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

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

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

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

Gemcitabine and carboplatin in intensively pretreated patients with metastatic breast cancer

Background: Patients with metastatic breast cancer (MBC) are increasingly exposed to anthracyclines and taxanes either during treatment of primary breast cancer or during initial therapy of metastatic disease. The combination of gemcitabine and carboplatin was therefore investigated as an anthracycline- and taxane-free treatment option. Patients and Methods: MBC patients previously treated with chemotherapy were enrolled in a multicenter phase II study. Treatment consisted of gemcitabine (1,000 mg/m(2) i.v. on days 1 and 8) and carboplatin (AUC 4 i.v. on day 1) applied every 3 weeks. Results: Thirty-nine patients were recruited, and a total of 207 treatment cycles were applied with a median of 5 cycles per patient. One complete response and 11 partial responses were observed for an overall response rate of 31% (95% CI: 17-48%). Twelve patients (31%) had stable disease. Median time to progression was 5.3 months (95% CI: 2.6-6.7 months) and median overall survival from start of treatment was 13.2 months (95% CI: 8.7-16.7 months). Grade 3/4 hematological toxicity included leukopenia (59%/5%), thrombo-cytopenia (26%/23%) and anemia (10%/0%). Nonhematological toxicity was rarely severe. Conclusion: Combination chemotherapy with gemcitabine and carboplatin is an effective and generally well-tolerated treatment option for intensively pretreated patients with MBC. Due to a considerable incidence of severe thrombocytopenia it would be reasonable to consider starting gemcitabine at the lower dose level of 800 mg/m(2). Copyright (c) 2008 S. Karger AG, Basel

Erbschaftsteuer: Neu ordnen statt nachbessern

Das Bundesverfassungsgericht hat im Dezember 2014 das geltende Erbschaftsteuerrecht in Deutschland als verfassungswidrig eingestuft. Demnach sei die bestehende steuerliche Verschonung betrieblichen Vermögens im Falle einer Erbschaft oder Schenkung angesichts des bisherigen Ausmaßes und der eröffneten Gestaltungsmöglichkeiten mit dem Grundgesetz unvereinbar. Politik und Verwaltung haben angekündigt, eine "minimalinvasive" Reform vornehmen zu wollen, um die Beanstandungen zu korrigieren. Das Urteil des Bundesverfassungsgerichts bietet jedoch die Chance zu einer grundlegenden Neuordnung der Erbschaftsteuer. Wie könnte demzufolge eine Neuregelung des Erbschaftsteuerrechts aussehen, die nicht nur verfassungskonform, sondern zugleich ökonomisch tragfähig ist? Der Kronberger Kreis, wissenschaftlicher Beirat der Stiftung Marktwirtschaft, präsentiert in der Studie sein Konzept für eine gerechtere und effizientere Erbschaftsteuer und geht auf den vorliegenden Entwurf aus dem Bundesfinanzministerium und die Kabinettsvorlage ein. Es zeigt sich, dass eine gerechte Besteuerung von Erbschaften, die eine Gefährdung von Arbeitsplätzen und unternehmerischen Investitionen vermeidet, mit hohen Steuersätzen und Verschonungsregeln nicht erreicht werden kann. Im Gegensatz zu den Reformvorschlägen der Politik fordert der Kronberger Kreis, die Erbschaftsteuersätze erheblich zu reduzieren und die Bemessungsgrundlage, unter Berücksichtigung ergänzender Stundungen und Freibeträge, zu verbreitern

Dismantling the boundaries of the ECB's monetary policy mandate: The CJEU's OMT judgement and its consequences

The German Federal Constitutional Court (Bundesverfassungsgericht) submitted an order for referral to the European Court of Justice (CJEU) in 2014, asking it to clarify the compatibility of the "Outright Monetary Transactions" (OMT)-Programme with European Union law. The OMT-Programme prepares the ground for the selective purchasing of government bonds of crisis-struck Member States of the European Monetary Union (EMU). A year later, the CJEU decided that the OMT-Programme is covered by the mandate of the European Central Bank (ECB) and does not violate the prohibition of the monetary financing of Member States. Concerns raised by the Federal Constitutional Court were only partially adressed. Now the ball has been passed back to the Federal Constitutional Court. In this study, the Kronberger Kreis, Scientific Council of the Stiftung Marktwirtschaft, explains why the CJEU's reasoning would have irreversable consequences, if the German Federal Constitutional Court were to follow. The CJEU's judgment dismantles the boundaries of the ECB's monetary policy mandate and significantly weakens the prohibition of the monetary financing of Member States in the long run. Effective judicial review of the scope of the ECB's competence would no longer be guaranteed. An act of crisis intervention by the ECB threatens to irrevocably turn the future structure of the EMU into the wrong direction. Nonetheless, the Federal Constitutional Court remains obliged to execute its ultra vires control in an EU-friendly manner. A rupture in the cooperative relationship between the German Federal Constitutional Court and the CJEU could have far-reaching consequences, especially considering the current crisis-riddled state of the EU. The Federal Constitutional Court may therefore want to follow the operative part of the CJEU's judgment, but base it on a different legal reasoning, so as to reserve itself the possibility for future judicial review of the acts of the ECB based on more demanding legal standards than those laid out by the CJEU

Effects of Varying the Three-Body Molecular Hydrogen Formation Rate in Primordial Star Formation

The transformation of atomic hydrogen to molecular hydrogen through three-body reactions is a crucial stage in the collapse of primordial, metal-free halos, where the first generation of stars (Population III stars) in the Universe are formed. However, in the published literature, the rate coefficient for this reaction is uncertain by nearly an order of magnitude. We report on the results of both adaptive mesh refinement (AMR) and smoothed particle hydrodynamics (SPH) simulations of the collapse of metal-free halos as a function of the value of this rate coefficient. For each simulation method, we have simulated a single halo three times, using three different values of the rate coefficient. We find that while variation between halo realizations may be greater than that caused by the three-body rate coefficient being used, both the accretion physics onto Population III protostars as well as the long-term stability of the disk and any potential fragmentation may depend strongly on this rate coefficient.Comment: 29 pages, 7 figures; Accepted for publication in The Astrophysical Journa

Использование метода моделирования ситуаций при обучении студентов вуза английскому языку

В статье описывается опыт проведения занятий по английскому языку у студентов второго курса направления "Горное дело" с использованием современного активного метода обучения case study. Отмечаются преимущества применения технологии моделирования ситуации при преподавании профессионально-ориентированного курса английского языка в вузе