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You searched for subject:( multistate design). Showing records 1 – 2 of 2 total matches.

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1. Moon, Nathalie. Topics in the Design of Life History Studies.

Degree: 2018, University of Waterloo

Substantial investments are being made in health research to support the conduct of large cohort studies with the objective of improving understanding of the relationships between diverse features (e.g. exposure to toxins, genetic biomarkers, demographic variables) and disease incidence, progression, and mortality. Longitudinal cohort studies are commonly used to study life history processes, that is patterns of disease onset, progression, and death in a population. While primary interest often lies in estimating the effect of some factor on a simple time-to-event outcome, multistate modelling offers a convenient and powerful framework for the joint consideration of disease onset, progression, and mortality, as well as the effect of one or more covariates on these transitions. Longitudinal studies are typically very costly, and the complexity of the follow-up scheme is often not fully considered at the design stage, which may lead to inefficient allocation of study resources and/or underpowered studies. In this thesis, several aspects of study design are considered to guide the design of complex longitudinal studies, with the general aim being to obtain efficient estimates of parameters of interest subject to cost constraints. Attention is focused on a general K state model where states 1, …, K-1 represent different stages of a chronic disease and state K is an absorbing state representing death. In Chapter 2, we propose an approach to design efficient tracing studies to mitigate the loss of information stemming from attrition, a common feature of prospective cohort studies. Our approach exploits observed information on state occupancy prior to loss-to-followup, covariates, and the time of loss-to-followup to inform the selection of individuals to be traced, leading to more judicious allocation of resources. Two settings are considered. In the first there are only constraints on the expected number of individuals to be traced, and in the second the constraints are imposed on the expected cost of tracing. In the latter, the fact that some types of data may be more costly to obtain via tracing than other types of data is dealt with. In Chapter 3, we focus on two key aspects of longitudinal cohort studies with intermittent assessments: sample size and the frequency of assessments. We derive the Fisher information as the basis for studying the interplay between these factors and to identify features of minimum-cost designs to achieve desired power. Extensions which accommodate the possibility of misclassification of disease status at the intermittent assessments times are developed. These are useful to assess the impact of imperfect screening or diagnostic tests in the longitudinal setting. In Chapter 4, attention is turned to state-dependent sampling designs for prevalent cohort studies. While incident cohorts involve recruiting individuals before they experience some event of interest (e.g. onset of a particular disease) and prospectively following them to observe this event, prevalent cohorts…

Subjects/Keywords: Multistate models; Life history studies; Study design; Intermittent observation schemes

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Moon, N. (2018). Topics in the Design of Life History Studies. (Thesis). University of Waterloo. Retrieved from http://hdl.handle.net/10012/13618

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Moon, Nathalie. “Topics in the Design of Life History Studies.” 2018. Thesis, University of Waterloo. Accessed July 05, 2020. http://hdl.handle.net/10012/13618.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Moon, Nathalie. “Topics in the Design of Life History Studies.” 2018. Web. 05 Jul 2020.

Vancouver:

Moon N. Topics in the Design of Life History Studies. [Internet] [Thesis]. University of Waterloo; 2018. [cited 2020 Jul 05]. Available from: http://hdl.handle.net/10012/13618.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Moon N. Topics in the Design of Life History Studies. [Thesis]. University of Waterloo; 2018. Available from: http://hdl.handle.net/10012/13618

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of Ottawa

2. Davey, James A. Multistate Computational Protein Design: Theories, Methods, and Applications .

Degree: 2016, University of Ottawa

Traditional computational protein design (CPD) calculations model sequence perturbations and evaluate their stabilities using a single fixed protein backbone template in an approach referred to as single‐state design (SSD). However, certain design objectives require the explicit consideration of multiple conformational states. Cases where a multistate framework may be advantageous over the single‐state approach include the computer aided discovery of new enzyme substrates, the prediction of protein stabilities, and the design of protein dynamics. These design objectives can be tackled using multistate design (MSD). However, it is often the case that a design objective requires the consideration of a protein state having no available structure information. For such circumstances the multistate framework cannot be applied. In this thesis I present the development of two template and ensemble preparation methodologies and their application to three projects. The purpose of which is to demonstrate the necessary ensemble modeling strategies to overcome limitations in available structure information. Particular emphasis is placed on the ability to recapitulate experimental data to guide modelling of the design space. Specifically, the use of MSD allowed for the accurate prediction of a methyltransferase recognition motif and new substrates, the prediction of mutant sequence stabilities with quantitative accuracy, and the design of dynamics into the rigid Gβ1 scaffold producing a set of dynamic variants whose tryptophan residue exchanges between two conformations on the millisecond timescale. Implementation of both the ensemble, coordinate perturbation followed by energy minimization (PertMin), and template, rotamer optimization followed by energy minimization (ROM), generation protocols developed here allow for exploration and manipulation of the structure space enabling the success of these applications.

Subjects/Keywords: computational protein design; multistate design; protein engineering; molecular modeling; substrate multispecificity; protein stability; protein dynamics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Davey, J. A. (2016). Multistate Computational Protein Design: Theories, Methods, and Applications . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/35541

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Davey, James A. “Multistate Computational Protein Design: Theories, Methods, and Applications .” 2016. Thesis, University of Ottawa. Accessed July 05, 2020. http://hdl.handle.net/10393/35541.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Davey, James A. “Multistate Computational Protein Design: Theories, Methods, and Applications .” 2016. Web. 05 Jul 2020.

Vancouver:

Davey JA. Multistate Computational Protein Design: Theories, Methods, and Applications . [Internet] [Thesis]. University of Ottawa; 2016. [cited 2020 Jul 05]. Available from: http://hdl.handle.net/10393/35541.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Davey JA. Multistate Computational Protein Design: Theories, Methods, and Applications . [Thesis]. University of Ottawa; 2016. Available from: http://hdl.handle.net/10393/35541

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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