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.

Take-all, caused by the soil-borne ascomycete fungus Gaeumannomyces graminis var. tritici, (Ggt), is a root disease that devastates wheat production worldwide. Current control measures consist of partially effective chemical seed dressings and cultural methods such as crop rotation. There is currently no genetic control of the disease. The first aim of this PhD project was to characterise a range of diploid and hexaploid wheat germplasm that possess a promising level of take-all resistance under field conditions. Both above and below ground phenotyping was carried out and soil moisture probes were used to evaluate upper root function for a range of hexaploid varieties. A diploid Triticum monococcum MDR037 (S) X MDR046 (R) mapping population was screened and revealed a good spread in susceptibility to take-all across two field seasons. The population has subsequently been genotyped and genetic analyses will be carried out to explore the genetic basis of resistance. Phialophora fungal species, belonging to the genus Gaeumannomyces, colonise wheat roots but do not destroy the vascular tissue and have previously been found to suppress take-all disease. In the second approach to control Ggt, winter wheat varieties on the AHDB Recommended List (RL) were screened for their ability to build-up natural populations of Phialophora fungi in the field. Differences were revealed in their potential to build-up Phialophora spp. under a first wheat crop. A Phialophora isolate collection was gathered and draft genomes were sequenced, assembled and annotated for the three Phialophora spp. found in UK soils. Preliminary analysis suggests that considerable polymorphism may exist between homologous genes found in all three species. These findings provide a novel contribution to the potential of these two differing control mechanisms against take-all disease.

With the world population estimated to be nine billion by 2050, the need to exploit plant genetic diversity in order to increase and diversify global food supply, and minimise the over-reliance for food on a few staple crops is of the utmost importance to address food security challenges. Bambara groundnut (Vigna subterranea (L) Verdc.), is an underutilised legume indigenous to Africa, rich in carbohydrates, with reasonable amounts of protein. It is known to be drought tolerant, able to grow on marginal lands where other major crops cannot with minimal rainfall ( < 700 mm) and no chemical inputs. The present study aimed to investigate and evaluate transcriptomic changes in two bambara groundnut genotypes; DipC and TN (Tiga Nicuru), derived from landraces, in response to drought stress using microarray XSpecies and next generation RNA sequencing approaches by utilising data, resources and approaches derived from major crops and model plants. Crop improvement for abiotic stress tolerance and increasing/stabilising yield have been difficult to achieve due to the complex nature of these stresses, and the genotype x environment interaction (GxE). Using bambara groundnut as an exemplar species this study also highlights how a number of recent technologies and approaches used for major crop research, can be translated for use in the research of minor crops for a better understanding of the genetics governing drought traits. To investigate the drought tolerance of bambara groundnut, microarray XSpecies and next generation RNA sequencing (RNA-seq) analysis was completed on leaf tissue from DipC and TN under drought and control (irrigation) conditions at different developmental stages (vegetative, reproductive and pod development). This is the first drought experiment reported in bambara groundnut employing the RNA-seq approach. Both investigation of mild (microarray XSpecies) and relatively severe (RNA-seq) drought stress for the DipC and TN genotypes, adapted to similar environmental conditions, provided initial evidence that the two genotypes used different sets of genes to achieve drought response traits (including; ABA synthesis, hormone signaling, osmotic adjustment, accumulation of antioxidants, lignin synthesis, down-regulation of photosynthesis related genes, carbohydrate metabolism, cell-wall modification and transporters). Hence, both genotypes may have adapted in different ways to enable them to grow in the semi-arid conditions, suggesting that there may be more than a single way to achieve resilience in the face of drought stress. The key enzymes involved in metabolic pathways, such as carbohydrate metabolism, redox homeostasis, lipid metabolism, photosynthesis, generation of precursor metabolites/energy, and cell wall component biogenesis were affected by drought stress in both genotypes. XSpecies microarray experiment identified several differentially expressed genes (DEG) in each genotype and the four potential drought candidate genes (PAL1, Beta-fructofuranosidase, COMT, UBC-2) identified were validated utilising quantitative reverse transcriptase PCR (qRT-PCR). In addition, both drought experiments (mild and severe) also showed that the two genotypes expressed a number of genes of what are classically considered to be ‘drought-response’ genes even under the control condition. These results suggest that high expression of drought-response genes even under control conditions in both genotypes may lead to greater root growth and other avoidance traits which prime the plant for future dry periods, hence preparing for drought conditions. Morphological differences and the rapid reduction in photosynthesis, stomatal conductance and transpiration observed in both genotypes under drought stress provides a platform to link these physiological data with gene expression data. The observed physiological responses (i.e reduction in stomatal conductance and photosynthesis) under drought stress were backed up by high expression of genes related to stomatal closure via ABA signaling and down-regulation of photosynthesis-associated genes. A selection of genes chosen from microarray XSpecies and RNA-seq experiments were further used to identify their approximate chromosomal location in bambara groundnut using a cross-species approach. A total of 4 genes (HOX, AUX_IAA, acid phosphatase and dehydrin) were found to be near or within the confidence intervals of the QTLs underlying two drought traits (stomatal density/leaf area and CID). The initial results suggest that some of the locations of genes identified in XSpecies microarray and RNA-seq experiments could underlie QTL involved in controlling drought traits in bambara groundnut. These data provide the basis for drought trait improvement in bambara groundnut, which will facilitate functional genomics studies. Analysis of this dataset have suggested that both genotypes are primed to respond to drought stress and have adapted in different ways to achieve drought tolerance. This will help in understanding the mechanisms underlying the ability of crops to produce viable yields under drought conditions. Future work should verify whether the identified genes are associated with the trait of interest.

Disease tolerance is defined as the ability to maintain grain yield in the presence of disease and could be a potential defence mechanism to be incorporated into breeding programmes. It is an attractive goal, as disease tolerance has the potential to be a broad-spectrum, durable defence mechanism while exerting little selection pressure on pathogen populations. Relatively little is known about how disease tolerance is conferred, but most of the hypotheses suggest resource capture and resource-use traits such as large green canopy area, increased light extinction coefficient and a high source to sink balance. Disease tolerance in current wheat genotypes is generally associated with low yield potential, and for disease tolerance to be incorporated into commercial breeding it is important to determine whether this link can be disassociated. In this study, an attempt was made to identify physiological traits conferring disease tolerance to Septoria tritici blotch (STB) in winter wheat. Wheat genotypes contrasting in disease tolerance were selected for in-depth phenotyping of selected physiological traits to determine their association with disease tolerance. A number of publications have attempted to link disease tolerance to physiological traits in wheat, based on their yield loss to disease symptom relationship. However, in this study it was proposed that variation in non-symptomatic disease could influence the appearance of disease tolerance which has not previously been investigated. The ratio of in-leaf pathogen biomass to visual disease symptoms was studied in both controlled-environment experiments and in field experiments to determine whether a high in-leaf pathogen biomass was associated with disease tolerance. Two field experiments were conducted during the field seasons 2011/12 and 2013/14 at Teagasc Oak Park, Carlow, Ireland and ADAS Rosemaund, Herefordshire, UK, respectively. A field experiment was also conducted in 2012/13 at Teagasc Oak Park, but due to dry conditions and little disease presence this field experiment was excluded from nearly all experimental analyses. In each experiment, there were two fungicide treatments, non-target disease control and full disease control. In order to increase genetic variability, 38 selected lines from a L14 x Rialto doubled-haploid (DH) mapping population developed by the International Maize and Wheat Improvement Centre (CIMMYT) were screened alongside 10 UK-adapted reference genotypes for contrasting disease tolerance in 2012. Tolerance was quantified as yield loss per unit of green lamina area index (GLAI) loss to disease. L14 is a CIMMYT spring wheat large-ear phenotype advanced line and Rialto is a UK winter wheat which has high radiation-use efficiency and stem soluble carbohydrate. The DH lines displayed an increased range of disease tolerance compared to the UK-adapted reference genotypes. Selected genotypes were subjected to in-depth phenotyping for an extended range of physiological traits in 2014 to identify traits associated with increased disease tolerance. The traits measured included pre- and post- anthesis radiation interception, light extinction coefficient at anthesis, pre- and post anthesis radiation-use efficiency and stem water soluble carbohydrate accumulation at ear emergence + 7 days. In general, there was a wide range of physiological traits displaying weak associations with disease tolerance. The main traits associated with disease tolerance were related to large and/or maintained source capacity in the presence of disease, such as increased GLAI at anthesis and increased post-anthesis light interception. There was also a general association with low grain yield in the absence of disease and decreased harvest index. Increased disease tolerance was associated with high source capacity and low sink capacity, and there was an association between a high source to sink balance, measured as increased Healthy Area Duration (HAD) per grain, and disease tolerance. The impact of genotype variation on the amount of non-symptomatic disease to visual disease expression was investigated in controlled-environment (CE) experiments. In-leaf Zymoseptoria tritici fungal biomass (pathogen load) was quantified by a Real Time qPCR assay targeting the β-tubulin gene (Accession no. AY547264) and compared to visual disease expression. In the first CE experiment, two wheat genotypes were exposed to increasing concentrations of Z. tritici inoculum. There were differences in rates of pathogen development and pathogen presence between inoculum concentrations in both visual disease symptoms and pathogen loads. In the following CE experiment, a wider range of genotypes exposed to a high inoculum level were shown to differ significantly in the relationship between visual disease symptoms and pathogen loads. In order to determine the impact of genotype variation on the visual disease symptoms to pathogen load ratio, flag leaves of genotypes screened for in-field disease tolerance in 2012 and 2014 were analysed. Large variations in the disease symptoms to pathogen load ratio were identified, which has not previously been shown in wheat experiments. An attempt was made to relate the visual symptoms – pathogen load ratio to non-lesion green area loss as a measure of a potential metabolic cost of increased pathogen pressure, but no such relationship was found. An increased pathogen load per unit visual symptoms did not account for larger yield losses than predicted for a given disease level and there was no direct relationship between symptom expression - pathogen load ratios and disease tolerance. The consistency of high/low displays of disease tolerance calculated by different disease measures was investigated using three different ways of measuring disease; HAD, area under disease progress curve (AUDPC) and pathogen DNA quantified by qPCR. In general, the two measures of pathogen presence (AUDPC and pathogen load) tended to quantify disease tolerance similarly, while the HAD-based tolerance contrasted. There were also differences in which traits were associated with disease tolerance for the different methods of calculating tolerance; the calculations based on AUDPC and pathogen DNA tended to associate a decreased source capacity to disease tolerance while the HAD-based tolerance indicated an association with increased source capacity. All methods, however, indicated that a low yield potential was associated with disease tolerance. In conclusion, there was a large range of disease tolerance found in the field experiments compared to previous investigations. The HAD-based disease tolerance seems to be mainly related to a large source capacity and a low sink capacity. However, the genotype ratings of high/low disease tolerance and associated physiological traits seem to vary according to the method of calculating tolerance. There were large differences in the ratio of visual symptoms-pathogen load between genotypes; even though this did not have a direct impact on disease tolerance or yield loss it could potentially be associated with increased metabolic costs.

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.

鞠瑋婕. / "2011年9月". / "2011 nian 9 yue". / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 83-96). / Abstract in Chinese and English. / Ju Weijie. / Chapter 第一章： --- 翻譯研究：一個概念史的方法 --- p.1 / Chapter 第一節、 --- 翻譯的角色：從被動到主動 --- p.1 / Chapter 第二節、 --- 「基本概念」（Grundbegriffe) --- p.3 / Chapter 第三節、 --- 概念史方法應用於翻譯研究 --- p.6 / Chapter 第四節、 --- 本研究介紹 --- p.9 / Chapter 第二章： --- Citizen概念：翻譯史和接受史 --- p.21 / Chapter 第一節、 --- Citizen概念的翻譯史 --- p.21 / Chapter 第二節、 --- 接受史：「國民」與「公民」的接受比較 --- p.39 / Chapter 第三節、 --- 小結 --- p.40 / Chapter 第三章： --- 「國民」譯名的接受 --- p.42 / Chapter 第一節、 --- 「民」作為citizen譯名中心語的成功 --- p.42 / Chapter 第二節、 --- 傳統的「國」概念 --- p.49 / Chapter 第三節、 --- 與日本的相互影響 --- p.59 / Chapter 第四節、 --- 小結 --- p.65 / Chapter 第四章： --- 「公民」譯名的接受 --- p.67 / Chapter 第一節、 --- 傳統的「公」概念 --- p.68 / Chapter 第二節、 --- 小結 --- p.78 / Chapter 第五章： --- 結語 --- p.79 / 引用文獻 --- p.83

Organizational culture is a significant driver of success for firms, especially for those considering expansion to foreign countries. The purpose of this single case study was to explore effective cultural-oriented strategies that senior business leaders use to align the organization's culture with foreign countries' cultures to improve organizational performance in foreign countries. The target population was 8 current and former senior managers of a firm operating in 16 countries. Data were collected via a mix of videoconference and face-to-face interviews and the firm's archival documents, the financial statements, the HR policy, and the internal control policy. The conceptual framework that grounded this study was Perlmutter and Hofstede's theory of cultural dimensions, including the ethnocentric, polycentric, and geocentric model. Data analysis was conducted using Yin's 5-step model, and 5 themes emerged from the data: general characteristics of the chosen organization culture, communication, adjustment to foreign environments, organizational and national cultures, and issues with employees. The implications for positive social change include the potential to enhance a firm's social responsibility and social acceptance in international markets for the benefit of the firm, its employees, and the local societies.

Plus de 20 % des cancers sont dus à une infection virale, bactérienne ou parasitaire. En effet, le parasite Cryptosporidium parvum (C. parvum) qui est capable d’induire, chez des souris immunodéprimées, le développement d'adénocarcinomes invasifs au niveau gastro-intestinal. Cependant, la compréhension de la pathogénicité de Cryptosporidium a été limitée par l'absence d'un système de culture en continu et à long terme. Il est donc indispensable d’améliorer les systèmes de culture in vitro en mimant le plus possible les conditions de l’in vivo. J’ai participé tout d’abord à la réalisation d’une étude épidémiologique sur des patients Libanais atteints ou non de néoplasies/adénocarcinomes digestifs. Le taux d’infection à Cryptosporidium était significativement plus élevé chez les patients atteints de cancers coliques comparativement aux autres groupes de patients. Offrant ainsi de nouveaux arguments en faveur d’un lien entre l’infection à Cryptosporidium et la pathologie cancéreuse chez l’homme. Ensuite, j’ai développé un modèle de culture tridimensionnelle (3D) à partir d’un côlon murin adulte. Ce système a permis le maintien de l’infection pendant 35 jours et il a mis en évidence le développement in vitro de lésions néoplasiques 27 jours post infection. Il s’agit, de la première description d'une induction de néoplasies intraépithéliales de bas grade dans un système de culture 3D, par un parasite. Afin d’automatiser ce système, j’y ai associé un dispositif de microfluidique. Ce dernier a permis le maintien de la culture pendant 8 jours. Il s’agit de la première description d'une culture tissulaire d’intestin sur un dispositif microfluidique viable pour 8 jours. / Almost 20% of cancers are due to a viral, bacterial or parasitic infection. For instance, Cryptosporidium parvum (C. parvum) was found to induce the development of an invasive digestive adenocarcinomas in an experimental model of SCID mice.However, the understanding of the pathogenesis of Cryptosporidium has been limited by the lack of a long-term culture system. It is therefore essential to improve the in vitro culture systems by trying to mimic the in vivo conditions. Firstly, the association between Cryptosporidium infection and cancer development was investigated through an epidemiological study among cohorts of Lebanese patients with or without recent diagnosis of digestive cancer before any treatment. A high rate of Cryptosporidium was detected in biopsies from Lebanese patients with digestive neoplasia/adenocarcinoma. These results showed that Cryptosporidium is associated with human colon cancer being maybe a potential etiological agent of this disease. In the second part, a three dimensional (3D) Cryptosporidium culture model was developed from adult murine colon. This system allowed the reproduction of neoplasic lesions at 27 days post-infection, providing new evidence of the role of the parasite in the induction of carcinogenesis. This is the first description of a low-grade intraepithelial neoplasia induction after parasite infection in a 3D culture. Finally, in order to automatize the culture, a microfluidics device for explant culture was designed. An explant culture was maintained for almost 8 days using this microfluidic device. To our knowledge, this is the first description of a gut tissue culture on a microfluidic device that was viable for 8 days.

acase@tulane.edu / 1 / XOSÉ PEREIRA BOÁN