Gallenwegskomplikationen nach orthotopen Lebertransplantationen – Inzidenz, Risikofaktoren und Therapieverfahren

Introduction: Biliary complications are still common problems after orthotopic liver transplantation with a prevalence of 8-37%. The aim of this study was to identify causes of the development of biliary complications and to illustrate possibilities of therapy. Material and Methods: This study consists of 150 orthotopic liver transplantations which took place at the University of Erlangen between 1997 and 2008. All transplantations without the use of a t-drain and all patients with a survival of at least 30 days after transplantation were included. Follow-up was until June 30, 2009 with a mean follow-up time of 5 years and 7 months. The biliary complications were studied retrospectively concerning indication, donor, transplant, recipient, surgical and postoperative criteria. Results: 50 biliary complications (33.3%) occurred in 150 transplantations. There were bile leaks (8.0%), anastomotic strictures (14.0%), nonanastomotic strictures (6.0%), multiple complications (4.0%), a biliary necrosis (0.7%) and a biliary abscess (0.7%). This study showed a relationship between biliary complications and biliary indication of transplantation, higher donor age, portal-venous reperfusion and thrombosis of the arteria hepatica. We recognized a significant higher prevalence of biliary complications in combination with end-to-end reconstruction of the biliary tract and with rejection. Also portal-venous reperfusion showed a significant higher prevalence of nonanastomotic strictures. There were good results for therapy of leckages (66.7%) and anastomotic strictures (71.4%). Whereas therapy of nonanastomotic strictures was difficult. Biliary stones were significantly correlated with biliary strictures. The outcome of the transplantations was good with a 1-year survival of 86.5% and a 5- and 10-year survival of 74.9% and 64.9%. There were better results in female transplant recipients and in patients without biliary complication. Conclusion: This study identified end-to-end reconstruction of the biliary tract as risk factor for biliary complications and portal-venous reperfusion as risk factor especially for nonanatomotic strictures. It showed a good outcome and results of endoscopic treatment. Nevertheless there is a need of development of interventional methods especially for nonanastomotic stricures. Thereby the good outcome after liver transplantation could be improved further on.Einleitung: Gallenwegskomplikationen stellen mit einer Prävalenz von 8-37% noch immer häufige Probleme nach orthotoper Lebertransplantation dar. Ziel dieser Arbeit ist es, Risikofaktoren für die Entstehung von Gallenwegskomplikationen zu identifizieren und Therapiemöglichkeiten aufzuzeigen. Material und Methoden: In dieser Arbeit sind 150 orthotope Lebertransplantationen enthalten, die zwischen 1997 und 2008 am Universitätsklinikum Erlangen stattgefunden haben. Einschlusskriterien waren eine Transplantation ohne Implantation eines T-Drains und ein postoperatives Überleben von mindestens 30 Tagen. Das Patientenkollektiv wurde bis zum 30. Juni 2009 nachbeobachtet, im Durchschnitt 5 Jahre 7 Monate. Die aufgetretenen Gallenwegskomplikationen wurden bezüglich der Indikation, Spender-, Transplantat- und Empfängerdaten und intra- und postoperativen Parametern ausgewertet. Ergebnisse: Bei 150 Transplantationen sind 50 Gallenwegskomplikationen (33,3%) aufgetreten. Darunter sind Gallengangsleckagen (8,0%), Anastomosenstenosen (14,0%), Nichtanastomosenstenosen (6,0%), Mehrfachkomplikationen (4,0%), eine Gallenwegsnekrose (0,7%) und ein Leberabszess (0,7%) enthalten. Ein Zusammenhang mit Gallenwegskomplikationen zeigte sich bei biliären Vorerkrankungen, höherem Spenderalter, portal-venöser Reperfusion und Thrombose der Arteria hepatica. Signifikanz erreichten die Ergebnisse für Gallenwegskomplikationen bei Verwendung der Choledochocholedochostomie und beim Auftreten von Abstoßungsreaktionen und speziell für Nichtanastomosenstenosen bei portal-venöser Reperfusion. Weiterhin zeigte sich ein gutes Behandlungsergebnis bei Leckagen (66,7%) und Anastomosenstenosen (71,4%). Dagegen gestaltete sich die Therapie von Nichtanastomosenstenosen schwieriger. Gallensteine traten signifikant häufig in Kombination mit Strikturen auf. Das Outcome nach Lebertransplantation war gut mit einem 1-Jahresüberleben von 86,5% und 5- und 10 Jahresüberlebensraten von 74,9% und 64,9%. Dabei schnitten Transplantatempfängerinnen und Patienten ohne Gallenwegskomplikation signifikant besser ab. Schlussfolgerung: In dieser Studie haben sich die Choledochocholedochostomie mit schräg-schräg Rekonstruktion als Risikofaktoren für Gallenwegskomplikationen und die portal-venöse Reperfusion speziell für Nichtanastomosenstenosen bestätigt. Es zeigten sich ein gutes Outcome und gute Behandlungsergebnisse mittels Endoskopie. Dennoch besteht vor allem bei Nichtanastomosenstenosen ein Weiterentwicklungsbedarf der interventionellen Therapieverfahren. Damit kann das bisher schon gute Gesamtüberleben nach Lebertransplantation weiter verbessert werden

How to overcome the governance challenges of implementing NREGA

Large-scale social safety net programs such as India�s National Rural Employment Guarantee Act (NREGA) are difficult to implement due to governance challenges related to elite capture, leakages, and corruption. The ability to identify how the governance challenges of program implementation can be met requires detailed insights into the actual process of program implementation, with clear views on the source of leakage and mismanagement, the sensitivity of program implementation to the influence of different actors, local power structures and informal bureaucratic processes. This paper uses a new participatory research method, referred to as Process-Influence Mapping, to shed light on these issues and related governance challenges, using the implementation of NREGA as an example. The Process-Influence Mapping tool helps identify the specific features of the NREGA implementation process that limit the program�s effectiveness (for example, elite capture in the definition of work and capacity limitations due to staff shortages and lack of training) and create scope for the misappropriation of funds. The insights gained can be used to identify policy options for reforming the administrative process of NREGA implementation so as to create an effective social safety net.Governance, National Rural Employment Guarantee Act, participatory research method, Process-Influence-Map,

Time- and spatially-resolved magnetization dynamics driven by spin-orbit torques

Current-induced spin-orbit torques (SOTs) represent one of the most effective ways to manipulate the magnetization in spintronic devices. The orthogonal torque-magnetization geometry, the strong damping, and the large domain wall velocities inherent to materials with strong spin-orbit coupling make SOTs especially appealing for fast switching applications in nonvolatile memory and logic units. So far, however, the timescale and evolution of the magnetization during the switching process have remained undetected. Here, we report the direct observation of SOT-driven magnetization dynamics in Pt/Co/AlO$_x$ dots during current pulse injection. Time-resolved x-ray images with 25 nm spatial and 100 ps temporal resolution reveal that switching is achieved within the duration of a sub-ns current pulse by the fast nucleation of an inverted domain at the edge of the dot and propagation of a tilted domain wall across the dot. The nucleation point is deterministic and alternates between the four dot quadrants depending on the sign of the magnetization, current, and external field. Our measurements reveal how the magnetic symmetry is broken by the concerted action of both damping-like and field-like SOT and show that reproducible switching events can be obtained for over $10^{12}$ reversal cycles

Time- and spatially-resolved magnetization dynamics driven by spin-orbit torques

Current-induced spin-orbit torques (SOTs) represent one of the most effective ways to manipulate the magnetization in spintronic devices. The orthogonal torque-magnetization geometry, the strong damping, and the large domain wall velocities inherent to materials with strong spin-orbit coupling make SOTs especially appealing for fast switching applications in nonvolatile memory and logic units. So far, however, the timescale and evolution of the magnetization during the switching process have remained undetected. Here, we report the direct observation of SOT-driven magnetization dynamics in Pt/Co/AlO$_x$ dots during current pulse injection. Time-resolved x-ray images with 25 nm spatial and 100 ps temporal resolution reveal that switching is achieved within the duration of a sub-ns current pulse by the fast nucleation of an inverted domain at the edge of the dot and propagation of a tilted domain wall across the dot. The nucleation point is deterministic and alternates between the four dot quadrants depending on the sign of the magnetization, current, and external field. Our measurements reveal how the magnetic symmetry is broken by the concerted action of both damping-like and field-like SOT and show that reproducible switching events can be obtained for over $10^{12}$ reversal cycles

Footprint-weighted tile approach for a spruce forest and a nearby patchy clearing using the ACASA model

The ACASA (Advanced Canopy-Atmosphere-Soil Algorithm) model, with a higher-order closure for tall vegetation, has already been successfully tested and validated for homogeneous spruce forests. The aim of this paper is to test the model using a footprint-weighted tile approach for a clearing with a heterogeneous structure of the underlying surface. The comparison with flux data shows a good agreement with a footprint-aggregated tile approach of the model. However, the results of a comparison with a tile approach on the basis of the mean land use classification of the clearing is not significantly different. It is assumed that the footprint model is not accurate enough to separate small-scale heterogeneities. All measured fluxes are corrected by forcing the energy balance closure of the test data either by maintaining the measured Bowen ratio or by the attribution of the residual depending on the fractions of sensible and latent heat flux to the buoyancy flux. The comparison with the model, in which the energy balance is closed, shows that the buoyancy correction for Bowen ratios > 1.5 better fits the measured data. For lower Bowen ratios, the correction probably lies between the two methods, but the amount of available data was too small to make a conclusion. With an assumption of similarity between water and carbon dioxide fluxes, no correction of the net ecosystem exchange is necessary for Bowen ratios > 1.5

Classical blood biomarkers identify patients with higher risk for relapse 6 months after alcohol withdrawal treatment

This naturalistic study among patients with alcohol dependence examined whether routine blood biomarkers could help to identify patients with high risk for relapse after withdrawal treatment. In a longitudinal study with 6-month follow-up among 133 patients with alcohol dependence who received inpatient alcohol withdrawal treatment, we investigated the usefulness of routine blood biomarkers and clinical and sociodemographic factors for potential outcome prediction and risk stratification. Baseline routine blood biomarkers (gamma-glutamyl transferase GGT, alanine aminotransferase ALT/GPT, aspartate aminotransferase AST/GOT, mean cell volume of erythrocytes MCV), and clinical and sociodemographic characteristics were recorded at admission. Standardized 6~months' follow-up assessed outcome variables continuous abstinence, days of continuous abstinence, daily alcohol consumption and current abstinence. The combined threshold criterion of an AST:ALT ratio > 1.00 and MCV > 90.0 fl helped to identify high-risk patients. They had lower abstinence rates (P = 0.001), higher rates of daily alcohol consumption (P < 0.001) and shorter periods of continuous abstinence (P = 0.027) compared with low-risk patients who did not meet the threshold criterion. Regression analysis confirmed our hypothesis that the combination criterion is an individual baseline variable that significantly predicted parts of the respective outcome variances. Routinely assessed indirect alcohol biomarkers help to identify patients with high risk for relapse after alcohol withdrawal treatment. Clinical decision algorithms to identify patients with high risk for relapse after alcohol withdrawal treatment could include classical blood biomarkers in addition to clinical and sociodemographic items

Разработка информационно-программного комплекса «Журнал учета рабочего времени»

Объектом исследования является учет рабочего времени в высших учебных заведениях. Цель работы – упростить и автоматизировать учет рабочих часов сотрудников, работающих посменно, сократить время, которое уходит на заполнение табеля в конце месяца. В результате реализована система учета рабочего времени сотрудников, работающих посменно, упрощающая процесс заполнения табеля учета рабочего времени.The object of this research is working time tracking in university. The main goal - to simplify and automate working time tracking. In result time tracking system was developed. The result is a system of accounting of working time of employees working in shifts, simplifying the process of filling out a timesheet

Single-Dose Intravenous Toxicity Study of IRDye 800CW in Sprague-Dawley Rats

Objective: Fluorophore-labeled contrast imaging agents are moving toward clinical use for a number of applications. The near-infrared dye IRDye 800CW is frequently used in its N-hydroxysuccinamide (NHS) ester form for labeling these agents. Following conjugation or breakdown of a labeled ligand, excess NHS ester is converted to the carboxylate form. To prepare for clinical use as a near-infrared fluorophore, a toxicity study was conducted on IRDye 800CW carboxylate. Methods: Male and female Sprague–Dawley rats were given a single intravenous or intradermal administration of IRDye 800CW carboxylate; Indocyanine Green was used as a comparative control. Animals were injected with varying doses of the test and control articles and observed for up to 14 days. Clinical chemistry, hematological, and pharmacokinetic analyses were performed on subgroups of animals. Organs were analyzed for content of the test article. Tissues were analyzed microscopically for pathological changes. Results: Based on hematologic, clinical chemistry, and histopathologic evaluation, single administration of IRDye 800CW carboxylate intravenously at dose levels of 1, 5, and 20 mg/kg or 20 mg/kg intradermally produced no pathological evidence of toxicity. Conclusion: A dose of 20 mg/kg was identified as the no observed adverse effect level following IV or ID routes of administration of IRDye 800CW

A multi-center study of their physicochemical characteristics, cell culture and in vivo experiments

PVP-capped silver nanoparticles with a diameter of the metallic core of 70 nm, a hydrodynamic diameter of 120 nm and a zeta potential of −20 mV were prepared and investigated with regard to their biological activity. This review summarizes the physicochemical properties (dissolution, protein adsorption, dispersability) of these nanoparticles and the cellular consequences of the exposure of a broad range of biological test systems to this defined type of silver nanoparticles. Silver nanoparticles dissolve in water in the presence of oxygen. In addition, in biological media (i.e., in the presence of proteins) the surface of silver nanoparticles is rapidly coated by a protein corona that influences their physicochemical and biological properties including cellular uptake. Silver nanoparticles are taken up by cell-type specific endocytosis pathways as demonstrated for hMSC, primary T-cells, primary monocytes, and astrocytes. A visualization of particles inside cells is possible by X-ray microscopy, fluorescence microscopy, and combined FIB/SEM analysis. By staining organelles, their localization inside the cell can be additionally determined. While primary brain astrocytes are shown to be fairly tolerant toward silver nanoparticles, silver nanoparticles induce the formation of DNA double-strand-breaks (DSB) and lead to chromosomal aberrations and sister-chromatid exchanges in Chinese hamster fibroblast cell lines (CHO9, K1, V79B). An exposure of rats to silver nanoparticles in vivo induced a moderate pulmonary toxicity, however, only at rather high concentrations. The same was found in precision-cut lung slices of rats in which silver nanoparticles remained mainly at the tissue surface. In a human 3D triple-cell culture model consisting of three cell types (alveolar epithelial cells, macrophages, and dendritic cells), adverse effects were also only found at high silver concentrations. The silver ions that are released from silver nanoparticles may be harmful to skin with disrupted barrier (e.g., wounds) and induce oxidative stress in skin cells (HaCaT). In conclusion, the data obtained on the effects of this well-defined type of silver nanoparticles on various biological systems clearly demonstrate that cell-type specific properties as well as experimental conditions determine the biocompatibility of and the cellular responses to an exposure with silver nanoparticles