This thesis reconsiders the work of art filmmakers in the People’s Republic of China between 1989 and 2001. These dates bookend the decade of the 1990s, comprising two defining moments in the reform era: the Tiananmen Square political crisis in 1989, and the entry of China into the WTO and the global market economy in 2001. The 1990s is therefore approached in this research as a transitional decade, in which the future direction of China was being decided. The term ‘art film’ is used to identify a distinct mode of film practice, characterised by a peripheral position, a clear directorial voice, and an emphasis on aesthetics. This rubric therefore incorporates films made by a range of auteur directors, rather than solely the ‘independent’ or ‘underground’ works commonly assessed in studies of the decade. By examining the representational modes used by art filmmakers in the 1990s, filmic innovations can be seen to constitute an artistic response to the restrictions placed on representation by the State. This thesis argues that historical reassessment was a key factor in the innovation of cinematic representation in the 1990s. Utilising a cultural history approach, the thesis engages in close textual analysis of seventeen films, identifying and contextualising the representational conventions drawn on by filmmakers. The thesis is structured around five thematic chapters, each dealing with a cluster of films focused on similar content. The first chapter examines filmic reassessments of China’s socialist history, and concludes that the limitations of the official narrative provided opportunities for the assertion of alternative histories. The subsequent chapters develop on the concept of historical reassessment by looking at changing modes of cinematic representation in relation to rural populations, women and gender, urban regeneration, and youth culture. By engaging in a wide-ranging survey of how key themes were represented in art films in the 1990s, the thesis reveals the critical role which historical reassessment played in pushing directors to new levels of artistry and experimentation in their filmmaking. This thesis concludes that by questioning the cinematic forms used historically to represent these issues and social groups, Chinese art filmmakers achieved a new level of artistic independence in their work by the end of the decade.

The Quaternary geologic history of Lake Thatcher, southeastern Idaho, is pivotal in determining when the Bear River carved its through-flowing channel into the Bonneville Basin. Bright's reconstruction of the history of Lake Thatcher was based on 14C dates that are now known to be inaccurate. Lava Creek B ash found interbedded with lacustrine sediment suggests that Thatcher Basin contained a lake well before Bright's original estimate of 34 ka. D/L ratios, which measure the extent of racemization in fossil gastropods, in conjunction with paleosols and tephra, were used to correlate between four localities across Thatcher Basin to reassess lake-level chronology. Lab-heating experiments were performed on four genera of molluscs to obtain integeneric conversions of D/L, which aided in chronostratigraphic correlation between beds that contained different genera. An age calibration curve for Lymnaea was developed using D/L ratios associated with the proto Mount St. Helens tephra (90±30 ka; D/L=0.21 [Valvata]) and Lake Bonneville sediment (20±5 ka; D/L=0.09 [lymnaea]). D/L ratios from non-dated lake deposits were assigned ages using this calibration curve, providing the basis for the late-Pleistocene Lake Thatcher chronology. Based on high D/L ratios in Valvata (~0.7) contained in the lower Thatcher sediment, lake level through early-middle Pleistocene was shallow, evidenced by numerous paleosols and organic-rich beds. A gap in the Lake Thatcher stratigraphic record exists for much of the middle Pleistocene. Lake Thatcher existed at its highest elevation from ~110 until ~80 ka, separated from the final Lake Thatcher high-water episode at ~40 ka by a middle-Wisconsin soil. This provides a maximum age on the breaching of the divide at Oneida Narrows and unimpeded flow of the Bear River into Bonneville Basin. By ~17 ka, Lake Bonneville backed up into Thatcher Basin, during its all-time highstand, which Bright believed was owned in part to the added inflow of the Bear River. However, evidence from this study suggests that the Bear River may have been spilling over the divide at Oneida Narrows into Bonneville Basin at ~110 ka.

My MSc thesis is focused on parametric designs of Phase I clinical trials, using the continual reassessment method. A parametric model with unknown parameters is assumed. The observations are either toxic or nontoxic. Observations of toxicities are used to update the posterior distribution. Dose selection for the next patient is based on the estimated toxicity probability. The objective is to identify the maximum tolerated dose to be used in Phase II clinical trials. We introduce a new class of parametric functions for the continual reassessment method. This class is formed with the cumulative distribution function of the normal distribution. The major advantage is that we can choose different normal distributions to model different toxicity probability functions. We conduct simulation studies and compare our new design with the existing parametric designs, and have found that our design performs better by choosing the appropriate values of the mean and variance. / October 2016

A computer interview has been found to be valuable in eliciting information. This thesis describes the use of a CIS in two different clinical settings (GP surgery and chiropractic clinic), with the aims of aiding recognition of patients with anxiety or depression and enhancing communication between patient and clinician. The Hospital Anxiety and Depression Scale (HADS) was included in the computer interview. 60 patients used the CIS in both settings, 6 GPs and 3 chiropractors were involved in the study. A high level of acceptance of the CIS was found in patients and clinicians in both settings. 99% of patients rated the system as “easy” or “extremely easy to use”. In the GP surgery, 80% of patients felt that they were “possibly” (68.33%) or “definitely” (11.67%) more focussed for the consultation. In the chiropractic clinic, 41.7% of patients said they disclosed new information and 33.3% felt better prepared for the consultation. The CIS aided the recognition of some individuals with anxiety or depression, more so within the chiropractic clinic than in the GP surgery. The information in the interview transcript was considered more useful by the chiropractors than the GPs (85% v 21.67%); this could be partially attributable to the fact that the chiropractors added 15 reassessment questions to the question set, whilst the GPs only added 4, more general, questions. The CIS also helped to highlight communication issues and show trends within the patient populations. Although the CIS was found to be of benefit in both settings, the GPs felt that it was more appropriate for use with specific patient groups. In the chiropractic clinic, the CIS was an effective addition to the periodic patient reassessment process. It would be possible to deliver other, individualised screening interviews using the CIS, delivery of which could be enhanced using handheld devices.

Phase I clinical trials in oncology aim to evaluate the toxicity risk of new therapies and identify a safe but also effective dose for future studies. Traditional Phase I trials of chemotherapies focus on estimating the maximum tolerated dose (MTD). The rationale for finding the MTD is that better therapeutic effects are expected at higher dose levels as long as the risk of severe toxicity is acceptable. With the advent of a new generation of cancer treatments such as the molecularly targeted agents (MTAs) and immunotherapies, higher dose levels no longer guarantee increased therapeutic effects, and the focus has shifted to estimating the optimal biological dose (OBD). The OBD is a dose level with the highest biologic activity with acceptable toxicity. The search for OBD requires joint evaluation of toxicity and efficacy. Although several seamleass phase I/II designs have been published in recent years, there is not a consensus regarding an optimal design and further improvement is needed for some designs to be widely used in practice. In this dissertation, we propose a modification to an existing seamless phase I/II design by Wages and Tait (2015) for locating the OBD based on binary outcomes, and extend it to time to event (TITE) endpoints. While the original design showed promising results, we hypothesized that performance could be improved by replacing the original adaptive randomization stage with a different randomization strategy. We proposed to calculate dose assigning probabilities by averaging all candidate models that fit the observed data reasonably well, as opposed to the original design that based all calculations on one best-fit model. We proposed three different strategies to select and average among candidate models, and simulations are used to compare the proposed strategies to the original design. Under most scenarios, one of the proposed strategies allocates more patients to the optimal dose while improving accuracy in selecting the final optimal dose without increasing the overall risk of toxicity. We further extend this design to TITE endpoints to address a potential issue of delayed outcomes. The original design is most appropriate when both toxicity and efficacy outcomes can be observed shortly after the treatment, but delayed outcomes are common, especially for efficacy endpoints. The motivating example for this TITE extension is a Phase I/II study evaluating optimal dosing of all-trans retinoic acid (ATRA) in combination with a fixed dose of daratumumab in the treatment of relapsed or refractory multiple myeloma. The toxicity endpoint is observed in one cycle of therapy (i.e., 4 weeks) while the efficacy endpoint is assessed after 8 weeks of treatment. The difference in endpoint observation windows causes logistical challenges in conducting the trial, since it is not acceptable in practice to wait until both outcomes for each participant have been observed before sequentially assigning the dose of a newly eligible participant. The result would be a delay in treatment for patients and undesirably long trial duration. To address this issue, we generalize the time-to-event continual reassessment method (TITE-CRM) to bivariate outcomes with potentially non-monotonic dose-efficacy relationship. Simulation studies show that the proposed TITE design maintains similar probability in selecting the correct OBD comparing to the binary original design, but the number of patients treated at the OBD decreases as the rate of enrollment increases. We also develop an R package for the proposed methods and document the R functions used in this research. The functions in this R package assist implementation of the proposed randomization strategy and design. The input and output format of these functions follow similar formatting of existing R packages such as "dfcrm" or "pocrm" to allow direct comparison of results. Input parameters include efficacy skeletons, prior distribution of any model parameters, escalation restrictions, design method, and observed data. Output includes recommended dose level for the next patient, MTD, estimated model parameters, and estimated probabilities of each set of skeletons. Simulation functions are included in this R package so that the proposed methods can be used to design a trial based on certain parameters and assess performance. Parameters of these scenarios include total sample size, true dose-toxicity relationship, true dose-efficacy relationship, patient recruit rate, delay in toxicity and efficacy responses.

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Introduction: Early graft dysfunction (EAD) complicates liver transplantation (LT). The aim of this analysis was to discriminate between the weight of each variable as for its predictive value toward patient and graft survival. Methods: We reviewed all LT performed at the Medical University of Innsbruck between 2007 and 2018. EAD was recorded when one of the following criteria was present: (i) aspartate aminotransferase (AST) levels >2,000 IU/L within the first 7 days, (ii) bilirubin levels 10mg/dL or (iii) international normalized ratio (INR) 1.6 on postoperative day 7. Results: Of 616 LT, 30.7% developed EAD. Patient survival did not differ significantly (P = 0.092; log rank-test = 2.87), graft survival was significantly higher in non-EAD patients (P = 0.008; log rank-test = 7.13). Bilirubin and INR on postoperative day 7 were identified as strong mortality predictors (Bilirubin HR = 1.71 [1.34, 2.16]; INR HR = 2.69 [0.51, 14.31]), in contrast to AST (HR = 0.91 [0.75, 1.10]). Similar results were achieved for graft loss estimation. A comparison with the Model for Early Allograft Function (MEAF) and the Liver Graft Assessment Following Transplantation (L-GrAFT) score identified a superior discrimination potential but lower specificity. Conclusion: Contrarily to AST, bilirubin and INR have strong predictive capacity for patient and graft survival. This fits well with the understanding, that bile duct injury and deprivation of synthetic function rather than hepatocyte injury are key factors in LT.

BACKGROUND & OBJECTIVES Overarching and decision-making frameworks may be used to facilitate the evaluation of prescription drug technologies to enable Health Technology Assessment (HTA) agency’s reassessment recommendations. The objectives of this thesis were to; 1) identify overarching and qualitative decision-making reassessment framework challenges and methodological gaps and; 2) develop and/or modify a framework to address challenges/gaps. The focus was on Canadian public prescription drug reimbursement with the hope that the findings may inform other jurisdictions. METHODS The first paper systematically identified drug disinvestment frameworks to describe framework components, challenges and solutions. A qualitative descriptive study was conducted in the second paper to explore whether a qualitative benefit-risk framework (Universal Methodology for Benefit-Risk Assessment (UMBRA)) could be used or modified to further enable Health Technology Reassessment (HTR) recommendations. The last research paper assessed the Canadian Agency for Drugs and Technologies in Health’s (CADTH’s) Therapeutic Review Process. Enhancements to this process were developed based on previous research and published frameworks. RESULTS Qualitative framework components were identified, disinvestment terms captured and challenges and solutions to drug disinvestment were compiled in Chapter 2. The participants interviewed in chapter 3 recognized that the Therapeutic Review assessment process did not include a qualitative deliberative framework. However, participants did not consider that all steps of the UMBRA framework were transferable to the assessment phase of HTR. Assessment of CADTH’s Therapeutic Review process, conducted in Chapter 4, found three areas for process enhancement: Therapeutic Review topic prioritization criteria; a qualitative assessment framework, and; publically accessible mechanisms for decision monitoring and performance measurement. CONCLUSION This thesis has identified reassessment framework enhancements that are hypothesized to address HTR challenges and specific solutions to enhance CADTH’s Therapeutic Review Framework. Next steps include further evaluation and pilot testing of these proposed enhancements to enable additional Canadian stakeholder feedback. / Thesis / Doctor of Philosophy (PhD) / This thesis focuses on overarching and decision-making assessment frameworks whose purpose is to aid policy-makers in recommending which prescription drugs should continue to be government-funded and/or if modifications to funding should occur. The goal of this work is to; 1) identify challenges and gaps in these frameworks and 2) develop or modify a framework to address findings. This thesis focuses on the Canadian public prescription drug reimbursement environment. Results identified Canadian reassessment framework enhancements which could address challenges to ultimately aid in maintaining financial and institutional stability of public health care systems.

The following is a case study of the University of New Orleans Disaster Resistant University project. The Disaster Resistant University project involved the creation, adoption, and implementation of an all-hazards campus mitigation plan. On August 29, 2005 Hurricane Katrina struck the City of New Orleans. This disaster caused the need for a reassessment of the original campus mitigation plan. Both the original plan, and its reassessment, are the subject of this case study.

Operation Enduring Freedom (OEF) (Afghanistan) and Operation Iraqi Freedom (OIF) represent one of the longest wartime deployments in the history of the American military. To date, 1.6 million American military members have deployed. Of these, an estimated 300,000 have returned with a mental health condition, such as depression or PTSD. The Department of Defense has established a robust screening program to identify and track deployment-related physical and psychiatric illnesses. The Post-Deployment Health Reassessment (PDHRA) is a primary tool to identify physical and psychiatric risk following a deployment. The PDHRA is a web-based survey, which is administered between 90-180 days after a deployment. This study seeks to evaluate the psychometric properties and clinical utility of the Post-Deployment Health Reassessment (PDHRA) for accurately identifying truama and depression among Airmen following a deployment. Descriptive statistics, confirmatory factor analysis and structural equation modeling were used to address separate research aims. Study aims assessed the impact of deployment on military members and the clinical utility and psychometric properties of the Post-Deployment Health Reassessment. Findings suggest that the Post-Deployment Health Reassessment is a useful triage tool to identify trauma and depression among Airmen following deployment. The study makes recommendations for improving the clinical utility and psychometric properties of the Post-Deployment Health Reassessment (PDHRA). / text