Systemic Sublingual Delivery of Octreotide Acetate Utilizing Low-Current Oral Electrical Stimulation in Rabbits

A sublingual electronic pill is a novel device designed to enhance delivery of drugs/biologics sublingually utilizing low-current electrical stimulation. Our primary aim was to explore safe limits of oral electrical stimulus in animals and conduct a randomized, sham-controlled animal study to quantify benefits of electrical stimulation on sublingual absorption of octreotide (a small peptide) as a first step in the development of this technology. A system to deliver low-current alternating and direct current stimuli to the oral mucosa of rabbits was constructed, and five groups were studied to determine the significance of sublingual octreotide diffusion in the presence of three different electrical stimulation scenarios: +DC (+4 mA), -DC (-4 mA), and AC (2 mA peak-to-peak, 20 Hz square wave). These were compared to an Oral Baseline Absorption Group (sublingual diffusion in the absence of stimulation) to determine statistical significance of electrical stimulus; and a Subcutaneous Control Group (bolus injection) to discern therapeutic significance. +DC stimulation (4mA) increased serum concentration 28x with high statistical significance (p-value=0.0008). -DC stimulation (-4mA) increased serum concentration by 19x with borderline significance (p=0.032). AC (20 Hz) stimulus (2mA peak-peak) increased serum concentration by 10x, but was not statistically significant. The absorption rate of octreotide was also calculated for each group and compared at t=10 minutes and t=30 minutes. The absorption rate of the +DC group was 28x greater than that of Baseline Group and was statistically significant (p=0.0008). The absorption rate of the -DC group was 19x greater than that of the Baseline Group and was statistically significant (p=0.032). The absorption rate of the AC group was 10x greater than the Baseline Group but was not statistically significant (p=0.135). While none of the sublingual groups reached therapeutically significant serum concentrations, therapeutic levels of sublingually-delivered octreotide could potentially be achieved by extending octreotide exposure and stimulation time, coupled with utilizing sublingual octreotide in higher concentrations. This research was a necessary first step in successful realization of the SEP device

A radiological assessment of nuclear power and propulsion operations near Space Station Freedom

Scenarios were identified which involve the use of nuclear power systems in the vicinity of Space Station Freedom (SSF) and their radiological impact on the SSF crew was quantified. Several of the developed scenarios relate to the use of SSF as an evolutionary transportation node for lunar and Mars missions. In particular, radiation doses delivered to SSF crew were calculated for both the launch and subsequent return of a Nuclear Electric Propulsion (NEP) cargo vehicle and a Nuclear Thermal Rocket (NTR) personnel vehicle to low earth orbit. The use of nuclear power on co-orbiting platforms and the storage and handling issues associated with radioisotope power systems were also explored as they relate to SSF. A central philosophy in these analyses was the utilization of a radiation dose budget, defined as the difference between recommended dose limits from all radiation sources and estimated doses received by crew members from natural space radiations. Consequently, for each scenario examined, the dose budget concept was used to identify and quantify constraints on operational parameters such as launch separation distances, returned vehicle parking distances, and reactor shutdown times prior to vehicle approach. The results indicate that realistic scenarios do not exist which would preclude the use of nuclear power sources in the vicinity of SSF. The radiation dose to the SSF crew can be maintained at safe levels solely by implementing proper and reasonable operating procedures

Comparison of Organ Dosimetry for Astronaut Phantoms: Earth-Based vs. Microgravity-Based Anthropometry and Body Positioning

The purpose of this study is to use NASA radiation transport codes to compare astronaut organ dose equivalents resulting from solar particle events (SPE), geomagnetically trapped protons, and free-space galactic cosmic rays (GCR) using phantom models representing Earth-based and microgravity-based anthropometry and positioning. Methods: The Univer sity of Florida hybrid adult phantoms were scaled to represent male and female astronauts with 5th, 50th, and 95th percentile heights and weights as measured on Earth. Another set of scaled phantoms, incorporating microgravity-induced changes, such as spinal lengthening, leg volume loss, and the assumption of the neutral body position, was also created. A ray-tracer was created and used to generate body self-shielding distributions for dose points within a voxelized phantom under isotropic irradiation conditions, which closely approximates the free-space radiation environment. Simplified external shielding consisting of an aluminum spherical shell was used to consider the influence of a spacesuit or shielding of a hull. These distributions were combined with depth dose distributions generated from the NASA radiation transport codes BRYNTRN (SPE and trapped protons) and HZETRN (GCR) to yield dose equivalent. Many points were sampled per organ. Results: The organ dos e equivalent rates were on the order of 1.5-2.5 mSv per day for GCR (1977 solar minimum) and 0.4-0.8 mSv per day for trapped proton irradiation with shielding of 2 g cm-2 aluminum equivalent. The organ dose equivalents for SPE irradiation varied considerably, with the skin and eye lens having the highest organ dose equivalents and deep-seated organs, such as the bladder, liver, and stomach having the lowest. Conclus ions: The greatest differences between the Earth-based and microgravity-based phantoms are observed for smaller ray thicknesses, since the most drastic changes involved limb repositioning and not overall phantom size. Improved self-shielding models reduce the overall uncertainty in organ dosimetry for mission-risk projections and assessments for astronaut

Early 21st century snow cover state over the western river basins of the Indus River system

In this paper we assess the snow cover and its dynamics for the western river basins of the Indus River system (IRS) and their sub-basins located in Afghanistan, China, India and Pakistan for the period 2001–2012. First, we validate the Moderate Resolution Imaging Spectroradiometer (MODIS) daily snow products from Terra (MOD10A1) and Aqua (MYD10A1) against the Landsat Thematic Mapper/Enhanced Thematic Mapper plus (TM/ETM+) data set, and then improve them for clouds by applying a validated non-spectral cloud removal technique. The improved snow product has been analysed on a seasonal and annual basis against different topographic parameters (aspect, elevation and slope). Our results show a decreasing tendency for the annual average snow cover for the westerlies-influenced basins (upper Indus basin (UIB), Astore, Hunza, Shigar and Shyok) and an increasing tendency for the monsoon-influenced basins (Jhelum, Kabul, Swat and Gilgit). Seasonal average snow cover decreases during winter and autumn, and increases during spring and summer, which is consistent with the observed cooling and warming trends during the respective seasons. Sub-basins at relatively higher latitudes/altitudes show higher variability than basins at lower latitudes/middle altitudes. Northeastern and northwestern aspects feature greater snow cover. The mean end-of-summer regional snow line altitude (SLA) zones range from 3000 to 5000 m a.s.l. for all basins. Our analysis provides an indication of a descending end-of-summer regional SLA zone for most of the studied basins, which is significant for the Shyok and Kabul basins, thus indicating a change in their water resources. Such results are consistent with the observed hydro-climatic data, recently collected local perceptions and glacier mass balances for the investigated period within the UIB. Moreover, our analysis shows a significant correlation between winter season snow cover and the North Atlantic Oscillation (NAO) index of the previous autumn. Similarly, the inter-annual variability of spring season snow cover and spring season precipitation explains well the inter-annual variability of the summer season discharge from most of the basins. These findings indicate some potential for the seasonal stream flow forecast in the region, suggesting snow cover as a possible predictor

Systemic Sublingual Delivery of Octreotide Acetate Utilizing Low-Current Oral Electrical Stimulation in Rabbits

A sublingual electronic pill is a novel device designed to enhance delivery of drugs/biologics sublingually utilizing low-current electrical stimulation. Our primary aim was to explore safe limits of oral electrical stimulus in animals and conduct a randomized, sham-controlled animal study to quantify benefits of electrical stimulation on sublingual absorption of octreotide (a small peptide) as a first step in the development of this technology. A system to deliver low-current alternating and direct current stimuli to the oral mucosa of rabbits was constructed, and five groups were studied to determine the significance of sublingual octreotide diffusion in the presence of three different electrical stimulation scenarios: +DC (+4 mA), -DC (-4 mA), and AC (2 mA peak-to-peak, 20 Hz square wave). These were compared to an Oral Baseline Absorption Group (sublingual diffusion in the absence of stimulation) to determine statistical significance of electrical stimulus; and a Subcutaneous Control Group (bolus injection) to discern therapeutic significance. +DC stimulation (4mA) increased serum concentration 28x with high statistical significance (p-value=0.0008). -DC stimulation (-4mA) increased serum concentration by 19x with borderline significance (p=0.032). AC (20 Hz) stimulus (2mA peak-peak) increased serum concentration by 10x, but was not statistically significant. The absorption rate of octreotide was also calculated for each group and compared at t=10 minutes and t=30 minutes. The absorption rate of the +DC group was 28x greater than that of Baseline Group and was statistically significant (p=0.0008). The absorption rate of the -DC group was 19x greater than that of the Baseline Group and was statistically significant (p=0.032). The absorption rate of the AC group was 10x greater than the Baseline Group but was not statistically significant (p=0.135). While none of the sublingual groups reached therapeutically significant serum concentrations, therapeutic levels of sublingually-delivered octreotide could potentially be achieved by extending octreotide exposure and stimulation time, coupled with utilizing sublingual octreotide in higher concentrations. This research was a necessary first step in successful realization of the SEP device

Inventory and changes of rock glacier creep speeds in Ile Alatau and Kungöy Ala-Too, northern Tien Shan, since the 1950s

This research has been supported by the European Research Council (ICEMASS (grant no. 320816)) and the European Space Agency (grant nos. 40001161196/15/I-NB, 4000123681/18/I-NB, 4000109873/14/I-NB, 4000127593/19/I-NS, and 4000127656/19/NL/FF/gp). This work was funded by the ESA projects GlobPermafrost (40001161196/15/I-NB), Permafrost_CCI (4000123681/18/I-NB), and Glaciers_CCI (4000109873/14/I-NB, 4000127593/19/I-NS) and the ESA EarthExplorer10 Mission Advisory Group (4000127656/19/NL/FF/gp) as well as by the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC grant agreement no. 320816.Spatio-temporal patterns related to the viscous creep in perennially frozen sediments of rock glaciers in cold mountains have rarely been studied outside the densely populated European Alps. This study investigates the spatial and temporal variability of rock glacier movement in the Ile Alatau and Kungöy Ala-Too mountain ranges, northern Tien Shan, a region with particularly large and fast rock glaciers. Over the study region of more than 3000 km2, an inventory of slope movements was constructed using a large number of radar interferograms and high-resolution optical imagery. The inventory includes more than 900 landforms, of which around 550 were interpreted as rock glaciers. Out of the active rock glaciers inventoried, 45 are characterized by a rate of motion exceeding 100 cm/a. From these fast rock glaciers we selected six (Gorodetzky, Morenny, Archaly, Ordzhonikidze, Karakoram, and Kugalan Tash) and studied them in more detail using offset tracking between repeat aerial images and historical and modern high-resolution optical satellite data. Two of these rock glaciers showed a steady increase in decadal surface velocities from the 1950s onwards, with speeds being roughly 2 to 4 times higher in recent years compared to the 1950s and 1960s. Three rock glaciers showed similar accelerations over the last 1 to 2 decades but also phases of increased speeds in the 1960s. This development indicates a possible significant increase in current sediment and ice fluxes through rock glaciers and implies that their material transport in the region might gain geomorphodynamic importance relative to material transport by glaciers, assuming the latter decreases together with the regional glacier shrinkage. The study demonstrates how air and satellite image archives are exploited to construct one of the longest decennial times series of rock glacier speeds currently available. Our results are in line with findings from Europe about rock glacier speeds increasing with atmospheric warming and underline local variability of such an overall response.Publisher PDFPeer reviewe

Interactive Exploration of EMIT Mission Data

The Earth Mineral dust source InvesTigation (EMIT) imaging spectrometer aboard the international space station measures the spectrum of light ranging from the visible to infrared for each location in an image. This data can then be used to identify the distinct spectral signatures or fingerprints of materials present and applied across many scientific domains to map things like mineral types, vegetation species and health, snow grain size, water quality, dust, and greenhouse gases. NASA’s Land Processes Distributed Active Archive Center (LP DAAC) created and maintains the EMIT-Data-Resources repository, which contains Python workflows and Jupyter Notebooks developed and utilized within the Pangeo Framework. These resources leverage Xarray and the HoloViz ecosystem to explore the data and create interactive visualizations. This showcase will demonstrate creating an interactive map linked to a per-pixel spectral plot that can be used to explore the surface reflectance at different locations. Additional notebooks demonstrate cloud-based access from NASA’s Earthdata Cloud, how to subset data based on points and areas of interest, and how to convert datasets to ENVI format. All resources shown are open to all from the EMIT-Data-Resources repository. Contributions to the repository are welcome!Work performed under USGS Contract G15PD00467 for NASA contract NN14HH33I

A regionally resolved inventory of High Mountain Asia surge-type glaciers, derived from a multi-factor remote sensing approach

Knowledge about the occurrence and characteristics of surge-type glaciers is crucial due to the impact of surging on glacier melt and glacier-related hazards. One of the super-clusters of surge-type glaciers is High Mountain Asia (HMA). However, no consistent region-wide inventory of surge-type glaciers in HMA exists. We present a regionally resolved inventory of surge-type glaciers based on their behaviour across High Mountain Asia between 2000 and 2018. We identify surge-type behaviour from surface velocity, elevation and feature change patterns using a multi-factor remote sensing approach that combines yearly ITS_LIVE velocity data, DEM differences and very-high-resolution imagery (Bing Maps, Google Earth). Out of the ≈95 000 glaciers in HMA, we identified 666 that show diagnostic surge-type glacier behaviour between 2000 and 2018, which are mainly found in the Karakoram (223) and the Pamir regions (223). The total area covered by the 666 surge-type glaciers represents 19.5 % of the glacierized area in Randolph Glacier Inventory (RGI) V6.0 polygons in HMA. Only 68 glaciers were already identified as “surge type” in the RGI V6.0. We further validate 107 glaciers previously labelled as “probably surge type” and newly identify 491 glaciers, not previously reported in other inventories covering HMA. We finally discuss the possibility of self-organized criticality in glacier surges. Across all regions of HMA, the surge-affected area within glacier complexes displays a significant power law dependency with glacier length

Immunomodulatory parasites and toll-like receptor-mediated tumour necrosis factor alpha responsiveness in wild mammals

BACKGROUND: Immunological analyses of wild populations can increase our understanding of how vertebrate immune systems respond to 'natural' levels of exposure to diverse infections. A major recent advance in immunology has been the recognition of the central role of phylogenetically conserved toll-like receptors in triggering innate immunity and the subsequent recruitment of adaptive response programmes. We studied the cross-sectional associations between individual levels of systemic toll-like receptor-mediated tumour necrosis factor alpha responsiveness and macro- and microparasite infections in a natural wood mouse (Apodemus sylvaticus) population. RESULTS: Amongst a diverse group of macroparasites, only levels of the nematode Heligmosomoides polygyrus and the louse Polyplax serrata were correlated (negatively) with innate immune responsiveness (measured by splenocyte tumour necrosis factor alpha responses to a panel of toll-like receptor agonists). Polyplax serrata infection explained a strikingly high proportion of the total variation in innate responses. Contrastingly, faecal oocyst count in microparasitic Eimeria spp. was positively associated with innate immune responsiveness, most significantly for the endosomal receptors TLR7 and TLR9. CONCLUSION: Analogy with relevant laboratory models suggests the underlying causality for the observed patterns may be parasite-driven immunomodulatory effects on the host. A subset of immunomodulatory parasite species could thus have a key role in structuring other infections in natural vertebrate populations by affecting the 'upstream' innate mediators, like toll-like receptors, that are important in initiating immunity. Furthermore, the magnitude of the present result suggests that populations free from immunosuppressive parasites may exist at 'unnaturally' elevated levels of innate immune activation, perhaps leading to an increased risk of immunopathology