Amelioration of Acute Sequelae of Blast Induced Mild Traumatic Brain Injury by N-Acetyl Cysteine: A Double-Blind, Placebo Controlled Study

Background: Mild traumatic brain injury (mTBI) secondary to blast exposure is the most common battlefield injury in Southwest Asia. There has been little prospective work in the combat setting to test the efficacy of new countermeasures. The goal of this study was to compare the efficacy of N-acetyl cysteine (NAC) versus placebo on the symptoms associated with blast exposure mTBI in a combat setting. Methods: This study was a randomized double blind, placebo-controlled study that was conducted on active duty service members at a forward deployed field hospital in Iraq. All symptomatic U.S. service members who were exposed to significant ordnance blast and who met the criteria for mTBI were offered participation in the study and 81 individuals agreed to participate. Individuals underwent a baseline evaluation and then were randomly assigned to receive either N-acetyl cysteine (NAC) or placebo for seven days. Each subject was re-evaluated at 3 and 7 days. Outcome measures were the presence of the following sequelae of mTBI: dizziness, hearing loss, headache, memory loss, sleep disturbances, and neurocognitive dysfunction. The resolution of these symptoms seven days after the blast exposure was the main outcome measure in this study. Logistic regression on the outcome of 'no day 7 symptoms' indicated that NAC treatment was significantly better than placebo (OR = 3.6, p = 0.006). Secondary analysis revealed subjects receiving NAC within 24 hours of blast had an 86% chance of symptom resolution with no reported side effects versus 42% for those seen early who received placebo. Conclusion: This study, conducted in an active theatre of war, demonstrates that NAC, a safe pharmaceutical countermeasure, has beneficial effects on the severity and resolution of sequelae of blast induced mTBI. This is the first demonstration of an effective short term countermeasure for mTBI. Further work on long term outcomes and the potential use of NAC in civilian mTBI is warranted. Trial Registration: ClinicalTrials.gov NCT00822263

Constructive Field Theory and Applications: Perspectives and Open Problems

In this paper we review many interesting open problems in mathematical physics which may be attacked with the help of tools from constructive field theory. They could give work for future mathematical physicists trained with the constructive methods well within the 21st century

The Global Renormalization Group Trajectory in a Critical Supersymmetric Field Theory on the Lattice Z^3

We consider an Euclidean supersymmetric field theory in $Z^3$ given by a supersymmetric $\Phi^4$ perturbation of an underlying massless Gaussian measure on scalar bosonic and Grassmann fields with covariance the Green's function of a (stable) L\'evy random walk in $Z^3$. The Green's function depends on the L\'evy-Khintchine parameter $\alpha={3+\epsilon\over 2}$ with $0<\alpha<2$. For $\alpha ={3\over 2}$ the $\Phi^{4}$ interaction is marginal. We prove for $\alpha-{3\over 2}={\epsilon\over 2}>0$ sufficiently small and initial parameters held in an appropriate domain the existence of a global renormalization group trajectory uniformly bounded on all renormalization group scales and therefore on lattices which become arbitrarily fine. At the same time we establish the existence of the critical (stable) manifold. The interactions are uniformly bounded away from zero on all scales and therefore we are constructing a non-Gaussian supersymmetric field theory on all scales. The interest of this theory comes from the easily established fact that the Green's function of a (weakly) self-avoiding L\'evy walk in $Z^3$ is a second moment (two point correlation function) of the supersymmetric measure governing this model. The control of the renormalization group trajectory is a preparation for the study of the asymptotics of this Green's function. The rigorous control of the critical renormalization group trajectory is a preparation for the study of the critical exponents of the (weakly) self-avoiding L\'evy walk in $Z^3$.Comment: 82 pages, Tex with macros supplied. Revision includes 1. redefinition of norms involving fermions to ensure uniqueness. 2. change in the definition of lattice blocks and lattice polymer activities. 3. Some proofs have been reworked. 4. New lemmas 5.4A, 5.14A, and new Theorem 6.6. 5.Typos corrected.This is the version to appear in Journal of Statistical Physic

Calculation of Forces at Focal Adhesions from Elastic Substrate Data: The Effect of Localized Force and the Need for Regularization

AbstractForces exerted by stationary cells have been investigated on the level of single focal adhesions by combining elastic substrates, fluorescence labeling of focal adhesions, and the assumption of localized force when solving the inverse problem of linear elasticity theory. Data simulation confirms that the inverse problem is ill-posed in the presence of noise and shows that in general a regularization scheme is needed to arrive at a reliable force estimate. Spatial and force resolution are restricted by the smoothing action of the elastic kernel, depend on the details of the force and displacement patterns, and are estimated by data simulation. Corrections arising from the spatial distribution of force and from finite substrate size are treated in the framework of a force multipolar expansion. Our method is computationally cheap and could be used to study mechanical activity of cells in real time

Cell organization in soft media due to active mechanosensing

Adhering cells actively probe the mechanical properties of their environment and use the resulting information to position and orient themselves. We show that a large body of experimental observations can be consistently explained from one unifying principle, namely that cells strengthen contacts and cytoskeleton in the direction of large effective stiffness. Using linear elasticity theory to model the extracellular environment, we calculate optimal cell organization for several situations of interest and find excellent agreement with experiments for fibroblasts, both on elastic substrates and in collagen gels: cells orient in the direction of external tensile strain, they orient parallel and normal to free and clamped surfaces, respectively, and they interact elastically to form strings. Our method can be applied for rational design of tissue equivalents. Moreover our results indicate that the concept of contact guidance has to be reevaluated. We also suggest that cell-matrix contacts are upregulated by large effective stiffness in the environment because in this way, build-up of force is more efficient.Comment: Revtex, 7 pages, 4 Postscript files include

On Automated Lemma Generation for Separation Logic with Inductive Definitions

Separation Logic with inductive definitions is a well-known approach for deductive verification of programs that manipulate dynamic data structures. Deciding verification conditions in this context is usually based on user-provided lemmas relating the inductive definitions. We propose a novel approach for generating these lemmas automatically which is based on simple syntactic criteria and deterministic strategies for applying them. Our approach focuses on iterative programs, although it can be applied to recursive programs as well, and specifications that describe not only the shape of the data structures, but also their content or their size. Empirically, we find that our approach is powerful enough to deal with sophisticated benchmarks, e.g., iterative procedures for searching, inserting, or deleting elements in sorted lists, binary search tress, red-black trees, and AVL trees, in a very efficient way