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Remote seismic observations of a glacial lake outburst flood highlight potential for improving early warning systems., Glacial lake outburst floods (GLOFs) are a substantial hazard for downstream communities in vulnerable regions, yet unpredictable triggers and remote source locations make GLOF dynamics difficult to measure and quantify. Here, we revisit a destructive GLOF that occurred in Bhutan in 1994 and apply cross-correlation–based seismic analyses to track the evolution of the GLOF remotely (~100 kilometers from the source region). We use the seismic observations along with eyewitness reports and a downstream gauge station to constrain a numerical flood model and then assess geomorphic change and current state of the unstable lakes via satellite imagery. Coherent seismic energy is evident from 1 to 5 hertz beginning approximately 5 hours before the flood impacted Punakha village, which originated at the source lake and advanced down the valley during the GLOF duration. Our analysis highlights potential benefits of using real-time seismic monitoring to improve early warning systems.

Glacier ice loss rates across the Himalayas have doubled over the past four decades, consistent with regional atmospheric warming., Himalayan glaciers supply meltwater to densely populated catchments in South Asia, and regional observations of glacier change over multiple decades are needed to understand climate drivers and assess resulting impacts on glacier-fed rivers. Here, we quantify changes in ice thickness during the intervals 1975–2000 and 2000–2016 across the Himalayas, using a set of digital elevation models derived from cold war–era spy satellite film and modern stereo satellite imagery. We observe consistent ice loss along the entire 2000-km transect for both intervals and find a doubling of the average loss rate during 2000–2016 [−0.43 ± 0.14 m w.e. year−1 (meters of water equivalent per year)] compared to 1975–2000 (−0.22 ± 0.13 m w.e. year−1). The similar magnitude and acceleration of ice loss across the Himalayas suggests a regionally coherent climate forcing, consistent with atmospheric warming and associated energy fluxes as the dominant drivers of glacier change.

Himalayan glaciers are important natural resources and climate indicators for densely populated regions in Asia. Remote sensing methods are vital for evaluating glacier response to changing climate over the vast and rugged Himalayan region; yet many platforms capable of glacier mass balance quantification are somewhat temporally limited considering typical glacier response times. We here rely on declassified spy satellite imagery and ASTER data to quantify surface lowering, ice volume change, and geodetic mass balance during 1974–2006 for glaciers in the eastern Himalayas, centered on the Bhutan-China border. The wide range of glacier types allows for the first mass balance comparison between clean, debris, and lake-terminating (calving) glaciers in the region. Measured glaciers show significant ice loss, with an estimated mean annual geodetic mass balance of −0.12 ± 0.06 m.w.e. yr−1 (meters of water equivalent per year) for 10 clean-ice glaciers, −0.15 ± 0.11 m.w.e. yr−1 for 5 debris-covered glaciers, −0.25 ± 0.10 m.w.e. yr−1 for 6 calving glaciers, and −0.16 ± 0.05 m.w.e. yr−1 for all glaciers combined. The similar mass balances for clean-ice and debris-covered glaciers suggests that melt pond, ice cliff, and englacial conduit mechanisms are likely playing important roles in the melt process for debris-covered glaciers. Calving glaciers comprise 24 % (80 km2) of the glacierized area, yet have contributed 37 % (−0.7 km3) to the total ice volume loss, highlighting the growing relevance of proglacial lake formation and associated calving for the future ice mass budget of the Himalayas as the number and size of glacial lakes increase.

Declassified historical imagery from the Hexagon spy satellite database has near-global coverage, yet remains a largely untapped resource for geomorphic change studies. Unavailable satellite ephemeris data make DEM (digital elevation model) extraction difficult in terms of time and accuracy. A new fully-automated pipeline for DEM extraction and image orthorectification is presented which yields accurate results and greatly increases efficiency over traditional photogrammetric methods, making the Hexagon image database much more appealing and accessible. A 1980 Hexagon DEM is extracted and geomorphic change computed for the Thistle Creek Landslide region in the Wasatch Range of North America to demonstrate an application of the new method. Surface elevation changes resulting from the landslide show an average elevation decrease of 14.4 ± 4.3 m in the source area, an increase of 17.6 ± 4.7 m in the deposition area, and a decrease of 30.2 ± 5.1 m resulting from a new roadcut. Two additional applications of the method include volume estimates of material excavated during the Mount St. Helens volcanic eruption and the volume of net ice loss over a 34-year period for glaciers in the Bhutanese Himalayas. These results show the value of Hexagon imagery in detecting and quantifying historical geomorphic change, especially in regions where other data sources are limited.

PURPOSE: Conventional bioavailability testing of dosage forms based on plasma concentration-time graphs of two products in a two-period, crossover-design, is not applicable to topical treatment of intestinal segments. We introduce an isotope dual-label approach ((13)C- and (15)N(2)-urea) for colon drug delivery systems that can be performed in a one-day, non-invasive study-design.METHODS: Four healthy volunteers took an uncoated or a ColoPulse-capsule containing (13)C-urea and an uncoated capsule containing (15)N(2)-urea. In case of colon-release (13)C-urea is fermented and (13)C detected as breath (13)CO(2). Absorbed (13)C-urea and (15)N-urea are detected in urine.RESULTS: C and (15)N in urine released from uncoated capsules showed a ratio of 1.01 ± 0.06. The (13)C/(15)N-recovery ratio after intake of a ColoPulse-capsule was constant and lower >12 h post-dose (median 0.22, range 0.13-0.48). The (13)C/(15)N-ratio in a single urine sample at t ≥ 12 h predicted the 24 h non-fermented fraction (13)C of 3 h) release and a fermented fraction (13)C >54 %.CONCLUSIONS: Breath and urine (13)C and (15)N data describe the release-profile and local bioavailability of a colon delivery device. This allows non-invasive bioavailability studies for evaluation of colon-specific drug delivery systems without radioactive exposure and with increased power and strongly reduced costs.

This paper describes various methodological aspects that were encountered during the development of a system to monitor the in vivo behaviour of a newly developed colon delivery device that enables oral drug treatment of inflammatory bowel diseases. [C-13]urea was chosen as the marker substance. Release of [C-13]urea in the ileocolonic region is proven by the exhalation of (CO2)-C-13 in breath due to bacterial fermentation of [C-13]urea. The (CO2)-C-13 exhalation kinetics allows the calculation of a lag time as marker for delay of release, a pulse time as marker for the speed of drug release and the fraction of the dose that is fermented. To determine the total bioavailability, also the fraction of the dose absorbed from the intestine must be quantified. Initially, this was done by calculating the time-dependent [C-13]urea appearance in the body urea pool via measurement of C-13 abundance and concentration of plasma urea. Thereafter, a new methodology was successfully developed to obtain the bioavailability data by measurement of the urinary excretion rate of [C-13]urea. These techniques required two experimental days, one to test the coated device, another to test the uncoated device to obtain reference values for the situation that 100 % of [C-13]urea is absorbed. This is hampered by large day-to-day variations in urea metabolism. Finally, a completely non-invasive, one-day test was worked out based on a dual isotope approach applying a simultaneous administration of [C-13]urea in a coated device and [N-15(2)]urea in an uncoated device. All aspects of isotope-related analytical methodologies and required calculation and correction systems are described.

After taking 35 tablets of flurazepam 15 mg, 50 tablets of diazepam 5 mg, a 38-year old female (105 kg, BMI 36) was hit by a vehicle at 80 km/h. Initially she had a coma that measured a 1-4-2 on the Glasgow Coma Scale (GCS), an impression fracture of the frontal bone with free air in cerebro, a right-sided frontal contusion and a mild traumatic subarachnoidal bleed. Several ribs on her right were broken without any injury to the organs. After a decompressive craniotomy, she was admitted to the ICU. At the time of admission, flurazepam (124 µg/L; therapeutic range 40–150 µg/L [1, 2]) and diazepam serum levels were therapeutic (439 µg/L; therapeutic range 100–750 µg/L [1, 2]). The active metabolite of diazepam, desmethyldiazepam, was toxic (5,971 µg/L; therapeutic range: 200–1,800 µg/L [2]). The other metabolites temazepam and oxazepam were low. Fentanyl and propofol, administered for analgesia and sedation, were stopped after 2 days; the patient received no other medication. A CT cerebrum was repeated on day 5 and revealed diffuse contusions. An electroencephalogram indicated diffuse encephalopathy. These findings were considered insufficient to explain her persistent coma. Desmethyldiazepam serum level remained high, despite the patients’ normal liver and kidney function. Flumazenil was administered, revealing a coma ofof 4-3-T on the GCS. As elimination of desmethyldiazepam seemed to be impaired, genotyping was performed. This revealed that she was an extensive cytochrome P450 (CYP) 2C19 metaboliser. To enhance elimination, rifampicin, a CYP3A4 and 2C19 inducer, 600 mg bid i.v., was started on day 12 (Fig. 1). Fig. 1 Time course of benzodiazepine serum levels before and during rifampicin administration (fen fentanyl). Except for a brief period directly after ICU-admission, the patient received no benzodiazepines or other sedatives, narcotics or analgesics. Due to ... When the serum level of desmethyldiazepam had fallen within therapeutic ranges at day 20, the patient improved. After 34 days she was transferred to a neurological medium care facility. Four months after her hospital discharge, she had a maximal GCS and was still recovering from her injuries. This case underscores two points. First, diazepam and its active metabolites can considerably prolong coma. This is due to the metabolic pathway of diazepam [6]. Diazepam is metabolized through CYP3A4 to temazepam and CYP3A4/2C19 to desmethyldiazepam which is then metabolized through CYP3A4 to oxazepam. Temazepam and oxazepam, which have a small effect compared to diazepam and desmethyldiazepam are eliminated through conjugation. The high levels of desmethyldiazepam and low levels of temazepam and oxazepam underscore impairment of CYP3A4/2C19. In benzodiazepine intoxications, focus on withdrawal and clearance of all active metabolites is advisable. Second, rifampicin accelerated clearance of the metabolites through induction of CYP2C19 and CYP3A4. The elimination half-life of desmethyldiazepam decreased from 194 h (normal range 40–200 h [5]) to 63 after start of rifampicin and may have shortened the comatose condition by 20 days. We preferred to use rifampicin for several reasons. Rifampicin is a well-characterised drug with established strong CYP3A4/2C19 inducing capabilities. Furthermore, the FDA [3, 4] considers rifampicin as the drug of choice for CYP450 inducer studies. Finally, other CYP3A4 inducers like antiretroviral agents and anti-epileptics have shortcomings like the advisable restricted use for HIV treatment and neurological side effects that could have complicated assessment of our patient or even provoked convulsions. We suggest that rifampicin may be considered in severe benzodiazepine intoxications if clearance of the drug appears to be problematic. Obviously, other drug interactions and development of rifampicin resistance should be kept in mind.

Glacial ogives are transverse topographic, wave-like surface features that form below icefalls on some alpine glaciers. Ground-penetrating radar surveys from the Gorner glacier system in the Swiss Alps reveal an along-flow periodicity in scattering intensity that correlates with ogives. The scattering appears in the ablation zone and occurs at 5–20 m depth. The geometry of the scattering mimics that of the ogives, although exaggerated in amplitude. We interpret the scattering to represent lateral variations in water content. We propose that as glacial ice accelerated and stretched through the icefall, seasonal fluctuations occurred in water infiltration to crevasses during the summer and subsequent freezing of that water in the crevasses in the winter. This seasonally varying infilling and freezing locally altered the distribution of temperature, creating zones of temperate ice with water inclusions that preferentially scatter radar energy. In addition to the scattering pattern, highly reflective planar features associated with these periodic regions of temperate ice are interpreted as water-filled fractures. A three-dimensional rendering of the orientation of these planar features precludes a "fold-and-thrust" hypothesis for the formation of the ogives.