Fine control of drug delivery for cochlear implant applications

Cochlear implants are neuroprostheses that are inserted into the inner ear to directly electrically stimulate the auditory nerve, thus replacing lost cochlear receptors, the hair cells. The reduction of the gap between electrodes and nerve cells will contribute to technological solutions simultaneously increasing the frequency resolution, the sound quality and the amplification of the signal. Recent findings indicate that neurotrophins (NTs) such as brain derived neurotrophic factor (BDNF) stimulate the neurite outgrowth of auditory nerve cells by activating Trk receptors on the cellular surface (1–3). Furthermore, small-size TrkB receptor agonists such as di-hydroxyflavone (DHF) are now available, which activate the TrkB receptor with similar efficiency as BDNF, but are much more stable (4). Experimentally, such molecules are currently used to attract nerve cells towards, for example, the electrodes of cochlear implants. This paper analyses the scenarios of low dose aspects of controlled release of small-size Trk receptor agonists from the coated CI electrode array into the inner ear. The control must first ensure a sufficient dose for the onset of neurite growth. Secondly, a gradient in concentration needs to be maintained to allow directive growth of neurites through the perilymph-filled gap towards the electrodes of the implant. We used fluorescein as a test molecule for its molecular size similarity to DHF and investigated two different transport mechanisms of drug dispensing, which both have the potential to fulfil controlled low-throughput drug-deliverable requirements. The first is based on the release of aqueous fluorescein into water through well-defined 60-μm size holes arrays in a membrane by pure osmosis. The release was both simulated using the software COMSOL and observed experimentally. In the second approach, solid fluorescein crystals were encapsulated in a thin layer of parylene (PPX), hence creating random nanometer-sized pinholes. In this approach, the release occurred due to subsequent water diffusion through the pinholes, dissolution of the fluorescein and then release by out-diffusion. Surprisingly, the release rate of solid fluorescein through the nanoscopic scale holes was found to be in the same order of magnitude as for liquid fluorescein release through microscopic holes.

Large-scale land acquisition and its effects on the water balance in investor and host countries

This study examines the validity of the assumption that international large-scale land acquisition (LSLA) is motivated by the desire to secure control over water resources, which is commonly referred to as ‘water grabbing’. This assumption was repeatedly expressed in recent years, ascribing the said motivation to the Gulf States in particular. However, it must be considered of hypothetical nature, as the few global studies conducted so far focused primarily on the effects of LSLA on host countries or on trade in virtual water. In this study, we analyse the effects of 475 intended or concluded land deals recorded in the Land Matrix database on the water balance in both host and investor countries. We also examine how these effects relate to water stress and how they contribute to global trade in virtual water. The analysis shows that implementation of the LSLAs in our sample would result in global water savings based on virtual water trade. At the level of individual LSLA host countries, however, water use intensity would increase, particularly in 15 sub-Saharan states. From an investor country perspective, the analysis reveals that countries often suspected of using LSLA to relieve pressure on their domestic water resources—such as China, India, and all Gulf States except Saudi Arabia—invest in agricultural activities abroad that are less water-intensive compared to their average domestic crop production. Conversely, large investor countries such as the United States, Saudi Arabia, Singapore, and Japan are disproportionately externalizing crop water consumption through their international land investments. Statistical analyses also show that host countries with abundant water resources are not per se favoured targets of LSLA. Indeed, further analysis reveals that land investments originating in water-stressed countries have only a weak tendency to target areas with a smaller water risk.

Lake-effect snow as the dominant control of mesic-forest distribution in Michigan, USA

1Recent studies demonstrated the sensitivity of northern forest ecosystems to changes in the amount and duration of snow cover at annual to decadal time scales. However, the consequences of snowfall variability remain uncertain for ecological variables operating at longer time scales, especially the distributions of forest communities. 2The Great Lakes region of North America offers a unique setting to examine the long-term effects of variable snowfall on forest communities. Lake-effect snow produces a three-fold gradient in annual snowfall over tens of kilometres, and dramatic edaphic variations occur among landform types resulting from Quaternary glaciations. We tested the hypothesis that these factors interact to control the distributions of mesic (dominated by Acer saccharum, Tsuga canadensis and Fagus grandifolia) and xeric forests (dominated by Pinus and Quercus spp.) in northern Lower Michigan. 3We compiled pre-European-settlement vegetation data and overlaid these data with records of climate, water balance and soil, onto Landtype Association polygons in a geographical information system. We then used multivariate adaptive regression splines to model the abundance of mesic vegetation in relation to environmental controls. 4Snowfall is the most predictive among five variables retained by our model, and it affects model performance 29% more than soil texture, the second most important variable. The abundance of mesic trees is high on fine-textured soils regardless of snowfall, but it increases with snowfall on coarse-textured substrates. Lake-effect snowfall also determines the species composition within mesic forests. The weighted importance of A. saccharum is significantly greater than of T. canadensis or F. grandifolia within the lake-effect snowbelt, whereas T. canadensis is more plentiful outside the snowbelt. These patterns are probably driven by the influence of snowfall on soil moisture, nutrient availability and fire return intervals. 5Our results imply that a key factor dictating the spatio-temporal patterns of forest communities in the vast region around the Great Lakes is how the lake-effect snowfall regime responds to global change. Snowfall reductions will probably cause a major decrease in the abundance of ecologically and economically important species, such as A. saccharum.