Using stable isotopes to inform water resource management in forested and agricultural ecosystems.

Present and future climatic trends are expected to markedly alter water fluxes and stores in the hydrologic cycle. In addition, water demand continues to grow due to increased human use and a growing population. Sustainably managing water resources requires a thorough understanding of water storage and flow in natural, agricultural, and urban ecosystems. Measurements of stable isotopes of water (hydrogen and oxygen) in the water cycle (atmosphere, soils, plants, surface water, and groundwater) can provide information on the transport pathways, sourcing, dynamics, ages, and storage pools of water that is difficult to obtain with other techniques. However, the potential of these techniques for practical questions has not been fully exploited yet. Here, we outline the benefits and limitations of potential applications of stable isotope methods useful to water managers, farmers, and other stakeholders. We also describe several case studies demonstrating how stable isotopes of water can support water management decision-making. Finally, we propose a workflow that guides users through a sequence of decisions required to apply stable isotope methods to examples of water management issues. We call for ongoing dialogue and a stronger connection between water management stakeholders and water stable isotope practitioners to identify the most pressing issues and develop best-practice guidelines to apply these techniques.

Soil-plant interactions modulated water availability of Swiss forests during the 2015 and 2018 droughts.

Central Europe has been experiencing unprecedented droughts during the last decades, stressing the decrease in tree water availability. However, the assessment of physiological drought stress is challenging, and feedback between soil and vegetation is often omitted because of scarce belowground data. Here we aimed to model Swiss forests' water availability during the 2015 and 2018 droughts by implementing the mechanistic soil-vegetation-atmosphere-transport (SVAT) model LWF-Brook90 taking advantage of regionalized depth-resolved soil information. We calibrated the model against soil matric potential data measured from 2014 to 2018 at 44 sites along a Swiss climatic and edaphic drought gradient. Swiss forest soils' storage capacity of plant-available water ranged from 53 mm to 341 mm, with a median of 137 ± 42 mm down to the mean potential rooting depth of 1.2 m. Topsoil was the primary water source. However, trees switched to deeper soil water sources during drought. This effect was less pronounced for coniferous trees with a shallower rooting system than for deciduous trees, which resulted in a higher reduction of actual transpiration (transpiration deficit) in coniferous trees. Across Switzerland, forest trees reduced the transpiration by 23% (compared to potential transpiration) in 2015 and 2018, maintaining annual actual transpiration comparable to other years. Together with lower evaporative fluxes, the Swiss forests did not amplify the blue water deficit. The 2018 drought, characterized by a higher and more persistent transpiration deficit than in 2015, triggered widespread early wilting across Swiss forests that was better predicted by the SVAT-derived mean soil matric potential in the rooting zone than by climatic predictors. Such feedback-driven quantification of ecosystem water fluxes in the soil-plant-atmosphere continuum will be crucial to predicting physiological drought stress under future climate extremes.

Pharmacokinetics-Pharmacodynamics of Enmetazobactam Combined with Cefepime in a Neutropenic Murine Thigh Infection Model.

Third-generation cephalosporin (3GC)-resistant Enterobacteriaceae are classified as critical priority pathogens, with extended-spectrum ß-lactamases (ESBLs) as principal resistance determinants. Enmetazobactam (formerly AAI101) is a novel ESBL inhibitor developed in combination with cefepime for empirical treatment of serious Gram-negative infections in settings where ESBLs are prevalent. Cefepime-enmetazobactam has been investigated in a phase 3 trial in patients with complicated urinary tract infections or acute pyelonephritis. This study examined pharmacokinetic-pharmacodynamic (PK-PD) relationships of enmetazobactam, in combination with cefepime, for ESBL-producing isolates of Klebsiella pneumoniae in 26-h murine neutropenic thigh infection models. Enmetazobactam dose fractionation identified the time above a free threshold concentration (fT > CT ) as the PK-PD index predictive of efficacy. Nine ESBL-producing isolates of K. pneumoniae, resistant to cefepime and piperacillin-tazobactam, were included in enmetazobactam dose-ranging studies. The isolates encoded CTX-M-type, SHV-12, DHA-1, and OXA-48 ß-lactamases and covered a cefepime-enmetazobactam MIC range from 0.06 to 2 µg/ml. Enmetazobactam restored the efficacy of cefepime against all isolates tested. Sigmoid curve fitting across the combined set of isolates identified enmetazobactam PK-PD targets for stasis and for a 1-log10 bioburden reduction of 8% and 44% fT > 2 µg/ml, respectively, with a concomitant cefepime PK-PD target of 40 to 60% fT > cefepime-enmetazobactam MIC. These findings support clinical dose selection and breakpoint setting for cefepime-enmetazobactam.

The Effect of Microgravity on Central Aortic Blood Pressure.

BACKGROUND: Blood pressure has been traditionally measured at peripheral arteries. In the past decade, evidence has grown that central aortic blood pressure may be a more powerful predictor for cardiovascular events, but data on its regulation are rare. The present work examines the impact of microgravity on central blood pressure for the first time. METHODS: We performed 7 parabolic flights with 22 seconds of weightlessness in each parabola. Hemodynamic parameters including central systolic blood pressure were measured noninvasively in a free-floating position in 20 healthy subjects (19-43 years of age). RESULTS: Arterial elasticity at rest was normal in all participants (augmentation index 14% (interquartile range (IQR) 10-22), pulse wave velocity 5.2 m/s (IQR 5.0-5.4)). Transition of 1g to 0g led to a significant increase of central systolic blood pressure from 124 (IQR 118-133) to 127 (IQR 119-133) mm Hg (P = 0.017). Cardiac index augmented significantly from 2.5 (IQR 2.2-2.8) to 2.7 (IQR 2.3-3.0) l/min/m2 (P < 0.001), while peripheral vascular resistance showed a decrease from 1.30 (IQR 1.14-1.48) to 1.25 (IQR 1.15-1.40) s × mm Hg/ml (P = 0.037). Peripheral systolic blood pressure did not change significantly (P > 0.05). CONCLUSION: Whereas there is a multitude of studies on the effects of microgravity on peripheral blood pressure, this study provides first data on central aortic blood pressure. An acute loss of gravity leads to a central blood volume shift with an augmentation of cardiac output. In healthy subjects with normal arterial stiffness, the compensatory decrease of peripheral resistance does not outweigh this effect resulting in an increase of central blood pressure.