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The response of plants to increasing atmospheric CO2 depends on the ecological context where the plants are found. Several experiments with elevated CO2 (eCO2) have been done worldwide, but the Amazonian forest understory has been neglected. As the central Amazon is limited by light and phosphorus, understanding how understory responds to eCO2 is important for foreseeing how the forest will function in the future. In the understory of a natural forest in the Central Amazon, we installed four open-top chambers as control replicates and another four under eCO2 (+250 ppm above ambient levels). Under eCO2, we observed increases in carbon assimilation rate (67%), maximum electron transport rate (19%), quantum yield (56%), and water use efficiency (78%). We also detected an increase in leaf area (51%) and stem diameter increment (65%). Central Amazon understory responded positively to eCO2 by increasing their ability to capture and use light and the extra primary productivity was allocated to supporting more leaf and conducting tissues. The increment in leaf area while maintaining transpiration rates suggests that the understory will increase its contribution to evapotranspiration. Therefore, this forest might be less resistant in the future to extreme drought, as no reduction in transpiration rates were detected.

We develop a compressible liquid-drop model to describe the crust of neutron stars for which the role of the nuclear clusters, the neutron gas, and the electrons are clearly identified. The novelty relies on the contribution of the neutron gas, which is qualitatively adjusted to reproduce 'ab initio' predictions in dilute neutron matter. We relate the properties of dilute neutron matter to the ones of neutron stars crust and we compare the mean field approximation to an improved approach which better describes dilute neutron matter. The latter is quite sensitive to the unitary limit, a universal feature of Fermi systems having a large value of the scattering length and a small interaction range. While the impact of the accurate description of dilute neutron matter is important in uniform matter (up to 30\% corrections with respect to a mean field calculations), we find a reduction of this impact in the context of the crust of neutron stars due to the additional matter components (nuclear clusters and electrons). In agreement with our previous works, dilute neutron matter is however a necessary ingredient for accurate predictions of the properties of the crust of neutron stars.

This study examines the ink used in an archive of >50 bilingual papyri (in Greek and Demotic) written by a single scribe that were found in two crocodile mummies excavated from Tebtunis by B.P. Grenfell and A.S. Hunt in 1900.

Mature spruce and beech were exposed to five drought and three recovery years in the KROOF experiment. Compared to beech showing only stomatal regulation, spruce more strongly reduced their water use by stronger stomatal control together with a reduction in total leaf area. After drought release, spruce fully recovered C transport speed and preferentially allocated recent and stored C to regrow their fine roots. Whole-tree C uptake and water use of spruce did not fully recover in contrast to beech due to slow recovery of leaf area, which, however, may be advantageous during next drought., Adulte Fichten und Buchen wurden fünf Dürre- und drei Erholungsjahren ausgesetzt. Die Fichte reduzierte, im Vergleich zur nur stomatär regulierten Buche, den Wasserverbrauch stärker durch stärkere stomatäre Kontrolle zusammen mit Abnahme der gesamten Blattfläche. Die Fichte erholte sich vollständig in der C Transportgeschwindigkeit und allozierte den neuen und gespeicherten C bevorzugt zum Feinwurzelzuwachs. Der gesamte Wasserverbrauch der Fichte pendelte sich im Gegensatz zur Buche nicht vollständig ein, was jedoch bei der nächsten Trockenheit von Vorteil sein könnte.

Background: To characterize the use of nephrotoxic medications in patients with chronic kidney disease (CKD) Stages G3-5 in routine care. Methods: We studied cohorts of adults with confirmed CKD G3-5 undergoing routine care from 1 January 2016 through 31 December 2018 in two health systems [Stockholm CREAtinine Measurements (SCREAM), Stockholm, Sweden (N = 57 880) and Geisinger, PA, USA (N = 16 255)]. We evaluated the proportion of patients receiving nephrotoxic medications within 1 year overall and by baseline kidney function, ranked main contributors and examined the association between receipt of nephrotoxic medication and age, sex, CKD G-stages comorbidities and provider awareness of the patient's CKD using multivariable logistic regression. Results: During a 1-year period, 20% (SCREAM) and 17% (Geisinger) of patients with CKD received at least one nephrotoxic medication. Among the top nephrotoxic medications identified in both cohorts were non-steroidal anti-inflammatory drugs (given to 11% and 9% of patients in SCREAM and Geisinger, respectively), antivirals (2.5% and 2.0%) and immunosuppressants (2.7% and 1.5%). Bisphosphonate use was common in SCREAM (3.3%) and fenofibrates in Geisinger (3.6%). Patients <65 years of age, women and those with CKD G3 were at higher risk of receiving nephrotoxic medications in both cohorts. Notably, provider awareness of a patient's CKD was associated with lower odds of nephrotoxic medication use {odds ratios [OR] 0.85[95% confidence interval (CI) 0.80-0.90] in SCREAM and OR 0.80 [95% CI 0.72-0.89] in Geisinger}. Conclusions: One in five patients with CKD received nephrotoxic medications in two distinct health systems. Strategies to increase physician's awareness of patients' CKD and knowledge of drug nephrotoxicity may reduce prescribing nephrotoxic medications and prevent iatrogenic kidney injury.

Mature beech and spruce trees were drought stressed for 5 consecutive years in the KROOF experiment. No signs of Carbon Starvation were found under the drought treatment, but overall the carbon pool sizes were reduced by about 40% in both species and carbon transport velocity in the phloem was reduced by about 50 %. Upon watering both species recovered their water household related physiology (water potential, osmotic acclimations and sap flow density) within the next vegetation period at the latest, displaying a high resilience potential, with beech recovering faster than spruce., Adulte Buchen und Fichten wurden im KROOF-Experiment für fünf Jahre trockengestresst. Dabei wurden keine Anzeichen für „Carbon Starvation“ gefunden, aber insgesamt reduzierte sich der Gesamtkohlenstoffpool um ca. 40 % und die Phloemtransportgeschwindigkeit um ca. 50 %. Der Wasserhaushalt (Wasserpotenzial, osmotische Änderungen und Saftflussdichte) beider Arten erholte sich in Folge der Bewässerung spätestens innerhalb der nächsten Vegetationsperiode und weißt damit ein hohe Resilienz auf, wobei sich die Buche oftmals schneller erholte als die Fichte.

IMPORTANCE: Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. OBJECTIVE: To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. DESIGN, SETTING, AND PARTICIPANTS: Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021. EXPOSURES: The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR). MAIN OUTCOMES AND MEASURES: The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses. RESULTS: Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associ

Item does not contain fulltext, SIGNIFICANCE STATEMENT: The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict 2- and 5-year risk of kidney failure in populations with eGFR <60 ml/min per 1.73 m 2 . However, the CKD-EPI 2021 creatinine equation for eGFR is now recommended for use but has not been fully tested in the context of KFRE. In 59 cohorts comprising 312,424 patients with CKD, the authors assessed the predictive performance and calibration associated with the use of the CKD-EPI 2021 equation and whether additional variables and accounting for the competing risk of death improves the KFRE's performance. The KFRE generally performed well using the CKD-EPI 2021 eGFR in populations with eGFR <45 ml/min per 1.73 m 2 and was not improved by adding the 2-year prior eGFR slope and cardiovascular comorbidities. BACKGROUND: The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict kidney failure risk in people with GFR <60 ml/min per 1.73 m 2 . METHODS: Using 59 cohorts with 312,424 patients with CKD, we tested several modifications to the KFRE for their potential to improve the KFRE: using the CKD-EPI 2021 creatinine equation for eGFR, substituting 1-year average ACR for single-measure ACR and 1-year average eGFR in participants with high eGFR variability, and adding 2-year prior eGFR slope and cardiovascular comorbidities. We also assessed calibration of the KFRE in subgroups of eGFR and age before and after accounting for the competing risk of death. RESULTS: The KFRE remained accurate and well calibrated overall using the CKD-EPI 2021 eGFR equation. The other modifications did not improve KFRE performance. In subgroups of eGFR 45-59 ml/min per 1.73 m 2 and in older adults using the 5-year time horizon, the KFRE demonstrated systematic underprediction and overprediction, respectively. We developed and tested a new model with a spline term in eGFR and incorporating the competing risk

Item does not contain fulltext, AIMS: Chronic kidney disease (CKD) increases risk of cardiovascular disease (CVD). Less is known about how CVD associates with future risk of kidney failure with replacement therapy (KFRT). METHODS AND RESULTS: The study included 25 903 761 individuals from the CKD Prognosis Consortium with known baseline estimated glomerular filtration rate (eGFR) and evaluated the impact of prevalent and incident coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) events as time-varying exposures on KFRT outcomes. Mean age was 53 (standard deviation 17) years and mean eGFR was 89 mL/min/1.73 m2, 15% had diabetes and 8.4% had urinary albumin-to-creatinine ratio (ACR) available (median 13 mg/g); 9.5% had prevalent CHD, 3.2% prior stroke, 3.3% HF, and 4.4% prior AF. During follow-up, there were 269 142 CHD, 311 021 stroke, 712 556 HF, and 605 596 AF incident events and 101 044 (0.4%) patients experienced KFRT. Both prevalent and incident CVD were associated with subsequent KFRT with adjusted hazard ratios (HRs) of 3.1 [95% confidence interval (CI): 2.9-3.3], 2.0 (1.9-2.1), 4.5 (4.2-4.9), 2.8 (2.7-3.1) after incident CHD, stroke, HF and AF, respectively. HRs were highest in first 3 months post-CVD incidence declining to baseline after 3 years. Incident HF hospitalizations showed the strongest association with KFRT [HR 46 (95% CI: 43-50) within 3 months] after adjustment for other CVD subtype incidence. CONCLUSION: Incident CVD events strongly and independently associate with future KFRT risk, most notably after HF, then CHD, stroke, and AF. Optimal strategies for addressing the dramatic risk of KFRT following CVD events are needed.

Item does not contain fulltext, IMPORTANCE: Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. OBJECTIVE: To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. DESIGN, SETTING, AND PARTICIPANTS: Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021. EXPOSURES: The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR). MAIN OUTCOMES AND MEASURES: The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses. RESULTS: Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associ

We present BSkG3, the latest entry in the Brussels-Skyrme-on-a-grid series of large-scale models of nuclear structure based on an energy density functional. Compared to its predecessors, the new model offers a more realistic description of nucleonic matter at the extreme densities relevant to neutron stars. This achievement is made possible by incorporating a constraint on the infinite nuclear matter properties at high densities in the parameter adjustment, ensuring in this way that the predictions of BSkG3 for the nuclear Equation of State are compatible with the observational evidence for heavy pulsars with M> 2 M⊙ .Instead of the usual phenomenological pairing terms, we also employ a more microscopically founded treatment of nucleon pairing, resulting in extrapolations to high densities that are in line with the predictions of advanced many-body methods and are hence more suited to the study of superfluidity in neutron stars. By adopting an extended form of the Skyrme functional, we are able to reconcile the description of matter at high densities and at saturation density: the new model further refines the description of atomic nuclei offered by its predecessors. A qualitative improvement is our inclusion of ground state reflection asymmetry, in addition to the spontaneous breaking of rotational, axial, and time-reversal symmetry. Quantitatively, the model offers lowered root-mean-square deviations on 2457 masses (0.631 MeV), 810 charge radii (0.0237 fm) and an unmatched accuracy with respect to 45 primary fission barriers of actinide nuclei (0.33 MeV). Reconciling the complexity of neutron stars with those of atomic nuclei establishes BSkG3 as a tool of choice for applications to nuclear structure, the nuclear equation of state and nuclear astrophysics in general., SCOPUS: ar.j, info:eu-repo/semantics/published

Accurate estimates of the binding energy of nuclei far from stability that cannot be produced in the laboratory are crucial to our understanding of nuclear processes in astrophysical scenarios. Models based on energy density functionals have shown that they are capable of reproducing all known masses with root-mean-square error better than 800 keV, while retaining a firm microscopic foundation. However, it was recently pointed out in [M. Hukkanen et al. arXiv:2210.10674] that the recent BSkG1 model fails to account for a contribution to the binding energy that is specific to odd-odd nuclei, and which can be studied by using appropriate mass difference formulas. We analyse here the (lacking) performance of three recent microscopic mass models with respect to such formulas and examine possibilities to remedy this deficiency in the future., SCOPUS: cp.p, info:eu-repo/semantics/published

We report here the current developments on the Brussels-Skyrme-on-a-Grid (BSkG) atomic mass models. In comparison with our previous models, BSkG3 improves the infinite nuclear matter (INM) properties which opens its applications to neutron stars. The results presented here show that BSkG3 preserve the excellent agreement with experimental nuclear masses and radii, together with fission barriers of actinides obtained by BSkG1 and BSkG2, while the nuclear matter properties are considerably improved., SCOPUS: cp.p, info:eu-repo/semantics/published

Fluid flow problems can be modeled by the Navier–Stokes or, after linearization, by the Oseen equations. Their discretization results in discrete saddle point problems. These systems of equations are typically very large and need to be solved iteratively. Standard (block-) preconditioning techniques for saddle point problems rely on an approximation of the Schur complement. Such an approximation can be obtained by a hierarchical (H-) matrix LU-decomposition, which first approximates the Schur complement explicitly. The computational complexity of this computation depends, among other things, on the hierarchical block structure of the involved matrices. However, widely used techniques do not consider the connection between the discretization grids for the velocity field and the pressure, respectively. Here, we present a hierarchical block structure for the finite element discretization of the gradient operator that is improved by considering the connection between the two involved grids. Numerical results imply that the improved block structure allows for a faster computation of the Schur complement, which is the bottleneck for the set-up of the H-matrix LU-decomposition.

Seeded free-electron laser driven by a compact laser plasma accelerator Free-electron lasers generate high-brilliance coherent radiation at wavelengths spanning from the infrared to the X-ray domains. The recent development of short-wavelength seeded free-electron lasers now allows for unprecedented levels of control on longitudinal coherence, opening new scientific avenues such as ultra-fast dynamics on complex systems and X-ray nonlinear optics. Although those devices rely on state-of-the-art large-scale accelerators, advancements on laser-plasma accelerators, which harness gigavolt-per-centimetre accelerating fields, showcase a promising technology as compact drivers for free-electron lasers. Using such footprint-reduced accelerators, exponential amplification of a shot-noise type of radiation in a self-amplified spontaneous emission configuration was recently achieved. However, employing this compact approach for the delivery of temporally coherent pulses in a controlled manner has remained a major challenge. Here we present the experimental demonstration of a laser-plasma accelerator-driven free-electron laser in a seeded configuration, where control over the radiation wavelength is accomplished. Furthermore, the appearance of interference fringes, resulting from the interaction between the phase-locked emitted radiation and the seed, confirms longitudinal coherence. Building on our scientific achievements, we anticipate a navigable pathway to extreme-ultraviolet wavelengths, paving the way towards smaller-scale free-electron lasers, unique tools for a multitude of applications in industry, laboratories and universities.

Deep reinforcement learning algorithms typically act on the same set of actions. However, this is not sufficient for a wide range of real-world applications where different subsets are available at each step. In this thesis, we consider the problem of interval restrictions as they occur in pathfinding with dynamic obstacles. When actions that lead to collisions are avoided, the continuous action space is split into variable parts. Recent research learns with strong assumptions on the number of intervals, is limited to convex subsets, and the available actions are learned from the observations. Therefore, we propose two approaches that are independent of the state of the environment by extending parameterized reinforcement learning and ConstraintNet to handle an arbitrary number of intervals. We demonstrate their performance in an obstacle avoidance task and compare the methods to penalties, projection, replacement, as well as discrete and continuous masking from the literature. The results suggest that discrete masking of action-values is the only effective method when constraints did not emerge during training. When restrictions are learned, the decision between projection, masking, and our ConstraintNet modification seems to depend on the task at hand. We compare the results with varying complexity and give directions for future work., Comment: Master Thesis

BackgroundPatients with chronic kidney disease (CKD) face risks of not only end-stage kidney disease (ESKD), cardiovascular disease (CVD) and death, but also decline in kidney function, quality of life (QOL) and mental and physical well-being. This study describes the multidimensional trajectories of CKD using clinical events, kidney function and patient-reported outcome measures (PROMs). We hypothesized that more advanced CKD stages would associate with more rapid decline in each outcome.MethodsAmong 3939 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study, we evaluated multidimensional disease trajectories by G- and A-stages of enrollment estimated glomerular filtration rate (eGFR) and albuminuria, respectively. These trajectories included clinical events (ESKD, CVD, heart failure and death), eGFR decline and PROMs [kidney disease QOL (KDQOL) burden, effects and symptoms questionnaires, as well as the 12-item short form mental and physical component summaries]. We also evaluated a group-based multitrajectory model to group participants on the basis of longitudinal PROMs and compared group assignments by enrollment G- and A-stage.ResultsThe mean participant age was 58 years, 45% were women, mean baseline eGFR was 44 mL/min/1.73 m2 and median urine albumin:creatinine ratio was 52 mg/g. The incidence of all clinical events was greater and eGFR decline was faster with more advanced G- and A-stages. While baseline KDQOL and physical component measures were lower with more advanced G- and A-stage of CKD, changes in PROMs were inconsistently related to the baseline CKD stage. Groups formed on PROM trajectories were fairly distinct from existing CKD staging (observed agreement 60.6%) and were associated with the risk of ESKD, CVD, heart failure and death.ConclusionsMore advanced baseline CKD stage was associated with a higher risk of clinical events and faster eGFR decline, and was only weakly related to changes in patient-reported metrics over ti

With the improved accuracy of neutron star observational data, it is necessary to derive new equation of state where the crust and the core are consistently calculated within a unified approach. For this purpose we describe non-uniform matter in the crust of neutron stars employing a compressible liquid-drop model, where the bulk and the neutron fluid terms are given from the same model as the one describing uniform matter present in the core. We then generate a set of fifteen unified equations of state for cold catalyzed neutron stars built on realistic modelings of the nuclear interaction, which belongs to two main groups: the first one derives from the phenomenological Skyrme interaction and the second one from $\chi_{EFT}$ Hamiltonians. The confrontation of these model predictions allows us to investigate the model dependence for the crust properties, and in particular the effect of neutron matter at low density. The new set of unified equations of state is available at the CompOSE repository.

Mature beech and spruce trees were drought stressed for 5 consecutive years in the KROOF experiment. No signs of Carbon Starvation were found under the drought treatment, but overall the carbon pool sizes were reduced by about 40% in both species and carbon transport velocity in the phloem was reduced by about 50 %. Upon watering both species recovered their water household related physiology (water potential, osmotic acclimations and sap flow density) within the next vegetation period at the latest, displaying a high resilience potential, with beech recovering faster than spruce., Adulte Buchen und Fichten wurden im KROOF-Experiment für fünf Jahre trockengestresst. Dabei wurden keine Anzeichen für „Carbon Starvation“ gefunden, aber insgesamt reduzierte sich der Gesamtkohlenstoffpool um ca. 40 % und die Phloemtransportgeschwindigkeit um ca. 50 %. Der Wasserhaushalt (Wasserpotenzial, osmotische Änderungen und Saftflussdichte) beider Arten erholte sich in Folge der Bewässerung spätestens innerhalb der nächsten Vegetationsperiode und weißt damit ein hohe Resilienz auf, wobei sich die Buche oftmals schneller erholte als die Fichte.

The mixed-valent iridate Ba3InIr2O9 has been discussed as a promising candidate for quantum spin-liquid behavior. The compound exhibits Ir4.5+ ions in face-sharing IrO6 octahedra forming Ir2O9 dimers with three t2g holes per dimer. Our results establish Ba3InIr2O9 as a cluster Mott insulator. Strong intradimer hopping delocalizes the three t2g holes in quasimolecular dimer states while interdimer charge fluctuations are suppressed by Coulomb repulsion. The magnetism of Ba3InIr2O9 emerges from spin-orbit entangled quasimolecular moments with yet unexplored interactions, opening up a new route to unconventional magnetic properties of 5d compounds. Using single-crystal x-ray diffraction we find the monoclinic space group C2/c already at room temperature. Dielectric spectroscopy shows insulating behavior. Resonant inelastic x-ray scattering reveals a rich excitation spectrum below 1.5 eV with a sinusoidal dynamical structure factor that unambiguously demonstrates the quasimolecular character of the electronic states. Below 0.3 eV, we observe a series of excitations. According to exact diagonalization calculations, such low-energy excitations reflect the proximity of Ba3InIr2O9 to a hopping-induced phase transition based on the condensation of a quasimolecular spin-orbit exciton. The dimer ground state roughly hosts two holes in a bonding j=1/2 orbital and the third hole in a bonding j=3/2 orbital.

Background: To characterize the use of nephrotoxic medications in patients with chronic kidney disease (CKD) Stages G3-5 in routine care. Methods: We studied cohorts of adults with confirmed CKD G3-5 undergoing routine care from 1 January 2016 through 31 December 2018 in two health systems [Stockholm CREAtinine Measurements (SCREAM), Stockholm, Sweden (N = 57 880) and Geisinger, PA, USA (N = 16 255)]. We evaluated the proportion of patients receiving nephrotoxic medications within 1 year overall and by baseline kidney function, ranked main contributors and examined the association between receipt of nephrotoxic medication and age, sex, CKD G-stages comorbidities and provider awareness of the patient's CKD using multivariable logistic regression. Results: During a 1-year period, 20% (SCREAM) and 17% (Geisinger) of patients with CKD received at least one nephrotoxic medication. Among the top nephrotoxic medications identified in both cohorts were non-steroidal anti-inflammatory drugs (given to 11% and 9% of patients in SCREAM and Geisinger, respectively), antivirals (2.5% and 2.0%) and immunosuppressants (2.7% and 1.5%). Bisphosphonate use was common in SCREAM (3.3%) and fenofibrates in Geisinger (3.6%). Patients <65 years of age, women and those with CKD G3 were at higher risk of receiving nephrotoxic medications in both cohorts. Notably, provider awareness of a patient's CKD was associated with lower odds of nephrotoxic medication use {odds ratios [OR] 0.85[95% confidence interval (CI) 0.80-0.90] in SCREAM and OR 0.80 [95% CI 0.72-0.89] in Geisinger}. Conclusions: One in five patients with CKD received nephrotoxic medications in two distinct health systems. Strategies to increase physician's awareness of patients' CKD and knowledge of drug nephrotoxicity may reduce prescribing nephrotoxic medications and prevent iatrogenic kidney injury.

Background: To characterize the use of nephrotoxic medications in patients with chronic kidney disease (CKD) Stages G3-5 in routine care. Methods: We studied cohorts of adults with confirmed CKD G3-5 undergoing routine care from 1 January 2016 through 31 December 2018 in two health systems [Stockholm CREAtinine Measurements (SCREAM), Stockholm, Sweden (N = 57 880) and Geisinger, PA, USA (N = 16 255)]. We evaluated the proportion of patients receiving nephrotoxic medications within 1 year overall and by baseline kidney function, ranked main contributors and examined the association between receipt of nephrotoxic medication and age, sex, CKD G-stages comorbidities and provider awareness of the patient's CKD using multivariable logistic regression. Results: During a 1-year period, 20% (SCREAM) and 17% (Geisinger) of patients with CKD received at least one nephrotoxic medication. Among the top nephrotoxic medications identified in both cohorts were non-steroidal anti-inflammatory drugs (given to 11% and 9% of patients in SCREAM and Geisinger, respectively), antivirals (2.5% and 2.0%) and immunosuppressants (2.7% and 1.5%). Bisphosphonate use was common in SCREAM (3.3%) and fenofibrates in Geisinger (3.6%). Patients <65 years of age, women and those with CKD G3 were at higher risk of receiving nephrotoxic medications in both cohorts. Notably, provider awareness of a patient's CKD was associated with lower odds of nephrotoxic medication use {odds ratios [OR] 0.85[95% confidence interval (CI) 0.80-0.90] in SCREAM and OR 0.80 [95% CI 0.72-0.89] in Geisinger}. Conclusions: One in five patients with CKD received nephrotoxic medications in two distinct health systems. Strategies to increase physician's awareness of patients' CKD and knowledge of drug nephrotoxicity may reduce prescribing nephrotoxic medications and prevent iatrogenic kidney injury.

Background: To characterize the use of nephrotoxic medications in patients with chronic kidney disease (CKD) Stages G3-5 in routine care. Methods: We studied cohorts of adults with confirmed CKD G3-5 undergoing routine care from 1 January 2016 through 31 December 2018 in two health systems [Stockholm CREAtinine Measurements (SCREAM), Stockholm, Sweden (N = 57 880) and Geisinger, PA, USA (N = 16 255)]. We evaluated the proportion of patients receiving nephrotoxic medications within 1 year overall and by baseline kidney function, ranked main contributors and examined the association between receipt of nephrotoxic medication and age, sex, CKD G-stages comorbidities and provider awareness of the patient's CKD using multivariable logistic regression. Results: During a 1-year period, 20% (SCREAM) and 17% (Geisinger) of patients with CKD received at least one nephrotoxic medication. Among the top nephrotoxic medications identified in both cohorts were non-steroidal anti-inflammatory drugs (given to 11% and 9% of patients in SCREAM and Geisinger, respectively), antivirals (2.5% and 2.0%) and immunosuppressants (2.7% and 1.5%). Bisphosphonate use was common in SCREAM (3.3%) and fenofibrates in Geisinger (3.6%). Patients <65 years of age, women and those with CKD G3 were at higher risk of receiving nephrotoxic medications in both cohorts. Notably, provider awareness of a patient's CKD was associated with lower odds of nephrotoxic medication use {odds ratios [OR] 0.85[95% confidence interval (CI) 0.80-0.90] in SCREAM and OR 0.80 [95% CI 0.72-0.89] in Geisinger}. Conclusions: One in five patients with CKD received nephrotoxic medications in two distinct health systems. Strategies to increase physician's awareness of patients' CKD and knowledge of drug nephrotoxicity may reduce prescribing nephrotoxic medications and prevent iatrogenic kidney injury.

Item does not contain fulltext

The mixed-valent iridate Ba3InIr2O9 has been discussed as a promising candidate for quantum spin-liquid behavior. The compound exhibits Ir4.5+ ions in face-sharing IrO6 octahedra forming Ir2O9 dimers with three t(2g) holes per dimer. Our results establish Ba3InIr2O9 as a cluster Mott insulator. Strong intradimer hopping delocalizes the three t(2g) holes in quasimolecular dimer states while interdimer charge fluctuations are suppressed by Coulomb repulsion. The magnetism of Ba3InIr2O9 emerges from spin-orbit entangled quasimolecular moments with yet unexplored interactions, opening up a new route to unconventional magnetic properties of 5d compounds. Using single-crystal x-ray diffraction we find the monoclinic space group C2/c already at room temperature. Dielectric spectroscopy shows insulating behavior. Resonant inelastic x-ray scattering reveals a rich excitation spectrum below 1.5 eV with a sinusoidal dynamical structure factor that unambiguously demonstrates the quasimolecular character of the electronic states. Below 0.3 eV, we observe a series of excitations. According to exact diagonalization calculations, such low-energy excitations reflect the proximity of Ba3InIr2O9 to a hopping-induced phase transition based on the condensation of a quasimolecular spin-orbit exciton. The dimer ground state roughly hosts two holes in a bonding j = 1/2 orbital and the third hole in a bonding j = 3/2 orbital., QC 20230227

Numerous genes for monogenic kidney diseases with classical patterns of inheritance, as well as genes for complex kidney diseases that manifest in combination with environmental factors, have been discovered. Genetic findings are increasingly used to inform clinical management of nephropathies, and have led to improved diagnostics, disease surveillance, choice of therapy, and family counseling. All of these steps rely on accurate interpretation of genetic data, which can be outpaced by current rates of data collection. In March of 2021, Kidney Diseases: Improving Global Outcomes (KDIGO) held a Controversies Conference on "Genetics in Chronic Kidney Disease (CKD)" to review the current state of understanding of monogenic and complex (polygenic) kidney diseases, processes for applying genetic findings in clinical medicine, and use of genomics for defining and stratifying CKD. Given the important contribution of genetic variants to CKD, practitioners with CKD patients are advised to "think genetic," which specifically involves obtaining a family history, collecting detailed information on age of CKD onset, performing clinical examination for extrarenal symptoms, and considering genetic testing. To improve the use of genetics in nephrology, meeting participants advised developing an advanced training or subspecialty track for nephrologists, crafting guidelines for testing and treatment, and educating patients, students, and practitioners. Key areas of future research, including clinical interpretation of genome variation, electronic phenotyping, global representation, kidney-specific molecular data, polygenic scores, translational epidemiology, and open data resources, were also identified.

Metabolomics genome wide association study (GWAS) help outline the genetic contribution to human metabolism. However, studies to date have focused on relatively healthy, population-based samples of White individuals. Here, we conducted a GWAS of 537 blood metabolites measured in the Chronic Renal Insufficiency Cohort (CRIC) Study, with separate analyses in 822 White and 687 Black study participants. Trans-ethnic meta-analysis was then applied to improve fine-mapping of potential causal variants. Mean estimated glomerular filtration rate was 44.4 and 41.5 mL/min/1.73m2 in the White and Black participants, respectively. There were 45 significant metabolite associations at 19 loci, including novel associations at PYROXD2, PHYHD1, FADS1-3, ACOT2, MYRF, FAAH, and LIPC. The strength of associations was unchanged in models additionally adjusted for estimated glomerular filtration rate and proteinuria, consistent with a direct biochemical effect of gene products on associated metabolites. At several loci, trans-ethnic meta-analysis, which leverages differences in linkage disequilibrium across populations, reduced the number and/or genomic interval spanned by potentially causal single nucleotide polymorphisms compared to fine-mapping in the White participant cohort alone. Across all validated associations, we found strong concordance in effect sizes of the potentially causal single nucleotide polymorphisms between White and Black study participants. Thus, our study identifies novel genetic determinants of blood metabolites in chronic kidney disease, demonstrates the value of diverse cohorts to improve causal inference in metabolomics GWAS, and underscores the shared genetic basis of metabolism across race.

Background: To characterize the use of nephrotoxic medications in patients with chronic kidney disease (CKD) Stages G3-5 in routine care. Methods: We studied cohorts of adults with confirmed CKD G3-5 undergoing routine care from 1 January 2016 through 31 December 2018 in two health systems [Stockholm CREAtinine Measurements (SCREAM), Stockholm, Sweden (N = 57 880) and Geisinger, PA, USA (N = 16 255)]. We evaluated the proportion of patients receiving nephrotoxic medications within 1 year overall and by baseline kidney function, ranked main contributors and examined the association between receipt of nephrotoxic medication and age, sex, CKD G-stages comorbidities and provider awareness of the patient's CKD using multivariable logistic regression. Results: During a 1-year period, 20% (SCREAM) and 17% (Geisinger) of patients with CKD received at least one nephrotoxic medication. Among the top nephrotoxic medications identified in both cohorts were non-steroidal anti-inflammatory drugs (given to 11% and 9% of patients in SCREAM and Geisinger, respectively), antivirals (2.5% and 2.0%) and immunosuppressants (2.7% and 1.5%). Bisphosphonate use was common in SCREAM (3.3%) and fenofibrates in Geisinger (3.6%). Patients <65 years of age, women and those with CKD G3 were at higher risk of receiving nephrotoxic medications in both cohorts. Notably, provider awareness of a patient's CKD was associated with lower odds of nephrotoxic medication use {odds ratios [OR] 0.85[95% confidence interval (CI) 0.80-0.90] in SCREAM and OR 0.80 [95% CI 0.72-0.89] in Geisinger}. Conclusions: One in five patients with CKD received nephrotoxic medications in two distinct health systems. Strategies to increase physician's awareness of patients' CKD and knowledge of drug nephrotoxicity may reduce prescribing nephrotoxic medications and prevent iatrogenic kidney injury.

Laser Plasma Accelerators (LPAs), harnessing gigavolt-per-centimeter accelerating fields, can generate high peak current, low emittance and GeV class electron beams paving the way for the realization of future compact free-electron lasers (FELs). Here, we report on the commissioning of the COXINEL beamline driven by the HZDR plasma accelerator and experimental demonstration of FEL lasing at 270 nm in a seeded configuration. Control over the radiation wavelength is achieved with an improved bandwidth stability. Furthermore, the appearance of interference fringes, resulting from the interaction between the phase-locked emitted radiation and the seed, confirms longitudinal coherence, representing a key feature of such a seeded FEL. These results are cross-checked with simulations, ELEGANT for beam optics and GENESIS for FEL radiation. We anticipate a navigable pathway toward smaller-scale free-electron lasers at extreme ultra-violet wavelengths.

Laser Plasma Accelerators (LPAs), harnessing gigavolt-per-centimeter accelerating fields, can generate high peak current, low emittance and GeV class electron beams paving the way for the realization of future compact free-electron lasers (FELs). Here, we report on the commissioning of the COXINEL beamline driven by the HZDR plasma accelerator and experimental demonstration of FEL lasing at 270 nm in a seeded configuration. Control over the radiation wavelength is achieved with an improved bandwidth stability. Furthermore, the appearance of interference fringes, resulting from the interaction between the phase-locked emitted radiation and the seed, confirms longitudinal coherence, representing a key feature of such a seeded FEL. These results are cross-checked with simulations, ELEGANT for beam optics and GENESIS for FEL radiation. We anticipate a navigable pathway toward smaller-scale free-electron lasers at extreme ultra-violet wavelengths.

Laser Plasma Accelerators (LPAs), harnessing gigavolt-per-centimeter accelerating fields, can generate high peak current, low emittance and GeV class electron beams paving the way for the realization of future compact free-electron lasers (FELs). Here, we report on the commissioning of the COXINEL beamline driven by the HZDR plasma accelerator and experimental demonstration of FEL lasing at 270 nm in a seeded configuration. Control over the radiation wavelength is achieved with an improved bandwidth stability. Furthermore, the appearance of interference fringes, resulting from the interaction between the phase-locked emitted radiation and the seed, confirms longitudinal coherence, representing a key feature of such a seeded FEL. These results are cross-checked with simulations, ELEGANT for beam optics and GENESIS for FEL radiation. We anticipate a navigable pathway toward smaller-scale free-electron lasers at extreme ultra-violet wavelengths.

Die traditionellen Behandlungspositionen der Zahnärzt/innen hinter, neben und vor dem/r Patienten/in führen zur asymmetrischen Neigung und Verdrehung des Kopfes sowie des Rumpfes. Die Folge können Fehlhaltungen sein, die Muskel-Skelett-Erkrankungen verursachen. Das erklärt wahrscheinlich die hohe Prävalenz bei Zahnärzt/innen und zahnmedizinischen Fachangestellten. Daher werden in dieser Übersicht mögliche Ursachen und Konsequenzen der Prävalenz sowie ergonomische Maßnahmen für diese Berufsgruppen aufgeführt. Zudem erläutern wir ergonomische Empfehlungen für die Sitzhaltung von Zahnärzt/innen auf Basis der vorhandenen Literatur., The traditional treatment positions of dentists behind, beside and in front of the patient lead to asymmetrical inclination and twisting of the head and torso. This can result in poor posture, which results in musculoskeletal disorders. This probably explains the high prevalence in dentists and dental assistants. Therefore, this overview lists possible causes and consequences of the prevalence, including ergonomic measures for these occupational groups. Ergonomic recommendations for the sitting posture of dentists are also explained based on the existing literature.

Quantum spin liquids represent a magnetic ground state arising in the presence of strong quantum fluctuations that preclude ordering down to zero temperature and leave clear fingerprints in the excitation spectra. While theory bears a variety of possible quantum spin liquid phases their experimental realization is still scarce. Here, we report experimental evidence for chiral solitons in the S = 1/2 spin chain compound LiCuVO4 from measurements of the complex permittivity epsilon* in the GHz range. In zero magnetic field our results show short-lived thermally activated chiral fluctuations above the multiferroic phase transition at T-N = 2.4 K. In epsilon* these fluctuations are seen as the slowing down of a relaxation with a critical dynamical exponent nu(xi)z approximate to 1.3 in agreement with mean-field predictions. When using a magnetic field to suppress T-N towards 0 K the influence of quantum fluctuations increases until the thermally activated fluctuations vanish and only an excitation can be observed in the dielectric response in close proximity to the phase transition below 400 mK. From direct measurements we find this excitation's energy gap as E-SE approximate to 14.1 mu eV, which is in agreement with a nearly gapless chiral soliton that has been proposed for LiCuVO4 based on quantum spin liquid theory. Quantum spin liquids describe a system where any type of long-range or local ordering is absent even at absolute zero but despite prominent theoretical studies definitive experimental evidence of such a system is difficult to obtain. Here, by analysing the complex permittivity of LiCuVO4 the authors find evidence of chiral solitons suggesting the presence of a quantum spin liquid state.

Background and Purpose The Save ChildS Study demonstrated that endovascular thrombectomy (EVT) is a safe treatment option for pediatric stroke patients with large vessel occlusions (LVOs) with high recanalization rates. Our aim was to determine the long-term cost, health consequences and cost-effectiveness of EVT in this patient population. Methods In this retrospective study, a decision-analytic Markov model estimated lifetime costs and quality-adjusted life years (QALYs). Early outcome parameters were based on the entire Save ChildS Study to model the EVT group. As no randomized data exist, the Save ChildS patient sub-group with unsuccessful recanalization was used to model the standard of care group. For model -ing of lifetime estimates, pediatric and adult input parameters were obtained from the current lit- erature. The analysis was conducted in a United States setting applying healthcare and societal perspectives. Probabilistic sensitivity analyses were performed. The willingness-to-pay threshold was set to $100,000 per QALY. Results The model results yielded EVT as the dominant (cost-effective as well as cost-saving) strategy for pediatric stroke patients. The incremental effectiveness for the average age of 11.3 years at first stroke in the Save ChildS Study was determined as an additional 4.02 lifetime QALYs, with lifetime cost-savings that amounted to $169,982 from a healthcare perspective and $254,110 when applying a societal perspective. Acceptability rates for EVT were 96.60% and 96.66% for the healthcare and societal perspectives. Conclusions EVT for pediatric stroke patients with LVOs resulted in added QALY and reduced lifetime costs. Based on the available data in the Save ChildS Study, EVT is very likely to be a cost-effective treatment strategy for childhood stroke.

The mixed-valent iridate Ba3InIr2O9 has been discussed as a promising candidate for quantum spin-liquid behavior. The compound exhibits Ir4.5+ ions in face-sharing IrO6 octahedra forming Ir2O9 dimers with three t(2g) holes per dimer. Our results establish Ba3InIr2O9 as a cluster Mott insulator. Strong intradimer hopping delocalizes the three t(2g) holes in quasimolecular dimer states while interdimer charge fluctuations are suppressed by Coulomb repulsion. The magnetism of Ba3InIr2O9 emerges from spin-orbit entangled quasimolecular moments with yet unexplored interactions, opening up a new route to unconventional magnetic properties of 5d compounds. Using single-crystal x-ray diffraction we find the monoclinic space group C2/c already at room temperature. Dielectric spectroscopy shows insulating behavior. Resonant inelastic x-ray scattering reveals a rich excitation spectrum below 1.5 eV with a sinusoidal dynamical structure factor that unambiguously demonstrates the quasimolecular character of the electronic states. Below 0.3 eV, we observe a series of excitations. According to exact diagonalization calculations, such low-energy excitations reflect the proximity of Ba3InIr2O9 to a hopping-induced phase transition based on the condensation of a quasimolecular spin-orbit exciton. The dimer ground state roughly hosts two holes in a bonding j = 1/2 orbital and the third hole in a bonding j = 3/2 orbital.

Background: Aldosterone production and mineralocorticoid receptor activation are implicated in myocardial fibrosis and cardiovascular events. Methods: Cardiac structure and function were assessed in 4547 participants without prevalent heart failure (HF) in the ARIC study (Atherosclerosis Risk in Communities), with echocardiography, aldosterone, and plasma renin activity measurement (2011-2013). Subjects were characterized by plasma renin activity as suppressed (<= 0.5 ng/mL per hour) or unsuppressed (>0.5 ng/mL per hour). Cross-sectional relationships with cardiac structure and function, and longitudinal relationships with outcomes (HF hospitalization; HF and all-cause death; HF, death, myocardial infarction, and stroke; and incident atrial fibrillation) were assessed. Models were adjusted for demographic and anthropometric characteristics and additively, for blood pressure and antihypertensives. Results: Evidence of primary aldosteronism physiology was prevalent (11.6% with positive screen) and associated with echocardiographic parameters. Renin suppression was associated with greater left ventricular mass, left ventricular volumes, and left atrial volume index, and a lower E/A ratio (adjusted P<0.001 for all). Higher aldosterone was associated with greater left ventricular mass and lower global longitudinal strain and lateral E . The highest tertile of aldosterone was associated with a hazard ratio of 1.37 (95% CI, 1.06-1.77; 5.5-year follow-up) for incident atrial fibrillation relative to the lowest. Renin suppression was associated with HF (hazard ratio, 1.34 [95% CI, 1.05-1.72]; 7.3-year follow-up), although these relationships did not remain statistically significant after additional adjustment for hypertension. Conclusions: Renin suppression and aldosterone excess, consistent with primary aldosteronism pathophysiology, were associated with cardiac structural and functional alterations and may represent an early target for mitigation of fi

Background: To characterize the use of nephrotoxic medications in patients with chronic kidney disease (CKD) Stages G3-5 in routine care. Methods: We studied cohorts of adults with confirmed CKD G3-5 undergoing routine care from 1 January 2016 through 31 December 2018 in two health systems [Stockholm CREAtinine Measurements (SCREAM), Stockholm, Sweden (N = 57 880) and Geisinger, PA, USA (N = 16 255)]. We evaluated the proportion of patients receiving nephrotoxic medications within 1 year overall and by baseline kidney function, ranked main contributors and examined the association between receipt of nephrotoxic medication and age, sex, CKD G-stages comorbidities and provider awareness of the patient's CKD using multivariable logistic regression. Results: During a 1-year period, 20% (SCREAM) and 17% (Geisinger) of patients with CKD received at least one nephrotoxic medication. Among the top nephrotoxic medications identified in both cohorts were non-steroidal anti-inflammatory drugs (given to 11% and 9% of patients in SCREAM and Geisinger, respectively), antivirals (2.5% and 2.0%) and immunosuppressants (2.7% and 1.5%). Bisphosphonate use was common in SCREAM (3.3%) and fenofibrates in Geisinger (3.6%). Patients <65 years of age, women and those with CKD G3 were at higher risk of receiving nephrotoxic medications in both cohorts. Notably, provider awareness of a patient's CKD was associated with lower odds of nephrotoxic medication use {odds ratios [OR] 0.85[95% confidence interval (CI) 0.80-0.90] in SCREAM and OR 0.80 [95% CI 0.72-0.89] in Geisinger}. Conclusions: One in five patients with CKD received nephrotoxic medications in two distinct health systems. Strategies to increase physician's awareness of patients' CKD and knowledge of drug nephrotoxicity may reduce prescribing nephrotoxic medications and prevent iatrogenic kidney injury.

With the improved accuracy of neutron star observational data, it is necessary to derive new equation of state where the crust and the core are consistently calculated within a unified approach. For this purpose we describe non-uniform matter in the crust of neutron stars employing a compressible liquid-drop model, where the bulk and the neutron fluid terms are given from the same model as the one describing uniform matter present in the core. We then generate a set of fifteen unified equations of state for cold catalyzed neutron stars built on realistic modelings of the nuclear interaction, which belongs to two main groups: the first one derives from the phenomenological Skyrme interaction and the second one from $\chi_{EFT}$ Hamiltonians. The confrontation of these model predictions allows us to investigate the model dependence for the crust properties, and in particular the effect of neutron matter at low density. The new set of unified equations of state is available at the CompOSE repository.

We present a detailed analysis of three models predicting the properties of non-uniform matter in the crust of neutron stars: the compressible liquid-drop model, the fourth order Extended Thomas Fermi (ETF) method, and ETF plus Strutinsky integral (ETFSI) correction. The former treats the nuclear clusters as uniform hard spheres, the second takes into account the density distribution which can be different for neutrons and protons, and the last one includes the proton shell effects within the Strutinsky approach. The purpose of this work is to understand the importance of the improvements in the nuclear modeling and to analyze the quantities which are the most sensitive to them. We find that thermodynamic quantities such as pressure, energy and chemical potential, as well as the electron fraction, are in very good agreement among the three models. This confirms previous results where we have shown that the improvement in the finite-size description of the nuclear clusters has a small impact on these quantities, since they are mainly constrained by the bulk properties. The refinements in the finite-size modeling are shown to impact mostly the composition of the nuclear clusters ( Z cl ,N cl ) in an ordering which ranks according to the leptodermous expansion. This analysis is performed considering both the r-cluster and the e-cluster representations. The proton shell effects are shown to stabilize Z cl ,which consequently impacts the neutron number N cl as well., SCOPUS: cp.p, info:eu-repo/semantics/published

Uromodulin (UMOD) is a major risk gene for monogenic and complex forms of kidney disease. The encoded kidney-specific protein uromodulin is highly abundant in urine and related to chronic kidney disease, hypertension, and pathogen defense. To gain insights into potential systemic roles, we performed genome-wide screens of circulating uromodulin using complementary antibody-based and aptamer-based assays. We detected 3 and 10 distinct significant loci, respectively. Integration of antibody-based results at the UMOD locus with functional genomics data (RNA-Seq, ATAC-Seq, Hi-C) of primary human kidney tissue highlighted an upstream variant with differential accessibility and transcription in uromodulin-synthesizing kidney cells as underlying the observed cis effect. Shared association patterns with complex traits, including chronic kidney disease and blood pressure, placed the PRKAG2 locus in the same pathway as UMOD. Experimental validation of the third antibody-based locus, B4GALNT2, showed that the p.Cys466Arg variant of the encoded N-acetylgalactosaminyltransferase had a loss-of-function effect leading to higher serum uromodulin levels. Aptamer-based results pointed to enzymes writing glycan marks present on uromodulin and to their receptors in the circulation, suggesting that this assay permits investigating uromodulin's complex glycosylation rather than its quantitative levels. Overall, our study provides insights into circulating uromodulin and its emerging functions.

Hydraulic Redistribution (HR) is the passive flux of water through plants along a moisture gradient. In split-root experiments HR by Central European tree saplings was quantified and driving factors were determined. A split-root plant (SRP) had its roots split between two pots with additional trees each. Moisture gradients were established and HR was observed via deuterium labeling. HR water was found in SRP roots, rhizosphere and neighboring trees. HR amounts depended on moisture gradients, root hydraulic conductivity and root length. HR could increase forest stability in a future drier climate., Hydraulic Redistribution (HR) ist der passive Wasserfluss durch Pflanzen entlang eines Feuchtegradienten. In Split-Root Experimenten wurde HR durch mitteleuropäische Bäumchen untersucht. Die Wurzel einer Split-Root Pflanze (SRP) wurde auf zwei Töpfe, mit je einem weiteren Bäumchen, verteilt. Feuchtegradienten wurden angelegt und HR mit Deuteriumlabeling beobachtet. HR Wasser wurde in SRP Wurzeln, Rhizosphäre und Nachbarbäumchen gefunden. Die HR Wassermenge war abhängig vom Feuchtegradient, der Wurzel-Wasserleitfähigkeit und der Wurzellänge. HR könnte die Stabilität von Wäldern unter trockeneren Klimabedingungen erhöhen.