Perceived risk of death in older primary care patients

There is a large gap between life expectancy and healthy life years at age 65. To reduce this gap, it is necessary that people with medical concerns perceived at higher risk of adverse outcomes are readily identified and treated. The same goes for the need to implement prevention plans. The main objectives of this study are to, in a first step, (a) estimate the percentage of medical concerns, (b) identify factors associated with this concern; in a second step, (c) estimate the perceived risk of death, and (d) evaluate the ability of medical concerns to predict this risk. Results show that the existence and severity of medical concerns are crucial in the prediction of perceived risk of death. Early identification of severity of medical concerns and the availability and adequacy of informal caregiving should allow healthcare professionals to promptly initiate an appropriate assessment and treatment of older patients.

Immunotherapy for the treatment of poor prognosis cancers

Cancer is amongst the leading causes of death worldwide and the number one cause in the developed world. Every year there are close to 10 million cancer related deaths and this corresponds to hundreds of millions of euro in health care costs and lost productivity, placing a substantial drain on the economy. The efficacy of traditional treatment modalities for cancer therapy, such as surgery, radiotherapy and chemotherapy has plateaued, and while they are undoubtedly effective at prolonging patient lifespan, there is a high rate of adverse side effects and fatal reoccurrence. Currently, there is a huge amount of interest in the areas of cancer immunosurveillance and cancer immuno-editing, which explain some of the complex interactions between the host immune system and cancer. If left unchecked, cancerous malignancies have the ability to generate an immunosuppressive microenvironment, effectively shielding themselves from elimination and promoting tumour growth and progression. To overcome this, the potential of the immune system must be harnessed and the work undertaken in this thesis sought to contribute to this goal. Focus was placed on using novel therapies, combining tumour ablation with immune-modulating antibodies to maximise tumour elimination in an immune dependent manner, to overcome immunosuppression and promote immune activation. Chapter 2 focuses on the use of ECT as a method of tumour ablation and its effects on the immune system. ECT proved to be effective at inhibiting the tumour growth both in vitro and in vivo, and conferred significant survival advantages in both small and large animal models. More importantly, ECT proved to cause tumour death in an immune dependent manner, displaying the hallmarks of Immunogenic Cell Death, increases in immune cell infiltration and generating tumour-specific immune responses. Chapter 3 focuses on combining ECT with immune checkpoint blockade inhibitors; anti- CTLA-4 and anti-PD-1. Both combinations proved to be effective at inhibiting both primary and distal tumour growth, indicating the generation of tumour specific immune responses and prolonged animal survival. In addition, the treatments caused increases in the levels of certain intra-tumoural immune cell subsets and modulated the cytokine profile of treated animals in a way that was favourable overall. Chapter 4 focuses on the combining ECT with an anti-iCOS agonist antibody, capable of causing immune co-stimulation. This novel combinational therapy proved to be the most effective by far, with a high cure rate achieved across a number of different in vivo tumour models. Total regression was seen in both primary and distal tumours, as well as spontaneous metastases, with the tumour specific immune response generated conferring total protection to animals on tumour rechallenge. Overall the data presented here adds further insight into the area of cancer immunotherapy with some of the novel combinational therapies demonstrating substantial clinic potential.

Saint, martyr, killer of Christ? The legend of Longinus in medieval Irish tradition

This dissertation is the first comprehensive and synthetic study of the Irish presentation and legends of Longinus. Longinus was the soldier at the crucifixion who pierced Christ with a spear, who believed and, according to some texts, was healed of his blindness by the blood and water issuing from the wound, and who later was martyred for his belief. In my thesis I survey the knowledge and use of the legend of Longinus in Ireland over genres and over time. Sources used for the analyses include iconographic representations of the spear-bearer in manuscripts, metalwork and stone and textual representations of the figure of Longinus ranging over the history of Irish literature from the early medieval to the early modern period, as well as over Irish and HibernoLatin texts. The thesis consists of four core chapters, the analyses of the presentations of Longinus in early-medieval Irish texts and in the iconographic tradition (I,II), the editions of the extant Irish and the earliest surviving Latin texts of the Passion of Longinus and of a little-known short tract describing the healing of Longinus from Leabhar Breac (III), and the discussion of the later medieval Irish popular traditions (IV). Particular attention is given to the study of two intriguing peculiarities of the Irish tradition. Most early Irish Gospel books feature an interpolation of the episode of the spear-thrust in Matthew 27:49, directly preceding the death of Christ, implying its reading as the immediate cause of death. The image of Longinus as 'iugulator Christi' ('killer of Christ') appears to have been crucial for the development of the legend. Also, the blindness motif, which rarely features in other European popular traditions until the twelfth century, is attested as early as the eighth century in Ireland, which has led some scholars to suggest a potential Irish origin.