A multimodal aftercare intervention improves the outcome after kidney transplantation - results of the KTx360° aftercare program using claims data.

Background: The after-care treatment project KTx360° aimed to reduce graft failure and mortality after kidney transplantation (KTx). Methods: The study was conducted in the study centers Hannover, Erlangen and Hannoversch Muenden from May 2017 to October 2020 under the trial registration ISRCTN29416382. The program provided a multimodal aftercare program including specialized case management, telemedicine support, psychological and exercise assessments, and interventions. For the analysis of graft failure, which was defined as death, re-transplantation or start of long-term dialysis, we used longitudinal claims data from participating statutory health insurances (SHI) which enabled us to compare participants with controls. To balance covariate distributions between these nonrandomized groups we used propensity score methodology, in particular the inverse probability of treatment weighting (IPTW) approach. Findings: In total, 930 adult participants were recruited at three different transplant centres in Germany, of whom 320 were incident (enrolled within the first year after KTx) and 610 prevalent (enrolled >1 year after KTx) patients. Due to differences in the availability of the claims data, the claims data of 411 participants and 418 controls could be used for the analyses. In the prevalent group we detected a significantly lower risk for graft failure in the study participants compared to the matched controls (HR = 0.13, 95% CI = 0.04-0.39, p = 0.005, n = 389 observations), whereas this difference could not be detected in the incident group (HR = 0.92, 95% CI = 0.54-1.56, p = 0.837, n = 440 observations). Interpretation: Our findings suggest that a multimodal and multidisciplinary aftercare intervention can significantly improve outcome after KTx, specifically in patients later after KTx. For evaluation of effects on these outcome parameters in patients enrolled within the first year after transplantation longer observation times are necessary. Funding: The study was funded by the Global Innovation fund of the Joint Federal Committee of the Federal Republic of Germany, grant number 01NVF16009.

Laser cooling ytterbium doped silica by 67 K from ambient temperature.

Laser cooling of a 5 cm long, 1 mm diameter ytterbium doped (6.56×1025 ions/m3) silica rod by 67 K from room temperature was achieved. For the pump source, a 100 W level ytterbium fiber amplifier was constructed along with a 1032 nm fiber Bragg grating seed laser. Experiments were done in vacuum and monitored with the non-contact differential luminescence thermometry method. Direct measurements of the absorption spectrum as a function of temperature were made, to avoid any possible ambiguities from site-selectivity and deviations from McCumber theory at low temperature. This allowed direct computation of the cooling efficiency versus temperature at the pump wavelength, permitting an estimated heat lift of 1.42 W/m as the sample cooled from ambient temperature to an absolute temperature of 229 K.

Physical activity and its impact on cardiovascular health in pediatric kidney transplant recipients.

BACKGROUND: Cardiovascular (CV) morbidity after kidney transplantation (KTx) in childhood is of increasing importance. In light of a high prevalence of CV risk factors, protective measures such as physical activity (PA) come into focus. Our aim was to comprehensively assess PA in pediatric KTx recipients and evaluate its impact on CV health. METHODS: Forty-eight patients were assessed for frequency, duration, intensity, and setting of PA using the "Motorik-Modul" PA questionnaire. Walking-based activity was measured by accelerometer in a subgroup (n = 23). CV risk factors and subclinical CV organ damage were determined. The impact of PA on CV parameters was analyzed using linear regression models. RESULTS: Fifty-two percent of pediatric KTx recipients did not reach WHO recommended PA level; 54% did not engage in PA with vigorous intensity (VPA). Twenty-nine percent indicated an extremely inactive lifestyle (< 120 min/week of moderate to vigorous intensity PA, MVPA). Compared to the healthy German KiGGS cohort, KTx recipients specifically lacked engagement in sport activities (KTx: 129 min/week; 95%CI, 97-162 vs. KiGGS, 242 min/week; 95%CI, 230-253). VPA was associated with lower systolic blood pressure (p = 0.024) and resting heart rate (p = 0.005), MVPA with fewer components of the post-transplant metabolic syndrome (p = 0.037), and better left ventricular diastolic function (p = 0.006). CONCLUSIONS: A considerable lack of PA, especially VPA, exists in young KTx recipients. PA was positively associated with important parameters of CV health. While long-term CV protection through PA seems promising in pediatric KTx recipients, specific educational approaches are most likely needed to increase patients' engagement in sport activities.

Impact of site-selective spectroscopy on laser cooling parameter characterization.

From laser design to optical refrigeration, experimentally measured fluorescence spectra are often utilized to obtain input parameters for predictive models. However, in materials that exhibit site-selectivity, the fluorescence spectra depend on the excitation wavelength employed to take the measurement. This work explores different conclusions that predictive models reach after inputting such varied spectra. Here, temperature-dependent site-selective spectroscopy is carried out on an ultra-pure Yb, Al co-doped silica rod fabricated by the modified chemical vapor deposition technique. The results are discussed in the context of characterizing ytterbium doped silica for optical refrigeration. Measurements made between 80 K and 280 K at several different excitation wavelengths yield unique values and temperature dependencies of the mean fluorescence wavelength. For the excitation wavelengths studied here, the variation in emission lineshapes ultimately lead to calculated minimum achievable temperatures (MAT) ranging between 151 K and 169 K, with theoretical optimal pumping wavelengths between 1030 nm and 1037 nm. Direct evaluation of the temperature dependence of the fluorescence spectra band area associated with radiative transitions out of the thermally populated 2F5/2 sublevel may be a better approach to identifying the MAT of a glass where site-selective behavior precludes unique conclusions.

Participating in a School-Integrated Daily Exercise Program Improves Motor Performance Significantly in School-Children.

Children's sedentary time has increased, while daily physical activity and motor performance have decreased. We evaluated an integrated school-based exercise program by assessing changes in motor skills after one year and comparing these changes to children who did not participate. We included 303 children from five schools in this longitudinal study and assigned them either to the exercise group (EG; n = 183 with daily exercise program) or the waiting group (WG; n = 120). Motor skills were assessed at baseline and after one year. Mixed modeling was used to analyze inter-group differences of change in motor skills and to determine the effect of sex, age group, and weight status. EG improved more strongly than WG for sprint, side jumps (both p = 0.017), stand and reach (p = 0.012), and ergometry (p ≤ 0.001) when compared to WG. Girls improved more strongly in the sit-ups than boys, second graders more than fifth graders in the backwards balance and the ergometry, and non-overweight children more in the standing long jump than overweight children. The exercise program is effective in increasing motor skills and physical fitness. Girls were not disadvantaged, and overweight children profited as much as their non-overweight peers in all categories but one.

Potential of ytterbium doped silica glass for solid-state optical refrigeration to below 200 K.

We report on the optical refrigeration of ytterbium doped silica glass by >40 K starting at room temperature, which represents more than a two-fold improvement over the previous state-of-the-art. A spectroscopic investigation of the steady-state and time-dependent fluorescence was carried out over the temperature range 80 K to 400 K. The calculated minimum achievable temperature for our Yb3+ doped silica sample is ≈150 K, implying the potential for utilizing ytterbium doped silica for solid-state optical refrigeration below temperatures commonly achieved by standard Peltier devices.

The potential impact of coagulation factor XIII in trauma-induced coagulopathy - a retrospective case series analysis.

BACKGROUND: The role of factor XIII (FXIII) in trauma-induced coagulopathy (TIC) is not fully understood. METHODS: We evaluated FXIII supplementation in severely injured patients with persistent bleeding. This was a retrospective case series analysis. RESULTS: Twenty-four patients received FXIII concentrate within 24 h of admission for bleeding that continued after transfusion of > 6 U red blood cells (RBCs); control patients (n = 27) did not receive FXIII concentrate. Both study groups were similar regarding injury severity score and global coagulation tests, but FXIII activity levels were significantly higher and lactate levels significantly lower in the control group, respectively. The differences in FXIII activity between the groups could be attributed to a more severe trauma-induced coagulopathy in FXIII-deficient patients, as demonstrated by lower fibrinogen and higher lactate levels. The median dose of FXIII concentrate within 24 h of admission was 2500 IU (IQR: 1250-4375). Median 24-h transfusion of RBCs (primary study endpoint) was significantly higher in the FXIII group versus controls (10.0 U, IQR 5-14 U vs. 2, IQR 0-6 U; p < 0.01). Subsequently, while patients were in the intensive care unit, there was no statistically significant difference regarding RBC transfusion anymore and the overall clinical outcomes were similar in both patient groups. CONCLUSIONS: The substitution of FXIII in patients who were more seriously compromised due to higher lactate levels and who presented with initially more severe bleedings than patients in the control group, resulted in a comparable transfusion necessity after 24 h. Thus, we guess that the substitution of FXIII in severely injured patients with ongoing bleeding might have an impact on their clinical outcome.

Hybrid membrane-external-cavity surface-emitting laser.

We develop, analyze, and demonstrate an optically-pumped semiconductor disk laser using an active mirror architecture formed by sandwiching the semiconductor gain membrane between two heatspreaders, one of which is coated with a high-reflectivity multilayer. Thermal modeling indicates that this structure outperforms traditional VECSELs. Employing an InGaAs/GaAs MQW gain structure, we demonstrate output powers of approximately 30 W at a center wavelength of λ ≈ 1178 nm in a TEM00 mode using an in-well pumped geometry.

Optical refrigeration of payloads to T < 125†K.

A modified all-solid-state optical cryocooler prototype based on anti-Stokes fluorescence in a 10%-doped Yb:YLF crystal cooled a payload to temperatures below 125 K starting from room temperature. To achieve this record performance, the optical refrigerator employed a novel, to the best of our knowledge, textured-MgF2 thermal link to improve the thermal transport and fluorescence escape. Additionally, it used spectrally selective, high-reflection coatings in the pump circulator cavity to suppress parasitic lasing and amplified spontaneous emission.

Laser cooling experiments to measure the quantum efficiency of Yb-doped silica fibers.

A detailed investigation into the wavelength-dependent cooling efficiencies of two ultra-pure large core diameter ytterbium-doped silica fibers is carried out by means of the laser-induced thermal modulation spectroscopy (LITMoS) method. From these measurements, an external quantum efficiency of 0.99 is obtained for both fibers. Optimal cooling is seen for pump wavelengths between 1032 and 1035 nm. The crossover wavelength from heating to cooling is identified to be between 1018 and 1021 nm. The fiber with higher Yb3+ ion density exhibits better cooling, seen by the input power normalized temperature differential.

Acceptance and safety of femoral versus radial access for percutaneous coronary intervention (PCI): results from a large monitor-controlled German registry (QuIK).

BACKGROUND: In 2015 and 2018, European Society of Cardiology guidelines for percutaneous coronary intervention (PCI) favoring radial access over femoral access were published. These recommendations were based on randomized trials suggesting that patients treated radially experienced reduced bleeding complications and all-cause mortality. We aimed to assess acceptance and results of radial access in a real-world scenario by analyzing all PCI cases in the Quality Assurance in Invasive Cardiology (QuIK) registry. METHODS: The QuIK registry prospectively collects data on all diagnostic and interventional coronary procedures from 148 private practice cardiology centers in Germany. Major adverse cardiac and cerebrovascular events (MACE) were defined as myocardial infarction, stroke, or death during hospitalization. RESULTS: From 2012 to 2018, 189,917 patients underwent PCI via either access method. The rate of radial approach steadily increased from 13 to 49%. The groups did not differ significantly with respect to age or extent of coronary disease. Femoral approach was significantly more common in patients with ST elevation myocardial infarction and cardiogenic shock. Overall, there were significant differences in MACE (radial 0.12%; femoral 0.24%; p < 0.0009) and access site complications (radial 0.2%; femoral 0.8% (p < 0.0009). CONCLUSION: Our data reveals an increase in use of radial access in recent years in Germany. The radial approach emerged as favorable regarding MACE in non-myocardial infarction patients, as well as favorable regarding access site complication regardless of indication for percutaneous intervention.

Laser cooling of a Yb doped silica fiber by 18 Kelvin from room temperature.

An ytterbium doped silica optical fiber with a core diameter of 900µm has been cooled by 18.4 K below ambient temperature by pumping with 20 W of 1035 nm light in vacuum. In air, cooling by 3.6 K below ambient was observed with the same 20 W pump. The temperatures were measured with a thermal imaging camera and differential luminescence thermometry. The cooling efficiency is calculated to be 1.2±0.1%. The core of the fiber was codoped with Al3+ for an Al to Yb ratio of 6:1, to allow for a larger Yb concentration and enhanced laser cooling.

Implementation of Laser-Induced Anti-Stokes Fluorescence Power Cooling of Ytterbium-Doped Silica Glass.

Laser cooling of a solid is achieved when a coherent laser illuminates the material, and the heat is extracted by annihilation of phonons resulting in anti-Stokes fluorescence. Over the past year, net solid-state laser cooling was successfully demonstrated for the first time in Yb-doped silica glass in both bulk samples and fibers. Here, we report more than 6 K of cooling below the ambient temperature, which is the lowest temperature achieved in solid-state laser cooling of silica glass to date to the best of our knowledge. We present details on the experiment performed using a 20 W laser operating at a 1035 nm wavelength and temperature measurements using both a thermal camera and the differential luminescence thermometry technique.

Open-aperture Z-scan study for absorption saturation: accurate measurement of saturation intensity in YLF:Yb for optical refrigeration.

Knowledge of saturation intensity of gain or absorption plays a fundamental role in a variety of applications ranging from lasers to many nonlinear optical processes. Here, we present an analytical expression for open-aperture Z-scan transmission for accurately measuring the saturation intensity in the low absorbance samples but at arbitrary pump intensities. We exploit this formalism to investigate the absorption saturation of LiYF4:Yb3+ (YLF:Yb) in the anti-Stokes excitation region for optical refrigeration at high pump intensities. An absorption saturation intensity of 14.5±1kW/cm2 was measured in YLF:Yb at 1020 nm (E||c) at room temperature.

Optical refrigeration: the role of parasitic absorption at cryogenic temperatures.

Optical cooling of a YLF:Yb single crystal to 87 K, well below the minimum achievable temperature predicted from existing theory, has been observed. This discrepancy between theory and data has motivated us to revisit the current model of optical refrigeration, in particular the critical role of parasitic background absorption. Challenging experiments that measured the cooling efficiency as a function of temperature reveal that the background absorption coefficient decreases with temperature, resulting in a significant enhancement of the cooling efficiency at cryogenic temperatures. These discoveries emphasize the high sensitivity of optical cooling to impurity-mediated processes and show the necessity of formulating a cooling model that includes the temperature dependence of the background absorption. To properly characterize the cooling properties of any sample, it is necessary to measure its low-temperature performance.

Tm-doped crystals for mid-IR optical cryocoolers and radiation balanced lasers.

We report the complete characterization of various cooling-grade Tm-doped crystals including, to the best of our knowledge, the first demonstration of optical refrigeration in Tm:YLF crystals. Room temperature laser cooling efficiencies of 1% and 2% (mol) Tm:YLF and 1% Tm:BYF crystals at different excitation polarizations are measured, and their external quantum efficiency and background absorption are extracted. By performing detailed low-temperature spectroscopic analysis of the samples, global minimum achievable temperatures of 160 to 110 K are estimated. The potential of Tm-doped crystals to realize mid-IR optical cryocoolers and radiation balanced lasers (RBLs) in the eye-safe region of the spectrum is discussed, and a promising two-tone RBL in a tandem structure of Tm:YLF and Ho:YLF crystals is proposed.

Radiation-balanced Yb:YAG disk laser.

A radiation-balanced Yb:YAG disk laser is demonstrated in an intracavity pumping geometry. Detailed analysis of the data reveals the feasibility of using the multi-kilowatt level "athermal" disk lasers with minimal modal instabilities, which arise from thermal lensing.

First demonstration of an all-solid-state optical cryocooler.

Solid-state optical refrigeration uses anti-Stokes fluorescence to cool macroscopic objects to cryogenic temperatures without vibrations. Crystals such as Yb3+-doped YLiF4 (YLF:Yb) have previously been laser-cooled to 91 K. In this study, we show for the first time laser cooling of a payload connected to a cooling crystal. A YLF:Yb crystal was placed inside a Herriott cell and pumped with a 1020-nm laser (47 W) to cool a HgCdTe sensor that is part of a working Fourier Transform Infrared (FTIR) spectrometer to 135 K. This first demonstration of an all-solid-state optical cryocooler was enabled by careful control of the various desired and undesired heat flows. Fluorescence heating of the payload was minimized by using a single-kink YLF thermal link between the YLF:Yb cooling crystal and the copper coldfinger that held the HgCdTe sensor. The adhesive-free bond between YLF and YLF:Yb showed excellent thermal reliability. This laser-cooled assembly was then supported by silica aerogel cylinders inside a vacuum clamshell to minimize undesired conductive and radiative heat loads from the warm surroundings. Our structure can serve as a baseline for future optical cryocooler devices.

Proteolytic Origin of the Soluble Human IL-6R In Vivo and a Decisive Role of N-Glycosylation.

Signaling of the cytokine interleukin-6 (IL-6) via its soluble IL-6 receptor (sIL-6R) is responsible for the proinflammatory properties of IL-6 and constitutes an attractive therapeutic target, but how the sIL-6R is generated in vivo remains largely unclear. Here, we use liquid chromatography-mass spectrometry to identify an sIL-6R form in human serum that originates from proteolytic cleavage, map its cleavage site between Pro-355 and Val-356, and determine the occupancy of all O- and N-glycosylation sites of the human sIL-6R. The metalloprotease a disintegrin and metalloproteinase 17 (ADAM17) uses this cleavage site in vitro, and mutation of Val-356 is sufficient to completely abrogate IL-6R proteolysis. N- and O-glycosylation were dispensable for signaling of the IL-6R, but proteolysis was orchestrated by an N- and O-glycosylated sequon near the cleavage site and an N-glycan exosite in domain D1. Proteolysis of an IL-6R completely devoid of glycans is significantly impaired. Thus, glycosylation is an important regulator for sIL-6R generation.

Ferrocenyl-Coupled N-Heterocyclic Carbene Complexes of Gold(I): A Successful Approach to Multinuclear Anticancer Drugs.

Four gold(I) carbene complexes featuring 4-ferrocenyl-substituted imidazol-2-ylidene ligands were investigated for antiproliferative and antivascular properties. They were active against a panel of seven cancer cell lines, including multidrug-resistant ones, with low micromolar or nanomolar IC50 (72 h) values, according to their lipophilicity and cellular uptake. The delocalized lipophilic cationic complexes 8 and 10 acted by increasing the reactive oxygen species in two ways: through a genuine ferrocene effect and by inhibiting the thioredoxin reductase. Both complexes gave rise to a reorganization of the F-actin cytoskeleton in endothelial and melanoma cells, associated with a G1 phase cell cycle arrest and a retarded cell migration. They proved antiangiogenic in tube formation assays with endothelial cells and vascular-disruptive on real blood vessels in the chorioallantoic membrane of chicken eggs. Biscarbene complex 10 was also tolerated well by mice where it led to a volume reduction of xenograft tumors by up to 80 %.