Task-dependent Modulation of Cortical Excitability and Balance Control in Individuals with Post-concussion Syndrome

In most cases, symptoms resolve between 7-10 days post-concussion. However, in 10-15% of the concussed population, symptoms can remain unresolved for months to years following the head injury. The purpose of this thesis was two-fold, and was broken up into two studies, where the same individuals participated in both studies. The purpose of the first study was to quantify the differences in balance control between individuals with PCS (i.e., had been experiencing symptoms for \u3c30 days) and non-concussed individuals during a lower-limb reaching task. Participants completed a static balance assessment before and after a lower-limb reaching task, which incorporated a Go/No-Go paradigm. Results from this study revealed no differences in the static stability assessments, however, individuals with PCS demonstrated increased medial-lateral COP displacement as well as greater trunk pitch during the reaching task. Overall, the findings reveal persistent balance impairments in individuals with PCS, which may put this population at an increased risk of further injury. The purpose of the second study was to assess task-dependent modulation of cortical excitability prior to planned index finger abduction contractions comparing a non-concussed population to a population with PCS. The protocol in this study consisted of both single and paired-pulse transcranial magnetic stimulation (TMS) which was applied prior to the beginning of 3 different tasks (i.e., a rest condition with no plan to contract, a precision contraction, and a powerful contraction). In addition to the three tasks, participants also had to respond to a Go/No-Go cue. The results of this study revealed an increase in excitability prior to a precision contraction in both non-concussed and PCS groups. No differences in task-dependent modulation were found between the two groups with respect to intracortical facilitation and inhibition, however a negative correlation between number of symptoms reported (SCAT3 symptom evaluation) and intracortical facilitation was revealed. The increase in corticospinal excitability prior to a precision contraction was not explained by the two cortical mechanisms we assessed and may therefore be due to spinal modulation or a different cortical mechanism. Overall, based on the results from this thesis, it appears that individuals with PCS have balance impairments, which may be a result of an inability to maximally activate their postural muscles. Furthermore, it appears that those individuals who reported a higher number of symptoms had greater reductions in intracortical facilitation, likely reflecting the heterogeneity of this clinical group

Spontaneous eye movements during passive spoken language comprehension reflect grammatical processing

Language is tightly connected to sensory and motor systems. Recent research using eye- tracking typically relies on constrained visual contexts, viewing a small array of objects on a computer screen. Some critiques of embodiment ask if people simply match their simulations to the pictures being presented. This study compared the comprehension of verbs with two different grammatical forms: the past progressive form (e.g., was walking), which emphasizes the ongoing nature of actions, and the simple past (e.g., walked), which emphasizes the end-state of an action. The results showed that the distribution and timing of eye movements mirrors the underlying conceptual structure of this linguistic difference in the absence of any visual stimuli. Thus, eye movement data suggest that visual inputs are unnecessary to solicit perceptual simulations

Group sequential designs for stepped-wedge cluster randomised trials.

BACKGROUND/AIMS: The stepped-wedge cluster randomised trial design has received substantial attention in recent years. Although various extensions to the original design have been proposed, no guidance is available on the design of stepped-wedge cluster randomised trials with interim analyses. In an individually randomised trial setting, group sequential methods can provide notable efficiency gains and ethical benefits. We address this by discussing how established group sequential methodology can be adapted for stepped-wedge designs. METHODS: Utilising the error spending approach to group sequential trial design, we detail the assumptions required for the determination of stepped-wedge cluster randomised trials with interim analyses. We consider early stopping for efficacy, futility, or efficacy and futility. We describe first how this can be done for any specified linear mixed model for data analysis. We then focus on one particular commonly utilised model and, using a recently completed stepped-wedge cluster randomised trial, compare the performance of several designs with interim analyses to the classical stepped-wedge design. Finally, the performance of a quantile substitution procedure for dealing with the case of unknown variance is explored. RESULTS: We demonstrate that the incorporation of early stopping in stepped-wedge cluster randomised trial designs could reduce the expected sample size under the null and alternative hypotheses by up to 31% and 22%, respectively, with no cost to the trial's type-I and type-II error rates. The use of restricted error maximum likelihood estimation was found to be more important than quantile substitution for controlling the type-I error rate. CONCLUSION: The addition of interim analyses into stepped-wedge cluster randomised trials could help guard against time-consuming trials conducted on poor performing treatments and also help expedite the implementation of efficacious treatments. In future, trialists should consider incorporating early stopping of some kind into stepped-wedge cluster randomised trials according to the needs of the particular trial

Student Perceptions of the Professional Behavior of Faculty Physicians

This study was conducted to obtain a baseline understanding of the professional behavior of clinical faculty physicians from the medical students’ perspective. Students completed a professionalism evaluation of supervising faculty at the end of each required third-year clerkship over a one year period. Results were analyzed by specific behaviors and across clerkships. Differences were noted in the frequency of the types of problems seen, and varied by clerkship discipline. The most common transgressions of professional behavior reported were the use of derogatory language towards other services or patients and the disrespectful treatment of others. Our study served to provide objective feedback to the faculty about student perceptions of faculty as role models for professionalism while on clinical rotations

Supersymmetric Higgs Yukawa Couplings to Bottom Quarks at next-to-next-to-leading Order

The effective bottom Yukawa couplings are analyzed for the minimal supersymmetric extension of the Standard Model at two-loop accuracy within SUSY-QCD. They include the resummation of the dominant corrections for large values of tg(beta). In particular the two-loop SUSY-QCD corrections to the leading SUSY-QCD and top-induced SUSY-electroweak contributions are addressed. The residual theoretical uncertainties range at the per-cent level.Comment: 25 pages, 9 figures, added comments and references, typos corrected, results unchanged, published versio

CX3CR1 Polymorphisms are associated with atopy but not asthma in German children

Chemokines and their receptors are involved in many aspects of immunity. Chemokine CX3CL1, acting via its receptor CX3CR1, regulates monocyte migration and macrophage differentiation as well as T cell-dependent inflammation. Two common, nonsynonymous polymorphisms in CX3CR1 have previously been shown to alter the function of the CX3CL1/CX3CR1 pathway and were suggested to modify the risk for asthma. Using matrix-assisted laser desorption/ionization time-of-flight technology, we genotyped polymorphisms Val249Ile and Thr280Met in a cross-sectional population of German children from Munich (n = 1,159) and Dresden ( n = 1,940). For 249Ile an odds ratio of 0.77 (95% confidence interval 0.63-0.96; p = 0.017) and for 280Met an odds ratio of 0.71 ( 95% confidence interval 0.56-0.89; p = 0.004) were found with atopy in Dresden but not in Munich. Neither polymorphism was associated with asthma. Thus, amino acid changes in CX3CR1 may influence the development of atopy but not asthma in German children. Potentially, other factors such as environmental effects may modify the role of CX3CR1 polymorphisms. Copyright (c) 2007 S. Karger AG, Basel

The promoters of human cell cycle genes integrate signals from two tumor suppressive pathways during cellular transformation

Deciphering regulatory events that drive malignant transformation represents a major challenge for systems biology. Here we analyzed genome-wide transcription profiling of an in-vitro transformation process. We focused on a cluster of genes whose expression levels increased as a function of p53 and p16INK4A tumor suppressors inactivation. This cluster predominantly consists of cell cycle genes and constitutes a signature of a diversity of cancers. By linking expression profiles of the genes in the cluster with the dynamic behavior of p53 and p16INK4A, we identified a promoter architecture that integrates signals from the two tumor suppressive channels and that maps their activity onto distinct levels of expression of the cell cycle genes, which in turn, correspond to different cellular proliferation rates. Taking components of the mitotic spindle as an example, we experimentally verified our predictions that p53-mediated transcriptional repression of several of these novel targets is dependent on the activities of p21, NFY and E2F. Our study demonstrates how a well-controlled transformation process allows linking between gene expression, promoter architecture and activity of upstream signaling molecules.Comment: To appear in Molecular Systems Biolog