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Statistical method for comparing the level of intracellular organization between cells.

ABSTRACT: Systems level approaches to analyzing complex emergent behavior require quantitative characterization of alterations of behavior on both the microscale and macroscale. Here we consider the problem of cellular organization and describe a statistical methodology for quantitative comparison of the internal organization between different populations of similar physical objects, such as cells. This comparison is achieved with several steps of analysis. Starting with three-dimensional or two-dimensional images of cells, images are segmented to identify individual cells. Locations of internal points of interest, such as organelles or proteins, are recorded. To define the configuration of internal points in each cell, the individual cells are subjected to bounded Voronoi tessellation: subdividing the bounded volume or area of the cell into subvolumes determined by the locations of the internal points of interest. A statistical methodology is applied to yield a metric for similarity in degree of organization between populations. We applied this methodology to test whether centrioles play a role in global cellular organization, using mutants of the green alga Chlamydomonas reinhardtii with known alterations in centriole number, structure, and position as a model system. Comparing mutant populations and wild-type populations revealed a dramatic difference in the degree of organization in the mutant strains. These computational and experimental results provide statistical support for prior observational studies and support the idea that centrioles play a role in generating or maintaining global cellular organization. Our results confirm that this method can be used to sensitively compare the extent and type of organization within cells.

SUBMITTER: Apte ZS

PROVIDER: S-EPMC3600484 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Statistical method for comparing the level of intracellular organization between cells.

Apte Zachary S ZS Marshall Wallace F WF

Proceedings of the National Academy of Sciences of the United States of America 20121126 11

Systems level approaches to analyzing complex emergent behavior require quantitative characterization of alterations of behavior on both the microscale and macroscale. Here we consider the problem of cellular organization and describe a statistical methodology for quantitative comparison of the internal organization between different populations of similar physical objects, such as cells. This comparison is achieved with several steps of analysis. Starting with three-dimensional or two-dimension ...[more]

PMID: 23185014

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Project description:BackgroundFinancial barriers in substance use disorder service systems have limited the widespread adoption-i.e., provider-level reach-of evidence-based practices (EBPs) for youth substance use disorders. Reach is essential to maximizing the population-level impact of EBPs. One promising, but rarely studied, type of implementation strategy for overcoming barriers to EBP reach is financing strategies, which direct financial resources in various ways to support implementation. We evaluated financing strategies for the Adolescent Community Reinforcement Approach (A-CRA) EBP by comparing two US federal grant mechanisms, organization-focused and state-focused grants, on organization-level A-CRA reach outcomes.MethodA-CRA implementation took place through organization-focused and state-focused grantee cohorts from 2006 to 2021. We used a quasi-experimental, mixed-method design to compare reach between treatment organizations funded by organization-focused versus state-focused grants (164 organizations, 35 states). Using administrative training records, we calculated reach as the per-organization proportion of trained individuals who received certification in A-CRA clinical delivery and/or supervision by the end of grant funding. We tested differences in certification rate by grant type using multivariable linear regression models that controlled for key covariates (e.g., time), and tested threats to internal validity from our quasi-experimental design through a series of sensitivity analyses. We also drew on interviews and surveys collected from the treatment organizations and (when relevant) interviews with state administrators to identify factors that influenced reach.ResultsThe overall certification rates were 27 percentage points lower in state-focused versus organization-focused grants (p = .01). Sensitivity analyses suggested these findings were not explained by confounding temporal trends nor by organizational or state characteristics. We did not identify significant quantitative moderators of reach outcomes, but qualitative findings suggested certain facilitating factors were more influential for organization-focused grants (e.g., strategic planning) and certain barrier factors were more impactful for state-focused grants (e.g., states finding it difficult to execute grant activities).DiscussionAs the first published comparison of EBP reach outcomes between financing strategies, our findings can help guide state and federal policy related to financing strategies for implementing EBPs that reduce youth substance use. Future work should explore contextual conditions under which different financing strategies can support the widespread implementation of EBPs for substance use disorder treatment.

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Statistical method for comparing the level of intracellular organization between cells.

Publications

Statistical method for comparing the level of intracellular organization between cells.

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