Influence of bed patchiness, slope, grain hiding, and form drag on gravel mobilization in very steep streams

Steep streams are a major portion of channel networks and provide a link to transport sediment from hillslopes to lower gradient rivers. Despite their importance, key unknowns remain, perhaps foremost of which is evaluating in steep streams empirical laws for fluvial sediment transport developed for low-gradient rivers. To address this knowledge gap, we painted sediment in situ over 3 years to monitor incipient sediment motion and sediment-patch development in five small (drainage areas of 0.04–2 km^2) and steep (slopes of 5–37%) tributaries of Elder Creek, California, United States. We found that channel beds organized into size-sorted sediment patches which displayed active fluvial transport of gravel annually, consistent year-to-year patch median grain sizes, partial transport of bed material, and significantly higher values of critical Shields stress for incipient sediment motion compared to that observed for lower gradient rivers. The high critical Shields stresses (up to ≈0.5 for the median grain size) agree within a factor of ~3 to theoretical predictions which account for slope-dependent hydraulics, grain hiding, and sediment patches. For grains of approximately the same size as the roughness length scale, slope-dependent hydraulics and bed patchiness are the dominant controls on critical Shields stress values, while grain hiding is important for grains larger or smaller than the roughness length scale. Form drag exists in our monitored tributaries but has a smaller influence than the above effects. Our field observations show fluvial processes contribute to sediment mobilization in steep channels which are often considered to be dominated by debris flows

A predictive in vitro model of the impact of drugs with anticholinergic properties on human neuronal and astrocytic systems

The link between off-target anticholinergic effects of medications and acute cognitive impairment in older adults requires urgent investigation. We aimed to determine whether a relevant in vitro model may aid the identification of anticholinergic responses to drugs and the prediction of anticholinergic risk during polypharmacy. In this preliminary study we employed a co-culture of human-derived neurons and astrocytes (NT2.N/A) derived from the NT2 cell line. NT2.N/A cells possess much of the functionality of mature neurons and astrocytes, key cholinergic phenotypic markers and muscarinic acetylcholine receptors (mAChRs). The cholinergic response of NT2 astrocytes to the mAChR agonist oxotremorine was examined using the fluorescent dye fluo-4 to quantitate increases in intracellular calcium [Ca2+]i. Inhibition of this response by drugs classified as severe (dicycloverine, amitriptyline), moderate (cyclobenzaprine) and possible (cimetidine) on the Anticholinergic Cognitive Burden (ACB) scale, was examined after exposure to individual and pairs of compounds. Individually, dicycloverine had the most significant effect regarding inhibition of the astrocytic cholinergic response to oxotremorine, followed by amitriptyline then cyclobenzaprine and cimetidine, in agreement with the ACB scale. In combination, dicycloverine with cyclobenzaprine had the most significant effect, followed by dicycloverine with amitriptyline. The order of potency of the drugs in combination frequently disagreed with predicted ACB scores derived from summation of the individual drug scores, suggesting current scales may underestimate the effect of polypharmacy. Overall, this NT2.N/A model may be appropriate for further investigation of adverse anticholinergic effects of multiple medications, in order to inform clinical choices of suitable drug use in the elderly