Novel renal replacement strategies for the elimination of serum free light chains in patients with kappa light chain nephropathy

Multiple myeloma (MM) is a malignancy with excessive production of monoclonal proteins. At disease presentation 30% of MM patients have significant renal impairment which may progress to renal failure requiring dialysis. Besides chemotherapy extracorporeal elimination procedures such as plasma exchange have been applied as adjuvant strategies to eliminate free light chains from circulating blood, however the efficacy was poor with older techniques. We report about a highly efficient method to eliminate serum free light chain (sFLC) using a newly designed protein leaking membrane in patients suffering from sFLC induced acute renal failure. The protein leaking membrane (HCO 1100) is characterized by increased pore size facilitating elimination of middle molecules such as sFLC kappa (22.5 kD). The HCO 1100 membrane was applied in a hemodialysis and hemodiafiltration mode and compared to standard procedures (high flux hemodialysis, hemodiafiltration and plasma exchange). Hemodiafiltration with the protein leaking membrane HCO 1100 was superior to all other extracorporeal replacement strategies in eliminating sFLC-kappa from circulating blood. A median blood reduction rate of 40.8% (range 13.9% - 66.4%) was achieved during hemodiafiltration. The corresponding peak clearance rate was 25 ml/min. Importantly, the poorest elimination rate was achieved by plasma exchange followed by standard high flux hemodialysis. Extracorporeal elimination strategies with the protein leaking membrane HCO 1100 may be a promising adjuvant treatment strategy for patients with sFLC nephropathy requiring dialysis. Hemodiafiltration and to lesser extend also hemodialysis with the HCO 1100 hemofilter are able to eliminate substantial amounts of sFLC kappa in MM patients

Satellite Data-Based Phenological Evaluation of the Nationwide Reforestation of South Korea

Through the past 60 years, forests, now of various age classes, have been established in the southern part of the Korean Peninsula through nationwide efforts to reestablish forests since the Korean War (1950-53), during which more than 65% of the nation's forest was destroyed. Careful evaluation of long-term changes in vegetation growth after reforestation is one of the essential steps to ensuring sustainable forest management. This study investigated nationwide variations in vegetation phenology using satellite-based growing season estimates for 1982-2008. The start of the growing season calculated from the normalized difference vegetation index (NDVI) agrees reasonably with the ground-observed first flowering date both temporally (correlation coefficient, r = 0.54) and spatially (r = 0.64) at the 95% confidence level. Over the entire 27-year period, South Korea, on average, experienced a lengthening of the growing season of 4.5 days decade(-1), perhaps due to recent global warming. The lengthening of the growing season is attributed mostly to delays in the end of the growing season. The retrieved nationwide growing season data were used to compare the spatial variations in forest biomass carbon density with the time-averaged growing season length for 61 forests. Relatively higher forest biomass carbon density was observed over the regions having a longer growing season, especially for the regions dominated by young (<30 year) forests. These results imply that a lengthening of the growing season related to the ongoing global warming may have positive impacts on carbon sequestration, an important aspect of large-scale forest management for sustainable development.open2

Die intravesikale Radioimmuntherapie mit Bi-213-anti-EGFR Immunkonjugaten verursacht keine Schäden am Urothel

Fragestellung Nach transurethraler Resektion des nicht-muskelinvasiven Urothelkarzinoms treten im weiteren Verlauf häufig Rezidive auf. Neue Therapieformen werden daher dringend benötigt. Im Mausmodell bewirkte die intravesikale Radioimmuntherapie mit Bi-213-markierten Anti-EGFR-Antikörpern eine signifikante Verlängerung des Überlebens. Bi-213-anti-EGFR Immunkonjugate zerstören aufgrund der geringen Reichweite des Alpha-Strahlers gezielt Tumorzellen an die die Immunkonjugate binden und sollten umliegendes normales Gewebe nicht beeinträchtigen. Das Ziel dieser Studie war daher die histopathologische Untersuchung möglicher Nebenwirkungen der intravesikalen Radioimmuntherapie mit Bi-213-anti-EGFR sowohl in der Blase als auch in der Niere. Methodik Swiss nu/nu-Mäuse wurden ohne vorherige Injektion von Tumorzellen bzw. zu verschiedenen Zeitpunkten nach intravesikaler Instillation von EJ28 Blasentumorzellen mit Bi-213-anti-EGFR Immunkonjugaten wie folgt behandelt: Einmalig mit 0,925 MBq (n=5; 3 Tiere mit / 2 ohne EJ28 Zellen), zweimalig mit 0,925 MBq (n=10; je 5 Tiere mit/ohne EJ28 Zellen), zweimalig mit 1,85 MBq (n=2; Tiere ohne EJ28 Zellen) oder zweimalig mit 3,7 MBq (n=2; Tiere ohne EJ28 Zellen). Blasen und Nieren der Tiere wurden 300 Tage nach Behandlung in Formalin fixiert und in Paraffin eingebettet. Paraffin-Schnitte (4 µm) wurden anschließend mit Hämatoxylin-Eosin gefärbt und lichtmikroskopisch analysiert. Ergebnis Nach einmaliger oder zweimaliger Therapie mit 0,925 MBq zeigten sich keine auffälligen Veränderungen des Urothels. Nach zweimaliger Applikation von je 1,85 oder 3,7 MBq, d.h. zwei- bis vierfach höheren Aktivitäten als die therapeutisch höchst effizienten 0,925 MBq, waren in allen untersuchten Blasen und Nieren diffuse bzw. fokale Entzündungen beobachtbar, die jedoch als geringgradig eingestuft wurden, Diese Veränderungen sind demnach ohne pathologische Bedeutung. Schlussfolgerungen Die effiziente Radioimmuntherapie des Blasenkarzinoms im Mausmodell mit Bi-213-anti-EGFR bewirkt keine Schäden in Blase und Niere. Selbst bei Applikation von sehr hohen Aktivitäten, jenseits der therapeutisch wirksamen Aktivitäten, wurden nur vereinzelt diskrete, pathologisch nicht relevante Veränderungen im Urothel und Nierenparenchym beobachtet.JRC.E.5-Nuclear chemistr

Fractionated intravesical radioimmunotherapy with 213Bi-anti-EGFR-MAb is effective without toxic side-effects in a nude mouse model of advanced human bladder carcinoma

Gold standard in therapy of superficial, non-muscle invasive urothelial tumors is transurethral resection followed by intravesical instillation therapies. However, relapse is commonly observed and therefore new therapeutic approaches are needed. Application of 213Bi-immunoconjugates targeting EGFR had shown promising results in early tumor stages. The aim of this study was the evaluation of fractionated application of 213Bi-anti-EGFR-MAb in advanced tumor stages in a nude mouse model. Luciferase-transfected EJ28 human bladder carcinoma cells were instilled intravesically into nude mice following electrocautery. Tumor development was monitored via bioluminescence imaging. One day after tumor detection mice were treated intravesically either two times with 0.93 MBq or three times with 0.46 MBq of 213Bi-anti-EGFR-MAb. Therapeutic efficacy was evaluated via overall survival and toxicity towards normal urothelium by histopathological analysis. Mice without treatment and those treated with the native anti-EGFR-MAb showed mean survivals of 65.4 and 57.6 d, respectively. After fractionated treatment with 0.93 MBq of 213Bi-anti-EGFR-MAb animals reached a mean survival of 141.5 d and 33% of the animals survived at least 268 d. Fractionated treatment with 0.46 MBq 213Bi-anti-EGFR-MAb resulted in a mean survival of 131.8 d and 30% of the animals survived longer than 300 d. Significant differences were only observed between the control groups and the group treated twice with 0.93 MBq of 213Bi-anti-EGFR-MAb. No toxic side-effects on the normal urothelium were observed even after treatment with 3.7 MBq of 213Bi-anti-EGFR-MAb. The study demonstrates that the fractionated intravesical radioimmunotherapy with 213Bi-anti-EGFR-MAb is a promising approach in advanced bladder carcinoma.JRC.E.5-Nuclear chemistr

THE LINE FOCUS X-RAY TUBE: AN X-RAY SOURCE FOR FLASH AND SPATIALLY FRACTIONATED RADIATION THERAPY

Background and Aims: FLASH and spatially fractionated radiationtherapy (SFRT) demonstrated reduced side effects at equal tumourcontrol compared to conventional radiotherapy. Currently onlylarge synchrotrons may facilitate clinical x-ray FLASH or SFRTtreatments. We are constructing a prototype of an innovative, table-top x-ray source that will allow FLASH and SFRT treatments. Thesource is based on the line focus x-ray tube (LFxT) concept and willeventually deliver dose rates of up to 200 Gy/s.Methods: We designed a thermionic electron gun that generatesa low-emittance, high-current electron beam at 300 keV. Twoquadrupole magnets focus the electrons onto a 50 micrometer wide focalspot on a tungsten-molybdenum target that spins at 250 Hz. Weassessed the radiation field, temperature and mechanical stressconditions with finite-element and Monte Carlo simulations. Theseparation tube equipped motor drive and liquid metal bearings fitfor operation in ultra-high vacuum. We developed a high-voltagesupply based on modular multi-level converter (MMC) technologyfor increased power in a future clinical source.Results: Finite element simulations showed an operation of theLFxT in the heat capacity limit permitting substantially enhanceddose rates at small focal spot sizes. Thermal and mechanical stressesare tolerated by the target design. An MMC based DCDC converterwith 320 battery-powered units can store enough energy to supplythe source with 2 MW electrical power in a duty cycle of 2%

Potenzial und Dynamik der Kohlenstoffspeicherung in Wald und Holz: Beitrag des deutschen Forst- und Holzsektors zum Klimaschutz

Der vorliegende Beitrag stellt erste Ergebnisse des BMBF Projektes „Potenzial und Dynamik der Kohlenstoffspeicherung in Wald und Holz“ vor (Förderkennzeichen BMBF 0330546). Anhand repräsentativer Modellbestände und komplexer Modellierungsansätze wurde die CO 2 -Senken- und Quellenwirkung bei unterschiedlich intensiven Nutzungseingriffen sowie dem Nutzungsverzicht für den Forst- und Holzsektor in Deutschland her- geleitet. Als Holzverwendung wird im Folgenden hypothetisch eine rein energetische Nutzung des geernteten Holzes unterstellt und auf die Berück- sichtigung der Speicherleistung und des Substituti- onspotenzials von Holzprodukten verzichtet. Diese konservative Betrachtungsweise schöpft nicht das volle klimarelevante Potenzial von Holzprodukten aus. Dennoch kann bereits damit gezeigt wer- den, dass bereits durch die Holzproduktion und die energetische Holzverwendung eine bessere CO 2 -Bilanz erreicht wird, als bei einer Erhöhung des C-Speichers im Wald durch Nutzungsverzich