Value Assessment of Orphan Drugs and Treatments for Rare Diseases

Thesis (Master's)--University of Washington, 2016-06

Causes of variability in light absorption by particles in snow at sites in Idaho and Utah.

This file accompanies “NAmer2014SnowBC_Dohertyetal_v1.xlsx”, which contains data on black carbon (BC) and other light-absorbing particles in snow in Utah and Idaho, for samples collected January-March 2014 in Jan/Feb 2013 and 2014 in Utah. Data are available as an Excel file with headers, or as a comma-separated data file, with no headers. There is one entry per layer of snow sampled. All entries (other than column titles in the .xlsx) are numeric. Detailed information on our measurements can be found in a series of publications, as given below.  Description of the instrument and method used to make the measurements: Grenfell, T. C., S. J. Doherty, A. D. Clarke, and S. G. Warren, Spectrophotometric determination of absorptive impurities in snow, Appl. Opt., 50(14), pp.2037-2048, 2011.  Summary and discussion of dataset “NAmer2014SnowBC_Dohertyetal.xlsx”, including maps of sample locations: Doherty, S. J., D. A. Hegg, P. K. Quinn, J. E. Johnson, J. P. Schwarz, C. Dang and S. G. Warren, Causes of variability in light absorption by particles in snow at sites in Idaho and Utah, J. Geophys. Res. Atmos., 121, doi:10.1002/2015JD024375, 2016. Note that the measurement and analysis techniques used to produce these data were also used in a broad Arctic survey (2006-2010) of BC and other light-absorbing particles snow, as reported here: Doherty, S. J., S. G. Warren, T. C. Grenfell, A. D. Clarke, and R. E. Brandt: Light-absorbing impurities in Arctic snow, Atmos. Chem. Phys., 10, 11647-11680, doi:10.5194/acp-10-11647-2010, 2010. http://www.atmos-chem-phys.net/10/11647/2010/acp-10-11647-2010.html

Remotely sensed data for ecosystem analyses: Combining hierarchy and scene models

Remotely sensed data have been used extensively for environmental monitoring and modeling at a number of spatial scales; however, a limited range of satellite imaging systems often. constrained the scales of these analyses. A wider variety of data sets is now available, allowing image data to be selected to match the scale of environmental structure(s) or process(es) being examined. A framework is presented for use by environmental scientists and managers, enabling their spatial data collection needs to be linked to a suitable form of remotely sensed data. A six-step approach is used, combining image spatial analysis and scaling tools, within the context of hierarchy theory. The main steps involved are: (1) identification of information requirements for the monitoring or management problem; (2) development of ideal image dimensions (scene model), (3) exploratory analysis of existing remotely sensed data using scaling techniques, (4) selection and evaluation of suitable remotely sensed data based on the scene model, (5) selection of suitable spatial analytic techniques to meet information requirements, and (6) cost-benefit analysis. Results from a case study show that the framework provided an objective mechanism to identify relevant aspects of the monitoring problem and environmental characteristics for selecting remotely sensed data and analysis techniques.

Phylogeography of an east Australian wet-forest bird, the satin bowerbird (Ptilonorhynchus violaceus), derived from mtDNA, and its relationship to morphology

Australian wet forests have undergone a contraction in range since the mid-Tertiary, resulting in a fragmented distribution along the east Australian coast incorporating several biogeographical barriers. Variation in mitochondrial DNA and morphology within the satin bowerbird was used to examine biogeographical structure throughout almost the entire geographical extent of these wet forest fragments. We used several genetic analysis techniques, nested clade and barrier analyses, that use patterns inherent in the data to describe the spatial structuring. We also examined the validity of the two previously described satin bowerbird subspecies that are separated by well-defined biogeographical barriers and tested existing hypotheses that propose divergence occurs within each subspecies across two other barriers, the Black Mountain corridor and the Hunter Valley. Our data showed that the two subspecies were genetically and morphologically divergent. The northern subspecies, found in the Wet Tropics region of Queensland, showed little divergence across the Black Mountain corridor, a barrier found to be significant in other Wet Tropics species. Biogeographical structure was found through southeastern Australia; three geographically isolated populations showed genetic differentiation, although minimal divergence was found across the proposed Hunter Valley barrier. A novel barrier was found separating inland and coastal populations in southern New South Wales. Little morphological divergence was observed within subspecies, bar a trend for birds to be larger in the more southerly parts of the species' range. The results from both novel and well-established genetic analyses were similar, providing greater confidence in the conclusions about spatial divergence and supporting the validity of these new techniques.

Robustness of mathematical models for biological systems

The robustness of mathematical models for biological systems is studied by sensitivity analysis and stochastic simulations. Using a neural network model with three genes as the test problem, we study robustness properties of synthesis and degradation processes. For single parameter robustness, sensitivity analysis techniques are applied for studying parameter variations and stochastic simulations are used for investigating the impact of external noise. Results of sensitivity analysis are consistent with those obtained by stochastic simulations. Stochastic models with external noise can be used for studying the robustness not only to external noise but also to parameter variations. For external noise we also use stochastic models to study the robustness of the function of each gene and that of the system.

The network structure of a regional tourism organization: Application of he social network theory in one region of Queensland

Regional tourism organizations (RTOs) plays a central role in planning, coordinating and marketing tourism in many areas, including Queensland, Australia. RTOs rely on interaction with a network of other organizations for their efficient functioning. This paper describes an exploratory case study that develops a method for use of social network analysis techniques to analyse the inter-organizational network in one RTO region in Queensland. Results indicate that differences exist in the structure of inter-organizational links between commercial tourism organizations and planning organizations, between tourism organizations and other sectoral clusters, and between organizations at local, regional and state levels. The results highlight areas or improvement in the role and responsibilities of RTOs in Queensland.

O ESTÉTICO E O SOCIAL, IMAGEM E CONTEXTO NA CAPA DA ILUSTRÍSSIMA

Esta pesquisa investiga a presença da imagem na capa do suplemento cultural dominical da Folha de S. Paulo, a Ilustríssima, a partir de um estudo de caso. O foco foi a análise das condições sociais e estéticas de produção dessa imagem de origem artística, levando em conta a mistura entre arte e jornalismo que o suplemento comporta e os conceitos de hibridação e de convergência. Técnicas da Análise de Discurso auxiliaram na análise da articulação entre as questões estéticas (condições textuais) e extratextuais (condições sociais), onde os sentidos são renovados a partir das tensões e contradições entre texto e contexto. A metodologia baseia-se nos Estudos Visuais, campo que tem o pensamento de Edgar Morin como principal influência, possibilitando-nos um olhar complexo sobre a produção da imagem presente na Ilustríssima.

"Action at a distance":accounting inscriptions and the reporting of episodes of clinical care

This paper reports on an aspect of the implementation of a sophisticated system of Casemix Budgeting within a large public hospital in New Zealand. The paper examines the role of accounting inscription in supporting a system of “remote” management control effected through the Finance function at the hospital. The paper provides detailed description and analysis of part of the casemix technology in use at the research site. The implementation of clinical budgeting through the Transition casemix system will be examined by describing an aspect of the casemix system in detail. The design and use of management reporting is described. Reporting to different levels of management and for differing parts of the organisation are discussed with particular emphasis on the adoption of traditional analysis of costs using standard costing and variance analysis techniques.

Response-based segmentation using Finite Mixture Partial Least Squares: theoretical foundations and an application to American Customer Satisfaction Index Data

When applying multivariate analysis techniques in information systems and social science disciplines, such as management information systems (MIS) and marketing, the assumption that the empirical data originate from a single homogeneous population is often unrealistic. When applying a causal modeling approach, such as partial least squares (PLS) path modeling, segmentation is a key issue in coping with the problem of heterogeneity in estimated cause-and-effect relationships. This chapter presents a new PLS path modeling approach which classifies units on the basis of the heterogeneity of the estimates in the inner model. If unobserved heterogeneity significantly affects the estimated path model relationships on the aggregate data level, the methodology will allow homogenous groups of observations to be created that exhibit distinctive path model estimates. The approach will, thus, provide differentiated analytical outcomes that permit more precise interpretations of each segment formed. An application on a large data set in an example of the American customer satisfaction index (ACSI) substantiates the methodology’s effectiveness in evaluating PLS path modeling results.

A concise guide to market research:the process, data, and methods using IBM SPSS Statistics

This accessible, practice-oriented and compact text provides a hands-on introduction to the principles of market research. Using the market research process as a framework, the authors explain how to collect and describe the necessary data and present the most important and frequently used quantitative analysis techniques, such as ANOVA, regression analysis, factor analysis, and cluster analysis. An explanation is provided of the theoretical choices a market researcher has to make with regard to each technique, as well as how these are translated into actions in IBM SPSS Statistics. This includes a discussion of what the outputs mean and how they should be interpreted from a market research perspective. Each chapter concludes with a case study that illustrates the process based on real-world data. A comprehensive web appendix includes additional analysis techniques, datasets, video files and case studies. Several mobile tags in the text allow readers to quickly browse related web content using a mobile device.

The design of robust protocols for distributed real-time systems

Modern distributed control systems comprise of a set of processors which are interconnected using a suitable communication network. For use in real-time control environments, such systems must be deterministic and generate specified responses within critical timing constraints. Also, they should be sufficiently robust to survive predictable events such as communication or processor faults. This thesis considers the problem of coordinating and synchronizing a distributed real-time control system under normal and abnormal conditions. Distributed control systems need to periodically coordinate the actions of several autonomous sites. Often the type of coordination required is the all or nothing property of an atomic action. Atomic commit protocols have been used to achieve this atomicity in distributed database systems which are not subject to deadlines. This thesis addresses the problem of applying time constraints to atomic commit protocols so that decisions can be made within a deadline. A modified protocol is proposed which is suitable for real-time applications. The thesis also addresses the problem of ensuring that atomicity is provided even if processor or communication failures occur. Previous work has considered the design of atomic commit protocols for use in non time critical distributed database systems. However, in a distributed real-time control system a fault must not allow stringent timing constraints to be violated. This thesis proposes commit protocols using synchronous communications which can be made resilient to a single processor or communication failure and still satisfy deadlines. Previous formal models used to design commit protocols have had adequate state coverability but have omitted timing properties. They also assumed that sites communicated asynchronously and omitted the communications from the model. Timed Petri nets are used in this thesis to specify and design the proposed protocols which are analysed for consistency and timeliness. Also the communication system is mcxielled within the Petri net specifications so that communication failures can be included in the analysis. Analysis of the Timed Petri net and the associated reachability tree is used to show the proposed protocols always terminate consistently and satisfy timing constraints. Finally the applications of this work are described. Two different types of applications are considered, real-time databases and real-time control systems. It is shown that it may be advantageous to use synchronous communications in distributed database systems, especially if predictable response times are required. Emphasis is given to the application of the developed commit protocols to real-time control systems. Using the same analysis techniques as those used for the design of the protocols it can be shown that the overall system performs as expected both functionally and temporally.

A new approach to neuroimaging with magnetoencephalography

We discuss the application of beamforming techniques to the field of magnetoencephalography (MEG). We argue that beamformers have given us an insight into the dynamics of oscillatory changes across the cortex not explored previously with traditional analysis techniques that rely on averaged evoked responses. We review several experiments that have used beamformers, with special emphasis on those in which the results have been compared to those observed in functional magnetic resonance imaging (fMRI) and on those studying induced phenomena. We suggest that the success of the beamformer technique, despite the assumption that there are no linear interactions between the mesoscopic local field potentials across distinct cortical areas, may tell us something of the balance between functional integration and segregation in the human brain. What is more, MEG beamformer analysis facilitates the study of these complex interactions within cortical networks that are involved in both sensory-motor and cognitive processes. © 2005 Wiley-Liss, Inc.

Continuous measurement of accommodation in human factor applications

It has long been sought to measure ocular accommodation continuously in human factor applications such as driving or flying. Open-field autorefractors such as the Canon R-1 could be converted to allow continuous, objective recording, but steady eye fixation and head immobilisation were essential for the measurements to be valid. Image analysis techniques utilised by newer open-view autorefractors such as the Shin-Nippon SRW-5000 are more tolerant to head and eye movements, but perhaps the technique with the greatest potential for the measurement of accommodation in human factor applications is photoretinoscopy. This paper examines the development of techniques for high temporal measurements of accommodation and reports on the tolerance of one such recent commercial instrument, the PowerRefractor (PlusOptiX). The instrument was found to be tolerant to eye movements from the optical axis of the instrument (∼0.50 DS change in apparent accommodation with gaze 25° eccentric to the optical axis), longitudinal head movement (<0.25 DS from 8 cm towards and 20 cm away from the correct photorefractor to eye distance) and changes in background illuminance (<0.25 DS from 0.5 to 20 cd m-2 target luminance). The PowerRefractor also quantifies the direction of gaze and pupil size, but is unable to take measurements with small pupils <3.7 ±1.0 mm. © 2002 The College of Optometrists.

Exploratory database visualisation: the application and assessment of data and dimensionality reduction

This thesis describes the development of a complete data visualisation system for large tabular databases, such as those commonly found in a business environment. A state-of-the-art 'cyberspace cell' data visualisation technique was investigated and a powerful visualisation system using it was implemented. Although allowing databases to be explored and conclusions drawn, it had several drawbacks, the majority of which were due to the three-dimensional nature of the visualisation. A novel two-dimensional generic visualisation system, known as MADEN, was then developed and implemented, based upon a 2-D matrix of 'density plots'. MADEN allows an entire high-dimensional database to be visualised in one window, while permitting close analysis in 'enlargement' windows. Selections of records can be made and examined, and dependencies between fields can be investigated in detail. MADEN was used as a tool for investigating and assessing many data processing algorithms, firstly data-reducing (clustering) methods, then dimensionality-reducing techniques. These included a new 'directed' form of principal components analysis, several novel applications of artificial neural networks, and discriminant analysis techniques which illustrated how groups within a database can be separated. To illustrate the power of the system, MADEN was used to explore customer databases from two financial institutions, resulting in a number of discoveries which would be of interest to a marketing manager. Finally, the database of results from the 1992 UK Research Assessment Exercise was analysed. Using MADEN allowed both universities and disciplines to be graphically compared, and supplied some startling revelations, including empirical evidence of the 'Oxbridge factor'.

Consumer evaluations of brand extensions in emerging economies : evidences from China

This project explored how consumers in emerging economies evaluate brand extension by using China as a case. Two separate but related studies were conducted, and university students were used as respondents in both the studies. Study one or replication study tested Aaker and Keller's brand extension model in China. Assuming similar methods to Aaker and Keller's, six well-recognised brands were chosen as parent brand and each was extended to three product categories. Totally, 469 respondents completed the survey questionnaire. As each was to evaluate six extensions, this made the cases 2814. The data was analysed using Optimal Least Square regression approach and "residual centred" approach respectively. The result confirmed most of the findings observed in developed countries. Specifically, consumer's attitude towards the extension is primarily driven by the brand affect, the fit between the two product categories, the difficulty of making the extension and moderated via the interactions between the brand affect and the fit variables. Study two refined and extended Aaker and Keller's model by adding new variables and making methodological adjustments. The same stimuli and data analysis techniques as those in the replication were employed. 252 respondents participated in the survey and each evaluated six extensions, making cases 1512. In addition to re-verifying the findings of the replication and providing cross validation to these findings, the extended study found that the image consistency between the parent brand and the extension, the competition intensity of the extension product market were important in determining the success of the extension. Further, consumer differed in evaluating durable extensions and non-durable extensions. The thesis detailed the two studies above, and discussed the findings and their implications by relating to branding literature, to the general situation of the emerging economies as well as the reality of China. It also presented the limitations of the research and the future research directions.