders such as laminitis and sole ulcer. There was a higher incidence of infectious foot disease in unit 2, the high input system. The incidence of subclinical lesions in the hooves was influenced by dietary treatment: unit 2 animals had more lesions 3-5 months postcalving, however there was no difference between treatments in the early postcalving period or during peak lesion incidence 2-3 months postcalving. This indicated that the increased use of concentrates may have sustained the level of subclinical lesions in unit 2 for a prolonged period. Unit 1 animals fed for longer than unit 2 animals, and autumn calvers on unit 1 reduced lying time apparently to maximise feeding time.

The thesis contains a collection of 195 refereed publications, dating from 1980 to 2013. The work has been classified into 3 broad themes. The first theme, biomedical research (undertaken between 1980 and 1987) concentrated mainly on the pharmacokinetics of anticancer drugs in vivo and their metabolism in vitro. and resulted in 13 refereed publications. The second theme, animal nutritional disorders (undertaken between 1987 and 2002) resulted in 58 refereed publications. Most of the work concentrated on the affects of vitamin/trace element deficiency (mainly on either cobalt/vitamin B12 or vitamin E/selenium deficiency) on animal producti0f.l (iisEJases and the metabolic perturbations accompanying those diseases. Some of the work focussed on title benefits of increased supplementation of animal diets with vitamin E.

It was hypothesised that the aetiopathology of the condition of headshaking involves abnormalities of either the structure, function or behaviour of the trigeminal nerve. Specifically it is believed that the second division of the trigeminal nerve, represented by the caudal nasal nerve (CNN) is involved. In addition it is hypothesised that such cases are equine analogues of the condition of trigeminal neuralgia (TgN) in humans. To answer these hypotheses the following work was undertaken: 1. Studies of a series of clinical cases of headshakers to assess similarities/dissimilaritie swith TgN. 2. Studies of the pharmacokinetics of carbarnazepine (CBZ) in headshakers. 3. Isolation and purification of equine P2 myelin protein and its use in investigating the serum levels of P2 myelin protein antibody in the normal population, cauda equina neuritis (CEN) and headshakers. Serum antibodies to P2 myelin protein have been identified in demyelinating diseases in humans - Guillain-Barré Syndrome (GBS), CEN and headshakers. 4. Studies of the macroscopic and microscopic anatomy of the trigeminal nerve in normal controls and headshakers. 5. Studies of the immunocytochernistry of the trigeminal ganglia, brainstem and root areas of normal controls and headshakers. 6. Magnetic Resonance Imaging (MRI) studies of the equine head. 7. Studies investigating total counts and sizes of nerve fibres of the trigeminal nerve. 8. Equivalent comparative studies of the physiology of the trigeminal nerve. The results of the clinical study support the hypothesis that headshaking is similar to TgN since both syndromes show evidence of seasonality and unilateral presentation of clinical signs, the presence of a trigger zone and a positive response to CBZ therapy in several cases. In headshakers, the trigger zone appears to be in the nasal cavity and the positive response to CNN anaesthesia supports the hypothesis that this branch of the trigeminal nerve is affected. CBZ therapy is effective in some cases of headshaking but pharmacokinetic studies demonstrate that the non-response in some cases is likely due to under dosing and problems of interference with absorption. Isolation of P2 myelin protein was successful but P2 myelin protein antibodies were not identified in CEN and headshaking cases. This suggests that there is no evidence that the aetiopathogenesis of headshaking involves an immune-mediated mechanism elicited by antibodies to P2 myelin protein. No gross or microscopic abnormalities were identified in the headshakers. Some differences were observed between normal controls and headshakers in total nerve counts and the identification of neuropeptides in the trigeminal system. However the significance of these findings is unknown due to the small numbers of cases involved. No vascular compression was identified at the trigeminal root entry zone (REZ) as reported in TgN cases. MRI techniques are of no use in post mortem specimens of the equine head for examination of the neurovascular relationships of the trigeminal nerve. More research on the use of intravascular contrast in post mortem head specimens is required, though in preference, the use of anglography with MRI in the anaesthetised animal, would likely be much more successful. Initial studies of the neurophysiology of the trigeminal nerve have demonstrated that the technique of evoked CNAPs applied to human TgN cases can be applied successfully to the horse. The equine trigeminal nerve has a very fast conduction velocity, faster than that reported in previous studies of other species. This work fails to conclusively support the hypothesis that headshaking is similar to TgN since no pathology or vascular compression at the REZ was identified. However, the clinical presentation and response to CBZ are similar in both syndromes. Further investigation of trigeminal nerve CNAPs in the horse appears to be the most promising method to investigate any alteration in function in headshaker cases as reported in TgN cases.

The objective of the work presented in this thesis was to develop valid, reliable and feasible indicators for the on-farm assessment of sheep welfare. In the absence of a reference test for animal welfare assessment, the welfare indicators in this thesis were developed within the Farm Animal Welfare Council( FAWC) Five Freedoms framework. A scientific literature review and the consensus opinion of a panel of experts were used to judge the face and consensual validity of a selection of indicators of sheep welfare. Experts identified 193 current on-farm welfare issues for sheep and subsequently suggested a range of animal- (n = 26), resource-( n = 13) and management-based indicators( n = 22) in order to assess the on-farm welfare of adult sheep( > 1 year-old), growing lambs (> 6 weeks -<I year-old) and young lambs (< 6 weeks-old). The diagnostic validity of 49 non-invasive, animal-based indicators was tested during a cross-sectional study in which 8 observers independently assessed the indicators on 4686 sheep and lambs from 50 farms in England and Wales. This study found that many indicators, including measures of lameness, body condition, and cleanliness, were reliable, sensitive and specific between observers of differing occupations and levels of training and experience. The measures were also feasible to apply and capable of detecting between-farm variation in conditions associated with sheep welfare. Studies in the use of qualitative behaviour assessment (QBA) also found good levels of reliability for observer assessments of video-clips of sheep behaviour. The ability of animal-based indicators to detect seasonal variation in sheep welfare conditions was investigated on 5740 adult sheep and growing lambs from 12 sheep farms during a one-year longitudinal study. Animal-based indicators including measures of lameness, body condition and QBA, were found to be capable of detecting seasonal variation, suggesting that the tests were valid under different management conditions and across the different events of the annual sheep production cycle. Overall, a low proportion of the sample population was observed with conditions that affected sheep welfare, which may have been the result of non-random sampling of farms. However, for the purposes of this thesis the ability of the indicators to detect important welfare conditions at a low prevalence provide further evidence of their validity. Resource-based assessments were feasible to perform but assessments were limited to certain periods of the production cycle. As management-based indicators relied on the accuracy of farmer interviews and access to farm records, the use of animal-based measures may be a more appropriate means of assessing some aspects of flock welfare. A final set of valid, reliable and feasible indicators of sheep welfare, comprising 28 animal- and II resource- and management-based measures, was recommended on the basis of field validation results and expert opinion. Key animal-based indicators that were found to be reliable, responsive and robust under extensive and intensive farming systems and suitable for assessing both sheep and lambs were lameness, demeanour and body condition. It is suggested that these indicators should be applied in future on-farm protocols by trained assessors who are calibrated to the StandardO Operating Procedures (SOP's). The interpretation of animal-based indicator assessments was guided by expert opinion in the form of preliminary cut-off points, which defined the level of acceptable and unacceptable flock welfare. As a result, the work presented in this thesis can inform the method of assessment and interpretation of a selection of valid, reliable and feasible on-farm indicators of sheep and lamb welfare.

No description available.

No description available.