Inflection points in longitudinal models: Tracking recovery and return to play following concussion.

The return to play (RTP) process may occur during longitudinal studies tracking recovery after concussion. This factor, which is often omitted within statistical designs, could affect the fit and overall interpretation of the statistical model. This article demonstrates the difference in results and interpretation between 2 linear mixed-model designs: (1) a between-group longitudinal (GROUP) analysis and (2) a between-group longitudinal model that used an inflection point to account for changes around the time of RTP (RTP analysis). These analyses were conducted on instrumented balance data collected on 23 concussed athletes and 25 controls over 8 weeks following concussion. Total sway area and the range of mediolateral acceleration were used as outcome measures. No significant findings were found in the GROUP design for either outcome measure. In contrast, the RTP analysis revealed significant effects of time (P = .007) and RTP change (P = .007), and group*time (P = .028) and group*RTP change (P = .022) interactions for total sway area, and effects of group (P = .011), time (P = .010), and RTP change (P = .014), and group*time (P = .013) and group*RTP change interactions (P = .013) for range of mediolateral acceleration. For both outcomes, the RTP model fit the data significantly better on comparison of likelihood ratios (P ≤ .027). These results suggest that allowing for an inflection point in the statistical design may assist understanding of what happens around clinically meaningful time points. The choice of statistical model had a considerable effect on the interpretation of findings, and provokes discussion around the best method for analyzing longitudinal datasets when important clinical time points like RTP exist.

Prediction of composite elastic modulus and polymerization shrinkage by computational micromechanics.

OBJECTIVES: The objective of this study was to simulate the elastic modulus and polymerization shrinkage of a light activated polymer matrix composite using a generalized method of cells (GMC) micromechanics model. Two hypotheses were tested: (1) the micromechanics model provides estimates of elastic modulus vs filler fraction with greater accuracy than the rule of mixtures, Hashin-Shtrikman and phenomenological models; (2) Micromechanics Analysis Code/Generalized Method of Cells accurately simulates experimental benchmarks of polymerization shrinkage strain. METHODS: The study applied mathematical algorithms to a representative volume element of a model polymer composite to yield value estimates of the elastic modulus and contraction strain. Mechanical properties of the composite constituents were derived from thermomechanical and dynamic mechanical analysis of BisGMA and TEGDMA filled and unfilled resins. Data from the micromechanics model were compared to results of other analytical methods as well as experimental benchmarks. RESULTS: Predictions of elastic modulus vs filler fraction from the micromechanics model provided greater accuracy than the rule of mixtures and the Hashin-Shtrikman models. Predictions of polymerization shrinkage strain were within 13% of experimental values. SIGNIFICANCE: The elastic micromechanics model presented accurately predicted elastic modulus and polymerization shrinkage strain as a function of filler fraction, superior to other analytical methods.

Contraction force rate of polymer composites is linearly correlated with irradiance.

OBJECTIVES: The force developed during cure of a composite represents the potential loads that can be induced into the dental adhesive and tooth structure that in turn affects the integrity of the dental adhesive and tooth. The purpose of this study was to evaluate the dependence of polymerization contraction force development on light energy density (product of irradiance and time). METHODS: Contraction force during polymerization was measured with a low compliance test fixture in which the composite specimen was placed between a glass plate and steel rod. The steel rod passed through a washer-type load cell that measured force development during cure. Six irradiance levels were evaluated as well as a 'pulse-delay' method. A generic composite consisting of a 1:1 blend of BisGMA and TEGDMA resin and 67 wt% unsilanated hybrid filler with 5 wt% fumed silica was used for all experiments. Contraction force was collected for 550 s. The first derivative of contraction force with respect to time (dF/dt) was calculated. Net contraction force at 550 s and max[dF/dt] was statistically analyzed as a function of irradiance and energy density (product of irradiance and time) with one-way ANOVA and Tukey's post-hoc test at the 0.05 level of significance. RESULTS: Contraction force increased most rapidly immediately following light activation. Force resulting from the pulse-delay method was significantly different from all other methods (p < 0.001). Force resulting from irradiation at 600 mW/cm2 was significantly different (p < 0.01) from all other methods and 500 mW/cm2 was significantly different from 100 and 200 mW/cm2. Maximum df/dt (max[dF/dt] over full range of time) was linearly related to irradiance, linear regression r2 = 0.98. All pairs of irradiance were significantly different except pulse-delay and 200-300 mW/cm2 and 300 and 400 mW/cm2. SIGNIFICANCE: The pulse-delay method demonstrated contraction force rates lower than what would be expected using energy considerations and lower force rates at each of the two light exposures than their single exposure counterparts. Since the adhesive resin and dentin are viscoelastic and thus strain rate dependent, time dependent contraction force should be an important consideration.

Norepinephrine and ß1-adrenergic signaling facilitate activation of hippocampal CA1 pyramidal neurons during contextual memory retrieval.

We previously described a role for adrenergic signaling in the hippocampus to promote contextual and spatial memory retrieval. A subsequent study performing expression analysis of the immediate-early gene (IEG) Arc suggested that activation of CA1 but not CA3 pyramidal neurons during memory retrieval is impaired in the absence of NE. The current study sought to confirm and extend those observations by performing expression analysis of a second IEG product, Fos, following a much greater variety of testing conditions. In mutant mice lacking NE, induction of Fos was normal in all regions of the hippocampus and amygdala shortly after fear conditioning. In contrast, when testing contextual fear 1 day after training, induction of Fos in CA1 and the central nucleus of the amygdala (CeA), but not CA3, the dentate gyrus or other amygdaloid nuclei, was impaired in the mutant mice. This pattern corresponded to the memory retrieval deficit exhibited by these mice. On the other hand, induction was normal in CA1 and CeA when testing cued fear 1 day after training, or contextual fear 1 week or 1 month after training, conditions in which retrieval are normal in the absence of NE. Acute restoration of NE in the mutant mice before testing but not before training rescued retrieval of contextual fear and restored Fos induction in CA1 and CeA. Because NE facilitates retrieval through the activation of ß(1)-adrenergic receptors, ß(1) knockout mice were also examined and found to exhibit reduced induction of Fos in CA1 and CeA following retrieval. Based on these and previous results, we hypothesize that adrenergic signaling is critical for the full activation of CA1 pyramidal neurons in response to excitatory input from CA3 pyramidal neurons conveying retrieved contextual information.