Deconstructing and reconstructing 'best interests': deciding for legally incompetent patients

'Best interests' is a panacea within medico-legal decisions for incapacitated patients. Its scope is extensive and its range of application situationally diverse, yet the meaning of best interests remains relatively obscure. To clarify its character this thesis deconstructs best interests by critically examining current law regarding treatment decisions for incompetent patients (Chapters 1 and 2). The conceptual implications of using 'interests' are then considered through exploration of philosophical approaches to sources of interests (Chapter 3). Certain important distinctions are raised and the notion of an 'interest network' is mooted. The possibilities for reconstruction of best interests are considered in Chapters 4 and 5. The importance of autonomy, including competence construction and patient perspective in alternative decision-making mechanisms, is considered. The meaning of welfare, together with quality of life and personhood are also explored in the context of incapacitated persons. Reconstruction then begins in earnest. 'Respect' is proffered as the most suitable ethic for governing 'best interests'. A new synthesis of respect is developed through Chapters 6,7 and 8. It is argued (Chapter 6) that we should admit a wider range of interests, recognise the importance of relationship, and differentiate between input and decision-making authority. A 'whole life, over time' approach is proffered in Chapter 7, including a reclassification of incompetence, and a process for ascertaining interests outlined. The final chapter embraces ethical issues, conflict resolution and criteria for justified decision-making. Discussion concludes by developing a normative framework to legally represent the improved respect synthesis within 'best interests'

Improving the efficiency and relevance of health technology assessent: the role of iterative decision analytic modelling

Decision making in health care involves two sets of related decisions: those concerning appropriate service provision on the basis of existing information; and those concerned with whether to fund additional research to reduce the uncertainty relating to the decision. Information acquisition is not costless, and the allocation of funds to the enhancement of the decision makers’ information set, in a budgetconstrained health service, reduces the ‘pot’ of resources available for health service provision. Hence, a framework is necessary to unify these decisions and ensure that HTA is subject to the same evaluation of efficiency as service provision. A framework is presented which addresses these two sets of decisions through the employment of decision analytic models and Bayesian value of information analysis, early and regularly within the health technology assessment process. The model becomes the vehicle of health technology assessment, managing and directing future research effort on an iterative basis over the lifetime of the technology. This ensures consistency in decision making between service provision, research and development priorities and research methods. Fulfilling the aim of the National Health Service HTA programme, that research is “produced in the most economical way” using “cost effective research protocols”. The proposed framework is applied to the decision concerning the appropriate management of female patients with symptoms of urinary tract infection, which was the subject of a recent NHS HTA call for proposals. A probabilistic model is employed to fully characterise and assess the uncertainty surrounding the decision. The expected value of perfect information (EVPI) is then calculated for the full model, for each individual management strategy and for particular model parameters. Research effort can then be focused on those areas where the cost of uncertainty is high and where additional research is potentially cost-effective. The analysis can be used to identify the most appropriate research protocol and to concentrate research upon particular parameters where more precise estimates would be of most value.assessment

Panax ginseng has no effect on indices of glucose regulation following acute or chronic ingestion in healthy volunteers

In the absence of effective pharmacotherapy for diabetes there has been an increase in the use of, and research into, alternative treatment strategies. These include exercise, dietary interventions and the use of supplements including extracts of ginseng. Two separate, placebo-controlled, double-blind, cross-over studies investigating the effects of chronic ingestion of Panax ginseng (study 1 used G115, study 2 used Cheong Kwan Jang) on glycated Hb (HbA1c; study 1, n 18; study 2, n 11), fasting plasma insulin (study 1, n 17; study 2, n 12), fasting plasma glucose and postprandial response (following breakfast) (study 1, n 23; study 2, n 14) in healthy volunteers are reported. In both studies it was found that Panax ginseng had no effect on any gluco-regulatory parameter investigated. These results are not consistent with those reported for a diabetic sample (albeit using slightly different outcomes). These results would suggest that chronic use of Panax ginseng by non-diabetic individuals will have little long-term effect on glucose regulation. The benefits to glucose regulation associated with long-term ginseng use may only be present in populations with compromised glucose control; however, further research is needed to confirm such a speculation

Traceable 89Zr imaging in positron emission tomography

Positron emission tomography (PET) is a powerful diagnostic tool in the field of nuclear medicine. The use of novel radioisotopes has significantly increased in recent years and there has been an international drive for new standards of radioactivity for radioisotopes such as 89Zr. To accurately quantify radioactivity distributions in PET images it is necessary to calibrate imaging equipment and perform verification measurements. This thesis presents results from the primary activity standardisation of 89Zr, measurement of a new half-life and gamma emission probabilities, and evaluation of the quantitative accuracy of PET imaging systems used for activity measurement of 89Zr. The measured half-life and gamma emission intensities were evaluated alongside existing work creating a new dataset with lower uncertainties. A methodology was developed for creating traceable imaging objects to be used for calibration and verification measurements in PET imaging. Uncertainties were estimated for each stage of the measurement chain and combined where appropriate to give overall uncertainty budgets. The results showed that traceable imaging measurements are achievable in both preclinical and clinical PET systems, but uncertainty assessment is challenging when dealing with proprietary acquisition and reconstruction algorithms. Several future projects are presented, and it is hoped these projects will further develop the metrology required for traceable PET imaging in the clinical environment and open the door to a new era of accuracy and precision in PET activity quantification

Relating Modulus and Poincaré Inequalities on Modified Sierpiński Carpets

This thesis investigates the question of whether a doubling metric measure space supports a Poincar\'e inequality and explains the relationship between the existence of such an inequality and the non-triviality of the respective modulus. It discusses in detail a general class of modified Sierpi\'nski carpets presented by Mackay, Tyson, and Wildrick~\cite{M & T & K}, which are the first examples of spaces that support Poincar\'e inequalities for a renormalized Lebesgue measure that are also compact subsets of Euclidean space with empty interior. It describes the intricate relationship between the sequence used in the construction of a modified Sierpi\'nski carpet and the validity of Poincar\'e inequalities on that space

Contrasting Patterns of Population Genetic Structure in Two Great Basin Stoneflies

Shifts in species distributions caused by climatic oscillations may lead to geographic isolation of populations and fewer opportunities for genetic exchange among locations. Examining trends in genetic relationships among stonefly populations can help us predict how organisms might respond to environmental changes. Prior work established that isolated montane populations of the stonefly Doroneuria baumanni had high levels of genetic structure within the Great Basin and that this diversification occurred during the Pleistocene. This differentiation may have resulted from historical climatic oscillations. With this in mind, we evaluated the contemporary genetic structure of another Great Basin stonefly, Hesperoperla pacifica. Because H. pacifica has relatively broader habitat requirements, we predicted its populations would display less genetic structure than those of D. baumanni. We estimated genetic differentiation among and within 12 populations of H. pacifica using 568 base pairs of the mitochondrial gene cytochrome b gene. FST estimates indicate that H. pacifica populations are less structured than D. baumanni, which had showed deep levels of divergence across limited geographic distances. These results confirm the benefits of a comparative approach to understanding the phylogeography and population genetic structure of stoneflies of the Great Basin

Urban transformation in the Central Medjerda Valley (north-west Tunisia) in late antiquity and the middle ages: a regional approach

ecent scholarship on North African cities has done much to dispel earlier assumptions about late antique collapse and demonstrate significant continuity into the Byzantine and medieval periods. Yet urban changes did not affect North Africa evenly. Far less is known about the differing regional trajectories that shaped urban transformation and the extent to which pre-Roman and Roman micro-regions continued to share meaningful characteristics in subsequent periods. This article provides a preliminary exploration of regional change from the fourth to the eleventh century focused on a zone in the Central Medjerda Valley (Tunisia) containing the well-known sites of Bulla Regia and Chimtou. We place these towns in their wider historical and geographical setting and interrogate urban change by looking at investment in public buildings and spaces, religious buildings and housing, and ceramic networks. The process of comparison identifies new commonalities (and differences) between the sites of this stretch of the Medjerda River and provides a framework for understanding the many transformations of North African cities over the long late antiquity

Hybrid kernelised expectation maximisation for Bremsstrahlung SPECT reconstruction in SIRT with 90Y micro-spheres

BACKGROUND: Selective internal radiation therapy with Yttrium-90 microspheres is an effective therapy for liver cancer and liver metastases. Yttrium-90 is mainly a high-energy beta particle emitter. These beta particles emit Bremsstrahlung radiation during their interaction with tissue making post-therapy imaging of the radioactivity distribution feasible. Nevertheless, image quality and quantification is difficult due to the continuous energy spectrum which makes resolution modelling, attenuation and scatter estimation challenging and therefore the dosimetry quantification is inaccurate. As a consequence a reconstruction algorithm able to improve resolution could be beneficial. METHODS: In this study, the hybrid kernelised expectation maximisation (HKEM) is used to improve resolution and contrast and reduce noise, in addition a modified HKEM called frozen HKEM (FHKEM) is investigated to further reduce noise. The iterative part of the FHKEM kernel was frozen at the 72nd sub-iteration. When using ordered subsets algorithms the data is divided in smaller subsets and the smallest algorithm iterative step is called sub-iteration. A NEMA phantom with spherical inserts was used for the optimisation and validation of the algorithm, and data from 5 patients treated with Selective internal radiation therapy were used as proof of clinical relevance of the method. RESULTS: The results suggest a maximum improvement of 56% for region of interest mean recovery coefficient at fixed coefficient of variation and better identification of the hot volumes in the NEMA phantom. Similar improvements were achieved with patient data, showing 47% mean value improvement over the gold standard used in hospitals. CONCLUSIONS: Such quantitative improvements could facilitate improved dosimetry calculations with SPECT when treating patients with Selective internal radiation therapy, as well as provide a more visible position of the cancerous lesions in the liver

Triple modality image reconstruction of PET data using SPECT, PET, CT information increases lesion uptake in images of patients treated with radioembolization with [Formula: see text] micro-spheres.

PURPOSE: Nuclear medicine imaging modalities like computed tomography (CT), single photon emission CT (SPECT) and positron emission tomography (PET) are employed in the field of theranostics to estimate and plan the dose delivered to tumors and the surrounding tissues and to monitor the effect of the therapy. However, therapeutic radionuclides often provide poor images, which translate to inaccurate treatment planning and inadequate monitoring images. Multimodality information can be exploited in the reconstruction to enhance image quality. Triple modality PET/SPECT/CT scanners are particularly useful in this context due to the easier registration process between images. In this study, we propose to include PET, SPECT and CT information in the reconstruction of PET data. The method is applied to Yttrium-90 ([Formula: see text]Y) data. METHODS: Data from a NEMA phantom filled with [Formula: see text]Y were used for validation. PET, SPECT and CT data from 10 patients treated with Selective Internal Radiation Therapy (SIRT) were used. Different combinations of prior images using the Hybrid kernelized expectation maximization were investigated in terms of VOI activity and noise suppression. RESULTS: Our results show that triple modality PET reconstruction provides significantly higher uptake when compared to the method used as standard in the hospital and OSEM. In particular, using CT-guided SPECT images, as guiding information in the PET reconstruction significantly increases uptake quantification on tumoral lesions. CONCLUSION: This work proposes the first triple modality reconstruction method and demonstrates up to 69% lesion uptake increase over standard methods with SIRT [Formula: see text]Y patient data. Promising results are expected for other radionuclide combination used in theranostic applications using PET and SPECT