Explaining the Establishment of the Independent Prosecutor of the International Criminal Court

The aim of this dissertation is to discern and explain why states established the International Criminal Court (ICC) with an independent Prosecutor with the aid of theories of international relations. The theories utilized were neorealism, neoliberal institutionalism, historical institutionalism, constructivism and liberal-pluralism. In order to complete the above-stated task, two supplemental questions were asked: first, how may one able to explain policy formulation in regards to the ICC; and second, what accounts for the victory of the supporters. The comparative case study method of the ‘method of agreement’ was employed. Canada and the United Kingdom – from among the supporters of the institutionalization of the independent Prosecutor – and the United States and Japan – from among the opponents of the initiative – were selected for the study at hand. Elite interviews and declassified diplomatic documents were consulted and supplemented by analyses of secondary sources documents such as negotiating transcripts and transcripts of parliamentary debates. In the final analysis constructivism and its liberal variant – liberal constructivism – in tandem with liberal-pluralism seem the best able to explain the establishment of the Court with an independent Prosecutor because these two theories are best able to account for the role of ideas and interests of key actors during the process of establishing the Court. In addition, and given that the establishment of the Court is a substantial departure from its institutional predecessors, liberal constructivism and liberal-pluralism are also able to account for this revolutionary change in the establishment of international institutions. The study at hand highlights the role of domestic political actors in the acceptance of international treaties as well. Therefore, this study underpins the need for further scholarship in regards to under what conditions do states allow themselves to be bound by international legal mechanisms

Semi-Supervised Learning of Cartesian Factors

The existence of place cells (PCs), grid cells (GCs), border cells (BCs), and head direction cells (HCs) as well as the dependencies between them have been enigmatic. We make an effort to explain their nature by introducing the concept of Cartesian Factors. These factors have specific properties: (i) they assume and complement each other, like direction and position and (ii) they have localized discrete representations with predictive attractors enabling implicit metric-like computations. In our model, HCs make the distributed and local representation of direction. Predictive attractor dynamics on that network forms the Cartesian Factor "direction." We embed these HCs and idiothetic visual information into a semi-supervised sparse autoencoding comparator structure that compresses its inputs and learns PCs, the distributed local and direction independent (allothetic) representation of the Cartesian Factor of global space. We use a supervised, information compressing predictive algorithm and form direction sensitive (oriented) GCs from the learned PCs by means of an attractor-like algorithm. Since the algorithm can continue the grid structure beyond the region of the PCs, i.e.,beyond its learning domain, thus the GCs and the PCs together form our metric-like Cartesian Factors of space. We also stipulate that the same algorithm can produce BCs. Our algorithm applies (a) a bag representation that models the "what system" and (b) magnitude ordered place cell activities that model either the integrate-and-fire mechanism, or theta phase precession, or both. We relate the components of the algorithm to the entorhinal-hippocampal complex and to its working. The algorithm requires both spatial and lifetime sparsification that may gain support from the two-stage memory formation of this complex

Challenges and proposed framework for formative research to inform systematic intervention development in rare and unstudied conditions: The case example of Xeroderma Pigmentosum

Purpose: To outline the challenges of applying existing systematic intervention development approaches in rare diseases, and to propose a novel framework within which these challenges can be met. Background: A gap in the provision of self-management and psychosocial interventions to change behaviour and improve health in rare diseases exists, partly due to the difficulty of conducting formative research in such conditions. Challenges include heterogeneity within already small sample sizes, patient burden, and the absence of prior research to guide decision-making. XP is a very rare inherited disease (~100 UK patients), involving an inability to repair ultraviolet radiation (UVR)-induced damage and increased melanoma risk; the only treatment is complete photoprotection. No research in XP has been conducted outside of the genetic literature. Methods: Using XP and improved photoprotection as a case example, we highlight the necessity of departing from the steps outlined by three intervention development approaches (intervention mapping, UK MRC guidelines for complex interventions, behaviour change wheel), and outline a framework that can be applied to the conduct of formative research in rare diseases. The framework focuses on the sequential or parallel use of mixed-methods (e.g., n-of-1, interviews, reviews of comparable conditions) and the triangulation of gathered data, and provides solutions to challenges including patient burden and the inability to pre-test study materials or intervention content in members of the target population. Conclusions: The proposed framework offers an alternative that may overcome the limitations associated with intervention development in rare diseases, which will hopefully encourage much-needed work in this field

Xeroderma pigmentosum: overview of pharmacology and novel therapeutic strategies for neurological symptoms

Xeroderma Pigmentosum (XP) encompasses a group of rare diseases characterised in most cases by nucleotide excision repair (NER) malfunction, resulting in an increased sensitivity to ultraviolet radiation in affected individuals. Approximately 25-30% of XP patients present with neurological symptoms, such as sensorineural deafness, mental deterioration, and ataxia. Although it is known that dysfunctional DNA repair is the primary pathogenesis in XP, growing evidence suggests that mitochondrial pathophysiology may also occur. This appears to be secondary to dysfunctional NER but may contribute to the neurodegenerative process in these patients. The available pharmacological treatments in XP mostly target the dermal manifestations of the disease. In the present review, we outline how current understanding of the pathophysiology of XP could be used to develop novel therapies to counteract the neurological symptoms. Moreover, the coexistence of cancer and neurodegeneration present in XP, lead us to focus on possible new avenues targeting mitochondrial pathophysiology

Understanding and predicting a complex behaviour using n-of-1 methods : Photoprotection in xeroderma pigmentosum

Acknowledgements: We would like to thank Lesley Foster (research nurse) for all her work in setting up the n-of-1 study with patients; the XP national clinical team (Hiva Fassihi, Tanya Henshaw, Sally Turner, Isabel Garrood, Alan Lehmann) and members of the PPI panel (Cathy Coleman, Ben Fowler, Sandra Webb, Ros Tobin) for input into design of materials. Funding: This research is funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research (RP-PG- 1212-20009). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR, NHS, or the Department of Health.Peer reviewedPostprin

Perforation in a patient with stercoral colitis and diverticulosis: who did it?

Stercoral colitis with perforation of the colon is an uncommon, yet life-threatening cause of the acute abdomen. No one defining symptom exists for stercoral colitis; it may present asymptomatically or with vague symptoms. Diagnostic delay may result in perforation of the colon resulting in complications, even death. Moreover, stercoral perforation of the colon can also present with localized left lower quadrant abdominal pain masquerading as diverticulitis. Diverticular diseases and stercoral colitis share similar pathophysiology; furthermore, they may coexist, further complicating the diagnostic dilemma. The ability to decide the cause of perforation in a patient with both stercoral colitis and diverticulosis has not been discussed. We, therefore, report this case of stercoral perforation in a patient with diverticulosis and include a discussion of the epidemiology, clinical presentation, and a review of helpful diagnostic clues for a rapid differentiation to allow for accurate diagnosis and treatment