FLT3 Length Mutations as Marker for Follow-Up Studies in Acute Myeloid Leukaemia

Length mutations within the FLT3 gene (FLT3-LM) can be found in 23% of acute myeloid leukaemia (AML) and thus are the most frequent mutations in AML. FLT3-LM are highly correlated with AML with normal karyotype and other cytogenetic aberrations of the prognostically intermediate group. This group is supposed to be a mixed group of AML with differences in the underlying pathogenesis. For more individualized treatment options it would be helpful to better characterize this large AML group not only by molecular mutations but also use these markers for the definition of minimal residual disease (MRD). However, so far the cytogenetically intermediate AML has been lacking suitable markers for PCR-based MRD detection like the fusion genes in the prognostically favourable subgroups. The suitability of the FLT3-LM as a target for PCR-based MRD was discussed controversially as it seemed to be a rather unstable marker. Thus, we aimed at the evaluation of FLT3-LM as a marker for residual disease in a large cohort of AML. Paired samples of 97 patients with AML at diagnosis and at relapse were analyzed. It could be shown that in only four cases a loss of the length mutation was detected. This is in the range of other well-characterized AML relapsing with a different geno- and/or phenotype. In contrast, a change in the ratio of the mutated allele in comparison to the wild-type allele was frequently observed. In detail, the FLT3-LM showed a tendency to accumulate during disease progression and was found more frequently at relapse than at diagnosis. In addition, 45 patients were analyzed at different time points during and after therapy. Using conventional PCR it clearly could be shown that for most of the patients positive at presentation FLT3-LM is a reliable PCR marker for monitoring treatment response. Even an early detection of relapse was possible in some cases. Copyright (C) 2004 S. Karger AG, Basel

Local Agenda 21 in Germany: An inter- and intranational comparison

More than ten years after the Rio Earth Summit in 1992, which marked the institutionalization of Agenda 21 and the beginning of Local Agenda 21 processes all over the world, it is time to summarize and evaluate the situation with respect to Local Agenda 21 in Germany. Even in Germany, which can be considered as a latecomer regarding the implementation of Local Agenda 21, the diffusion of this policy innovation seems to have reached its end. This paper starts from an international, comparative perspective and Germany’s position as a latecomer regarding Local Agenda 21 initiation; however, it focuses primarily on the intranational, comparative standpoint. We analyze the diffusion of Local Agenda 21 in four German states (Länder) (Berlin, North Rhine-Westphalia, Bavaria, and Thuringia). The comparisons between Germany and other countries at international level and between the Länder at national level demonstrate that the diffusion of Local Agenda 21 depends above all on three factors: (1) local authorities’ capacities for action; (2) financial and political support from national and regional governmental organizations; and (3) (trans)national and regional agenda transfer institutions which facilitate the exchange of knowledge and know-how between local authorities, and thus accelerate the diffusion of Local Agenda 21 processes. Local authorities, which have greater capacities for action, which are better supported by the particular German state (Land) where they are located, and which show a higher degree of integration into transfer networks are more active and innovative in the area of Local Agenda 21.Mehr als zehn Jahre nach dem Umweltgipfel in Rio 1992, der die Institutionalisierung der Agenda 21 und den Beginn von Lokalen Agenda 21-Prozessen überall in der Welt kennzeichnete, ist es an der Zeit, die Situation der Lokalen Agenda 21 in Deutschland zu bilanzieren und zu evaluieren. Sogar in Deutschland, das als Nachzügler im Bereich der Implementation der Lokalen Agenda 21 betrachtet werden kann, scheint die Diffusion dieser Politikinnovation an ihrem Ende angelangt zu sein. Als Ausgangspunkt dieses Artikels dient die international vergleichende Perspektive und Deutschlands Position als Nachzügler im Hinblick auf die Initiierung der Lokalen Agenda 21. Die Analyse konzentriert sich allerdings vor allem auf die intranational vergleichende Perspektive. Wir analysieren die Diffusion der Lokalen Agenda 21 in vier ausgewählten deutschen Ländern (Berlin, Nordrhein- Westfalen, Bayern und Thüringen). Die Vergleiche zwischen Deutschland und anderen Ländern auf der internationalen Ebene und zwischen den deutschen Ländern auf der nationalen Ebene zeigen, dass die Diffusion der Lokalen Agenda 21 vor allem von drei Faktoren abhängt: (1) den Handlungskapazitäten der Städte und Gemeinden, (2) der finanziellen und politischen Unterstützung durch nationale und regionale Regierungsorganisationen sowie (3) den (trans)nationalen und regionalen Institutionen des Agenda-Transfers, die den Erfahrungsaustausch zwischen den Kommunen verbessern und die Diffusion von Lokalen Agenda 21- Prozessen beschleunigen. Städte und Gemeinden, die über mehr Handlungskapazitäten verfügen, von dem Bundesland, in dem sie liegen, besser unterstützt werden, und einen höheren Grad der Integration in Transfernetzwerke aufweisen, sind im Bereich der Lokalen Agenda 21 aktiver und innovativer

Local Agenda 21 in Germany: an inter- and intranational comparison

"More than ten years after the Rio Earth Summit in 1992, which marked the institutionalization of Agenda 21 and the beginning of Local Agenda 21 processes all over the world, it is time to summarize and evaluate the situation with respect to Local Agenda 21 in Germany. Even in Germany, which can be considered as a latecomer regarding the implementation of Local Agenda 21, the diffusion of this policy innovation seems to have reached its end. This paper starts from an international, comparative perspective and Germany's position as a latecomer regarding Local Agenda 21 initiation however, it focuses primarily on the intranational, comparative standpoint. We analyze the diffusion of Local Agenda 21 in four German states (Länder) (Berlin, North Rhine-Westphalia, Bavaria, and Thuringia). The comparisons between Germany and other countries at international level and between the Länder at national level demonstrate that the diffusion of Local Agenda 21 depends above all on three factors: (1) local authorities' capacities for action(2) financial and political support from national and regional governmental organizations and (3) (trans)national and regional agenda transfer institutions which facilitate the exchange of knowledge and know-how between local authorities, and thus accelerate the diffusion of Local Agenda 21 processes. Local authorities, which have greater capacities for action, which are better supported by the particular German state (Land) where they are located, and which show a higher degree of integration into transfer networks are more active and innovative in the area of Local Agenda 21." (author's abstract)"Mehr als zehn Jahre nach dem Umweltgipfel in Rio 1992, der die Institutionalisierung der Agenda 21 und den Beginn von Lokalen Agenda 21-Prozessen überall in der Welt kennzeichnete, ist es an der Zeit, die Situation der Lokalen Agenda 21 in Deutschland zu bilanzieren und zu evaluieren. Sogar in Deutschland, das als Nachzügler im Bereich der Implementation der Lokalen Agenda 21 betrachtet werden kann, scheint die Diffusion dieser Politikinnovation an ihrem Ende angelangt zu sein. Als Ausgangspunkt dieses Artikels dient die international vergleichende Perspektive und Deutschlands Position als Nachzügler im Hinblick auf die Initiierung der Lokalen Agenda 21. Die Analyse konzentriert sich allerdings vor allem auf die intranational vergleichende Perspektive. Wir analysieren die Diffusion der Lokalen Agenda 21 in vier ausgewählten deutschen Ländern (Berlin, Nordrhein- Westfalen, Bayern und Thüringen). Die Vergleiche zwischen Deutschland und anderen Ländern auf der internationalen Ebene und zwischen den deutschen Ländern auf der nationalen Ebene zeigen, dass die Diffusion der Lokalen Agenda 21 vor allem von drei Faktoren abhängt: (1) den Handlungskapazitäten der Städte und Gemeinden, (2) der finanziellen und politischen Unterstützung durch nationale und regionale Regierungsorganisationen sowie (3) den (trans)nationalen und regionalen Institutionen des Agenda-Transfers, die den Erfahrungsaustausch zwischen den Kommunen verbessern und die Diffusion von Lokalen Agenda 21-Prozessen beschleunigen. Städte und Gemeinden, die über mehr Handlungskapazitäten verfügen, von dem Bundesland, in dem sie liegen, besser unterstützt werden, und einen höheren Grad der Integration in Transfernetzwerke aufweisen, sind im Bereich der Lokalen Agenda 21 aktiver und innovativer." (Autorenreferat

20 years of BILDUNGSNETZWERK STEIERMARK (EDUCATION NETWORK STYRIA). Networks thrive on human qualities

Das Bildungsnetzwerk Steiermark ist die Service- und Koordinationsstelle der Erwachsenenbildungseinrichtungen in der Steiermark und bietet Bildungsinformation und -beratung wie auch eine Weiterbildungsdatenbank für die steirische Bevölkerung. Es ist mit rund 170 Einrichtungen vernetzt. Das Bildungsnetzwerk hat verschiedene Kommunikationsformate etabliert, damit die Netzwerkarbeit gelingen kann: großflächige schriftliche Information an die Mitglieder ebenso wie persönliches Nachsetzen bei einzelnen Netzwerkpartner*innen, interne ARGE-Netzwerktreffen, monatliche informelle "Donnerstags-Austausche" oder der jährliche Tag der Weiterbildung zur Vernetzung auch außerhalb der Partnereinrichtungen. Ihre Netzwerkarbeit resümierend schreiben die Autorinnen: Netzwerke leben von menschlichen Qualitätsfaktoren. Sie brauchen kontinuierliches Anstoßen, aber auch Geduld und Wertschätzung, persönliches Engagement, persönliche Beziehungsarbeit und geeignete Kommunikationsformate. Um nachhaltig wirken zu können, brauchen sie aber auch Ressourcen, finanziell wie personell. (DIPF/Orig.)Education Network Styria is the service and coordination centre for adult education institutions in Styria and offers educational information and guidance as well as a continuing education databank for the Styrian population. It has ties to around 170 institutions. The network has established different forms of communication for successful networking: frequent electronic mailings to members as well as individual follow-ups with specific network partners, internal working group network meetings, informal "Thursday exchanges" once a month or the annual Continuing Education Day for networking outside the partner institutions. The authors summarize their networking as follows: Networks thrive on human qualities. They require continual nudging as well as patience and appreciation, personal commitment, personal relationship building and suitable communication formats. To have a sustainable effect, however, they need resources - financial as well as human. (DIPF/Orig.

Differential effects of dietary supplements on metabolomic profile of smokers versus non-smokers.

BackgroundCigarette smoking is well-known to associate with accelerated skin aging as well as cardiovascular disease and lung cancer, in large part due to oxidative stress. Because metabolites are downstream of genetic variation, as well as transcriptional changes and post-translational modifications of proteins, they are the most proximal reporters of disease states or reversal of disease states.MethodsIn this study, we explore the potential effects of commonly available oral supplements (containing antioxidants, vitamins and omega-3 fatty acids) on the metabolomes of smokers (n = 11) compared to non-smokers (n = 17). At baseline and after 12 weeks of supplementation, metabolomic analysis was performed on serum by liquid and gas chromatography with mass spectroscopy (LC-MS and GC-MS). Furthermore, clinical parameters of skin aging, including cutometry as assessed by three dermatologist raters blinded to subjects' age and smoking status, were measured.ResultsLong-chain fatty acids, including palmitate and oleate, decreased in smokers by 0.76-fold (P = 0.0045) and 0.72-fold (P = 0.0112), respectively. These changes were not observed in non-smokers. Furthermore, age and smoking status showed increased glow (P = 0.004) and a decrease in fine wrinkling (P = 0.038). Cutometry showed an increase in skin elasticity in smokers (P = 0.049) but not in non-smokers. Complexion analysis software (VISIA) revealed decreases in the number of ultraviolet spots (P = 0.031), and cutometry showed increased elasticity (P = 0.05) in smokers but not non-smokers.ConclusionsAdditional future work may shed light on the specific mechanisms by which long-chain fatty acids can lead to increased glow, improved elasticity measures and decreased fine wrinkling in smokers' skin. Our study provides a novel, medicine-focused application of available metabolomic technology to identify changes in sera of human subjects with oxidative stress, and suggests that oral supplementation (in particular, commonly available antioxidants, vitamins and omega-3 fatty acids) affects these individuals in a way that is unique (compared to non-smokers) on a broad level

AbspectroscoPY, a Python toolbox for absorbance-based sensor data in water quality monitoring

The long-term trend of increasing natural organic matter (NOM) in boreal and north European surface waters represents an economic and environmental challenge for drinking water treatment plants (DWTPs). High-frequency measurements from absorbance-based online spectrophotometers are often used in modern DWTPs to measure the chromophoric fraction of dissolved organic matter (CDOM) over time. These data contain valuable information that can be used to optimise NOM removal at various stages of treatment and/or diagnose the causes of underperformance at the DWTP. However, automated monitoring systems generate large datasets that need careful preprocessing, followed by variable selection and signal processing before interpretation. In this work we introduce AbspectroscoPY ("Absorbance spectroscopic analysis in Python"), a Python toolbox for processing time-series datasets collected by in situ spectrophotometers. The toolbox addresses some of the main challenges in data preprocessing by handling duplicates, systematic time shifts, baseline corrections and outliers. It contains automated functions to compute a range of spectral metrics for the time-series data, including absorbance ratios, exponential fits, slope ratios and spectral slope curves. To demonstrate its utility, AbspectroscoPY was applied to 15-month datasets from three online spectrophotometers in a drinking water treatment plant. Despite only small variations in surface water quality over the time period, variability in the spectrophotometric profiles of treated water could be identified, quantified and related to lake turnover or operational changes in the DWTP. This toolbox represents a step toward automated early warning systems for detecting and responding to potential threats to treatment performance caused by rapid changes in incoming water quality

Entwicklung von Oligonukleotidarrays für den Mikrobennachweis

Anordnungen von biomolekularen Sonden auf Festkörperoberflächen (Arrays, Chips) sind das Herzstück von Konzepten zum Aufbau von parallel arbeitenden miniaturisierten Analysesystemen, die die heute üblichen Verfahren beim chemisch-biologischen Screening und der molekularen Diagnostik ersetzen werden. Die Arrays werden nach der Art der immobilisierten Sonden bzw. nach Art der Herstellung der Sonden unterteilt. Die DNA-Sonden werden entweder in situ mittels photolithographischer Methoden unter Verwendung physikalischer Masken auf der Matrix synthetisiert oder durch verschiedene Verfahren aufgedruckt. Die Herstellung von gedruckten DNA Mikroarrays gliedert sich in die Schritte der Aktivierung bzw. Beschichtung der festen Chipmatrix, an die Biomoleküle über eine geeignete Kopplungschemie fixiert werden. Zur Herstellung von Oligonukleotidarrays für den Mikrobennachweis wurden Glasobjektträger mit Polymermaterialien beschichtet und mit unmodifizierten oder amino-modifizierten 18-50mer Oligonukleotiden bedruckt. Die Oligonukleotide wurden mit dem piezoelektrischen BioChip Arrayer von Packard in Volumina von 0,35-2 nl auf dem Chip aufgebracht. Die Spotmorphologie wurde in Abhängigkeit vom Spotvolumen, dem Druckpuffer und der Polymereigenschaften untersucht

Molecular analysis of myelodysplastic syndrome with isolated deletion of the long arm of chromosome 5 reveals a specific spectrum of molecular mutations with prognostic impact: a study on 123 patients and 27 genes

The only cytogenetic aberration defining a myelodysplastic syndrome subtype is the deletion of the long arm of chromosome 5, which, along with morphological features, leads to the diagnosis of myelodysplastic syndrome with isolated deletion of the long arm of chromosome 5. These patients show a good prognosis and respond to treatment such as lenalidomide, but some cases progress to acute myeloid leukemia; however, the molecular mutation pattern is rarely characterized. Therefore, we investigated a large cohort of 123 myelodysplastic syndrome patients with isolated deletion of the long arm of chromosome 5, diagnosed following the World Health Organization classifications 2008 and 2016, by sequencing 27 genes. A great proportion of patients showed no or only one mutation. Only seven genes showed mutation frequencies >5% (SF3B1, DNMT3A, TP53, TET2, CSNK1A1, ASXL1, JAK2). However, the pattern of recurrently mutated genes was comparable to other myelodysplastic syndrome subtypes by comparison to a reference cohort, except that of TP53 which was significantly more often mutated in myelodysplastic syndrome with isolated deletion of the long arm of chromosome 5. As expected, SF3B1 was frequently mutated and correlated with ring sider-oblasts, while JAK2 mutations correlated with elevated platelet counts. Surprisingly, SF3B1 mutations led to significantly worse prognosis within cases with isolated deletion of the long arm of chromosome 5, but showed a comparable outcome to other myelodysplastic syndrome subtypes with SF3B1 mutation. However, addressing genetic stability in follow-up cases might suggest different genetic mechanisms for progression to secondary acute myeloid leukemia compared to overall myelodysplastic syndrome patients

“Revista-Valise”: from its creation to its editing experience

This article aims to convey the reflections implemented throughout the preparation process of “Revista-Valise”, as well as its development and creation experience. “Revista-Valise” is a biannual visual arts-oriented academic journal managed by the alumni at Federal University of Rio Grande do Sul (UFRGS)’s Graduate Program in Visual Arts. Here, we will present all the steps taken to build it, such as the project’s goals, the editorial team’s formation, the delineation of the journal’s scope, tutorials, invitation of peers, editals and details on receiving and forwarding articles to peers for evaluation