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SUMMARY Quantitative estimation of pore fractions filled with liquid water, ice and air is crucial for a process-based understanding of permafrost and its hazard potential upon climate-induced degradation. Geophysical methods offer opportunities to image distributions of permafrost constituents in a non-invasive manner. We present a method to jointly estimate the volumetric fractions of liquid water, ice, air and the rock matrix from seismic refraction and electrical resistivity data. Existing approaches rely on conventional inversions of both data sets and a suitable a priori estimate of the porosity distribution to transform velocity and resistivity models into estimates for the four-phase system, often leading to non-physical results. Based on two synthetic experiments and a field data set from an Alpine permafrost site (Schilthorn, Bernese Alps and Switzerland), it is demonstrated that the developed petrophysical joint inversion provides physically plausible solutions, even in the absence of prior porosity estimates. An assessment of the model covariance matrix for the coupled inverse problem reveals remaining petrophysical ambiguities, in particular between ice and rock matrix. Incorporation of petrophysical a priori information is demonstrated by penalizing ice occurrence within the first two meters of the subsurface where the measured borehole temperatures are positive. Joint inversion of the field data set reveals a shallow air-rich layer with high porosity on top of a lower-porosity subsurface with laterally varying ice and liquid water contents. Non-physical values (e.g. negative saturations) do not occur and estimated ice saturations of 0–50 per cent as well as liquid water saturations of 15–75 per cent are in agreement with the relatively warm borehole temperatures between −0.5  and 3 ° C. The presented method helps to improve quantification of water, ice and air from geophysical observations.

Background and ObjectiveSemaglutide is a glucagon-like peptide-1 analogue in development for the once-weekly treatment of type 2 diabetes mellitus. Its effect on the rate and extent of absorption of concomitant oral medications (metformin, warfarin, atorvastatin and digoxin) was evaluated in healthy subjects.MethodsSubjects received metformin (500 mg twice daily for 3.5 days), warfarin (25 mg, single dose), atorvastatin (40 mg, single dose) or digoxin (0.5 mg, single dose) before and with subcutaneous semaglutide treatment at steady state (1.0 mg). Lack of drug–drug interaction was concluded if the 90% confidence intervals for the area under the plasma concentration–time curve ratio before and with semaglutide were within a pre-specified interval (0.80–1.25).ResultsOverall, metformin, warfarin, atorvastatin and digoxin pharmacokinetics were not affected to a clinically relevant degree with semaglutide co-administration. Estimated area under the plasma concentration–time curve ratios for all concomitant medications before and with semaglutide treatment were within the pre-specified interval. In addition, semaglutide did not affect maximum plasma concentration of concomitant medications to a relevant degree. Furthermore, no clinically relevant change in international normalised ratio response to warfarin was observed with semaglutide co-administration. Most adverse events with semaglutide treatment were mild or moderate. Adverse events with semaglutide and co-administered medication were comparable to those reported during treatment with semaglutide alone, and were mostly gastrointestinal related.ConclusionsNo clinically significant pharmacokinetic or pharmacodynamic interactions were identified and no new safety issues observed with combined treatment with semaglutide. This suggests that no dose adjustments should be required when semaglutide is administered concomitantly with these medications.

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Shear fracture propagation in rock is accompanied by localized microcracking in a process zone surrounding the fracture tip. We investigated the crack microstructures along experimentally formed shear fractures from four granite samples (uniaxial compression tests). Five transects across a macroscopic fracture were inspected optically in transmitted light. Five hundred thirty-two photomicrographs were taken from seven study areas along each transect. We determined length, width, density, and orientation of open cracks and their assignment to intra-, transgranular, or grainboundary cracks. Crack density decreases with increasing distance to the macroscopic shear fracture and toward the fracture tip. The highest crack densities correlate with the maximum number of acoustic emissions. Most cracks enclose a small angle (0±20) with the macroscopic shear fracture. Intragranular cracks are more abundant than transgranular and grain-boundary cracks. The number of transgranular cracks increases towards the macroscopic shear fracture, but the number of grain-boundary cracks decreases. The decrease in crack density with increasing distance to the fault is accompanied by a change from strongly preferred crack orientation in the fault core to a random crack distribution away from the fault. Fracture process zone widths range from 2.10.8 mm (Ag51r) to 5.61.9 mm (Ag18r). The ratio of process zone width to fault length is approximately 0.04±0.07. This observation agrees with observations from natural fault zones. The fracture surface energy ranges from 0.2 to 1.2 J. This corresponds to <10% of the total strain energy.

High quality coastal aquifer systems provide vast quantities of potable groundwater for millions of people worldwide. Managing this setting has economic and environmental consequences. Specific knowledge of the dynamic relationship between fresh terrestrial groundwater discharging to the ocean and seawater intrusion is necessary. We present multi- disciplinary research that assesses the relationships between groundwater throughflow and seawater intrusion. This combines numerical simulation, geophysics, and analysis of more than 30 years of data from a seawater intrusion monitoring site. The monitoring wells are set in a shallow karstic aquifer system located along the southwest coast of Western Australia, where hundreds of gigalitres of fresh groundwater flow into the ocean annually. There is clear evidence for seawater intrusion along this coastal margin. We demonstrate how hydraulic anisotropy will impact on the landward extent of seawater for a given groundwater throughflow. Our examples show how the distance between the ocean and the seawater interface toe can shrink by over 100% after increasing the rotation angle of hydraulic conductivity anisotropy when compared to a homogeneous aquifer. We observe extreme variability in the properties of the shallow aquifer from ground penetrating radar, hand samples, and hydraulic parameters estimated from field measurements. This motived us to complete numerical experiments with sets of spatially correlated random hydraulic conductivity fields, representative of karstic aquifers. The hydraulic conductivity proximal to the zone of submarine groundwater discharge is shown to be significant in determining the overall geometry and landward extent of the seawater interface. Electrical resistivity imaging (ERI) data was acquired and assessed for its ability to recover the seawater interface. Imaging outcomes from field ERI data are compared with simulated ERI outcomes derived from transport modelling with a range of hydraulic conductivity distributions. This process allows for interpretation of the approximate geometry of the seawater interface, however recovery of an accurate resistivity distribution across the wedge and mixing zone remains challenging. We reveal extremes in groundwater velocity, particularly where fresh terrestrial groundwater discharges to the ocean, and across the seawater recirculation cell. An overarching conclusion is that conventional seawater intrusion monitoring wells may not be suitable to constrain numerical simulation of the seawater intrusion. Based on these lessons, we present future options for groundwater monitoring that are specifically designed to quantify the distribution of; (i) high vertical and horizontal pressure gradients, (ii) sharp variations in subsurface flow velocity, (iii) extremes in hydraulic properties, and (iv) rapid changes in groundwater chemistry. These extremes in parameter distribution are common in karstic aquifer systems at the transition from land to ocean. Our research provides new insights into the behaviour of groundwater in dynamic, densely populated, and ecologically sensitive coastal environments found worldwide.