Form and function in hillslope hydrology : in situ imaging and characterization of flow-relevant structures

Thanks to Elly Karle and the Engler-BunteInstitute, KIT, for the IC measurements of bromide. We are grateful to Selina Baldauf, Marcel Delock, Razije Fiden, Barbara Herbstritt, Lisei Köhn, Jonas Lanz, Francois Nyobeu, Marvin Reich and Begona Lorente Sistiaga for their support in the lab and during fieldwork, as well as Markus Morgner and Jean Francois Iffly for technical support and Britta Kattenstroth for hydrometeorological data acquisition. Laurent Pfister and Jean-Francois Iffly from the Luxembourg Institute of Science and Technology (LIST) are acknowledged for organizing the permissions for the experiments. Moreover, we thank Markus Weiler (University of Freiburg) for his strong support during the planning of the hillslope experiment and the preparation of the manuscript. This study is part of the DFG-funded CAOS project “From Catchments as Organised Systems to Models based on Dynamic Functional Units” (FOR 1598). The manuscript was substantially improved based on the critical and constructive comments of the anonymous reviewers, Christian Stamm and Alexander Zimmermann, and the editor Ross Woods during the open review process, which is highly appreciated.Peer reviewedPublisher PD

Form and function in hillslope hydrology : Characterization of subsurface ow based on response observations

Acknowledgements. We are grateful to Marcel Delock, Lisei Köhn, and Marvin Reich for their support during fieldwork, as well as Markus Morgner and Jean Francois Iffly for technical support, Britta Kattenstroth for hydrometeorological data acquisition and isotope sampling, and Barbara Herbstritt and Begoña Lorente Sistiaga for laboratory work. Laurent Pfister and Jean-Francois Iffly from the Luxembourg Institute of Science and Technology (LIST) are acknowledged for organizing the permissions for the experiments and providing discharge data for Weierbach 1 and Colpach. We also want to thank Frauke K. Barthold and the two anonymous reviewers, whose thorough remarks greatly helped to improve the manuscript. This study is part of DFG-funded CAOS project “From Catchments as Organised Systems to Models based on Dynamic Functional Units” (FOR 1598). The article processing charges for this open-access publication were covered by a Research Centre of the Helmholtz Association.Peer reviewedPublisher PD

Neutrophil swarms require LTB4 and integrins at sites of cell death in vivo

Neutrophil recruitment from blood to extravascular sites of sterile or infectious tissue damage is a hallmark of early innate immune responses, and the molecular events leading to cell exit from the bloodstream have been well defined1,2. Once outside the vessel, individual neutrophils often show extremely coordinated chemotaxis and cluster formation reminiscent of the swarming behaviour of insects3,4,5,6,7,8,9,10,11. The molecular players that direct this response at the single-cell and population levels within the complexity of an inflamed tissue are unknown. Using two-photon intravital microscopy in mouse models of sterile injury and infection, we show a critical role for intercellular signal relay among neutrophils mediated by the lipid leukotriene B4, which acutely amplifies local cell death signals to enhance the radius of highly directed interstitial neutrophil recruitment. Integrin receptors are dispensable for long-distance migration12, but have a previously unappreciated role in maintaining dense cellular clusters when congregating neutrophils rearrange the collagenous fibre network of the dermis to form a collagen-free zone at the wound centre. In this newly formed environment, integrins, in concert with neutrophil-derived leukotriene B4 and other chemoattractants, promote local neutrophil interaction while forming a tight wound seal. This wound seal has borders that cease to grow in kinetic concert with late recruitment of monocytes and macrophages at the edge of the displaced collagen fibres. Together, these data provide an initial molecular map of the factors that contribute to neutrophil swarming in the extravascular space of a damaged tissue. They reveal how local events are propagated over large-range distances, and how auto-signalling produces coordinated, self-organized neutrophil-swarming behaviour that isolates the wound or infectious site from surrounding viable tissue

Adaptive servo-ventilation for central sleep apnea in heart failure

Background Central sleep apnea is associated with poor prognosis and death in patients with heart failure. Adaptive servo-ventilation is a therapy that uses a noninvasive ventilator to treat central sleep apnea by delivering servo-controlled inspiratory pressure support on top of expiratory positive airway pressure. We investigated the effects of adaptive servo-ventilation in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea. Methods We randomly assigned 1325 patients with a left ventricular ejection fraction of 45% or less, an apnea–hypopnea index (AHI) of 15 or more events (occurrences of apnea or hypopnea) per hour, and a predominance of central events to receive guideline-based medical treatment with adaptive servo-ventilation or guideline-based medical treatment alone (control). The primary end point in the time-to-event analysis was the first event of death from any cause, lifesaving cardiovascular intervention (cardiac transplantation, implantation of a ventricular assist device, resuscitation after sudden cardiac arrest, or appropriate lifesaving shock), or unplanned hospitalization for worsening heart failure. Results In the adaptive servo-ventilation group, the mean AHI at 12 months was 6.6 events per hour. The incidence of the primary end point did not differ significantly between the adaptive servo-ventilation group and the control group (54.1% and 50.8%, respectively; hazard ratio, 1.13; 95% confidence interval [CI], 0.97 to 1.31; P=0.10). All-cause mortality and cardiovascular mortality were significantly higher in the adaptive servo-ventilation group than in the control group (hazard ratio for death from any cause, 1.28; 95% CI, 1.06 to 1.55; P=0.01; and hazard ratio for cardiovascular death, 1.34; 95% CI, 1.09 to 1.65; P=0.006). Conclusions Adaptive servo-ventilation had no significant effect on the primary end point in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea, but all-cause and cardiovascular mortality were both increased with this therapy. (Funded by ResMed and others; SERVE-HF ClinicalTrials.gov number, NCT00733343. opens in new tab.

Enzyme replacement therapy in mice lacking arylsulfatase B targets bone-remodeling cells, but not chondrocytes

Mucopolysaccharidosis type VI (MPS-VI), caused by mutational inactivation of the glycosaminoglycan-degrading enzyme arylsulfatase B (Arsb), is a lysosomal storage disorder primarily affecting the skeleton. We have previously reported that Arsb-deficient mice display high trabecular bone mass and impaired skeletal growth. In the present study, we treated them by weekly injection of recombinant human ARSB (rhARSB) to analyze the impact of enzyme replacement therapy (ERT) on skeletal growth and bone remodeling. We found that all bone-remodeling abnormalities of Arsb-deficient mice were prevented by ERT, whereas chondrocyte defects were not. Likewise, histologic analysis of the surgically removed femoral head from an ERT-treated MPS-VI patient revealed that only chondrocytes were pathologically affected. Remarkably, a side-by-side comparison with other cell types demonstrated that chondrocytes have substantially reduced capacity to endocytose rhARSB, together with low expression of the mannose receptor. We finally took advantage of Arsb-deficient mice to establish quantification of chondroitin sulfation for treatment monitoring. Our data demonstrate that bone-remodeling cell types are accessible to systemically delivered rhARSB, whereas the uptake into chondrocytes is inefficient

LPMLE3 : a novel 1-D approach to study water flow in streambeds using heat as a tracer

We introduce LPMLE3, a new 1-D approach to quantify vertical water flow components at streambeds using temperature data collected in different depths. LPMLE3 solves the partial differential equation for coupled water flow and heat transport in the frequency domain. Unlike other 1-D approaches it does not assume a semi-infinite halfspace with the location of the lower boundary condition approaching infinity. Instead, it uses local upper and lower boundary conditions. As such, the streambed can be divided into finite subdomains bound at the top and bottom by a temperature-time series. Information from a third temperature sensor within each subdomain is then used for parameter estimation. LPMLE3 applies a low order local polynomial to separate periodic and transient parts (including the noise contributions) of a temperature-time series and calculates the frequency response of each subdomain to a known temperature input at the streambed top. A maximum-likelihood estimator is used to estimate the vertical component of water flow, thermal diffusivity, and their uncertainties for each streambed subdomain and provides information regarding model quality. We tested the method on synthetic temperature data generated with the numerical model STRIVE and demonstrate how the vertical flow component can be quantified for field data collected in a Belgian stream. We show that by using the results in additional analyses, nonvertical flow components could be identified and by making certain assumptions they could be quantified for each subdomain. LPMLE3 performed well on both simulated and field data and can be considered a valuable addition to the existing 1-D methods

Deep lithospheric structures along the southern central Chile Margin from wide-angle P-wave modellilng

Crustal- and upper-mantle structures of the subduction zone in south central Chile, between 42 degrees S and 46 degrees S, are determined from seismic wide-angle reflection and refraction data, using the seismic ray tracing method to calculate minimum parameter models. Three profiles along differently aged segments of the subducting Nazca Plate were analysed in order to study subduction zone structure dependencies related to the age, that is, thermal state, of the incoming plate. The age of the oceanic crust at the trench ranges from 3 Ma on the southernmost profile, immediately north of the Chile triple junction, to 6.5 Ma old about 100 km to the north, and to 14.5 Ma old another 200 km further north, off the Island of Chiloe. Remarkable similarities appear in the structures of both the incoming as well as the overriding plate. The oceanic Nazca Plate is around 5 km thick, with a slightly increasing thickness northward, reflecting temperature changes at the time of crustal generation. The trench basin is about 2 km thick except in the south where the Chile Ridge is close to the deformation front and only a small, 800-m-thick trench infill could develop. In south central Chile, typically three quarters (1.5 km) of the trench sediments subduct below the decollement in the subduction channel. To the north and south of the study area, only about one quarter to one third of the sediments subducts, the rest is accreted above. Similarities in the overriding plate are the width of the active accretionary prism, 35-50 km, and a strong lateral crustal velocity gradient zone about 75-80 km landward from the deformation front, where landward upper-crustal velocities of over 5.0-5.4 km s<SU-1</SU decrease seaward to around 4.5 km s<SU-1</SU within about 10 km, which possibly represents a palaeo-backstop. This zone is also accompanied by strong intraplate seismicity. Differences in the subduction zone structures exist in the outer rise region, where the northern profile exhibits a clear bulge of uplifted oceanic lithosphere prior to subduction whereas the younger structures have a less developed outer rise. This plate bending is accompanied by strongly reduced rock velocities on the northern profile due to fracturing and possible hydration of the crust and upper mantle. The southern profiles do not exhibit such a strong alteration of the lithosphere, although this effect may be counteracted by plate cooling effects, which are reflected in increasing rock velocities away from the spreading centre. Overall there appears little influence of incoming plate age on the subduction zone structure which may explain why the M-w = 9.5 great Chile earthquake from 1960 ruptured through all these differing age segments. The rupture area, however, appears to coincide with a relatively thick subduction channel

Worsening calcification propensity precedes all-cause and cardiovascular mortality in haemodialyzed patients

A novel in-vitro test (T-50-test) assesses ex-vivo serum calcification propensity which predicts mortality in HD patients. The association of longitudinal changes of T-50 with all-cause and cardiovascular mortality has not been investigated. We assessed T-50 in paired sera collected at baseline and at 24 months in 188 prevalent European HD patients from the ISAR cohort, most of whom were Caucasians. Patients were followed for another 19 [interquartile range: 11-37] months. Serum T-50 exhibited a significant decline between baseline and 24 months (246 +/- 64 to 190 +/- 68 minutes;p < 0.001). With serum Delta-phosphate showing the strongest independent association with declining T-50 (r = -0.39;p < 0.001) in multivariable linear regression. The rate of decline of T-50 over 24 months was a significant predictor of all-cause (HR = 1.51 per 1SD decline, 95% CI: 1.04 to 2.2;p = 0.03) and cardiovascular mortality (HR = 2.15;95% CI: 1.15 to 3.97;p = 0.02) in Kaplan Meier and multivariable Cox-regression analysis, while cross-sectional T-50 at inclusion and 24 months were not. Worsening serum calcification propensity was an independent predictor of mortality in this small cohort of prevalent HD patients. Prospective larger scaled studies are needed to assess the value of calcification propensity as a longitudinal parameter for risk stratification and monitoring of therapeutic interventions