Weekly irinotecan in a patient with metastatic colorectal cancer on hemodialysis due to chronic renal failure

Background: The cytotoxic treatment of patients suffering from advanced or metastatic cancer undergoing hemodialysis due to chronic renal failure still remains a problem, since for those patients pharmacokinetic and pharmacodynamic data on most cytotoxic agents are lacking. Case Report: We report a 45-year-old male who suffered from chronic renal failure and was diagnosed with stage-3 colorectal cancer (CRC) in February 2000. After surgical removal of the tumor an adjuvant chemotherapy of dose-reduced i.v. bolus 5-fluorouracil and folinic acid was begun (Mayo protocol). Due to excessive gastrointestinal toxicity, therapy was discontinued after the first cycle. In April 2000 liver metastases were diagnosed. The patient was then put on a weekly schedule of dose-reduced CPT-11 (50 mg/m(2), 80 mg total). No hematological or non-hematological toxicity grade 3/4 was observed. Due to excellent tolerability and lack of severe side effects the dose was increased up to 80 mg/m2 (140 mg total) weekly. A dose escalation to 100 mg/m(2) (180 mg total) resulted in severe diarrhea (grade 4). Within 2 months of treatment the patient achieved a lasting partial remission until April 2001 (12 months). A significant progression of hepatic metastases required an alternative treatment regimen beginning in July 2001 (HAI, hepatic artery infusion). Conclusion: This case report demonstrates the feasibility and efficacy of a weekly treatment with dose-reduced CPT-11 in a patient with metastatic CRC on hemodialysis due to chronic renal failure

The Effect of Fluctuating Temperatures During Development on Fitness-Related Traits of Scatophaga stercoraria (Diptera: Scathophagidae)

Development of ectotherms is highly temperature dependent. Studies using variable thermal environments can improve ecological relevance of data because organisms naturally face day-to-day stochastic temperature fluctuations as well as seasonal changes in the amplitude of such daily fluctuations. The objective of this study was to investigate if, and to what extent, the use of constant temperatures is justified in studies of the model species, yellow dung fly, Scatophaga stercoraria (L.). We examined the effect of temperature fluctuation on the expression of several life history traits and the effect on subsequent adult longevity. We used two fluctuating temperature treatments with the same mean but different amplitudes (15/21°C, 12/24°C; 12/12 h), and three constant temperature treatments spanning the wide temperature range faced in the wild (12, 18, and 24°C). Large temperature fluctuation was mostly detrimental (lower juvenile survival, slower growth, smaller body size, and longer development), whereas moderate temperature fluctuation usually gave responses similar to the constant regime. When developing in fluctuating temperatures, adult longevity (no effect), body size (lower), and wing shape (narrower wings) deviated from the expectations based on the constant temperature reaction norms, presumably because of acclimation responses. Contrary to some studies no obvious beneficial effects of moderate temperature fluctuation were observed. Instead, yellow dung flies seem to canalize development in the face of temperature fluctuation up to a point when detrimental effects become unavoidable. The relatively greater effects of extreme constant developmental temperatures question their biological relevance in experiment

Electrocardiographic assessments and cardiac events after fingolimod first dose – a comprehensive monitoring study

Background First dose observation for cardiac effects is required for fingolimod, but recommendations on the extent vary. This study aims to assess cardiac safety of fingolimod first dose. Individual bradyarrhythmic episodes were evaluated to assess the relevance of continuous electrocardiogram (ECG) monitoring. Methods START is an ongoing open-label, multi-center study. At the time of analysis 3951 patients were enrolled. The primary endpoints are the incidence of bradycardia (heart rate < 45 bpm) and second-/third-degree AV blocks during treatment initiation. The relevance of Holter was assessed by matching ECG findings with the occurrence of clinical symptoms as well as by rigorous analysis of AV blocks with regard to the duration of pauses and the minimal heart rate recorded during AV block. Results Thirty-one patients (0.8%) developed bradycardia (<45 bpm), 62 patients (1.6%) had second-degree Mobitz I and/or 2:1 AV blocks with a lowest reading (i.e. mean of ten consecutive beats) of 35 bpm and the longest pause lasting for 2.6 s. No Mobitz II or third-degree AV blocks were observed. Only one patient complained about mild chest discomfort and fatigue. After 1 week, there was no second -/third-degree AV block. Conclusions Continuous Holter ECG monitoring in this large real-life cohort revealed that bradycardia and AV conduction abnormalities were rare, transient and benign. No further unexpected abnormalities were detected. The data presented here give an indication that continuous Holter ECG monitoring does not add clinically relevant value to patients’ safety. Trial registration NCT01585298; registered April 23, 2012

Pathogenomic analysis of Lichtheimia species as a model for basal human pathogens of the order Mucorales

Despite the increasing recognition of life-threatening infections with members of the Mucorales (mucormycosis), little is known about genomics and the molecular basis of pathogenicity in these fungi. More than 20 mucoralean species are known to cause infections in humans. Although these species are only distantly related, all infections are described by the term mucormycosis and species-specific features are only rarely discussed. Moreover, research on virulence factors is mainly limited to the two derived mucoralean genera Rhizopus and Mucor. Lichtheimia species are basal mucoralean pathogens and represent the second most common cause of mucormycosis in Europe. This work focused on species of the genus Lichtheimia as novel model organisms to study human pathogenic mucoralean fungi. A combination of genomic and transcriptomic approaches was used to get first insights into general genomic features of Lichtheimia as one of the most basal human pathogenic genera among mucoralean fungi and to identify putative virulence factors. In addition, the response of human pathogenic and non-pathogenic Lichtheimia species to infection-associated stress conditions was analysed to investigate the evolution of pathogenicity in these fungi. The comprehensive genome and transcriptome data produced during this study give first insights into the stress response of basal fungi and reveal severe differences compared to other fungi. These data represent a valuable resource for future research and will help to identify virulence factors as well as targets for new antifungals

Bildungsfinanzierung neu gestalten

In Deutschland sind die privaten Bildungsausgaben anders zusammengesetzt als in vergleichbaren Industrieländern. Der private Finanzierungsanteil an den gesamten Bildungsausgaben ist hierzulande für die vorschulische Bildung deutlich höher als für die Schul-, Betriebs- und Hochschulbildung. Im internationalen Vergleich zeigt sich: Diese Aufteilung ist nicht geeignet, Chancengerechtigkeit herzustellen und bedarf daher einer gründlichen Überarbeitung. Der Kronberger Kreis fordert den Staat auf, sich an der Finanzierung der vorschulischen Bildung stärker zu beteiligen, so dass einkommensschwache Familien keine Kindergartengebühren zahlen müssen. Das letzte Kindergartenjahr vor der Einschulung könnte verpflichtend sein. Im Hochschulbereich plädiert der Kronberger Kreis hingegen für die Wiedereinführung von Studiengebühren. In dieser Studie finden sich darüber hinaus konkrete Vorschläge zur Stärkung des Wettbewerbs zwischen öffentlichen und privaten Schulen sowie zur Ausgestaltung der steuerlichen Förderung von Bildungsinvestitionen

Time Pressure, Time Autonomy, and Sickness Absenteeism in Hospital Employees: A Longitudinal Study on Organizational Absenteeism Records

Background Although work absenteeism is in the focus of occupational health, longitudinal studies on organizational absenteeism records in hospital work are lacking. This longitudinal study tests time pressure and lack of time autonomy to be related to higher sickness absenteeism. Methods Data was collected for 180 employees (45% nurses) of a Swiss hospital at baseline and at follow-up after 1 year. Absent times (hours per month) were received from the human resources department of the hospital. One-year follow-up of organizational absenteeism records were regressed on self-reported job satisfaction, time pressure, and time autonomy (i.e., control) at baseline. Results A multivariate regression showed significant prediction of absenteeism by time pressure at baseline and time autonomy, indicating that a stress process is involved in some sickness absenteeism behavior. Job satisfaction and the interaction of time pressure and time autonomy did not predict sickness absenteeism. Conclusion Results confirmed time pressure and time autonomy as limiting factors in healthcare and a key target in work redesign. Keywords healthcare ; occupational health ; time autonomy ; work absenteeism ; work stres

In-depth characterization of as-deposited and annealed Fe-W coatings electrodeposited from glycolate-citrate plating bath

Fe-W coatings with 4, 16 and 24 at.% of W were electrodeposited under galvanostatic conditions from a new environmental friendly Fe(III)-based glycolate-citrate bath. This work aims to find correlations between composition including the light elements, internal structure of the electrodeposited Fe-W alloys and functional properties of material. The obtained alloys were characterized by Glow Discharge Optical Emission Spectrometry (GD-OES), Scanning Electron Microscopy (SEM) with Energy Dispersive X-ray Spectroscopy (EDS), Transmission Electron Microscopy (TEM), and X-ray Diffraction (XRD). Compositional depth profiles of 10 μm thick coatings obtained by GD-OES show that the distribution of metals is uniform along the entire film thickness, while SEM imaging depicted the presence of cracks and O- and W-rich areas inside the Fe-W coating with 4 at.% W. In the samples with 16 and 24 at.% of W, oxygen and hydrogen are present mostly at the surface about 1 μm from the top while traces of carbon are distributed within the entire coatings. With increasing W content, the structure of the coatings changes from nanocrystalline to amorphous which was shown by XRD and TEM analysis. Also, the surface of coatings becomes smoother and brighter, that was explained based on the local adsorption of intermediates containing iron and tungsten species. Annealing experiments coupled with XRD analysis show that the thermal stability of Fe-W alloys increases when the W content increases, i.e. the coating with 24 at.% W retains the amorphous structure up to 600 °C, where a partially recrystallized structure was observed. Upon recrystallization of the amorphous samples the following crystalline phases are formed: α-Fe, Fe2W, Fe3W3C, Fe6W6C, and FeWO4. Hence, the Fe-W coatings with higher W content (>25 at.%) can be considered as suitable material for high temperature applications

Wie viel Koordinierung braucht Europa?

Die Europäische Wirtschafts- und Währungsunion steht am Scheideweg. Einige Mitgliedstaaten leiden unter Verschuldung und hohen Kapitalmarktzinsen. Der strukturelle Reformbedarf ist enorm. Zu Beginn der Krise noch undenkbar fordern manche eine Fiskalunion mit vergemeinschafteter Staatsverschuldung, während andere die einzige Lösung in einer Aufsplittung oder gar Auflösung der Währungsunion sehen. Das Konzept des Kronberger Kreises für eine erfolgreiche europäische Zukunft besteht indes in einer national verantworteten Stabilitätsunion mit einer einvernehmlichen Festlegung auf unverrückbare fiskalpolitische Regeln. So werden die nationalen Unterschiede in der präferierten Ausgaben- und Einnahmestruktur respektiert. Lehnt ein Staat hingegen eine verantwortliche Stabilitätspolitik ab, so hat er die Mitgliedschaft in der Währungsunion verwirkt. Des Weiteren erläutert der Kronberger Kreis in dieser Studie seine Empfehlungen zur europäischen Geldpolitik, insbesondere seine Warnung vor dem Aufkauf von Staatsanleihen, und hinsichtlich einer rigoroseren Bankenregulierung

Renaissance der Angebotspolitik

Von der europäischen Schulden- und Wirtschaftskrise scheint Deutschland unbeeindruckt. Doch die derzeitige wirtschaftliche Stärke bedeutet nicht, dass das deutsche Reformmodell auch zukünftigen Herausforderungen, wie der demografischen Entwicklung und den Belastungen durch Schulden- und Finanzkrise, gewachsen ist. Wenn der bestehende Reformbedarf nicht ernst genommen wird, kann Deutschland sehr schnell wieder zum "kranken Mann Europas" werden. Der Kronberger Kreis empfiehlt der neuen Bundesregierung, sich auf die Angebotspolitik zu konzentrieren und so die deutsche Wettbewerbsfähigkeit zu stärken. In dieser Studie finden sich sorgfältig konzipierte Politikvorschläge für die Gestaltung der öffentlichen Finanzen, der Steuer- und Arbeitsmarktpolitik, der Renten-, Kranken- und Pflegeversicherung, der Energiewende sowie der Privatisierung und Deregulierung. Die Analyse der deutschen Probleme und das Aufzeigen der Lösungskonzepte erfolgen grundsätzlich im europäischen Kontext