As veterinary graduates will take up an ethically challenging role, initiatives fostering reflective thinking and moral development are being increasingly promoted in the veterinary curriculum. The aim of this study was to develop and validate a structured, reflective learning tool to promote ethical awareness in pre-clinical veterinary students. The Animal Welfare Associated Reflective Exercise (AWARE) focused on the ethical content of animal welfare related issues witnessed by pre-clinical students during extra mural study (EMS) placements. The AWARE had five sections: demographic information, animal welfare related event, personal reflection, ethical reflection and round up. Students were invited to identify, and give details of, a relevant incident that had an animal welfare impact. The AWARE guided students to reflect on their emotional reaction to the event, and its ethical basis, with reference to three well established ethical frameworks. A computer based teaching package was created to accompany the AWARE. The AWARE was piloted with 25 first year veterinary undergraduate students. Most students reflected on an experience on a lambing placement and feedback from the pilot study was positive with the majority of students self-reporting that their awareness of animal welfare and ethical issues had improved. Validation of the AWARE was then completed with a full cohort of first year veterinary students using a mixed-methods approach. Qualitative analysis revealed that students exhibited higher levels of reflection in the AWAREs than they did in the unstructured reflections previously completed by students following EMS placements. Ethically relevant text was also significantly increased in the AWAREs than in the unstructured reflections. However, completion of the AWARE did not improve scores on standardised measures of ethical sensitivity or moral reasoning, two components of moral development. Following validation, the AWARE was adapted for use in clinical EMS contexts. Fourth year veterinary students completed either the AWARE using a clinical situation which impacted animal welfare or a modified version of the AWARE, the Reflection on Professional Ethics (ROPE) which focused on a professional ethical dilemma. Three different frameworks were utilised in the ROPE – RCVS’s ten guiding principles, the bioethical principles and virtue ethics. Engagement with the AWARE was similar in clinical and pre-clinical students but fewer clinical students left responses blank and more considered their future actions. Findings from analyses of the ROPEs indicated that veterinary surgeons struggled to meet all of their ethical obligations in difficult situations, that respect for client autonomy was met in the majority of cases, and that virtue ethics was poorly understood by students completing the exercise. Investigations into moral reasoning abilities of vet students at various points in the curriculum were also carried out, using a well-established measure, the Defining Issues Test (DIT). First year students were found to have a wide range of moral reasoning abilities but their mean scores were similar to that expected for students of their age and stage. The moral reasoning scores of clinical stage veterinary students were no higher than those of first year veterinary students. Application of the DIT to qualified veterinary surgeons also revealed a wide range of moral reasoning ability, with practising veterinarians scoring no higher than members of the public and over a quarter relying primarily on a basic form of moral reasoning, normally reserved for pre-adolescent children. These findings raise important questions regarding the impact of veterinary education on moral reasoning and concern for animal welfare and veterinary well-being. Ethical development is an area where both undergraduates and qualified veterinarians could benefit from improved training of ethical skills. Collectively, the findings show that the AWARE reliably elicits ethically relevant content, is viewed positively by students and has several learning benefits including improved ability to recognise and reflect on animal welfare and ethical issues. The AWARE now forms part of the veterinary curriculum at the University of Glasgow and is available to other UK vet schools.

Cellular senescence is an end point of a signal transduction programme leading to irreversible cell cycle arresst accompanied by characteristic alterations to cell morphology, biochemical properties and gene expression profile. This phenotype can be triggered by a variety of stimuli including telomere shortening, DNA damage or activated oncogenes. Senescence is now recognised as a tumour suppressor mechanism mediated by p53 and pRB pathways which act to prevent the proliferatio of cells that are at risk of tumourigenic transformation. RUNX1 is a transcription factor essential for definitive hematopoiesis and is frequently targeted in human leukaemias by chromosomal rearrangements. RUNX1 has been also demonstrated to act as a dominant oncogene in mice and the ectopic expression of RUNX1 in murine embryonic fibroblasts has been shown to cause senescence. The central aim of this study was to investigate the mechanism of senescence induction by RUNX1 and its fusion derived leukaemogenic oncoproteins in primary fibroblasts. My work showed that RUNX1 induces a strong senescence-like response in murine and human primary fibroblasts that requires intact DNA binding, CBFB interaction and C-terminal transcriptional activation/repression domains. However, surprising differences were found between the major RUNX1 fusion oncoprotein derivatives. The N-terminal fusion protein TEL-RUNX1 fails to induce senescence despite retention of a virtually full-lenght RUNX1 moiety, while the senescence-inducing potential is exaggerated in the truncated C-terminal fusion protein RUNX1-ETO (AML1-ETO). The potential to drive senescence is retained by the deletion mutant RUNX1-ETO[]469 which lacks critical corepressor binding sites suggesting that the repression of target genes may be a primary mechanism implicated in RUNX1-ETO induced senescence. Interestingly, CBFB-MYH11 fusion oncoprotein that affects RUNX1 indirectly by targeting CBFB cn also induce senescence when ectopically expressed in human primary cells. The RUNX1 and RUNX1-ETO induced senescent phenotypes differ from archetypal H-Ras [superscript v12] as arrest occurs without a preliminary phase of proliferation and the arrested cells lack prominent foci of DNA strand breaks and chromatin condensation. Notably however, RUNX1 and RUNX1-ETO display differences in their potency and the extent of engagement of p53 and Rb effector pathways. RUNX1-ETO is highly dependent on p53 function and unlike RUNX1 drives senescence in cells lacking intact p16Ink4a. RUNX1-ETO appears to exert its unique effects through potent induction of reactive oxygen species and p38MAPK phosphorylation. These findings illustrate the heterogeneous manifestations of senescence-like growth arrest and elucidate the distinctive biology and oncogenic properies of RUNX1 and its fusion derivatives.

Optimal conditions for preparation and storage of haemolysin were determined using spirochaetes harvested from rabbit serum broth. Haemolysin was purified by fractionation on Whatman DEAE Cellulose and Sephadex G100, purity being assessed by SDS-PAGE. The molecular weight of the haemolysin was estimated by gel filtration to be 19,000 daltons although analysis on SDS-PAGE suggested that the molecular weight of haemolysin dissociated from the RNA-core carrier was much lower. The purified haemolysin was not antigenic. The unpurified haemolysin caused lysis of several species of erythrocyte and was cytotoxic towards a range of cell monolayers, embryo bovine lung fibroblasts being the most sensitive. The cytotoxic activity of the haemolysin was quantified using a 51Chromium release assay. Of the porcine inflammatory cells tested, lymphocytes were the most sensitive. After purification the preparation was haemolytic and leucotoxic but was less cytotoxic. Lower concentrations of haemolysin were produced by an avirulent strain of T. hyody4enteniae than from the virulent strain and it was not toxic for embryo bovine lung fibroblasts. No toxic effect of haemolysin from virulent strains of T. hyody4entetiae was demonstrated either by inoculation of high concentrations into ligated colonic loops in pigs or by intragastric inoculation of CFI mice. The treponemal haemolysin is similar to Streptolysin S in the requirement for a carrier molecule to demonstrate invino haemol. ysis, and with respect to molecular weight, lack of antigenicity, cytotoxic activity and the effect on lymphocytes. When T. hyodyzente4iaew as incubated with excised colonic tissue slices and inoculated into ligated colonic loops in pigs, spirochaetes associated with the mucus rather than attaching to the colonic epithelium. Within 2 hours, spirochaetes were observed in the bottom of crypts suggested that a chemotactic mechanism may be more important than attachment in enabling T. hyodyzenten£ae to establish in the colon. iii

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.