ABSTRACT
There is growing evidence that processing speed (PS) deficits in youth with neuropsychiatric conditions are associated with functional difficulties. However, there is no consistent definition of slower PS; specifically, whether slower PS should be defined as a discrepancy from same-aged peers (normative weakness) or as an intrapersonal deficit relative to overall cognitive ability (relative weakness). In a sample of clinically-referred youth, we calculated slower PS both ways and examined the impact on adaptive, academic, and psychopathology outcomes in relation to different levels of cognitive ability. Significant PS x cognitive ability interactions were found on adaptive and academic outcomes. A norm-based weakness in PS (PSI Standard Score <85) was associated with lower adaptive skills and lower academic skills regardless of cognitive ability. In the above average cognitive ability group, relatively lower PS (PSI >15 point difference from VCI) was associated with significantly lower academic performance. No significant associations were found for general psychopathology. Results suggest a normative weakness in PS impacts functional outcomes interactively and differently with level of general cognitive ability. Data suggest that higher cognitive ability may be somewhat protective from the impact of normatively weak PS on adaptive outcomes; however, youth across all abilities with normatively weak PS showed weaker academic performance. Second, children with high cognitive abilities and relatively weak PS showed discrepant performance compared to comparison group. Implications and areas for future research are discussed.
Subject(s)
Academic Performance , Cognition , Adolescent , Child , Family , Humans , PsychopathologyABSTRACT
There continues to be a significant increase in the number and complexity of hydrophobic nanomaterials that are engineered for a variety of commercial purposes making human exposure a significant health concern. This study uses a combination of biophysical, biochemical and computational methods to probe potential mechanisms for uptake of C60 nanoparticles into various compartments of living immune cells. Cultures of RAW 264.7 immortalized murine macrophage were used as a canonical model of immune-competent cells that are likely to provide the first line of defense following inhalation. Modes of entry studied were endocytosis/pinocytosis and passive permeation of cellular membranes. The evidence suggests marginal uptake of C60 clusters is achieved through endocytosis/pinocytosis, and that passive diffusion into membranes provides a significant source of biologically-available nanomaterial. Computational modeling of both a single molecule and a small cluster of fullerenes predicts that low concentrations of fullerenes enter the membrane individually and produce limited perturbation; however, at higher concentrations the clusters in the membrane causes deformation of the membrane. These findings are bolstered by nuclear magnetic resonance (NMR) of model membranes that reveal deformation of the cell membrane upon exposure to high concentrations of fullerenes. The atomistic and NMR models fail to explain escape of the particle out of biological membranes, but are limited to idealized systems that do not completely recapitulate the complexity of cell membranes. The surprising contribution of passive modes of cellular entry provides new avenues for toxicological research that go beyond the pharmacological inhibition of bulk transport systems such as pinocytosis.
