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Extended Fixed Attribute Dynamics Method and an Illustrative Application in Bio-demographic-genetic Analysis on Longevity.

ABSTRACT: This chapter presents and discuss the extended Fixed Attributes Dynamics (FAD) method to estimate the independent effect of a genetic variant (or other fixed attribute) in the absence of another relevant genetic variant (or another relevant fixed attribute), the joint effects when both are present and the effects of interactions between them. We present an illustrative application of the extended FAD method for estimating the general, independent and joint effects of the FOXO genotypes on longevity, based on the genotypic data of 760 centenarians from the Chinese Longitudinal Healthy Longevity Survey, and the 1,060 middle-age controls. We also discuss the strengths and limitations of the FAD method.

SUBMITTER: Zeng Y

PROVIDER: S-EPMC4191865 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Extended Fixed Attribute Dynamics Method and an Illustrative Application in Bio-demographic-genetic Analysis on Longevity.

Zeng Yi Y

Annual review of gerontology & geriatrics 20130101 1

This chapter presents and discuss the extended Fixed Attributes Dynamics (FAD) method to estimate the independent effect of a genetic variant (or other fixed attribute) in the absence of another relevant genetic variant (or another relevant fixed attribute), the joint effects when both are present and the effects of interactions between them. We present an illustrative application of the extended FAD method for estimating the general, independent and joint effects of the FOXO genotypes on longev ...[more]

PMID: 25309014

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Project description:We present a conceptual approach to determine the optimal solution to delivering a health technology, consistent with the objective of maximizing patient outcomes subject to resources available to a publicly funded health system. The article addresses two key policy questions: 1) adding system values through appropriate planning of health services delivery and 2) considering the tradeoff between patient outcomes and costs to the health system through appropriate use of health technologies for conditions with time-dependent treatment outcomes. We develop a health technology optimization framework that considers geographical variation and searches for the best delivery method through a pairwise comparison of all possible strategies, factoring in controlled variables including disease epidemiology, time or distance to hospitals, available medical services, treatment eligibility, treatment efficacy, and costs. Taking variations of these factors into account would help support a more efficient allocation of health resources. Drawing identified strategies together then creates a map of optimal strategies. We apply the proposed method to a policy-relevant health technology assessment of endovascular therapy (EVT) for treating acute ischemic stroke. The best strategy for providing EVT relies on the geographical location of stroke onset and the decision maker's preference for either patient outcomes or economic efficiency. The proposed method produced an optimization map showing the optimal strategy for EVT delivery, which maximizes patient outcomes while minimizing health system costs. In the illustrative case study, there were no tradeoffs between health outcomes and costs, meaning that the delivery strategies that were clinically optimal for patients were also the most cost-effective. In conclusion, the health technology optimization approach is a useful tool for informing implementation decisions and coordinating the delivery of complex health services such as EVT.

Project description:The multi-attribute method (MAM), a recent advance in the application of liquid chromatography-mass spectrometry within the pharmaceutical industry, enables the simultaneous monitoring of multiple product quality attributes in a single analytical method. While MAM is coupled with automated data processing and reporting, the sample preparation, based on proteolytic peptide mapping, remains cumbersome and low throughput. The standard sample preparation for MAM relies on protein denaturation, reduction, and alkylation prior to proteolytic digestion, but often a desalting step is required to maintain enzymatic activity. While most of the sample preparation can be automated on a standard robotic liquid handling system, a streamlined approach for protein desalting and temperature modulation is required for a viable, fully automated digestion. In this work, for the first time, a complete tip-based MAM sample preparation is automated on a single robotic liquid handling system, leveraging a deck layout that integrates both heating and cooling functionalities. The fully automated method documented herein achieves a high-throughput sample preparation for MAM, while maintaining superior method performance.Abbreviations: MAM: multi-attribute method; PQAs: product quality attributes; CE: capillary electrophoresis; IEX: ion-exchange chromatography; HILIC-FLR: hydrophilic interaction liquid chromatography coupled to a fluorescence detector; RP-LC/UV: reversed-phase liquid chromatography coupled to a UV detector; MS: mass spectrometry; NPD: new peak detection; GdnHCl: guanidine hydrochloride; TIC: total ion current; pAb: polyclonal antibody; IgG: immunoglobulin G; DTT: dithiothreitol; IAA: iodoacetic acid; TFA: trifluoroacetic acid; A280: absorbance at 280 nm wavelength; 96MPH: 96-channel multi-probe head; CPAC: Cold Plate Air Cooled; HHS: Hamilton Heater Shaker; DWP: Deep-Well Plate; PCR: Polymerase Chain Reaction; NTR: Nested Tip Rack; Met: methionine; Trp: tryptophan; N-term pQ: N-terminal glutamine cyclization; Lys: lysine; PAM: peptidylglycine α-amidating monooxygenase; G0F: asialo-, agalacto-, bi-antennary, core substituted with fucose; G1F: asialo-, mono-galactosylated bi-antennary, core substituted with fucose; G2F: asialo-, bi-galactosylated bi-antennary, core substituted with fucose; G0: asialo-, agalacto-, bi-antennary; Man5: oligomannose 5; Man8: oligomannose 8; TriF: asialo-, tri-galactosylated tri-antennary, core substituted with fucose.

Dataset Information

Extended Fixed Attribute Dynamics Method and an Illustrative Application in Bio-demographic-genetic Analysis on Longevity.

Publications

Extended Fixed Attribute Dynamics Method and an Illustrative Application in Bio-demographic-genetic Analysis on Longevity.

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