This thesis develops the scant existing literature which explores the ethical justifications for living animal donation in the veterinary setting and contributes to the considerable research on social and ethical aspects of human living donation. The work argues that whilst some justifications for human living donation are not-transferable, others may be adapted and applied to the veterinary setting. The unique social context of veterinary donation is analysed, using novel empirical analysis to refine and contextualize the ethical arguments made. The research methods entail an innovative comparative ethical analysis and a qualitative empirical study which are integrated using an empirical bioethics approach. The main justificatory arguments for human living donation are identified as informed consent and donor best interest. These arguments stem from a human’s acknowledged rights to bodily integrity and the human medical professional’s duty not to harm their patients. The reduced capacity of animal donors means that donor consent arguments are not directly transferable to the veterinary setting and an animal owner’s informed consent is shown to have reduced moral authority. Whilst animal donors may lack comparable bodily rights, veterinary living donation practices can conflict with a veterinary surgeon’s professional obligations. A comparable justification for living animal donation is argued to exist only when the procedure is in the donor animal’s best interest. An empirical analysis of canine blood donation to a UK animal blood bank develops understanding of the social context of living animal donation. The analysis indicates that animal owners may not always be motivated by the best interest of donor animals; furthermore, consistent themes such as trust, optimism and human-animal comparisons have implications for the quality of a donor owner’s consent. These ethical and empirical findings are used to construct an ethical framework for living animal donation with detailed provisions for owner consent, donor best interest, donor harm and benefit, recipient benefit, fairness and transparency. The ethical framework is used to argue for the development of regulatory approaches to companion animal blood banking and feline renal transplantation in the UK. The work also has wider implications for veterinary ethics, veterinary policy and the social and ethical understanding of human living donation.

The relationship between antiretroviral treatment of HIV infection, body fat distribution, insulin resistance (HOMA), adipocytokine and apolipoprotein-B (apoB) kinetics was investigated in 12 HIV negative controls and 55 HIV-infected patients including antiretroviral treatment-naïve patients (n=15) and patients taking two nucleoside analogues plus either a protease inhibitor (PI, n=15) or non-nucleoside reverse transcriptase inhibitor (NNRTI, n = 25). The HIV positive treatment groups had mild dyslipidaemia. The apo-B fractional clearance rate (FCR) was reduced in the HIV positive groups. Peripheral fat was lower in treated patients and correlated with duration of therapy. There was a positive correlation between peripheral fat and apo-B clearance rate and a negative correlation with apo-B pool size. Adiponectin was reduced in all HIV positive groups and correlated positively with HDL-cholesterol, apo-B FCR and limb fat and correlated negatively with plasma triglycerides and HOMA. In a linear regression model which included HOMA, adiponectin level but not HOMA was predictive of apo-B FCR and HDL cholesterol. These results suggest that mild dyslipidaemia resulting from antiretroviral therapy is due to a decrease in apo-B FCR which is strongly related to loss of peripheral fat. Adiponectin may have a direct effect on lipoprotein metabolism which may be independent of insulin.

Aim: To evaluate the role and utility of acute kidney injury biomarkers in renal transplantation. Method: Analysis of levels of a panel of biomarkers in deceased organ donors correlated to renal graft outcome; ABO incompatible renal transplant recipients correlated to rejection and HLA incompatible renal transplant correlated to rejection. Results: The panel of biomarkers showed comparable ability to creatinine in predicting the outcome of the renal graft following transplant from deceased donors. Of the panel of biomarkers tested to predict rejection, notably NGAL and IP-10 had good ability to predict those HLAi recipients who subsequently developed rejection. Conclusion: Biomarkers previously identified in the context of AKI may have a role in the assessment of deceased organ donor suitability but more promisingly have an excellent ability to identify those patients at risk of rejection following HLAi transplant and would now benefit from evaluation in a wider population prior to adoption in a clinical trial.

Introduction Squamous cell carcinoma of the auricle has an unusually high rate of lymph node metastases when compared to similar tumours at other sites. The lymph nodes affected are close to the base of the skull and in the neck. Development of metastasis carries a poor prognosis and most patients will subsequently die of failure of loco-regional control. Despite the likelihood of a poor outcome nothing can be done for patients prior to development of metastasis, as the risk of spread is not sufficiently high to warrant intervention in all patients. They are therefore treated with a ‘wait and see policy’ and only offered treatment once clinical evidence of metastatic spread is detected. This thesis sets out to examine what can be done, at the time of initial presentation with an auricular squamous cell carcinoma to identify patients who would benefit from treatment to the regional lymph node basins. Materials and Methods The thesis is divided into four separate studies. A systematic review examines the evidence available to date, an anatomical study examines the lymphatic drainage of the auricle in cadavers, a sentinel lymph node biopsy study examines the use of this technique to identify early tumour spread and a retrospective analysis of cases of auricular squamous cell carcinoma in our unit examines histopathological prognostic indictors of metastatic spread. Results The systematic review found that these tumours have a metastatic rate of about 11%. Patients developing metastasis usually die from failure of loco-regional control. Depth of tumour invasion, tumour size and mode of invasion seem to be potential indicators of metastatic risk. There is a strong argument for prophylactic intervention to the regional lymph nodes but there is no consensus of opinion as to when this should be carried out The anatomical study comprised 5 cadaveric dissections. They showed that the first echelon nodes draining the auricle lie in the superficial parotid gland, post-auricular/ mastoid nodal group and level II of the neck. There are anastamotic pathways around the mastoid and post-auricular nodes that could permit embolic tumour cells to bypass them. Five lymphatic pathways draining the auricle are described and some of these lie on the lateral and anterior surfaces of the mastoid bone and traverse the insertion of sternocleidomastoid. 28 cases of auricular squamous cell carcinoma were enrolled for sentinel lymph node biopsy. None of them were found to have any metastatic spread. One case showed non-viable tumour cells in a lymph node. There was a high incidence of complications (14%) directly related to the sentinel node biopsy procedure. The retrospective analysis identified 229 cases of auricular squamous cell carcinoma treated in our unit from 1992 - 2004. 212 of these cases had the primary pathology available for analysis. 24 (of 212) patients developed metastasis. 17 patients died as a result of their disease usually due to failure of control at the regional lymph node basin. Primary tumours with a depth of invasion greater than 8mm have metastatic rate of 56%. Tumours with a depth of invasion between 2-8mm and evidence of cartilage destruction, lymphovascular invasion or a non-cohesive invasive front have 24% metastatic rate. Tumours outwith these high-risk groups did not metastasise. Conclusions Elective lymph node dissections of the superficial parotid gland, post-auricular/mastoid and level II nodes should be considered in patients with primary auricular squamous cell carcinomas with a depth of invasion >8mm or a depth of invasion between 2 - 8 mm and evidence of cartilage destruction, lymphatic invasion or a non-cohesive invasive front. This should ideally be done as part of an observational study to evaluate the cost / benefit ratio for these patients. The neck dissection must clear the mastoid bone to a sub-periosteal level on its anterior and lateral surfaces. This will require the removal of the upper portion of sternocleidomastoid. Sentinel lymph node biopsy requires further study to evaluate it as a method for early detection of metastatic spread in auricular squamous cell carcinoma. This could be done as part of an observational study of elective neck dissections.

No description available.

Attention deficit/hyperactivity disorder (ADHD) frequently co-occurs with language disorders including reading disabilities (RD) and language impairment (LI). Results from recent genetic studies have implicated Cadherin 13 (CDH13) and Contactin Associated Protein-like 2 (CNTNAP2) as ADHD and LI candidate genes, respectively. Studies have also indicated genomic regions of overlap between ADHD and reading disability (RD), suggesting a shared genetic etiology for both disorders. In the present study, we conducted a family based association analysis to investigate whether CDH13 and CNTNAP2 genes are associated with ADHD, RD and language ability in ADHD and RD samples. Although we found several trends for associations between CDH13, CNTNAP2 and ADHD and language measures, none would remain significant following corrections for multiple tests. However, the study represents the first time CDH13 and CNTNAP2 have been studied for a relationship with language in ADHD/RD samples. Further studies employing larger sample sizes are necessary to confirm our findings.

Attention deficit/hyperactivity disorder (ADHD) frequently co-occurs with language disorders including reading disabilities (RD) and language impairment (LI). Results from recent genetic studies have implicated Cadherin 13 (CDH13) and Contactin Associated Protein-like 2 (CNTNAP2) as ADHD and LI candidate genes, respectively. Studies have also indicated genomic regions of overlap between ADHD and reading disability (RD), suggesting a shared genetic etiology for both disorders. In the present study, we conducted a family based association analysis to investigate whether CDH13 and CNTNAP2 genes are associated with ADHD, RD and language ability in ADHD and RD samples. Although we found several trends for associations between CDH13, CNTNAP2 and ADHD and language measures, none would remain significant following corrections for multiple tests. However, the study represents the first time CDH13 and CNTNAP2 have been studied for a relationship with language in ADHD/RD samples. Further studies employing larger sample sizes are necessary to confirm our findings.

Attention deficit/hyperactivity disorder (ADHD) frequently co-occurs with language disorders including reading disabilities (RD) and language impairment (LI). Results from recent genetic studies have implicated Cadherin 13 (CDH13) and Contactin Associated Protein-like 2 (CNTNAP2) as ADHD and LI candidate genes, respectively. Studies have also indicated genomic regions of overlap between ADHD and reading disability (RD), suggesting a shared genetic etiology for both disorders. In the present study, we conducted a family based association analysis to investigate whether CDH13 and CNTNAP2 genes are associated with ADHD, RD and language ability in ADHD and RD samples. Although we found several trends for associations between CDH13, CNTNAP2 and ADHD and language measures, none would remain significant following corrections for multiple tests. However, the study represents the first time CDH13 and CNTNAP2 have been studied for a relationship with language in ADHD/RD samples. Further studies employing larger sample sizes are necessary to confirm our findings.

Attention deficit/hyperactivity disorder (ADHD) frequently co-occurs with language disorders including reading disabilities (RD) and language impairment (LI). Results from recent genetic studies have implicated Cadherin 13 (CDH13) and Contactin Associated Protein-like 2 (CNTNAP2) as ADHD and LI candidate genes, respectively. Studies have also indicated genomic regions of overlap between ADHD and reading disability (RD), suggesting a shared genetic etiology for both disorders. In the present study, we conducted a family based association analysis to investigate whether CDH13 and CNTNAP2 genes are associated with ADHD, RD and language ability in ADHD and RD samples. Although we found several trends for associations between CDH13, CNTNAP2 and ADHD and language measures, none would remain significant following corrections for multiple tests. However, the study represents the first time CDH13 and CNTNAP2 have been studied for a relationship with language in ADHD/RD samples. Further studies employing larger sample sizes are necessary to confirm our findings.

Colorectal cancer is a significant cause of morbidity and mortality in the West of Scotland. Socio-economic circumstances are known to be related with variations in health behaviour, risk factor exposure and outcome for a variety of diseases. However, the relationship between socio-economic circumstances and the risk of developing and surviving from colorectal cancer have been inconsistently reported using a variety of methodological approaches over recent decades in this region. Therefore, the principal aim of this body of work was to explore the relationship between socio-economic circumstances and the mortality, incidence and survival from colorectal cancer in the West of Scotland using robust methodology. Firstly, a population-based study was undertaken to explore recent temporal trends in colorectal cancer-specific mortality and the relationship with socio-economic circumstances. Incidence data from the Scottish Cancer Registry (SMR06) were linked to General Registry Office for Scotland (GROS) death records to produce age-standardised colorectal cancer-specific mortality rates. From 1985 to 2007, both colon and rectal cancer-specific mortality fell among women but remained unchanged in men. From 1996 to 2007, increasing levels of socio-economic deprivation were associated with higher rates of rectal cancer-specific mortality in both sexes and colon cancer-specific mortality in males only. This socio-economic inequality accounted for an estimated 859 excess deaths from colorectal cancer over 12 years in the West of Scotland. Further study of the underlying influences of the association between socio-economic deprivation and colorectal cancer-specific mortality was subsequently performed. Secondly, a population-based study to explore temporal trends in colorectal cancer incidence and the relationship with socio-economic circumstances was performed. Incidence data from the SMR06 were used to produce age-standardised incidence rates of colorectal cancer. From 1981 to 2007, colon and rectal cancer incidence rates increased significantly among men while remaining stable among women. From 1996 to 2007, the incidence rate of colon cancer in either sex and female rectal cancer were not associated with socio-economic circumstances. However, from 2002 a relationship between deprivation and a higher incidence of male rectal cancer became evident due to a significant reduction in incidence among the most affluent men. This emerging socio-economic inequality accounted for an estimated excess of 286 cases of male rectal cancer over the 6 year period to 2007. Subsequently, a detailed examination of temporal trends in relative survival following the diagnosis of colorectal cancer was performed. The relationship between survival from colorectal cancer and socio-economic circumstances was also examined using a population-based approach. SMR06 and GROS death record data were linked and relative survival analyses were performed. From 1991 to 2005, 5-year relative survival from colon and rectal cancer significantly improved in both sexes, especially in the first year after diagnosis. From 1996 to 2005, deprivation was associated with poorer survival from male colon cancer and rectal cancer in both sexes. This “deprivation gap” at 5 years arose due to early survival differentials between socio-economic groups in the first year after diagnosis. Furthermore, patients from the most deprived areas were more likely to be older at diagnosis, have rectal tumours, present with more advanced stage disease and were more likely to undergo non-curative treatment compared to the most affluent group. The association between deprivation and poorer survival was also found to become progressively stronger as stage of disease became more advanced. Even after adjustment for other factors associated with survival, deprivation remained independently associated with poorer survival, especially in the first year after diagnosis. Finally, to examine the association between socio-economic circumstances and short and longer-term survival after surgery for colorectal cancer, a study using clinical audit data linked to SMR06, Scottish Inpatient and Day-case Morbidity (SMR01) data and GROS death records was performed. From 2001 to 2004, this study confirmed that deprivation was independently associated with poorer post-operative (<30 days) and 5-year relative survival following surgery for colorectal cancer. Higher post-operative mortality among patients from more deprived areas was the main determinant of the longer-term deprivation gap in survival. This suggests that the main determinant of the observed longer-term socio-economic survival gradient occurred within the early post-operative period in patients undergoing surgery for colorectal cancer. Poorer short-term survival after surgery is likely to be influenced by higher levels of medical co-morbidity and reduced physiological reserve among more deprived groups. Therefore, by using a variety of data sources and robust methodological approaches, this thesis explores the relationship between socio-economic circumstances and colorectal cancer mortality, incidence and survival over recent decades in the West of Scotland. It demonstrates that deprivation was associated with poor short and longer-term survival, high cancer-specific mortality rates and became associated with higher rates of male rectal cancer incidence in the West of Scotland. These findings suggest that early survival differentials play a significant role in the observed deprivation gap in longer-term outcomes. Successful strategies to tackle this inequality are likely to involve multimodal interventions aimed at overall health improvements that are equitable to all. Strategies to improve early detection of colorectal cancer including national bowel screening initiatives and public health campaigns need to be further evaluated and, should they prove effective, tailored to ensure that high risk groups are engaged to participate. Additional interventions aimed at reducing post-operative mortality and morbidity in high risk individuals may also help reduce the observed socio-economic inequality in longer-term outcome. However, further detailed research using high-resolution prospectively collected clinical audit data is required so that modifiable determinants of socio-economic survival inequality can be identified to target future interventions.