Acute reduction of microglia does not alter axonal injury in a mouse model of repetitive concussive traumatic brain injury

The pathological processes that lead to long-term consequences of multiple concussions are unclear. Primary mechanical damage to axons during concussion is likely to contribute to dysfunction. Secondary damage has been hypothesized to be induced or exacerbated by inflammation. The main inflammatory cells in the brain are microglia, a type of macrophage. This research sought to determine the contribution of microglia to axon degeneration after repetitive closed-skull traumatic brain injury (rcTBI) using CD11b-TK (thymidine kinase) mice, a valganciclovir-inducible model of macrophage depletion. Low-dose (1 mg/mL) valganciclovir was found to reduce the microglial population in the corpus callosum and external capsule by 35% after rcTBI in CD11b-TK mice. At both acute (7 days) and subacute (21 days) time points after rcTBI, reduction of the microglial population did not alter the extent of axon injury as visualized by silver staining. Further reduction of the microglial population by 56%, using an intermediate dose (10 mg/mL), also did not alter the extent of silver staining, amyloid precursor protein accumulation, neurofilament labeling, or axon injury evident by electron microscopy at 7 days postinjury. Longer treatment of CD11b-TK mice with intermediate dose and treatment for 14 days with high-dose (50 mg/mL) valganciclovir were both found to be toxic in this injury model. Altogether, these data are most consistent with the idea that microglia do not contribute to acute axon degeneration after multiple concussive injuries. The possibility of longer-term effects on axon structure or function cannot be ruled out. Nonetheless, alternative strategies directly targeting injury to axons may be a more beneficial approach to concussion treatment than targeting secondary processes of microglial-driven inflammation

Post‐traumatic stress disorder\u27s relation with positive and negative emotional avoidance: The moderating role of gender

Post‐traumatic stress disorder (PTSD) is characterized by avoidance of trauma‐related emotions. Research indicates that this avoidance may extend to any emotional experience that elicits distress, including those that are unrelated to the trauma. Literature in this area has been limited in its exclusive focus on negative emotions. Despite evidence of gender differences in PTSD and emotional avoidance separately, no studies to date have examined gender as a moderator of their association. The goal of the current study was to extend research by exploring the moderating role of gender in the relation between PTSD symptom severity and positive and negative emotional avoidance. Participants were 276 trauma‐exposed individuals (65.9% female, 65.6% White, Mage = 19.24) from a university in the north‐eastern United States. Moderation results indicated a main effect for PTSD symptom severity on both positive (b = 0.07, p \u3c .001) and negative (b = 0.04, p = .03) emotional avoidance. The interaction of gender and PTSD symptom severity was significant for positive emotion avoidance (b = 0.97, p = .01). Analysis of simple slopes revealed that PTSD symptom severity was significantly associated with positive emotional avoidance for males (b = 0.13, p \u3c .001) but not females (b = 0.03, p = .08). Results suggest the importance of gender‐sensitive recommendations for assessment and treatment of emotional avoidance in PTSD

Decoding the Encoding of Functional Brain Networks: an fMRI Classification Comparison of Non-negative Matrix Factorization (NMF), Independent Component Analysis (ICA), and Sparse Coding Algorithms

Brain networks in fMRI are typically identified using spatial independent component analysis (ICA), yet mathematical constraints such as sparse coding and positivity both provide alternate biologically-plausible frameworks for generating brain networks. Non-negative Matrix Factorization (NMF) would suppress negative BOLD signal by enforcing positivity. Spatial sparse coding algorithms ($L1$ Regularized Learning and K-SVD) would impose local specialization and a discouragement of multitasking, where the total observed activity in a single voxel originates from a restricted number of possible brain networks. The assumptions of independence, positivity, and sparsity to encode task-related brain networks are compared; the resulting brain networks for different constraints are used as basis functions to encode the observed functional activity at a given time point. These encodings are decoded using machine learning to compare both the algorithms and their assumptions, using the time series weights to predict whether a subject is viewing a video, listening to an audio cue, or at rest, in 304 fMRI scans from 51 subjects. For classifying cognitive activity, the sparse coding algorithm of $L1$ Regularized Learning consistently outperformed 4 variations of ICA across different numbers of networks and noise levels (p$<$0.001). The NMF algorithms, which suppressed negative BOLD signal, had the poorest accuracy. Within each algorithm, encodings using sparser spatial networks (containing more zero-valued voxels) had higher classification accuracy (p$<$0.001). The success of sparse coding algorithms may suggest that algorithms which enforce sparse coding, discourage multitasking, and promote local specialization may capture better the underlying source processes than those which allow inexhaustible local processes such as ICA

Scalar Quantum Field Theory with Cubic Interaction

In this paper it is shown that an i phi^3 field theory is a physically acceptable field theory model (the spectrum is positive and the theory is unitary). The demonstration rests on the perturbative construction of a linear operator C, which is needed to define the Hilbert space inner product. The C operator is a new, time-independent observable in PT-symmetric quantum field theory.Comment: Corrected expressions in equations (20) and (21

Canonical form of Hamiltonian matrices

On the basis of shell model simulations, it is conjectured that the Lanczos construction at fixed quantum numbers defines---within fluctuations and behaviour very near the origin---smooth canonical matrices whose forms depend on the rank of the Hamiltonian, dimensionality of the vector space, and second and third moments. A framework emerges that amounts to a general Anderson model capable of dealing with ground state properties and strength functions. The smooth forms imply binomial level densities. A simplified approach to canonical thermodynamics is proposed.Comment: 4 pages 6 figure

Quantum Chaos in A=46--50 Atomic Nuclei

The spectral statistics of low--lying states of several $fp$ shell nuclei are studied with realistic shell--model calculations. For Ca isotopes, we find significant deviations from the predictions of the random--matrix theory which suggest that some spherical nuclei are not as chaotic in nature as the conventional view assumes.Comment: 12 pages, LaTex, 2 figures available upon request, to be published in Physics Letters

Energetic efficiency of egg production and the influence of live weight thereon.

Publication authorized February 23, 1938.Digitized 2007 AES.Includes bibliographical references

Mean Free Path and Energy Fluctuations in Quantum Chaotic Billiards

The elastic mean free path of carriers in a recently introduced model of quantum chaotic billiards in two and three dimensions is calculated. The model incorporates surface roughness at a microscopic scale by randomly choosing the atomic levels at the surface sites between -W/2 and W/2. Surface roughness yields a mean free path l that decreases as L/W^2 as W increases, L being the linear size of the system. But this diminution ceases when the surface layer begins to decouple from the bulk for large enough values of W, leaving more or less unperturbed states on the bulk. Consequently, the mean free path shows a minimum of about L/2 for W of the order of the band width. Energy fluctuations reflect the behavior of the mean free path. At small energy scales, strong level correlations manifest themselves by small values of the number of levels variance Sigma^2(E) that are close to Random Matrix Theory (RMT) in all cases. At larger energy scales, fluctuations are below the logarithmic behavior of RMT for l > L, and above RMT value when l < L.Comment: 8 twocolumn pages, seven figures, revtex and epsf macros. To be published in Physical Review B

17β-Estradiol dysregulates innate immune responses to Pseudomonas aeruginosa respiratory infection and is modulated by estrogen receptor antagonism

ABSTRACT Females have a more severe clinical course than males in terms of several inflammatory lung conditions. Notably, females with cystic fibrosis (CF) suffer worse outcomes, particularly in the setting of Pseudomonas aeruginosa infection. Sex hormones have been implicated in experimental and clinical studies; however, immune mechanisms responsible for this sex-based disparity are unknown and the specific sex hormone target for therapeutic manipulation has not been identified. The objective of this study was to assess mechanisms behind the impact of female sex hormones on host immune responses to P. aeruginosa . We used wild-type and CF mice, which we hormone manipulated, inoculated with P. aeruginosa , and then examined for outcomes and inflammatory responses. Neutrophils isolated from mice and human subjects were tested for responses to P. aeruginosa . We found that female mice inoculated with P. aeruginosa died earlier and showed slower bacterial clearance than males ( P &lt; 0.0001). Ovariectomized females supplemented with 17β-estradiol succumbed to P. aeruginosa challenge earlier than progesterone- or vehicle-supplemented mice ( P = 0.0003). 17β-Estradiol-treated ovariectomized female mice demonstrated increased lung levels of inflammatory cytokines, and when rendered neutropenic the mortality difference was abrogated. Neutrophils treated with 17β-estradiol demonstrated an enhanced oxidative burst but decreased P. aeruginosa killing and earlier cell necrosis. The estrogen receptor (ER) antagonist ICI 182,780 improved survival in female mice infected with P. aeruginosa and restored neutrophil function. We concluded that ER antagonism rescues estrogen-mediated neutrophil dysfunction and improves survival in response to P. aeruginosa . ER-mediated processes may explain the sex-based mortality gap in CF and other inflammatory lung illnesses, and the ER blockade represents a rational therapeutic strategy. </jats:p

Transitions In Spectral Statistics

We present long range statistical properties of a recently introduced unitary random matrix ensemble, whose short range correlations were found to describe a transition from Wigner to Poisson type as a function of a single parameter.Comment: 12 pp. late