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peer-reviewed Increasing emergency admissions place significant demands on limited hospital resources. We assessed national practices and resources for initiatives to reduce length of stay (LOS) and thereby improve efficiency of resource utilisation. Consultant members of the Irish Association of Coloproctology received a questionnaire seeking information about available initiatives aimed at reducing LOS. 20 out of 32 (62.5%) consultants responded to the questionnaire. Pre-assessment clinics for day surgery were available to 18(90%). Only 13 (65%) had access to pre-assessment clinics for patients requiring longer admissions. 11 (55%) could admit major cases on the day of surgery. Only 9 (45%) surgeons could guarantee immediate re-admission of patients discharged from hospital if needed. There was a divergence of opinion regarding the acceptable average LOS and percentage suitable for day surgery for a variety of common surgical procedures. This study highlights a number of key areas in which certain well-established initiatives could improve efficiency.

peer-reviewed Introduction Recent advances in our understanding of mesenteric anatomy clarify its shape distal to the duodenojejunal flexure. Investigation of mesenteric anatomy has raised several questions about its overall shape. These include the shape of the mesentery proximal to the duodenum, its anatomical relationship with fascia at this level, the distribution of the peritoneal reflection, and how the overall structure of the mesentery arises from its embryological forerunner. This thesis aimed to characterise embryological development and anatomical form of the abdominal mesentery in humans. Methods An appraisal of mesenteric development was performed. As part of this appraisal, three-dimensional models and dynamic models of the mesentery at consecutive stages of development were generated. Next, a dissection was performed using cadavers to comprehensively investigate mesenteric shape in adulthood. This dissection applied a mesenteric-based approach that is commonly used in oncologic surgery rather than a peritoneal-based one. A comprehensive appraisal of the cross sectional appearance of mesenteric anatomy and reconstruction of its in situ anatomical shape was performed. To overcome the innate challenges in communicating the mesenteric model of abdominal anatomy, digital sculpting techniques and three-dimensional printing were used to generate virtual and physical models of the mesentery. Results The mesentery (in its ex vivo and in situ state) is continuous from oesophagogastric junction to mesorectal level. In most cases, abdominal digestive organs are connected to the mesentery, rather than the abdominal wall. Moreover, the peritoneal landscape is explained by the mesenteric landscape. The human mesentery remains a continuous structure throughout development and does not become fragmented. The mesentery develops according to a set developmental program during which a foundation shape is acquired (primary mesenteric organogenesis) and undergoes subsequent alterations at a sub-regional level (secondary mesenteric organogenesis). Hence, the abdomen is organised along mesenteric lines, into two principal compartments: the mesenteric and non-mesenteric domain. This system of organisation is referred to as the mesenteric model of abdominal anatomy. Digital sculpting and three-dimensional printing were used to communicate results relating to mesenteric anatomy and development. Conclusions The findings reported in this thesis identify a new level of organisation of abdominal contents that may reconcile embryological, anatomical and surgical approaches to the abdomen. The classic model of mesenteric anatomy, which is complex and fragmented, may be replaced with a mesenteric-based model in which digestive organs are organised around a single mesentery that attaches to the posterior abdominal wall. Limitations were present in each arm of this study. For example, the anatomical study required excision of the mesentery and so its shape was altered. The embryological study required interpolation between stages. Lastly, some structures were challenging to identify during cross-sections analysis. However, collectively, findings from embryological, foetal, anatomical and cross-sectional analysis of the mesentery provide an opportunity to propose a definition for the mesentery: the organ that, in the embryo, supports development of all abdominal digestive organs, and following birth, maintains all abdominal digestive organs in position and in continuity with other systems. This system, which may be more broadly applied to mammalian species in general, requires further investigation.

peer-reviewed Introduction: Many self-help guides advise patients that spreading fluid intake throughout the day can reduce symptoms of overactive bladder (OAB).A,B However, although animal studies suggest a link between faster filling rates and increased afferent nerve firing, the relationship between filling rate and bladder sensation has not been examined in humans. The aim of this research is to investigate the effect of bladder volume and rate of bladder filling on bladder sensation and voiding patterns, in the physiological and pathological bladder in a non-clinical, natural filling environment. Methods: Forty female volunteers (control group) were recruited by open advertisement. A further 24 female patients with OAB were recruited from the urology outpatients department. Each participant completed a UDI-6, IIQ-7 and 3-day sensation-related bladder diary. Results: There was a negative correlation between the rate of bladder filling and the length of intervoiding interval in both groups (p=

peer-reviewed Infectious mononucleosis (IM) is a constellation of clinical features largely seen in adolescence and young adults. It is typified by pharyngitis, prominent cervical lymphadenopathy and high fevers. It therefore can be difficult to distinguish the disease from the far more common presentation of bacterial tonsillitis (BT). Epstein Barr Virus (EBV) causes IM in the majority of cases, and thus a distinguishing feature is an associated lymphocytosis, rather than the neutrophilia seen in BT. Along with the different aetiology and diagnostic pathways, there are a number of aspects of the disease that warrant further research. This thesis aims to investigate the epidemiology, diagnosis and management of the disease, as well as providing a review of a number of areas of controversy. IM is associated with a high lymphocyte count and recent publications have sought to exploit this as a screening tool. I examined 1000 laboratory results but found that the lymphocyte to white cell count alone was not sufficient to act as a screening tool in IM. IM tends to present as a more severe infection than BT, but there was no literature to collaborate what many physicians had noted. The admission rates to a tertiary hospital of both diseases were examined over a 20-year period. This allowed us to show that IM had a significantly longer hospital stay, providing evidence for the first time of the severity of the disease. As 90% of cases are viral in origin, antibiotics would unsurprisingly not usually have a role in the treatment of IM. However, the virally driven pharyngitis can lead to anaerobic overgrowth in the oral cavity contributing to the severity of the symptoms. carried out a randomised controlled trial to demonstrate a significant length of stay decrease in those treated with anaerobic antibiotics. Finally a comprehensive review of multiple controversial topics associated with IM was undertaken. I discussed subjects such as the association of IM with Multiple Sclerosis (MS), chronic fatigue, splenic rupture, and relationship with malignancies and treatment with steroids. Findings from this thesis may have important clinical implications in the epidemiology, diagnosis and management of infectious mononucleosis

peer-reviewed Osteoporosis and osteoarthritis are common diseases with significant rates of morbidity associated with same. The search continues for effective treatment strategies for both diseases. Mesenchymal stem cells (MSCs) are critical components in the effective formation and repair of healthy bone and cartilage. Understanding the characteristics and behaviour of MSC’s in osteoarthritic and osteoporotic patients can help delineate and characterise the pathogenesis of these diseases further. The first aim of this study involves the creation of a biobank of osteoporotic and osteoarthritic MSC’s. The second aim includes analysing differentiation potential and cell migration/homing capabilities of these diseased MSC’s. Continuing from these results, a third aim is to explore aspects of how diseased MSC’s may interfere with TGF-β1 signalling, given the potent role of this pathway in regulating bone and cartilage metabolism. Bone marrow aspirates were obtained from osteoarthritic, osteoporotic and healthy donors undergoing scheduled hip surgery in the University of Limerick hospital group. Bone marrow aspirates were extracted through the exposed acetabulum during arthroplasty surgery. MSCs were isolated through standard in vitro culture conditions and underwent characterisation and differentiation as per the criteria outlined by the International Society of Cellular Therapy guidelines. Osteoporotic and osteoarthritic MSCs were then analysed for their osteogenic and adipogenic differentiation potential, migratory capacity and interplay with aspects of TGF-β1 signalling. A total of 10 donors were included in the study with no difficulties or complications arising from obtaining bone marrow aspirates during necessary arthroplasty surgery. MSCs were characterised using flow cytometry and by demonstration of their capacity to differentiate along adipogenic, chondrogenic and osteogenic lineages. Osteoporotic MSCs had an increased propensity to differentiate along the adipogenic lineage in comparison to their osteoarthritic counterparts. Both osteoporotic and osteoarthritic MSCs had altered chemokinetic profiles in comparison to healthy controls. Of particular interest, whilst healthy MSCs migrate towards TGF-β1, osteoporotic MSCs failed to migrate towards this important chemoattractant. The results of this research detail the successful extraction and isolation of MSCs from patients with osteoarthritis and osteoporosis. The surgical location and technique incorporates a transferable skill that could result in largescale collection of both healthy and diseased MSCs. A critical finding includes the altered migration of MSCs towards TGF-β1. This has implications both in the basic understanding of the pathogenesis of osteoporosis and in the development of future therapeutic targets.

peer-reviewed Breast cancer is a leading cause of morbidity and mortality amongst adult women in Western Europe and North America. Within the last decade our understanding of this condition has improved. This has led to the emergence of new treatment algorithms and prognostic instruments. Examples of the former include taxane-based therapy and trastuzumab; further examples of the latter are novel prognostic instruments such as Nottingham Prognostic Index (NPI) and Adjuvant! Online (AO). The aim of this thesis is to determine if the application of these is associated with improved cancer-specific outcomes. To this end, we conducted a retrospective population-based determination of cancer-specific outcomes associated with newer treatment algorithms. In addition we determined the correlation between prognosis and actual outcome for NPI and AO. These were compared with outcomes associated with prior treatment approaches. The thesis finishes with a comparison of both to determine the optimal treatment management paradigm. Adjuvant taxane therapy was not associated with improved cancer-specific outcome compared with non-taxane based therapy. However, third-generation (taxane-based) therapy was associated improved cancer-specific outcome compared with first- and second-generation (taxane- and non-taxane based) therapy. Adjuvant trastuzumab treatment was associated with improved cancer-specific outcome. Prognostic accuracy differed for NPI and AO. In conclusion, these practice changes have had a mixed effect on outcomes for patients with early-stage breast cancer (EBC).