Towards on-line plan adaptation of unified intensity-modulated arc therapy using a fast-direct aperture optimization algorithm

External beam radiotherapy (EBRT) plays a vital role in the treatment of cancer, with close to half of all cancer patients receiving EBRT at some point over their course of treatment. Although EBRT is a well-established form of treatment, there are a number of ways in which EBRT could still be improved in terms of quality and efficiency for treatment planning and radiation dose delivery. This thesis reports a series of improvements made to EBRT. First, we developed and evaluated a new treatment planning technique called unified intensity-modulated arc therapy (UIMAT) which combines the optimization and delivery of rotational volumetric modulated arc therapy (VMAT) and fixed-gantry intensity-modulated radiation therapy (IMRT). When retrospectively compared to clinical treatment plans using VMAT or IMRT alone, UIMAT plans reduced the dose to nearby critical structures by as much as 23% without compromising tumour volume coverage. The UIMAT plans were also more efficient to deliver. The reduction in normal tissue dose could help lower the probability of treatment-related toxicities, or alternatively could be used to improve tumour control probability, via dose escalation, while maintaining current dose limits for organs at risk. Second, we developed a new fast inverse direct aperture optimization (FIDAO) algorithm for IMRT, VMAT, and UIMAT treatment planning. FIDAO introduces modifications to the direct aperture optimization (DAO) process that help improve its computational efficiency. As demonstrated in several test cases, these modifications do not significantly impact the plan quality but reduced the DAO time by as much as 200-fold. If implemented with graphical processing units (GPUs), this project may allow for applications such as on-line treatment adaptation. Third, we investigated a method of acquiring tissue density information from cone-beam computed tomography (CBCT) datasets for on-line dose calculations, plan assessment, and potentially plan adaptation using FIDAO. This calibration technique accounts for patient-specific scattering conditions, demonstrated high dosimetric accuracy, and can be easily automated for on-line plan assessment. Collectively, these three projects will help reduce the normal tissue doses from EBRT, improve the planning and delivery efficiency, and pave the way for application like on-line plan assessment and adaptive radiotherapy in response to anatomical changes

Managing the Future Imaginary: Does ‘Post-Normal’ Science need Public Relations?

Contemporary conditions of so-called ‘post-normal’ science characterised by fundamental uncertainty and high decision stakes have been met by the call for an ‘extended peer community’ to include a full range potential stakeholders in the assessment and evaluation of future research policy (Functowicz and Ravetz, 1993; 1994). Correspondingly, the term ‘Anticipatory Governance’ (AG) has entered currency within Science and Technology Studies (STS) circles, where the phrase refers sympathetically to the fields involvement with an array of novel practices routinely carried-out in the name of increasingly public-focused, conscientious management of emerging science and technology. Existing literature in this area has typically focused on perceived benefits of social-scientist driven AG as ‘Real Time Technology Assessment’ (RTTA), rather than address how such participation — in line with STS’s contemporary post-social, object-centred, anti-normative research character — relates to a lack of institutional protection for most STS practitioners today. I argue the activities of social science researchers enrolled in AG-styled programmes appears to closely resemble those of PR professionals, and as such, in today’s knowledge economy the field could have much to gain by turning to clarify and formalise the unique cognitive-base and normative horizons befitting of a closed occupational group. I suggest an occupational restructuring in line with the ‘professional project’ (Macdonald, 1995) could bring about increased autonomy for STS practitioners, as well as purposeful direction for future research

The techno-centred imagination: a multi-sited ethnographic study of technological human enhancement advocacy (THEA)

This thesis explores the social construction and performance of Technological Human Enhancement Advocacy through multi-sited ethnographically inspired participant observation across a range of sites. It argues that advocacy efforts surrounding the ideal of technological human enhancement share the ideational feature of Techno-centrism – an object-level belief embedded in the material present while simultaneously future-oriented and thus principally immaterial. This purposive neo-dualism blurs ‘real' and ‘imagined' futures to satiate the materialist ontological grounding associated with the scientific worldview, while granting extended licence to more indulgent, compelling visions for technology as an enabler of affirmative, forward-facing action – including revivifying pursuit of humanist ideals associated with the modernisation project. The thesis makes contributions to three areas. Firstly, in substantive terms, it contributes towards sociological knowledge by detailing the intersubjective values, semiotic framing mechanisms and narrative tropes evoked to both justify and promote the notion of Technological Human Enhancement Advocacy (THEA), an area which remains under-researched. Secondly, the thesis makes a theoretical contribution through its modelling of a non- spatially determined constant which recurs across sites associated with THEA: The Techno-centred Imagination (TCI). Finally, the thesis offers a methodological contribution through its novel and creative application of multi-sited research strategy for the study of non-spatially determined cultures of extreme support for science and technology. A 24-month programme of fieldwork was undertaken, comprising multi-locational participant-observation, interviews and surveys. The thesis concludes that far from being new, the emerging social forms associated with THEA capture ambivalences which have long cast a shadow over late-modern society and culture. Although TCI appears most pronounced in the practice of transhumanism – where it is acted out in extreme, almost hyperbolic ways – the phenomena mirrors broader concerns around the future of science, technology and human self-identity in the new millennium. As such, it is deserving of further study

Profil et cheminement appuis pour le développement des compétences pédagogiques, linguistiques et culturelles des enseignants du FLS /

Titre de l'écran-titre (visionné le 4 déc. 2009

Showers, Sweating and Suing: Legionnaires’ Disease and ‘New’ Infections in Britain, 1977–90

Legionnaires’ disease is now routinely discussed as an ‘emerging infectious disease’ (EID) and is said to be one of the earliest such diseases to be recognised. It first appeared in 1976 and its cause was identified in 1977, the same year that Ebola fever, Hantaan virus and Campylobacter jejuni arrived. The designation of Legionnaires’ disease as an EID was retrospective; it was not and could not be otherwise as the category only gained currency in the early 1990s. In this article we reflect on the changing medical understanding and social profile of Legionnaires’ disease in the decade or so from its recognition to the creation of EIDs, especially its ambivalent position between public health and clinical medicine. However, we question any simple opposition, between public health experts who approached Legionnaires’ disease as a new and worrying environmental threat that could be prevented, and clinicians who saw it as another cause of pneumonia that could be managed by improved diagnosis and treatment. We argue that in the British context of public spending cuts and the reform of public health, the category of ‘new’ diseases, in which Legionnaires’ disease was central, was mobilised ahead of the EID lobby of the early 1990s, by interested groups in medicine to defend infectious diseases services

Identifying biomarkers to predict the biological behaviour of canine cutaneous mast cell tumours

This thesis aimed to identify biomarkers which could be used to determine the biological behaviour of canine mast cell tumours. The rationale for this was that there is a relative paucity of objective biomarkers, which can be established without the need to perform an act of surgery. In order to do this, the potential array of biomarkers available were reviewed. It was considered that markers attainable by interrogation of a blood sample may be most appropriate to fulfil the identified need. After positive results in human oncology, the first analyses focused on the relationships between routinely measured parameters, both proteins (the albumin to globulin ratio) and leukocytes (the neutrophil to lymphocyte ratio). Blood samples were taken from dogs with mast cell tumours prior to any treatment intervention. The neutrophil to lymphocyte ratio was identified as a biomarker which could identify canine mast cell tumours with an aggressive biological behaviour. Building a hypothesis from results in both veterinary and human oncology it was thought that further analysis of the serum proteome could identify further biomarkers of interest. Using the same blood samples, one-dimensional serum protein electrophoresis identified that dogs with biologically aggressive mast cell tumours had more significantly increased α-2 protein concentrations than those with low grade mast cell tumours. In an attempt to identify which specific proteins were responsible for changes in the proteome between dogs with mast cell tumours and also when compared to health control dogs, two dimensional serum protein electrophoresis was then performed. Twelve proteins were identified in dogs with aggressive mast cell tumours and not in healthy controls. Some of these proteins are acute phase proteins, reflecting the inflammatory nature of this neoplasm. Others are protease inhibitors which may have a role in tumour pathogenesis. This research has identified biomarkers, which with further validation could have a role in identifying tumours likely to have a severe effect on dogs’ quality of life and allow prompt treatment. It has also identified areas for future research

Anxiety's effect on the experience of supervision of genetic counseling students

University of Minnesota Ph.D. dissertation. August 2013. Major: Educational Psychology. Advisor: Dr. Patricia McCarthy Veach. 1 computer file (PDF); xi, 269 pages, appendices A-I.Genetic counseling has been a recognized profession in North America for over 40 years. Supervised clinical experiences with patients comprise a critical component of genetic counseling student education. Previous research has found genetic counseling students s tend to be more anxiety prone than the general population (Jungbluth et al., 2011), and anxiety related to supervision has been found in genetic counseling (e.g., Hendrickson et al., 2002) and related fields (e.g., Skovholt & Ronnestad, 2003). The present study investigated how anxiety affects the experience of supervision for genetic counseling students. Second year genetic counseling students (~N = 200) were invited to participate through email invitations distributed via training directors of the 33 programs accredited by the American Board of Genetic Counseling. The initial online survey contained the trait scale of the State-Trait Anxiety Inventory (STAI; Spielberger et al., 1983) to estimate anxiety proneness in this population and an invitation to participate in a 1-hour interview focusing on students' experiences in supervision. The interviews questions investigated seven research questions focusing on satisfaction with training, interactions with patients and supervisors, perceptions of the structure and processes of supervision, and experiences related to anxiety. High, moderate, and low trait anxiety groups were created using STAI scores, and the high and low groups' interview responses were compared using consensual qualitative research methodology (CQR; Hill, 2012). Analysis discovered relatively few differences between groups. The high anxiety group was more likely to describe problematic supervisory relationships, appreciate the supervisor's ability to help them when they get stuck in sessions, and feel their anxiety had a negative effect on their performance in general and in supervision. Common themes included supervisors' balancing support and guidance, the importance of feedback, ego-centric responses, and supervisors as focal points. Students unanimously reported positive levels of satisfaction with their clinical rotations in general and supervision specifically. The results of the present study are largely consistent with the literature, including recently published supervision competencies (Eubanks Higgins et al., 2013). Further research findings and research, practice, and training recommendations are provided

Critiques of student engagement

Student engagement initiatives at the national, institutional and classroom level have emerged against a backdrop of rising participation rates and the marketizsation of higher education. This context has informed the development of a literature that is heavily influenced by cause-effect framing and a focus on effectiveness. However, in recent years an alternative, critical literature has emerged that challenges some of the assumptions of the student engagement movement on the grounds of student rights and freedoms as learners. This review article identifies the following six critiques of student engagement based on an analysis of the literature and arguments stemming from analyses of the effects of neoliberalism, namely performativity, marketing, infantilisation, surveillance, gamification and opposition. It is concluded that at a policy and institutional governance level, there is a need to shift the emphasis from what and how questions concerning student engagement to consider its broader political, economic and ethical implications as a means of challenging the prevailingpolicy narrative

Causes of prehospital misinterpretations of ST elevation myocardial infarction

Objectives: To determine the causes of software misinterpretation of ST elevation myocardial infarction (STEMI) compared to clinically identified STEMI to identify opportunities to improve prehospital STEMI identification. Methods: We compared ECGs acquired from July 2011 through June 2012 using the LIFEPAK 15 on adult patients transported by the Los Angeles Fire Department. Cases included patients ≥18 years who received a prehospital ECG. Software interpretation of the ECG (STEMI or not) was compared with data in the regional EMS registry to classify the interpretation as true positive (TP), true negative (TN), false positive (FP), or false negative (FN). For cases where classification was not possible using registry data, 3 blinded cardiologists interpreted the ECG. Each discordance was subsequently reviewed to determine the likely cause of misclassification. The cardiologists independently reviewed a sample of these discordant ECGs and the causes of misclassification were updated in an iterative fashion. Results: Of 44,611 cases, 50% were male (median age 65; inter-quartile range 52–80). Cases were classified as 482 (1.1%) TP, 711 (1.6%) FP, 43371 (97.2%) TN, and 47 (0.11%) FN. Of the 711 classified as FP, 126 (18%) were considered appropriate for, though did not undergo, emergent coronary angiography, because the ECG showed definite (52 cases) or borderline (65 cases) ischemic ST elevation, a STEMI equivalent (5 cases) or ST-elevation due to vasospasm (4 cases). The sensitivity was 92.8% [95% CI 90.6, 94.7%] and the specificity 98.7% [95% CI 98.6, 98.8%]. The leading causes of FP were ECG artifact (20%), early repolarization (16%), probable pericarditis/myocarditis (13%), indeterminate (12%), left ventricular hypertrophy (8%), and right bundle branch block (5%). There were 18 additional reasons for FP interpretation (<4% each). The leading causes of FN were borderline ST-segment elevations less than the algorithm threshold (40%) and tall T waves reducing the ST/T ratio below threshold (15%). There were 11 additional reasons for FN interpretation occurring ≤3 times each. Conclusion: The leading causes of FP automated interpretation of STEMI were ECG artifact and non-ischemic causes of ST-segment elevation. FN were rare and were related to ST-segment elevation or ST/T ratio that did not meet the software algorithm threshold