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- Creators: Ira A. Fulton Schools of Engineering
- Member of: Programs and Communities
This brief article, written for a symposium on "Collaboration and the Colorado River," evaluates the U.S. Department of the Interior's Glen Canyon Dam Adaptive Management Program ("AMP"). The AMP has been advanced as a pioneering collaborative and adaptive approach for both decreasing scientific uncertainty in support of regulatory decision-making and helping manage contentious resource disputes -- in this case, the increasingly thorny conflict over the Colorado River's finite natural resources. Though encouraging in some respects, the AMP serves as a valuable illustration of the flaws of existing regulatory processes purporting to incorporate collaboration and regulatory adaptation into the decision-making process. Born in the shadow of the law and improvised with too little thought as to its structure, the AMP demonstrates the need to attend to the design of the regulatory process and integrate mechanisms that compel systematic program evaluation and adaptation. As such, the AMP provides vital information on how future collaborative experiments might be modified to enhance their prospects of success.
The Glen Canyon Dam Adaptive Management Program (AMP) has been identified as a model for natural resource management. We challenge that assertion, citing the lack of progress toward a long-term management plan for the dam, sustained extra-programmatic conflict, and a downriver ecology that is still in jeopardy, despite over ten years of meetings and an expensive research program. We have examined the primary and secondary sources available on the AMP’s design and operation in light of best practices identified in the literature on adaptive management and collaborative decision-making. We have identified six shortcomings: (1) an inadequate approach to identifying stakeholders; (2) a failure to provide clear goals and involve stakeholders in establishing the operating procedures that guide the collaborative process; (3) inappropriate use of professional neutrals and a failure to cultivate consensus; (4) a failure to establish and follow clear joint fact-finding procedures; (5) a failure to produce functional written agreements; and (6) a failure to manage the AMP adaptively and cultivate long-term problem-solving capacity.
Adaptive management can be an effective approach for addressing complex ecosystem-related processes like the operation of the Glen Canyon Dam, particularly in the face of substantial complexity, uncertainty, and political contentiousness. However, the Glen Canyon Dam AMP shows that a stated commitment to collaboration and adaptive management is insufficient. Effective management of natural resources can only be realized through careful attention to the collaborative design and implementation of appropriate problem-solving and adaptive-management procedures. It also requires the development of an appropriate organizational infrastructure that promotes stakeholder dialogue and agency learning. Though the experimental Glen Canyon Dam AMP is far from a success of collaborative adaptive management, the lessons from its shortcomings can foster more effective collaborative adaptive management in the future by Congress, federal agencies, and local and state authorities.
Methods: The traditional methodology (Forced-Stare [FS]) measures TFBUT and IBI separately. TFBUT is measured under forced-stare conditions by an examiner using a stopwatch, while IBI is measured as the subject watches television. The new methodology (video capture manual analysis [VCMA]) involves retrospective analysis of video data of fluorescein-stained eyes taken through a slit lamp while the subject watches television, and provides TFBUT and BUA for each IBI during the 1-minute video under natural blink conditions. The FS and VCMA methods were directly compared in the same set of dry-eye subjects. The VCMA method was evaluated for the ability to discriminate between dry-eye subjects and normal subjects. The VCMA method was further evaluated in the dry eye subjects for the ability to detect a treatment effect before, and 10 minutes after, bilateral instillation of an artificial tear solution.
Results: Ten normal subjects and 17 dry-eye subjects were studied. In the dry-eye subjects, the two methods differed with respect to mean TFBUTs (5.82 seconds, FS; 3.98 seconds, VCMA; P = 0.002). The FS variables alone (TFBUT, IBI) were not able to successfully distinguish between the dry-eye and normal subjects, whereas the additional VCMA variables, both derived and observed (BUA, BUA/IBI, breakup rate), were able to successfully distinguish between the dry-eye and normal subjects in a statistically significant fashion. TFBUT (P = 0.034) and BUA/IBI (P = 0.001) were able to distinguish the treatment effect of artificial tears in dry-eye subjects.
Conclusion: The VCMA methodology provides a clinically relevant analysis of tear film stability measured in the context of a natural blink pattern.
Methods: Thirty-three dry eye subjects completed a single-center, single-visit, pilot CAE study. The primary endpoint was mean break-up area (MBA) as assessed by the OPI 2.0 system. Secondary endpoints included corneal fluorescein staining, tear film break-up time, and OPI 2.0 system measurements. Subjects were also asked to rate their ocular discomfort throughout the CAE. Dry eye endpoints were measured at baseline, immediately following a 90-minute CAE exposure, and again 30 minutes after exposure.
Results: The post-CAE measurements of MBA showed a statistically significant decrease from the baseline measurements. The decrease was relatively specific to those patients with moderate to severe dry eye, as measured by baseline MBA. Secondary endpoints including palpebral fissure size, corneal staining, and redness, also showed significant changes when pre- and post-CAE measurements were compared. A correlation analysis identified specific associations between MBA, blink rate, and palpebral fissure size. Comparison of MBA responses allowed us to identify subpopulations of subjects who exhibited different compensatory mechanisms in response to CAE challenge. Of note, none of the measures of tear film break-up time showed statistically significant changes or correlations in pre-, versus post-CAE measures.
Conclusion: This pilot study confirms that the tear film metric MBA can detect changes in the ocular surface induced by a CAE, and that these changes are correlated with other, established measures of dry eye disease. The observed decrease in MBA following CAE exposure demonstrates that compensatory mechanisms are initiated during the CAE exposure, and that this compensation may provide the means to identify and characterize clinically relevant subpopulations of dry eye patients.
Grading schemes for breast cancer diagnosis are predominantly based on pathologists' qualitative assessment of altered nuclear structure from 2D brightfield microscopy images. However, cells are three-dimensional (3D) objects with features that are inherently 3D and thus poorly characterized in 2D. Our goal is to quantitatively characterize nuclear structure in 3D, assess its variation with malignancy, and investigate whether such variation correlates with standard nuclear grading criteria.
Methodology
We applied micro-optical computed tomographic imaging and automated 3D nuclear morphometry to quantify and compare morphological variations between human cell lines derived from normal, benign fibrocystic or malignant breast epithelium. To reproduce the appearance and contrast in clinical cytopathology images, we stained cells with hematoxylin and eosin and obtained 3D images of 150 individual stained cells of each cell type at sub-micron, isotropic resolution. Applying volumetric image analyses, we computed 42 3D morphological and textural descriptors of cellular and nuclear structure.
Principal Findings
We observed four distinct nuclear shape categories, the predominant being a mushroom cap shape. Cell and nuclear volumes increased from normal to fibrocystic to metastatic type, but there was little difference in the volume ratio of nucleus to cytoplasm (N/C ratio) between the lines. Abnormal cell nuclei had more nucleoli, markedly higher density and clumpier chromatin organization compared to normal. Nuclei of non-tumorigenic, fibrocystic cells exhibited larger textural variations than metastatic cell nuclei. At p<0.0025 by ANOVA and Kruskal-Wallis tests, 90% of our computed descriptors statistically differentiated control from abnormal cell populations, but only 69% of these features statistically differentiated the fibrocystic from the metastatic cell populations.
Conclusions
Our results provide a new perspective on nuclear structure variations associated with malignancy and point to the value of automated quantitative 3D nuclear morphometry as an objective tool to enable development of sensitive and specific nuclear grade classification in breast cancer diagnosis.