Guidance of collective cell migration by substrate geometry.

Collective behavior refers to the emergence of complex migration patterns over scales larger than those of the individual elements constituting a system. It plays a pivotal role in biological systems in regulating various processes such as gastrulation, morphogenesis and tissue organization. Here, by combining experimental approaches and numerical modeling, we explore the role of cell density ('crowding'), strength of intercellular adhesion ('cohesion') and boundary conditions imposed by extracellular matrix (ECM) proteins ('constraints') in regulating the emergence of collective behavior within epithelial cell sheets. Our results show that the geometrical confinement of cells into well-defined circles induces a persistent, coordinated and synchronized rotation of cells that depends on cell density. The speed of such rotating large-scale movements slows down as the density increases. Furthermore, such collective rotation behavior depends on the size of the micropatterned circles: we observe a rotating motion of the overall cell population in the same direction for sizes of up to 200 μm. The rotating cells move as a solid body, with a uniform angular velocity. Interestingly, this upper limit leads to length scales that are similar to the natural correlation length observed for unconfined epithelial cell sheets. This behavior is strongly altered in cells that present a downregulation of adherens junctions and in cancerous cell types. We anticipate that our system provides a simple and easy approach to investigate collective cell behavior in a well-controlled and systematic manner.

Parametric guidance for turbulent noise reduction from poroelastic trailing edges and owls

The interaction of a turbulent eddy with a semi-infinite, poroelastic edge is examined with respect to the effects of both elasticity and porosity on the efficiency of aerodynamic noise generation. The edge is modelled as a thin plate poroelastic plate, which is known to admit fifth-, sixth-, and seventh-power noise dependences on a characteristic velocity U of the turbulent eddy. The associated acoustic scattering problem is solved using the Wiener-Hopf technique for the case of constant plate properties. For the special cases of porous-rigid and impermeable-elastic plate conditions, asymptotic analysis of the Wiener- Hopf kernel function furnishes the parameter groups and their ranges where U5, U6, and U7 behaviours are expected to occur. Results from this analysis attempt to help guide the search for passive edge treatments to reduce trailing-edge noise that are inspired by the wing features of silently flying owls. Furthermore, the appropriateness of the present model to the owl noise problem is discussed with respect to the acoustic frequencies of interest, wing chord-lengths, and foraging behaviour across a representative set of owl species.

Trust-Level Risk Evaluation and Risk Control Guidance in the NHS East of England

In recent years, the healthcare sector has adopted the use of operational risk assessment tools to help understand the systems issues that lead to patient safety incidents. But although these problem-focused tools have improved the ability of healthcare organizations to identify hazards, they have not translated into measurable improvements in patient safety. One possible reason for this is a lack of support for the solution-focused process of risk control. This article describes a content analysis of the risk management strategies, policies, and procedures at all acute (i.e., hospital), mental health, and ambulance trusts (health service organizations) in the East of England area of the British National Health Service. The primary goal was to determine what organizational-level guidance exists to support risk control practice. A secondary goal was to examine the risk evaluation guidance provided by these trusts. With regard to risk control, we found an almost complete lack of useful guidance to promote good practice. With regard to risk evaluation, the trusts relied exclusively on risk matrices. A number of weaknesses were found in the use of this tool, especially related to the guidance for scoring an event's likelihood. We make a number of recommendations to address these concerns. The guidance assessed provides insufficient support for risk control and risk evaluation. This may present a significant barrier to the success of risk management approaches in improving patient safety. © 2013 Society for Risk Analysis.

Nonautonomous contact guidance signaling during collective cell migration.

Directed migration of groups of cells is a critical aspect of tissue morphogenesis that ensures proper tissue organization and, consequently, function. Cells moving in groups, unlike single cells, must coordinate their migratory behavior to maintain tissue integrity. During directed migration, cells are guided by a combination of mechanical and chemical cues presented by neighboring cells and the surrounding extracellular matrix. One important class of signals that guide cell migration includes topographic cues. Although the contact guidance response of individual cells to topographic cues has been extensively characterized, little is known about the response of groups of cells to topographic cues, the impact of such cues on cell-cell coordination within groups, and the transmission of nonautonomous contact guidance information between neighboring cells. Here, we explore these phenomena by quantifying the migratory response of confluent monolayers of epithelial and fibroblast cells to contact guidance cues provided by grooved topography. We show that, in both sparse clusters and confluent sheets, individual cells are contact-guided by grooves and show more coordinated behavior on grooved versus flat substrates. Furthermore, we demonstrate both in vitro and in silico that the guidance signal provided by a groove can propagate between neighboring cells in a confluent monolayer, and that the distance over which signal propagation occurs is not significantly influenced by the strength of cell-cell junctions but is an emergent property, similar to cellular streaming, triggered by mechanical exclusion interactions within the collective system.