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Concept: Diffusion


BACKGROUND: Although collaborative team models (CTM) improve care processes and health outcomes, their diffusion poses challenges related to difficulties in securing their adoption by primary care clinicians. The objectives of this study are to understand: (1) how the perceived characteristics of a CTM influenced clinicians' decision to adopt -or not- the model; and (2) the model’s diffusion process. METHODS: We conducted a longitudinal case study based on the Diffusion of Innovations Theory. First, diffusion curves were developed for all 175 primary care physicians (PCPs) and 59 nurses practicing in one borough of Paris. Second, semi-structured interviews were conducted with a representative sample of 40 PCPs and 15 nurses to better understand the implementation dynamics. RESULTS: Diffusion curves showed that 3.5 years after the start of the implementation, 100% of nurses and over 80% of PCPs had adopted the CTM. The dynamics of the CTM’s diffusion were different between the PCPs and the nurses. The slopes of the two curves are also distinctly different. Among the nurses, the critical mass of adopters was attained faster, since they adopted the CTM earlier and more quickly than the PCPs. Results of the semi-structured interviews showed that these differences in diffusion dynamics were mostly founded in differences between the PCPs' and the nurses' perceptions of the CTM’s compatibility with norms, values and practices and its relative advantage (impact on patient management and work practices). Opinion leaders played a key role in the diffusion of the CTM among PCPs. CONCLUSION: CTM diffusion is a social phenomenon that requires a major commitment by clinicians and a willingness to take risks; the role of opinion leaders is key. Paying attention to the notion of a critical mass of adopters is essential to developing implementation strategies that will accelerate the adoption process by clinicians. Key-words: primary care, primary care physician, nurses, chronic disease, collaboration, health service research, diffusion of innovation.

Concepts: Sociology, Diffusion, Adoption, Case study, Innovation, Primary care physician, Diffusion of innovations, Opinion leadership


BACKGROUND: Diffusion tensor imaging (DTI) is increasingly used in various diseases as a clinical tool for assessing the integrity of the brain’s white matter. Reduced fractional anisotropy (FA) and an increased apparent diffusion coefficient (ADC) are nonspecific findings in most pathological processes affecting the brain’s parenchyma. At present, there is no gold standard for validating diffusion measures, which are dependent on the scanning protocols, methods of the softwares and observers. Therefore, the normal variation and repeatability effects on commonly-derived measures should be carefully examined. METHODS: Thirty healthy volunteers (mean age 37.8 years, SD 11.4) underwent DTI of the brain with 3T MRI. Region-of-interest (ROI) -based measurements were calculated at eleven anatomical locations in the pyramidal tracts, corpus callosum and frontobasal area. Two ROI-based methods, the circular method (CM) and the freehand method (FM), were compared. Both methods were also compared by performing measurements on a DTI phantom. The intra- and inter-observer variability (coefficient of variation, or CV%) and repeatability (intra-class correlation coefficient, or ICC) were assessed for FA and ADC values obtained using both ROI methods. RESULTS: The mean FA values for all of the regions were 0.663 with the CM and 0.621 with the FM. For both methods, the FA was highest in the splenium of the corpus callosum. The mean ADC value was 0.727 x10-3 mm2/s with the CM and 0.747 x10-3 mm2/s with the FM, and both methods found the ADC to be lowest in the corona radiata. The CV percentages of the derived measures were < 13% with the CM and < 10% with the FM. In most of the regions, the ICCs were excellent or moderate for both methods. With the CM, the highest ICC for FA was in the posterior limb of the internal capsule (0.90), and with the FM, it was in the corona radiata (0.86). For ADC, the highest ICC was found in the genu of the corpus callosum (0.93) with the CM and in the uncinate fasciculus (0.92) with FM. CONCLUSIONS: With both ROI-based methods variability was low and repeatability was moderate. The circular method gave higher repeatability, but variation was slightly lower using the freehand method. The circular method can be recommended for the posterior limb of the internal capsule and splenium of the corpus callosum, and the freehand method for the corona radiata.

Concepts: Brain, Neuroimaging, Magnetic resonance imaging, Cerebrum, Diffusion, Diffusion MRI, Corpus callosum, Atomic diffusion


There is significant interest in whether diffusion-weighted MR imaging indices, such as the minimum apparent diffusion coefficient, may be useful clinically for preoperative tumor grading and treatment planning. To help establish the pathologic correlate of minimum ADC, we undertook a study investigating the relationship between minimum ADC and maximum FDOPA PET uptake in patients with newly diagnosed glioblastoma multiforme.

Concepts: Brain tumor, Diffusion, Temozolomide


We quantitatively analyzed particle tracking data on insulin granules expressing fluorescent fusion proteins in MIN6 cells to better understand the motions contributing to intracellular transport and, more generally, the means for characterizing systems far from equilibrium. Care was taken to ensure that the statistics reflected intrinsic features of the individual granules rather than details of the measurement and overall cell state. We find anomalous diffusion. Interpreting such data conventionally requires assuming that a process is either ergodic with particles working against fluctuating obstacles (fractional Brownian motion) or nonergodic with a broad distribution of dwell times for traps (continuous-time random walk). However, we find that statistical tests based on these two models give conflicting results. We resolve this issue by introducing a subordinated scheme in which particles in cages with random dwell times undergo correlated motions owing to interactions with a fluctuating environment. We relate this picture to the underlying microtubule structure by imaging in the presence of vinblastine. Our results provide a simple physical picture for how diverse pools of insulin granules and, in turn, biphasic secretion could arise.

Concepts: Cell, Statistics, Cell biology, Diffusion, Stochastic process, Brownian motion, Stochastic processes, Random walk


A ubiquitous observation in cell biology is that the diffusive motion of macromolecules and organelles is anomalous, and a description simply based on the conventional diffusion equation with diffusion constants measured in dilute solution fails. This is commonly attributed to macromolecular crowding in the interior of cells and in cellular membranes, summarizing their densely packed and heterogeneous structures. The most familiar phenomenon is a sublinear, power-law increase of the mean-square displacement (MSD) as a function of the lag time, but there are other manifestations like strongly reduced and time-dependent diffusion coefficients, persistent correlations in time, non-Gaussian distributions of spatial displacements, heterogeneous diffusion and a fraction of immobile particles. After a general introduction to the statistical description of slow, anomalous transport, we summarize some widely used theoretical models: Gaussian models like fractional Brownian motion and Langevin equations for visco-elastic media, the continuous-time random walk model, and the Lorentz model describing obstructed transport in a heterogeneous environment. Particular emphasis is put on the spatio-temporal properties of the transport in terms of two-point correlation functions, dynamic scaling behaviour, and how the models are distinguished by their propagators even if the MSDs are identical. Then, we review the theory underlying commonly applied experimental techniques in the presence of anomalous transport like single-particle tracking, fluorescence correlation spectroscopy (FCS) and fluorescence recovery after photobleaching (FRAP). We report on the large body of recent experimental evidence for anomalous transport in crowded biological media: in cyto- and nucleoplasm as well as in cellular membranes, complemented by in vitro experiments where a variety of model systems mimic physiological crowding conditions. Finally, computer simulations are discussed which play an important role in testing the theoretical models and corroborating the experimental findings. The review is completed by a synthesis of the theoretical and experimental progress identifying open questions for future investigation.

Concepts: Cell nucleus, Cell, Cytosol, Organelle, Cell biology, Diffusion, Macromolecule, Random walk


We report the first demonstration of a microfluidic platform that captures the full physiological range of mass transport in 3-D tissue culture. The basis of our method used long microfluidic channels connected to both sides of a central microtissue chamber at different downstream positions to control the mass transport distribution within the chamber. Precise control of the Péclet number (Pe), defined as the ratio of convective to diffusive transport, over nearly five orders of magnitude (0.0056 to 160) was achieved. The platform was used to systematically investigate the role of physiological mass transport on vasculogenesis. We demonstrate, for the first time, that vasculogenesis can be independently stimulated by interstitial flow (Pe > 10) or hypoxic conditions (Pe < 0.1), and not by the intermediate state (normal living tissue). This simple platform can be applied to physiological and biological studies of 3D living tissue followed by pathological disease studies, such as cancer research and drug screening.

Concepts: Cancer, Biology, Histology, Diffusion, Ratio, English-language films, Microfluidics, Train station


OBJECTIVE: To assess the role of apparent diffusion coefficient (ADC) measured with diffusion-weighted imaging (DWI) in predicting and assessing response of hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE). METHODS: Thirty-six patients with cirrhosis and untreated HCC who underwent TACE and MRI within 3 months before and after TACE were assessed. MRI included DWI and contrast-enhanced T1-weighted imaging. Two observers measured ADC of HCCs and liver parenchyma on pre- and post-TACE MRIs and measured degree of tumor necrosis on subtracted post-contrast images on post-TACE MRI. Pre-, post-TACE tumor ADC, and changes in tumor ADC (ΔADC) were compared between lesions stratified by degree of tumor necrosis (measured on post-TACE MRI). RESULTS: Forty seven HCCs were evaluated (mean size 4.4cm, range 1.0-14.1cm). HCCs with poor and incomplete response to TACE (<50% necrosis on post-TACE MRI) had significantly lower pre-treatment ADC and lower post TACE ADC compared to HCCs with good/complete response (≥50% necrosis): ADC pre-TACE 1.35±0.42 vs. 1.64±0.39×10(-3)mm(2)/s (p=0.042); post-TACE ADC 1.34±0.36 vs. 1.92±0.47 (p=0.0008). There was no difference in ΔADC values. CONCLUSION: This preliminary data suggests that pre-TACE tumor ADC can be used to predict HCC response to TACE.

Concepts: Cancer, Medical imaging, Prediction, Futurology, Magnetic resonance imaging, Assessment, Diffusion, Diffusion MRI


The 2-1-1 helpline is a social services innovation that has spread rapidly throughout the U.S. Policy diffusion theory suggests that policymakers seek to reduce uncertainty by anticipating the effects of a proposed innovation through tools such as cost-benefit analyses. Few policy diffusion studies have examined use of information, such as cost-benefit analyses, in the diffusion process. The purpose of this study is to examine how cost-benefit analyses were used during the rapid diffusion of 2-1-1 across states. The paper also describes components of 2-1-1 cost-benefit analyses.

Concepts: Sociology, Decision theory, Diffusion, Policy, Cultural studies, Cost-benefit analysis, Diffusion of innovations, Benefit-cost ratio


We present a method that allows for a quantitative measurement of the surface self-diffusion on nanostructures, such as nanoparticles, at the atomic scale using aberration-corrected high-resolution transmission electron microscopy (HRTEM). The diffusion coefficient can be estimated by measuring the fluctuation of the atom column occupation at the surface of Au nanoparticles, which is directly observable in temporal sequences of HRTEM images. Both a Au icosahedron and a truncated Au octahedron are investigated, and their diffusion coefficients are found to be in the same order of magnitude, D = 10(-17) to 10(-16) cm(2)/s. It is to be assumed that the measured surface diffusion is affected by the imaging electron beam. This assumption is supported by the observed instability of a (5 × 1) surface reconstruction on a {100} Au facet.

Concepts: Electron, Quantum mechanics, Measurement, Atom, Diffusion, Quantity, Number sense


Films of ethyl cellulose (EC) and water-soluble hydroxypropyl cellulose (HPC) can be used for extended release coatings in oral formulations. The permeability and microstructure of free EC/HPC films with 30% w/w HPC were studied to investigate effects of EC molecular weight. Phase separation during film spraying and subsequent HPC leaching after immersion in aqueous media cause pore formation in such films. It was found that sprayed films were porous throughout the bulk of the film after water immersion. The molecular weight affected HPC leaching, pore morphology and film permeability; increasing the molecular weight resulted in decreasing permeability. A model to distinguish the major factors contributing to diffusion retardation in porous films showed that the trend in permeability was determined predominantly by factors associated with the geometry and arrangement of pores, independent of the diffusing species. The film with the highest molecular weight did, however, show an additional contribution from pore wall/permeant interactions. In addition, rapid drying and increasing molecular weight resulted in smaller pores, which suggest that phase separation kinetics affects the final microstructure of EC/HPC films. Thus, the molecular weight influences the microstructural features of pores, which are crucial for mass transport in EC/HPC films.

Concepts: Effect, Chemistry, Mass, Affect, Molecular diffusion, Diffusion, Hydroxypropyl cellulose