Collective effects in cellular structure formation mediated by compliant environments: a Monte Carlo study

Compliant environments can mediate interactions between mechanically active cells like fibroblasts. Starting with a phenomenological model for the behaviour of single cells, we use extensive Monte Carlo simulations to predict non-trivial structure formation for cell communities on soft elastic substrates as a function of elastic moduli, cell density, noise and cell position geometry. In general, we find a disordered structure as well as ordered string-like and ring-like structures. The transition between ordered and disordered structures is controlled both by cell density and noise level, while the transition between string- and ring-like ordered structures is controlled by the Poisson ratio. Similar effects are observed in three dimensions. Our results suggest that in regard to elastic effects, healthy connective tissue usually is in a macroscopically disordered state, but can be switched to a macroscopically ordered state by appropriate parameter variations, in a way that is reminiscent of wound contraction or diseased states like contracture.Comment: 45 pages, 7 postscript figures included, revised version accepted for publication in Acta Biomateriali

Developing a standardized tool for interpretation of radiology diagnostic accuracy trials

Summary Within the health sciences, action research is a methodology well suited to the goal of collaboratively improving practice. As the Royal College of Radiology recommends the use of published clinical trials as guides for achieving higher standards of accuracy, it is important for radiologists to reflect deeply on the results from diagnostic accuracy studies. When the results of the gold standard (or reference standard) are used to confirm a particular diagnosis or disease by comparing the diagnostic accuracy to a newer or index test, this is referred to as diagnostic accuracy research. In the reporting of all research, every effort must be made to reduce the incidence of bias. In 2003, the STARD (Standards for Reporting Diagnostic Accuracy) tool was developed for clinicians to enhance the quality of reporting diagnostic accuracy studies. Based on previous studies, experiential knowledge, and an extensive review of the literature, this research demonstrates that the STARD tool is not being fully optimized. The overall aim of this research was to conduct a work-based project within the department of radiology to develop a revised tool, based on the current STARD, which could then be used to more accurately report and interpret the results of radiology diagnostic accuracy trials. This study was conducted in accordance with participatory action research. Methods The development of this new reporting tool was conducted in collaboration with a group of physicians, and in two distinct phases. First, a needs assessment was sent to eight radiological experts who had agreed to participate in the study. Based on their responses, and feedback from my mentor and colleagues, the next phase of tool development was done using the Delphi technique, after two rounds of which consensus was met. Each phase and cycle iteration to complete the needs assessment and Delphi technique are synonymous with the cycles of action research. The new reporting tool was named the RadSTARD (Radiology Standards for the Reporting of Diagnostic Accuracy Studies), and an elaboration document was written to provide guidance to the end-user. Radiology residents and Fellows at The Ottawa Hospital were then asked to rate their level of confidence in interpreting a diagnostic accuracy article specific to radiology while referring to the RadSTARD. They were also provided a second diagnostic article, the STARD tool, and an elaboration document for comparison. Data was collected using questionnaires that allowed for additional comments. Findings The validation phase of the RadSTARD tool was completed via triangulation of data, as both a quantitative and qualitative analysis was completed. The results found no significant statistical difference between the two groups as per the Mann-Whitney and chi-square analysis. Likewise, both physician groups indicated that they found RadSTARD increased their level of confidence when interpreting the diagnostic accuracy article. Concomitantly, when combined, 96% of the two physician groups indicated they would use the tool again. Interpretation These results may be interpreted as generalizable, as there was no discrepancy or statistical difference found in the results between the radiology residents’ and Fellows’ scores, despite the differences in their level of training. Both groups found the RadSTARD tool and elaboration document to be beneficial to them when interpreting the literature. RadSTARD is thus a reliable tool that can be used to validate the results of diagnostic accuracy studies specific to radiology. It will aid radiologists in reporting and interpreting radiology diagnostic accuracy studies, impacting their practice for generations to come

The Unexpected Impact of Information-Sharing on US Pharmaceutical Supply-Chains

This paper examines the introduction of information-sharing into the supply chains for pharmaceutical products in the United States. This introduction was unusual for several reasons. First, it was catalyzed from outside the industry, by a Securities and Exchange Commission (SEC) investigation into improper financial reporting by a single manufacturer. Second, it was initiated by pharmaceutical manufacturers in order to keep distributor inventories low. Third, although its effect on pharmaceutical distributors has been profound, evidence indicates that information-sharing has had no impact on pharmaceutical manufacturers' own inventorymanagement practices.

Role of anisotropy for protein-protein encounter

Protein-protein interactions comprise both transport and reaction steps. During the transport step, anisotropy of proteins and their complexes is important both for hydrodynamic diffusion and accessibility of the binding site. Using a Brownian dynamics approach and extensive computer simulations, we quantify the effect of anisotropy on the encounter rate of ellipsoidal particles covered with spherical encounter patches. We show that the encounter rate $k$ depends on the aspect ratios $\xi$ mainly through steric effects, while anisotropic diffusion has only a little effect. Calculating analytically the crossover times from anisotropic to isotropic diffusion in three dimensions, we find that they are much smaller than typical protein encounter times, in agreement with our numerical results.Comment: 4 pages, Revtex with 3 figures, to appear as a Rapid Communication in Physical Review

Nondecoupling of Maximal Supergravity from the Superstring

We consider the conditions necessary for obtaining perturbative maximal supergravity in d dimensions as a decoupling limit of type II superstring theory compactified on a (10-d) torus. For dimensions d=2 and d=3, it is possible to define a limit in which the only finite-mass states are the 256 massless states of maximal supergravity. However, in dimensions d>=4, there are infinite towers of additional massless and finite-mass states. These correspond to Kaluza-Klein charges, wound strings, Kaluza-Klein monopoles, or branes wrapping around cycles of the toroidal extra dimensions. We conclude that perturbative supergravity cannot be decoupled from string theory in dimensions >=4. In particular, we conjecture that pure [script N]=8 supergravity in four dimensions is in the Swampland

Focal adhesions as mechanosensors: the two-spring model

Adhesion-dependent cells actively sense the mechanical properties of their environment through mechanotransductory processes at focal adhesions, which are integrin-based contacts connecting the extracellular matrix to the cytoskeleton. Here we present first steps towards a quantitative understanding of focal adhesions as mechanosensors. It has been shown experimentally that high levels of force are related to growth of and signaling at focal adhesions. In particular, activation of the small GTPase Rho through focal adhesions leads to the formation of stress fibers. Here we discuss one way in which force might regulate the internal state of focal adhesions, namely by modulating the internal rupture dynamics of focal adhesions. A simple two-spring model shows that the stiffer the environment, the more efficient cellular force is built up at focal adhesions by molecular motors interacting with the actin filaments.Comment: Latex, 17 pages, 5 postscript figures include

Effects of movements in equities prices on M2 demand

Large swings in stock prices are sometimes associated with a redirection of household savings flows. Such changes can lead to transitory increases in M2 as investors temporarily “park” funds in depository assets while they determine the funds’ ultimate destination. The authors find that, although stock price changes are statistically significant as an explanation for M2 growth, they do not account for much of M2’s recent strength.Stock - Prices ; Demand for money

Focal adhesions as mechanosensors: the two-spring model

Adhesion-dependent cells actively sense the mechanical properties of their environment through mechanotransductory processes at focal adhesions, which are integrin-based contacts connecting the extracellular matrix to the cytoskeleton. Here we present first steps towards a quantitative understanding of focal adhesions as mechanosensors. It has been shown experimentally that high levels of force are related to growth of and signaling at focal adhesions. In particular, activation of the small GTPase Rho through focal adhesions leads to the formation of stress fibers. Here we discuss one way in which force might regulate the internal state of focal adhesions, namely by modulating the internal rupture dynamics of focal adhesions. A simple two-spring model shows that the stiffer the environment, the more efficient cellular force is built up at focal adhesions by molecular motors interacting with the actin filaments.Comment: Latex, 17 pages, 5 postscript figures include