Clearance of inflammatory cytokines in patients with septic acute kidney injury during renal replacement therapy using the EMiC2 filter (Clic-AKI study)

BACKGROUND: The EMiC2 membrane is a medium cut-off haemofilter (45 kiloDalton). Little is known regarding its efficacy in eliminating medium-sized cytokines in sepsis. This study aimed to explore the effects of continuous veno-venous haemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance. METHODS: This was a prospective observational study conducted in critically ill patients with sepsis and acute kidney injury requiring kidney replacement therapy. We measured concentrations of 12 cytokines [Interleukin (IL) IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, vascular endothelial growth factor, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF)] in plasma at baseline (T0) and pre- and post-dialyzer at 1, 6, 24, and 48 h after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, mass balances, and changes in serial serum concentrations. RESULTS: Twelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 h (p < 0.001). The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-γ, IL-1α, IL-1β, and EGF, to 19.0 ml/min for TNF-α. Negative or minimal adsorption was observed. The effluent and adsorptive clearance rates remained steady over time. The percentage of cytokine removal was low for most cytokines throughout the 48-h period. CONCLUSION: EMiC2-CVVHD achieved modest removal of most cytokines and demonstrated small to no adsorptive capacity despite a decline in plasma cytokine concentrations. This suggests that changes in plasma cytokine concentrations may not be solely influenced by extracorporeal removal. TRIAL REGISTRATION: NCT03231748, registered on 27th July 2017

Effects of regional citrate anticoagulation on thrombin generation, fibrinolysis and platelet function in critically ill patients receiving continuous renal replacement therapy for acute kidney injury: a prospective study

Background: Regional citrate anticoagulation (RCA) is recommended for continuous renal replacement therapy (CRRT). However, filter life varies and premature filter clotting can occur. The aims of this explorative prospective study were to investigate the effects of RCA on thrombin generation, fibrinolysis and platelet function in critically ill patients receiving CRRT, to compare clotting parameters between systemic and intra-circuit blood samples, and to screen participants for coagulation disorders. We recruited critically ill adult patients admitted to a 30-bedded Intensive care unit in a tertiary care hospital who required CRRT with RCA for acute kidney injury (AKI). Patients with pre-existing thrombotic, bleeding tendencies or a CRRT duration less than 48 h were excluded. We measured coagulation and thrombophilia parameters at baseline. Thrombin generation, D-dimer and platelet function were measured pre-CRRT and at 12, 24, 36, 48 and 72 h after commencing CRRT using blood samples taken from the arterial line and the circuit. Results: At baseline, all eleven patients (mean age 62.4 years, 82% male) had Factor VIII and von Willebrand Factor concentrations above reference range and significantly increased peak thrombin generation. During CRRT, there were no significant changes in systemic maximum peak thrombin generation, time to peak thrombin generation, fibrinogen, D-dimer and platelet function analysis. We observed no significant difference between paired samples taken from the patient's arterial line and the circuit. Conclusions: Critically ill patients with AKI requiring CRRT are hypercoagulable. Citrate used for anticoagulation during CRRT does not affect thrombin generation, D-dimer or platelet function. Systemic clotting parameters reflect intra-circuit results. Trial registration: ClinicalTrials.gov Identifier: NCT02486614. Registered 01 July 2015—Registered after recruitment of first patient. https://clinicaltrials.gov/ct2/show/NCT0248661

The effect of regional citrate anti-coagulation on the coagulation system in critically ill patients receiving continuous renal replacement therapy for acute kidney injury - An observational cohort study

BACKGROUND: Regional anticoagulation with citrate is the recommended first line treatment for patients receiving continuous renal replacement therapy (CRRT). There is wide variability in filter patency which may be due to differences in patient characteristics and local practice. It is also possible that citrate has effects on primary and secondary haemostasis, fibrinolysis and platelet function that are still unknown. The primary aim of the study is to describe the effect of citrate on coagulation and fibrinolysis pathways in both the patient and the haemodialysis circuit. METHODS: The study will recruit 12 adult patients admitted to the intensive care unit, requiring CRRT with regional citrate anticoagulation for acute kidney injury. Patients with pre-existing thrombotic or bleeding tendencies will be excluded. Thrombin generation, clot lysis and platelet function will be measured at baseline and at 12, 24, 36, 48 and 72 h after commencing CRRT (from the patient and from the circuit). We will describe the evolution of parameters over time as well as the differences in parameters between the patient and the circuit. DISCUSSION: The study will provide new data on the effects of citrate during continuous renal replacement therapy which is not currently available. We will minimise confounding factors through the use of tight exclusion criteria and accept that this will slow down recruitment. Depending on the results, we hope to incorporate the findings into existing clinical guidelines and clinical practice with the aim to prevent premature filter clotting and interruptions in treatment. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov on 10th June 2015 (NCT02486614)

Importance of correlation effects in hcp iron revealed by a pressure-induced electronic topological transition

We discover that hcp phases of Fe and Fe0.9Ni0.1 undergo an electronic topological transition at pressures of about 40 GPa. This topological change of the Fermi surface manifests itself through anomalous behavior of the Debye sound velocity, c/a lattice parameter ratio and M\"ossbauer center shift observed in our experiments. First-principles simulations within the dynamic mean field approach demonstrate that the transition is induced by many-electron effects. It is absent in one-electron calculations and represents a clear signature of correlation effects in hcp Fe

Trace formulae for non-equilibrium Casimir interactions, heat radiation and heat transfer for arbitrary objects

We present a detailed derivation of heat radiation, heat transfer and (Casimir) interactions for N arbitrary objects in the framework of fluctuational electrodynamics in thermal non-equilibrium. The results can be expressed as basis-independent trace formulae in terms of the scattering operators of the individual objects. We prove that heat radiation of a single object is positive, and that heat transfer (for two arbitrary passive objects) is from the hotter to a colder body. The heat transferred is also symmetric, exactly reversed if the two temperatures are exchanged. Introducing partial wave-expansions, we transform the results for radiation, transfer and forces into traces of matrices that can be evaluated in any basis, analogous to the equilibrium Casimir force. The method is illustrated by (re)deriving the heat radiation of a plate, a sphere and a cylinder. We analyze the radiation of a sphere for different materials, emphasizing that a simplification often employed for metallic nano-spheres is typically invalid. We derive asymptotic formulae for heat transfer and non-equilibrium interactions for the cases of a sphere in front a plate and for two spheres, extending previous results. As an example, we show that a hot nano-sphere can levitate above a plate with the repulsive non-equilibrium force overcoming gravity -- an effect that is not due to radiation pressure.Comment: 29 pages, 6 figures (v2: Sentence added in Sec. 1

The Atacama Cosmology Telescope: Physical Properties of Sunyaev-Zel'dovich Effect Clusters on the Celestial Equator

We present the optical and X-ray properties of 68 galaxy clusters selected via the Sunyaev-Zel'dovich Effect at 148 GHz by the Atacama Cosmology Telescope (ACT). Our sample, from an area of 504 square degrees centered on the celestial equator, is divided into two regions. The main region uses 270 square degrees of the ACT survey that overlaps with the co-added ugriz imaging from the Sloan Digital Sky Survey (SDSS) over Stripe 82 plus additional near-infrared pointed observations with the Apache Point Observatory 3.5-meter telescope. We confirm a total of 49 clusters to z~1.3, of which 22 (all at z>0.55) are new discoveries. For the second region the regular-depth SDSS imaging allows us to confirm 19 more clusters up to z~0.7, of which 10 systems are new. We present the optical richness, photometric redshifts, and separation between the SZ position and the brightest cluster galaxy (BCG). We find no significant offset between the cluster SZ centroid and BCG location and a weak correlation between optical richness and SZ-derived mass. We also present X-ray fluxes and luminosities from the ROSAT All Sky Survey which confirm that this is a massive sample. One of the newly discovered clusters, ACT-CL J0044.4+0113 at z=1.1 (photometric), has an integrated XMM-Newton X-ray temperature of kT_x=7.9+/-1.0 keV and combined mass of M_200a=8.2(-2.5,+3.3)x10^14 M_sun/h70 placing it among the most massive and X-ray-hot clusters known at redshifts beyond z=1. We also highlight the optically-rich cluster ACT-CL J2327.4-0204 (RCS2 2327) at z=0.705 (spectroscopic) as the most significant detection of the whole equatorial sample with a Chandra-derived mass of M_200a=1.9(-0.4,+0.6)x10^15 M_sun/h70, comparable to some of the most massive known clusters like "El Gordo" and the Bullet Cluster.Comment: 18 pages, 12 figures. Accepted to the Astrophysical Journal. New version includes minor changes in the accepted pape

Immersive multi-user decision training games with ARLearn

Serious gaming approaches so far focus mainly on skill development, motivational aspects or providing immersive learning situations. Little work has been reported to foster awareness and decision competencies in complex deci-sion situations involving incomplete information and multiple stakeholders. We address this issue exploring the technical requirements and possibilities to de-sign games for such situations in three case studies: a hostage taking situation, a multi-stakeholder logistics case, and a health-care related emergency case. To implement the games, we use a multi-user enabled mobile game development platform (ARLearn). We describe the underlying real world situations and edu-cational challenges and analyse how these are reflected in the ARLearn games realized. Based on these cases we propose a way to increase the immersiveness of mobile learning games.SALOM