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Obesity is recognised as the leading cause of malnutrition in cats and dogs (Legrand-Defretin 1994) and is reported to be one of the most important and frequently seen welfare issues in small animal practice (Yeates and Main 2011). Despite the recognised burden of overweight/obesity on the companion animal population, a review of the published literature identified several gaps. This thesis aimed to address three of the those gaps. Gap A: No published national prevalence estimates for cats, dogs and rabbits in Great Britain were available and no studies had explored whether prevalence varied across Great Britain. Chapter 3 and 4 estimated the national prevalence of overweight/obesity in cats, dogs and rabbits to be 11.5%, 25% and 7.6% respectively. After adjusting for differences in demographics between locations, there was a significantly higher prevalence of canine overweight/obesity in Scotland compared to England and Wales. But no spatial variations were found in the prevalence of feline overweight/obesity within Great Britain. Gap B: There was a lack of consistency in the risk factors found to be associated with overweight/obesity between previous published studies and no assessment of the impact of various risk factors on the prevalence of canine and feline overweight/obesity was apparent in the literature. Non modifiable risk factors identified for dogs in Chapter 3 included being female, neutered status, and age with peak of risk at 5 to 8 years of age. These effects were independent of location. Chapter 4 identified neutered status, being male and middle age (around 7 years) as feline non modifiable risk factors. Neutered status was the only significant risk factor found for rabbit overweight. Chapter 5 and 7 expanded the canine and feline overweight/obesity risk factor analyses to include modifiable risk factors. Risk factors for canine overweight/obesity (Chapter 5) identified were owner income, owner age, frequency of snacks and treats and hours of exercise the dog received each week. For cats (Chapter7), the significant risk factors were frequency of feeding and neutered status. The calculated population attributable risks (Chapter 3 and 4) showed possible differences in the impact of non modifiable risk factors between cats and dogs. For cats, neutered status was the most important factor whereas in dogs age and neutered status were equally important. Gap C: Misperception of body shape has been recognised to play an important role in human obesity management. Previous studies had only described owner misperception of pet body shape as a risk factor for obesity/overweight. The objective of Chapter 6 and, in part, Chapter 7 was to explore the concept of owner misperception of canine and feline body shape. Owners of cats and dogs appeared to “normalise” their animal’s body shape i.e owners of overweight animals were more likely to think their pet was an ideal shape rather than overweight and owners of underweight animals were more likely to think they were an ideal shape rather than underweight. Risk factors identified for misperception in dog owners were gender of owner and age of the dog. Only one risk factor was identified for misperception by cat owners; that is whether the cat was long haired or not. In conclusion, this thesis demonstrates that overweight/obesity in cats, dogs and rabbits is widespread. Despite the limitations of these data, the results show the complexity of risk factors that contribute to overweight/obesity in companion animals and highlight areas for future research.

Parasitic nematode infections worldwide cause a significant impact on human health, as well as economic and welfare losses to the animal and agriculture industries. The principal method of control for parasitic nematode infections is currently limited to repeated treatments with anthelmintic drugs, but widespread resistance to all major classes of these drugs is a growing problem. As a result, there is an urgent need for alternative methods of controlling these infections, and the development of molecular vaccines and novel drugs represent two possible approaches. However, both these approaches require a deeper understanding of gene function in order to identify suitable control targets. This project examines RNA interference (RNAi) in the parasitic nematode Haemonchus contortus to determine if this could be developed as a functional tool and advance the discovery of novel control targets for parasitic nematodes. RNAi has proven less effective in parasitic nematodes than in the free-living model nematode Caenorhabditis elegans and it is unclear why this is so. This project examined the reliability of RNAi in H. contortus, and several genes were successfully silenced using RNAi. Further analysis of RNAi susceptible genes revealed that RNAi silencing appears to be related to the site of expression of the target gene; genes expressed in tissues which are accessible to the environment such as intestine, excretory cell and amphids were silenced by RNAi. Upstream promoter regions of RNAi susceptible genes were examined for the presence of motifs which may regulate spatial gene expression, an approach that could be used to predict gene susceptibility to RNAi. RNAi treated larvae were subsequently used to infect sheep in the first in vivo RNAi study, resulting in a significant impact on worm survival in vivo. In addition, several components of the RNAi pathway in H. contortus were characterised in this project, demonstrating the presence of a functional RNAi pathway that is capable of reliably silencing genes. In conclusion, the findings presented in this project suggest that RNAi may be used in the future to evaluate the function of a novel vaccine or drug target for controlling H. contortus infections in sheep.

Musculoskeletal conditions and exercise-induced pulmonary haemorrhage are commonly diagnosed in Thoroughbred racehorses worldwide, and have serious consequences for racehorse welfare and the racing economy. Despite increasing interest in the study of genetic susceptibility to disease from the veterinary research community as a whole over past decades, the Thoroughbred has been largely ignored as a study group. The availability of software capable of complex genetic analyses using large, unbalanced pedigrees has made the study of genetic susceptibility to disease a realistic prospect for veterinary researchers. This study aimed to complete preliminary analyses of the genetics of a number of important musculoskeletal conditions, and of exercise-induced pulmonary haemorrhage, in two different Thoroughbred populations. Multivariable regression analyses were performed to identify important environmental risk factors for each condition in each population, and heritability analyses were conducted. Genetic correlations between disease conditions were also investigated. Fracture, tendon injury, suspensory ligament injury, osteoarthritis and EIPH/epistaxis were found to be heritable traits in the Hong Kong population. Distal limb fracture, SDFT injury and epistaxis were also found to be heritable in the UK Thoroughbred population. Most heritability estimates were small or moderate in magnitude. Selective breeding strategies that identify those animals with low genetic risk could play a part in future efforts to reduce the incidence of these conditions, in conjunction with favourable environmental manipulations based on research evidence. Due to low heritability, most of the conditions studied here would reduce in incidence slowly if selective breeding were implemented, thus strategic environmental manipulations would be warranted alongside such longer-term efforts to provide effective incidence reductions. A number of conditions were found to be positively genetically correlated, suggesting that risk reduction through breeding could reduce the risk of multiple diseases concurrently. For example, fracture and osteoarthritis were found to be positively genetically correlated (0.85 – 0.89) in the Hong Kong racehorse population. However, using the Hong Kong Thoroughbred population dataset, EIPH/epistaxis and tendon injury were negatively genetically correlated, which suggests that reduction in genetic risk of one of these may lead to increased genetic risk of the other. iii Measures of the durability and performance of racehorses were investigated to assess whether they were heritable traits in the UK and Hong Kong racehorse populations, and to assess their relationship to the disease conditions studied. Selection based on more holistic measures of horse health and longevity such as ‘career length’ could be a more attractive prospect for stakeholders, as this could forego the need to select for many different traits individually. Career length, number of starts over the career, and the level of earnings were all heritable traits in both populations. These holistic traits were found to have variable relationships with the disease conditions studied in each population. These analyses are the first to assess the genetic contribution to risk for many important diseases in the Thoroughbred. They provide a starting point from which further investigations into the applicability of genetic manipulations could yield realistic and achievable tools for racing stakeholders to use to ‘improve’ the breed in future.

Physical inactivity is a major contributor to non-communicable diseases and many adults and children are insufficiently active to maintain good health. The proportion of children who meet the United Kingdom recommendations for physical activity (at least 60 minutes of moderate-vigorous intensity physical activity each day) has been reported to be as low as 3% for boys and 2% for girls. Systematic reviews on interventions to promote physical activity in childhood have shown that although physical activity is modifiable to some degree most interventions have had only modest and short-term impacts on physical activity. Therefore, novel approaches to physical activity promotion in childhood are required. Dog ownership is a significant societal factor that may be used to encourage and sustain health behaviour change at individual and population levels. A number of observational studies have reported that dog ownership and/or dog walking are associated with increased levels of physical activity. However, evidence is lacking as to whether and how interventions with families and their dogs can be used to promote physical activity. Therefore, the major aim of this thesis was to assess the feasibility, acceptability and potential efficacy of a theory-driven, family-based, dog walking intervention for 9–11 year old children and their families. However, prior to this it was essential to develop ActiGraph cut-points for measuring physical activity intensity in dogs. The ability to measure the intensity of dog physical activity accurately was important as it allows for the effectiveness of dog walking interventions to be tested, therefore another aim of this thesis was to calibrate and cross-validate ActiGraph cut points that can be used to describe physical activity in dogs by intensity. Similarly, no studies have been published previously that assess which factors are related to dog physical activity when measured using ActiGraph accelerometry. It was therefore desirable to explore whether body condition score, breed, age, and neutered status are associated with ActiGraph measured dog physical activity. Furthermore, no published studies have described the spontaneous changes in dog physical activity during substantial weight loss; therefore, another aim of this thesis was to explore changes in physical activity in dogs during a 6 month calorie controlled weight loss programme. Using Receiver Operating Curve analyses Chapter 2 showed that the ActiGraph GT3X can accurately measure the amount of time a dog spends sedentary, in light-moderate intensity physical activity and in vigorous intensity physical activity. The sensitivity and specificity of the cut-points developed when using both the integrated axes and vertical axis accelerometry data were high. Agreement between the accelerometer data and direct observation in the cross-validation subset was also ‘very good’ (as measured by Cohen’s Kappa). This indicates that the ActiGraph GT3X accelerometer is accurate when measuring the intensity of physical activity in dogs, facilitating the use of the ActiGraph GT3X to describe the frequency, intensity and duration of dog physical activity in Chapters 3-6 of this thesis. Chapter 3 shows that, in a sample of dogs of varying breed and body condition scores, obese dogs spend significantly less time in ActiGraph measured vigorous intensity physical activity than ideal weight dogs (6 ± 3minutes/day versus 20 ± 14 minutes/day). Chapter 4 focussed on the factors related with physical activity in the two most commonly registered dog breeds in the United Kingdom, Labrador Retrievers and Cocker Spaniels. Five potential correlates (age, sex, breed, neuter status, body condition score) were tested with associations with ActiGraph measured physical activity. Age and breed were associated with total volume of physical activity, light-moderate intensity physical activity and sedentary behaviour in the final models and age was also associated with vigorous intensity physical activity. Unlike Chapter 3 body condition score was not related with any physical activity variables. Chapter 5 explored the changes in physical activity and sedentary time during weight loss in dogs enrolled in a 6 month calorie controlled weight loss programme. Despite an average weight loss of 15% body weight from baseline there was no marked increase in any ActiGraph measured physical activity variable. Chapter 6 describes the results of the Children Parents and Pets Exercising Together (CPET) Study. CPET was the first exploratory randomised controlled trial to develop and evaluate an intervention aimed at dog-based physical activity promotion in children, their parents and pet dogs. The results show that the CPET intervention was both feasible and acceptable to study participants. Eighty-nine percent of families enrolled in CPET were retained at follow up. Ninety-five percent of intervention sessions were delivered and ActiGraph measured physical activity data were collected for 100% of children, 96% of parents and 96% of dogs at baseline, and 100% of children, 96% of parents and 96% of dogs available at follow up. Despite the apparent feasibility and acceptability of CPET there was no significant change in the primary outcome measure (child physical activity) or the majority of the secondary measures. This thesis shows that the ActiGraph GT3X accelerometer is capable of accurately measuring the intensity of dog physical activity. It also shows that obesity may be related to lower levels of objectively measured vigorous intensity physical activity and the physical activity levels in dogs decline with age and vary by breed. However, it appears that physical activity levels do not increase spontaneously as dogs lose substantial amounts of body weight. Using pet dogs as the agent of lifestyle change in physical activity interventions in children and their parents is both feasible and acceptable; however, the lack of any apparent increase in child physical activity suggests that the intervention may need to be modified in a future, more definitive trial. In summary, the findings of this thesis have important implications for the measurement of physical activity intensity in dogs, the understanding of factors associated with dog physical activity and for the development of dog-walking interventions in children and their parents.