Gastrointestinal Motility in Health and Disease

Michael Zabinski (with Biancani, P., M. P. Zabinski, M. D. Kerstein, and J. Behar) is a contributing author, Comparison of mechanical characteristics of the lower oesophageal sphincter and pyloric sphincter, p.547-551. Book description: Proceedings of the 6th International Symposium on Gastrointestinal Motility, held at the Royal College of Surgeons of Edinburgh, 12–16th September, 1977.https://digitalcommons.fairfield.edu/engineering-books/1036/thumbnail.jp

Shift in the velocity of a front due to a cut-off

We consider the effect of a small cut-off epsilon on the velocity of a traveling wave in one dimension. Simulations done over more than ten orders of magnitude as well as a simple theoretical argument indicate that the effect of the cut-off epsilon is to select a single velocity which converges when epsilon tends to 0 to the one predicted by the marginal stability argument. For small epsilon, the shift in velocity has the form K(log epsilon)^(-2) and our prediction for the constant K agrees very well with the results of our simulations. A very similar logarithmic shift appears in more complicated situations, in particular in finite size effects of some microscopic stochastic systems. Our theoretical approach can also be extended to give a simple way of deriving the shift in position due to initial conditions in the Fisher-Kolmogorov or similar equations.Comment: 12 pages, 3 figure

The Thermonuclear Explosion Of Chandrasekhar Mass White Dwarfs

The flame born in the deep interior of a white dwarf that becomes a Type Ia supernova is subject to several instabilities. We briefly review these instabilities and the corresponding flame acceleration. We discuss the conditions necessary for each of the currently proposed explosion mechanisms and the attendant uncertainties. A grid of critical masses for detonation in the range $10^7$ - $2 \times 10^9$ g cm$^{-3}$ is calculated and its sensitivity to composition explored. Prompt detonations are physically improbable and appear unlikely on observational grounds. Simple deflagrations require some means of boosting the flame speed beyond what currently exists in the literature. ``Active turbulent combustion'' and multi-point ignition are presented as two plausible ways of doing this. A deflagration that moves at the ``Sharp-Wheeler'' speed, $0.1 g_{\rm eff} t$, is calculated in one dimension and shows that a healthy explosion is possible in a simple deflagration if the front moves with the speed of the fastest floating bubbles. The relevance of the transition to the ``distributed burning regime'' is discussed for delayed detonations. No model emerges without difficulties, but detonation in the distributed regime is plausible, will produce intermediate mass elements, and warrants further study.Comment: 28 pages, 4 figures included, uses aaspp4.sty. Submitted to Ap

The role of cell-cell adhesion in wound healing

We present a stochastic model which describes fronts of cells invading a wound. In the model cells can move, proliferate, and experience cell-cell adhesion. We find several qualitatively different regimes of front motion and analyze the transitions between them. Above a critical value of adhesion and for small proliferation large isolated clusters are formed ahead of the front. This is mapped onto the well-known ferromagnetic phase transition in the Ising model. For large adhesion, and larger proliferation the clusters become connected (at some fixed time). For adhesion below the critical value the results are similar to our previous work which neglected adhesion. The results are compared with experiments, and possible directions of future work are proposed.Comment: to appear in Journal of Statistical Physic

Prospective, multicenter study of managing lower extremity venous ulcers

Seventy patients with 90 venous ulcers were randomly assigned to hydrocolloid or conventional dressing and compression therapy at four study centers. The ulcers had been present for a mean of 47.8 in the control and 46.2 weeks in the treatment group and 42% of all patients had recurrent ulcers. Ulcers treated with hydrocolloid dressings reduced 71% and control treated wounds reduced 43% in area after 7.2 weeks of treatment. Thirty-four percent of all ulcers healed. Mean time to healing was 7 weeks for the hydrocolloid dressing group and 8 weeks for the control group. Most ulcers were less painful at final evaluation, but reduction in pain was more pronounced in hydrocolloid-dressed ulcers ( p =0.03). At baseline as well as during follow-up, significant differences between study centers were observed. Ulcers in patients in the United Kingdom were larger and less likely to heal ( p =0.001). Size of the ulcer at baseline was associated with treatment response and time to healing ( p =0.002). Percent reduction in ulcer area after 2 weeks was also correlated with treatment outcome ( p =0.004) and time to healing ( p =0.002). When all treatment outcome predictors were analyzed together, only percent reduction in area after 2 weeks remained statistically significant ( p =0.002), with percent reduction during the first 2 weeks of treatment >30% predicting healing .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41373/1/10016_2005_Article_BF02132997.pd

Pharmacologic prophylaxis for atrial fibrillation following cardiac surgery: a systematic review

Atrial Fibrillation (AF) is the most common arrhythmia occurring after cardiac surgery. Its incidence varies depending on type of surgery. Postoperative AF may cause hemodynamic deterioration, predispose to stroke and increase mortality. Effective treatment for prophylaxis of postoperative AF is vital as reduces hospitalization and overall morbidity. Beta - blockers, have been proved to prevent effectively atrial fibrillation following cardiac surgery and should be routinely used if there are no contraindications. Sotalol may be more effective than standard b-blockers for the prevention of AF without causing an excess of side effects. Amiodarone is useful when beta-blocker therapy is not possible or as additional prophylaxis in high risk patients. Other agents such as magnesium, calcium channels blocker or non-antiarrhythmic drugs as glycose-insulin - potassium, non-steroidal anti-inflammatory drugs, corticosteroids, N-acetylcysteine and statins have been studied as alternative treatment for postoperative AF prophylaxis

Mechanosensing is critical for axon growth in the developing brain.

During nervous system development, neurons extend axons along well-defined pathways. The current understanding of axon pathfinding is based mainly on chemical signaling. However, growing neurons interact not only chemically but also mechanically with their environment. Here we identify mechanical signals as important regulators of axon pathfinding. In vitro, substrate stiffness determined growth patterns of Xenopus retinal ganglion cell axons. In vivo atomic force microscopy revealed a noticeable pattern of stiffness gradients in the embryonic brain. Retinal ganglion cell axons grew toward softer tissue, which was reproduced in vitro in the absence of chemical gradients. To test the importance of mechanical signals for axon growth in vivo, we altered brain stiffness, blocked mechanotransduction pharmacologically and knocked down the mechanosensitive ion channel piezo1. All treatments resulted in aberrant axonal growth and pathfinding errors, suggesting that local tissue stiffness, read out by mechanosensitive ion channels, is critically involved in instructing neuronal growth in vivo.This work was supported by the German National Academic Foundation (scholarship to D.E.K.), Wellcome Trust and Cambridge Trusts (scholarships to A.J.T.), Winston Churchill Foundation of the United States (scholarship to S.K.F.), Herchel Smith Foundation (Research Studentship to S.K.F.), CNPq 307333/2013-2 (L.d.F.C.), NAP-PRP-USP and FAPESP 11/50761-2 (L.d.F.C.), UK EPSRC BT grant (J.G.), Wellcome Trust WT085314 and the European Research Council 322817 grants (C.E.H.); an Alexander von Humboldt Foundation Feodor Lynen Fellowship (K.F.), UK BBSRC grant BB/M021394/1 (K.F.), the Human Frontier Science Program Young Investigator Grant RGY0074/2013 (K.F.), the UK Medical Research Council Career Development Award G1100312/1 (K.F.) and the Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health under Award Number R21HD080585 (K.F.).This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/nn.439

Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation

Background: The neuroinflammatory response following traumatic brain injury (TBI) is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials. Main body: We suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI. Indeed, evidence suggests that the transient receptor potential cation channels (TRP channels), TRPV1 and TRPA1, are polymodal receptors that are activated by a variety of stimuli associated with TBI, including mechanical shear stress, leading to the release of neuropeptides such as substance P (SP). SP augments many aspects of the classical inflammatory response via activation of microglia and astrocytes, degranulation of mast cells, and promoting leukocyte migration. Furthermore, SP may initiate the earliest changes seen in blood-brain barrier (BBB) permeability, namely the increased transcellular transport of plasma proteins via activation of caveolae. This is in line with reports that alterations in transcellular transport are seen first following TBI, prior to decreases in expression of tight-junction proteins such as claudin-5 and occludin. Indeed, the receptor for SP, the tachykinin NK1 receptor, is found in caveolae and its activation following TBI may allow influx of albumin and other plasma proteins which directly augment the inflammatory response by activating astrocytes and microglia. Conclusions: As such, the neurogenic inflammatory response can exacerbate classical inflammation via a positive feedback loop, with classical inflammatory mediators such as bradykinin and prostaglandins then further stimulating TRP receptors. Accordingly, complete inhibition of neuroinflammation following TBI may require the inhibition of both classical and neurogenic inflammatory pathways.Frances Corrigan, Kimberley A. Mander, Anna V. Leonard and Robert Vin

Cost-effectiveness of replacing versus discarding the nail in children with nail bed injury

Every year in the UK, around 10 000 children need to have operations to mend injuries to the bed of their fingernails. Currently, most children have their fingernail placed back on the injured nail bed after the operation. The NINJA trial found that children were slightly less likely to have an infection if the nail was thrown away rather than being put back, but the difference between groups was small and could have be due to chance. This study looked at whether replacing the nail is cost-effective compared with throwing it away. Using data from the NINJA trial, we compared costs, healthcare use, and quality of life and assessed the cost-effectiveness of replacing the nail. It was found that throwing the nail away after surgery would save the National Health Service (NHS) £75 (€85) per operation compared with placing the nail back on the nail bed. Changing clinical practice could save the NHS in England £720 000 (€819 000) per year