The development of a validated clinically meaningful endpoint for the evaluation of tear film stability as a measure of ocular surface protection for use in the diagnosis and evaluation of dry eye disease

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Description
This dissertation presents methods for the evaluation of ocular surface protection during natural blink function. The evaluation of ocular surface protection is especially important in the diagnosis of dry eye and the evaluation of dry eye severity in clinical trials.

This dissertation presents methods for the evaluation of ocular surface protection during natural blink function. The evaluation of ocular surface protection is especially important in the diagnosis of dry eye and the evaluation of dry eye severity in clinical trials. Dry eye is a highly prevalent disease affecting vast numbers (between 11% and 22%) of an aging population. There is only one approved therapy with limited efficacy, which results in a huge unmet need. The reason so few drugs have reached approval is a lack of a recognized therapeutic pathway with reproducible endpoints. While the interplay between blink function and ocular surface protection has long been recognized, all currently used evaluation techniques have addressed blink function in isolation from tear film stability, the gold standard of which is Tear Film Break-Up Time (TFBUT). In the first part of this research a manual technique of calculating ocular surface protection during natural blink function through the use of video analysis is developed and evaluated for it's ability to differentiate between dry eye and normal subjects, the results are compared with that of TFBUT. In the second part of this research the technique is improved in precision and automated through the use of video analysis algorithms. This software, called the OPI 2.0 System, is evaluated for accuracy and precision, and comparisons are made between the OPI 2.0 System and other currently recognized dry eye diagnostic techniques (e.g. TFBUT). In the third part of this research the OPI 2.0 System is deployed for use in the evaluation of subjects before, immediately after and 30 minutes after exposure to a controlled adverse environment (CAE), once again the results are compared and contrasted against commonly used dry eye endpoints. The results demonstrate that the evaluation of ocular surface protection using the OPI 2.0 System offers superior accuracy to the current standard, TFBUT.
Date Created
2012
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An analytical approach to lean six sigma deployment strategies: project identification and prioritization

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Description
The ever-changing economic landscape has forced many companies to re-examine their supply chains. Global resourcing and outsourcing of processes has been a strategy many organizations have adopted to reduce cost and to increase their global footprint. This has, however, resulted

The ever-changing economic landscape has forced many companies to re-examine their supply chains. Global resourcing and outsourcing of processes has been a strategy many organizations have adopted to reduce cost and to increase their global footprint. This has, however, resulted in increased process complexity and reduced customer satisfaction. In order to meet and exceed customer expectations, many companies are forced to improve quality and on-time delivery, and have looked towards Lean Six Sigma as an approach to enable process improvement. The Lean Six Sigma literature is rich in deployment strategies; however, there is a general lack of a mathematical approach to deploy Lean Six Sigma in a global enterprise. This includes both project identification and prioritization. The research presented here is two-fold. Firstly, a process characterization framework is presented to evaluate processes based on eight characteristics. An unsupervised learning technique, using clustering algorithms, is then utilized to group processes that are Lean Six Sigma conducive. The approach helps Lean Six Sigma deployment champions to identify key areas within the business to focus a Lean Six Sigma deployment. A case study is presented and 33% of the processes were found to be Lean Six Sigma conducive. Secondly, having identified parts of the business that are lean Six Sigma conducive, the next steps are to formulate and prioritize a portfolio of projects. Very often the deployment champion is faced with the decision of selecting a portfolio of Lean Six Sigma projects that meet multiple objectives which could include: maximizing productivity, customer satisfaction or return on investment, while meeting certain budgetary constraints. A multi-period 0-1 knapsack problem is presented that maximizes the expected net savings of the Lean Six Sigma portfolio over the life cycle of the deployment. Finally, a case study is presented that demonstrates the application of the model in a large multinational company. Traditionally, Lean Six Sigma found its roots in manufacturing. The research presented in this dissertation also emphasizes the applicability of the methodology to the non-manufacturing space. Additionally, a comparison is conducted between manufacturing and non-manufacturing processes to highlight the challenges in deploying the methodology in both spaces.
Date Created
2011
Agent

Multivariate charts for multivariate poisson-distributed data

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Description
There has been much research involving simultaneous monitoring of several correlated quality characteristics that rely on the assumptions of multivariate normality and independence. In real world applications, these assumptions are not always met, particularly when small counts are of interest.

There has been much research involving simultaneous monitoring of several correlated quality characteristics that rely on the assumptions of multivariate normality and independence. In real world applications, these assumptions are not always met, particularly when small counts are of interest. In general, the use of normal approximation to the Poisson distribution seems to be justified when the Poisson means are large enough. A new two-sided Multivariate Poisson Exponentially Weighted Moving Average (MPEWMA) control chart is proposed, and the control limits are directly derived from the multivariate Poisson distribution. The MPEWMA and the conventional Multivariate Exponentially Weighted Moving Average (MEWMA) charts are evaluated by using the multivariate Poisson framework. The MPEWMA chart outperforms the MEWMA with the normal-theory limits in terms of the in-control average run lengths. An extension study of the two-sided MPEWMA to a one-sided version is performed; this is useful for detecting an increase in the count means. The results of comparison with the one-sided MEWMA chart are quite similar to the two-sided case. The implementation of the MPEWMA scheme for multiple count data is illustrated, with step by step guidelines and several examples. In addition, the method is compared to other model-based control charts that are used to monitor the residual values such as the regression adjustment. The MPEWMA scheme shows better performance on detecting the mean shift in count data when positive correlation exists among all variables.
Date Created
2010
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