A Three-dimensional Printed Low-cost Anterior Shoulder Dislocation Model for Ultrasound-guided Injection Training.

Anterior shoulder dislocations are the most common, large joint dislocations that present to the emergency department (ED). Numerous studies support the use of intraarticular local anesthetic injections for the safe, effective, and time-saving reduction of these dislocations. Simulation training is an alternative and effective method for training compared to bedside learning. There are no commercially available ultrasound-compatible shoulder dislocation models. We utilized a three-dimensional (3D) printer to print a model that allows the visualization of the ultrasound anatomy (sonoanatomy) of an anterior shoulder dislocation. We utilized an open-source file of a shoulder, available from embodi3D® (Bellevue, WA, US). After approximating the relative orientation of the humerus to the glenoid fossa in an anterior dislocation, the humerus and scapula model was printed with an Ultimaker-2 Extended+ 3D® (Ultimaker, Cambridge, MA, US) printer using polylactic acid filaments. A 3D model of the external shoulder anatomy of a live human model was then created using Structure Sensor®(Occipital, San Francisco, CA, US), a 3D scanner. We aligned the printed dislocation model of the humerus and scapula within the resultant external shoulder mold. A pourable ballistics gel solution was used to create the final shoulder phantom. The use of simulation in medicine is widespread and growing, given the restrictions on work hours and a renewed focus on patient safety. The adage of see one, do one, teach one is being replaced by deliberate practice. Simulation allows such training to occur in a safe teaching environment. The ballistic gel and polylactic acid structure effectively reproduced the sonoanatomy of an anterior shoulder dislocation. The 3D printed model was effective for practicing an in-plane ultrasound-guided intraarticular joint injection. 3D printing is effective in producing a low-cost, ultrasound-capable model simulating an anterior shoulder dislocation. Future research will determine whether provider confidence and the use of intraarticular anesthesia for the management of shoulder dislocations will improve after utilizing this model

Undulation Instability of Epithelial Tissues

Treating the epithelium as an incompressible fluid adjacent to a viscoelastic stroma, we find a novel hydrodynamic instability that leads to the formation of protrusions of the epithelium into the stroma. This instability is a candidate for epithelial fingering observed in vivo. It occurs for sufficiently large viscosity, cell-division rate and thickness of the dividing region in the epithelium. Our work provides physical insight into a potential mechanism by which interfaces between epithelia and stromas undulate, and potentially by which tissue dysplasia leads to cancerous invasion.Comment: 4 pages, 3 figure

Fast adaptation of cooperative channels engenders Hopf bifurcations in auditory hair cells

Since the pioneering work of Thomas Gold, published in 1948, it has been known that we owe our sensitive sense of hearing to a process in the inner ear that can amplify incident sounds on a cycle-by-cycle basis. Called the active process, it uses energy to counteract the viscous dissipation associated with sound-evoked vibrations of the ear’s mechanotransduction apparatus. Despite its importance, the mechanism of the active process and the proximate source of energy that powers it have remained elusive, especially at the high frequencies characteristic of amniote hearing. This is partly due to our insufficient understanding of the mechanotransduction process in hair cells, the sensory receptors and amplifiers of the inner ear. It has been proposed previously that cyclical binding of Ca2+ ions to individual mechanotransduction channels could power the active process. That model, however, relied on tailored reaction rates that structurally forced the direction of the cycle. Here we ground our study on our previous model of hair-cell mechanotransduction, which relied on cooperative gating of pairs of channels, and incorporate into it the cyclical binding of Ca2+ ions. With a single binding site per channel and reaction rates drawn from thermodynamic principles, the current model shows that hair cells behave as nonlinear oscillators that exhibit Hopf bifurcations, dynamical instabilities long understood to be signatures of the active process. Using realistic parameter values, we find bifurcations at frequencies in the kilohertz range with physiological Ca2+ concentrations. The current model relies on the electrochemical gradient of Ca2+ as the only energy source for the active process and on the relative motion of cooperative channels within the stereociliary membrane as the sole mechanical driver. Equipped with these two mechanisms, a hair bundle proves capable of operating at frequencies in the kilohertz range, characteristic of amniote hearing

Forces between clustered stereocilia minimize friction in the ear on a subnanometre scale

The detection of sound begins when energy derived from acoustic stimuli deflects the hair bundles atop hair cells. As hair bundles move, the viscous friction between stereocilia and the surrounding liquid poses a fundamental challenge to the ear's high sensitivity and sharp frequency selectivity. Part of the solution to this problem lies in the active process that uses energy for frequency-selective sound amplification. Here we demonstrate that a complementary part involves the fluid-structure interaction between the liquid within the hair bundle and the stereocilia. Using force measurement on a dynamically scaled model, finite-element analysis, analytical estimation of hydrodynamic forces, stochastic simulation and high-resolution interferometric measurement of hair bundles, we characterize the origin and magnitude of the forces between individual stereocilia during small hair-bundle deflections. We find that the close apposition of stereocilia effectively immobilizes the liquid between them, which reduces the drag and suppresses the relative squeezing but not the sliding mode of stereociliary motion. The obliquely oriented tip links couple the mechanotransduction channels to this least dissipative coherent mode, whereas the elastic horizontal top connectors stabilize the structure, further reducing the drag. As measured from the distortion products associated with channel gating at physiological stimulation amplitudes of tens of nanometres, the balance of forces in a hair bundle permits a relative mode of motion between adjacent stereocilia that encompasses only a fraction of a nanometre. A combination of high-resolution experiments and detailed numerical modelling of fluid-structure interactions reveals the physical principles behind the basic structural features of hair bundles and shows quantitatively how these organelles are adapted to the needs of sensitive mechanotransduction.Comment: 21 pages, including 3 figures. For supplementary information, please see the online version of the article at http://www.nature.com/natur

Coherent motion of stereocilia assures the concerted gating of hair-cell transduction channels

The hair cell's mechanoreceptive organelle, the hair bundle, is highly sensitive because its transduction channels open over a very narrow range of displacements. The synchronous gating of transduction channels also underlies the active hair-bundle motility that amplifies and tunes responsiveness. The extent to which the gating of independent transduction channels is coordinated depends on how tightly individual stereocilia are constrained to move as a unit. Using dual-beam interferometry in the bullfrog's sacculus, we found that thermal movements of stereocilia located as far apart as a bundle's opposite edges display high coherence and negligible phase lag. Because the mechanical degrees of freedom of stereocilia are strongly constrained, a force applied anywhere in the hair bundle deflects the structure as a unit. This feature assures the concerted gating of transduction channels that maximizes the sensitivity of mechanoelectrical transduction and enhances the hair bundle's capacity to amplify its inputs.Comment: 24 pages, including 6 figures, published in 200

Homeostatic competition drives tumor growth and metastasis nucleation

We propose a mechanism for tumor growth emphasizing the role of homeostatic regulation and tissue stability. We show that competition between surface and bulk effects leads to the existence of a critical size that must be overcome by metastases to reach macroscopic sizes. This property can qualitatively explain the observed size distributions of metastases, while size-independent growth rates cannot account for clinical and experimental data. In addition, it potentially explains the observed preferential growth of metastases on tissue surfaces and membranes such as the pleural and peritoneal layers, suggests a mechanism underlying the seed and soil hypothesis introduced by Stephen Paget in 1889 and yields realistic values for metastatic inefficiency. We propose a number of key experiments to test these concepts. The homeostatic pressure as introduced in this work could constitute a quantitative, experimentally accessible measure for the metastatic potential of early malignant growths.Comment: 13 pages, 11 figures, to be published in the HFSP Journa

Advances on antiviral activity of Morus spp. plant extracts: Human coronavirus and virus-related respiratory tract infections in the spotlight

(1) Background: Viral respiratory infections cause life-threatening diseases in millions of people worldwide every year. Human coronavirus and several picornaviruses are responsible for worldwide epidemic outbreaks, thus representing a heavy burden to their hosts. In the absence of specific treatments for human viral infections, natural products offer an alternative in terms of innovative drug therapies. (2) Methods: We analyzed the antiviral properties of the leaves and stem bark of the mulberry tree (Morus spp.). We compared the antiviral activity of Morus spp. on enveloped and nonenveloped viral pathogens, such as human coronavirus (HCoV 229E) and different members of the Picornaviridae family—human poliovirus 1, human parechovirus 1 and 3, and human echovirus 11. The antiviral activity of 12 water and water–alcohol plant extracts of the leaves and stem bark of three different species of mulberry—Morus alba var. alba, Morus alba var. rosa, and Morus rubra—were evaluated. We also evaluated the antiviral activities of kuwanon G against HCoV-229E. (3) Results: Our results showed that several extracts reduced the viral titer and cytopathogenic effects (CPE). Leaves’ water-alcohol extracts exhibited maximum antiviral activity on human coronavirus, while stem bark and leaves’ water and water-alcohol extracts were the most effective on picornaviruses. (4) Conclusions: The analysis of the antiviral activities of Morus spp. offer promising applications in antiviral strategies

The ATLAS High Level Trigger Steering

The High Level Trigger (HLT) of the ATLAS experiment at the Large Hadron Collider receives events which pass the LVL1 trigger at ~75 kHz and has to reduce the rate to ~200 Hz while retaining the most interesting physics. It is a software trigger and performs the reduction in two stages: the LVL2 trigger and the Event Filter (EF). At the heart of the HLT is the Steering software. To minimise processing time and data transfers it implements the novel event selection strategies of seeded, step-wise reconstruction and early rejection. The HLT is seeded by regions of interest identified at LVL1. These and the static configuration determine which algorithms are run to reconstruct event data and test the validity of trigger signatures. The decision to reject the event or continue is based on the valid signatures, taking into account pre-scale and pass-through. After the EF, event classification tags are assigned for streaming purposes. Several powerful new features for commissioning and operation have been added: comprehensive monitoring is now built in to the framework; for validation and debugging, reconstructed data can be written out; the steering is integrated with the new configuration (presented separately), and topological and global triggers have been added. This paper will present details of the final design and its implementation, the principles behind it, and the requirements and constraints it is subject to. The experience gained from technical runs with realistic trigger menus will be described

On the Milnor formula in arbitrary characteristic

The Milnor formula $\mu=2\delta-r+1$ relates the Milnor number $\mu$, the double point number $\delta$ and the number $r$ of branches of a plane curve singularity. It holds over the fields of characteristic zero. Melle and Wall based on a result by Deligne proved the inequality $\mu\geq 2\delta-r+1$ in arbitrary characteristic and showed that the equality $\mu=2\delta-r+1$ characterizes the singularities with no wild vanishing cycles. In this note we give an account of results on the Milnor formula in characteristic $p$. It holds if the plane singularity is Newton non-degenerate (Boubakri et al. Rev. Mat. Complut. (2010) 25) or if $p$ is greater than the intersection number of the singularity with its generic polar (Nguyen H.D., Annales de l'Institut Fourier, Tome 66 (5) (2016)). Then we improve our result on the Milnor number of irreducible singularities (Bull. London Math. Soc. 48 (2016)). Our considerations are based on the properties of polars of plane singularities in characteristic $p$.Comment: 18 page