Modeling Correlated Discrete Uncertainties in Event Trees with Copulas.

Modeling the dependence between uncertainties in decision and risk analyses is an important part of the problem structuring process. We focus on situations where correlated uncertainties are discrete, and extend the concept of the copula-based approach for modeling correlated continuous uncertainties to the representation of correlated discrete uncertainties. This approach reduces the required number of probability assessments significantly compared to approaches requiring direct estimates of conditional probabilities. It also allows the use of multiple dependence measures, including product moment correlation, rank order correlation and tail dependence, and parametric families of copulas such as normal copulas, t-copulas, and Archimedean copulas. This approach can be extended to model the dependence between discrete and continuous uncertainties in the same event tree.

Current status and future prospects for electronic point-of-care clinical decision support in diabetes care.

Early efforts to use point-of-care clinical decision support (CDS) were limited to the use of prompts and reminders, which improved test ordering but not intermediate outcomes of care, such as glucose, blood pressure, or lipid levels. More sophisticated diabetes CDS tools are now available that use electronic medical record data to provide patient-specific advice on medication use on the basis of previous treatment, distance from goal, and other clinical data. These tools have shown modest but significant improvement in glucose and blood pressure control. Promising next-generation developments will include prioritizing clinical actions that have maximum benefit to a given patient at the point of care and developing effective methods to communicate CDS information to patients to better incorporate patient preferences in care decisions.

Effects of electronic decision support on high-tech diagnostic imaging orders and patients.

OBJECTIVE: To evaluate the effects of providing appropriateness criteria through guideline-based electronic health record (EHR) decision support for high-tech diagnostic imaging (HTDI) procedures. STUDY DESIGN: Chart audits were performed on a random sample of adult primary care orders for 3 HTDI procedures (computed tomography [CT] and magnetic resonance imaging [MRI] of the head, and MRI of the lumbar spine) before and after implementation of an EHR decision support system. OUTCOME MEASURES: Level of appropriateness, abnormal findings, and apparent effects on patient care. RESULTS: A total of 299 eligible audits were performed. Decision support was associated with a 20% to 36% drop in spine MRI and head CT orders, but head MRI order volume was unaffected. Combined results for the 3 procedures showed that a larger proportion of studies ordered after implementing decision support (89.2% vs 79.5%, P = .02) fit appropriateness criteria, and more postimplementation studies had A ratings (highest utility rating) (81.8% vs 70%, P = .04). However, there were no differences in the proportion of tests with positive findings (42/132 vs 28/120, P = .16 among procedures that met definite criteria) or the proportion with a likely impact on patients (6.6% vs 10.8%, P = .07). CONCLUSIONS: These data support the feasibility of using chart audits to assess the relationship between appropriateness criteria and HTDI orders. Although introduction of EHR clinical decision support for diagnostic imaging orders was associated with reduced volume and increased appropriateness of orders, there was little apparent impact on either findings or patients.

Self-organized gels in DNA/F-actin mixtures without crosslinkers: networks of induced nematic domains with tunable density.

We examine mixtures of DNA and filamentous actin (F-actin) as a model system of like-charged rigid rods and flexible chains. Confocal microscopy reveals the formation of elongated nematic F-actin domains reticulated via defect-free vertices into a network embedded in a mesh of random DNA. Synchrotron x-ray scattering results indicate that the DNA mesh squeezes the F-actin domains into a nematic state with an interactin spacing that decreases with increasing DNA concentration as d(actin) proportional, variantrho(DNA)(-1/2). Interestingly, the system changes from a counterion-controlled regime to a depletion-controlled regime with added salt, with drastic consequences for the osmotic pressure induced phase behavior.

Counterions between charged polymers exhibit liquid-like organization and dynamics.

Current understanding of electrostatics in water is based on mean-field theories like the Poisson-Boltzmann formalism and its approximations, which are routinely used in colloid science and computational biology. This approach, however, breaks down for highly charged systems, which exhibit counterintuitive phenomena such as overcharging and like-charge attraction. Models of counterion correlations have been proposed as possible explanations, but no experimental comparisons are available. Here, collective dynamics of counterions that mediate like-charge attraction between F-actin filaments have been directly observed in aqueous solution using high-resolution inelastic x-ray scattering down to molecular length-scales. We find a previously undescribed acoustic-like phonon mode associated with correlated counterions. The excitation spectra at high wave-vector Q reveal unexpected dynamics due to ions interacting with their "cages" of nearest neighbors. We examine this behavior in the context of intrinsic charge density variations on F-actin. The measured speed of sound and collective relaxation rates in this liquid agree surprisingly well with simple model calculations.

Structure and dynamics of liquid crystalline pattern formation in drying droplets of DNA.

We investigate the formation of ringlike deposits in drying drops of DNA. In analogy with the colloidal "coffee rings," DNA is transported to the perimeter by the capillary flow. At the droplet edge, however, DNA forms a lyotropic liquid crystal (LC) with concentric chain orientations to minimize the LC elastic energy. During the final stages of drying, the contact line retracts, and the radial stress causes undulations at the rim that propagate inward through the LC and form a periodic zigzag structure. We examine the phenomenon in terms of a simple model based on LC elasticity.

Ion multivalence and like-charge polyelectrolyte attraction.

It is known empirically that multivalent ions generate attractions between like-charged polyelectrolytes, with different valence requirements for different systems. How multivalent must an ion be before it can condense a given polyelectrolyte? Using charge-tunable M13 virus rods and a family of artificial homologous "dumbbell" divalent ions of different sizes, we have constructed a multivalent ion-polyelectrolyte phase diagram, and find an experimentally motivated general criterion for like-charged attraction based on the ion valence, ion size, and the Gouy-Chapman length.